Scottish Referral Guidelines for Suspected Cancer 2025

Cancer Referral Guidelines

Brain and Central Nervous System (CNS) Cancers

There are around 1,000 incidences of brain and central nervous system (CNS) tumours in Scotland a year. Approximately 50% of these are malignant brain cancers. Currently around one in three people (34% of adults aged 15-99) diagnosed with brain and CNS cancers in Scotland survive their disease for one year or more (data covering years of diagnosis 2015-2019)^[19]. Brain cancer patients in Scotland are more likely than other groups of cancer patients to be diagnosed via an emergency route, with greater than 70% of brain and other CNS cancer patients being diagnosed through emergency routes.

Timely diagnosis of brain and CNS cancers is challenging. Most patients with neurological symptoms are diagnosed with benign disease, meaning primary healthcare professionals encounter brain and CNS cancers infrequently^[20]. Multiple consultations prior to referral can occur commonly among adults subsequently diagnosed with primary brain cancers. Evaluation of the National Cancer Patient Experience Surveys (CPES) (England) showed that 39% of brain and CNS cancer patients had three or more pre-referral consultations with a GP compared with an average of 25% for all cancers^[21].

Assessment for Suspected Brain & CNS Cancers

The anatomical location of brain and CNS cancers influences presenting features that include physical, cognitive and psychological components. Better safe than tumour contains more information on possible symptoms of brain cancer.

If there is concern that a person may have a brain/CNS cancer the following should be assessed for:

• Headache suggestive of raised intracranial pressure (ache generalised over the cranium, worst on awakening, may awaken the person from sleep, aggravated by bending or stooping, severity gradually progresses, associated nausea/vomiting)
• Papilloedema (optic nerve head swelling due to raised intracranial pressure) - if there is uncertainty, the person should be referred urgently to an optometrist for assessment
• Focal neurological deficit
• New seizures (will often require a witness account) including those without collapse (e.g. vacant episodes, transient self-limiting motor, or sensory change)
• Changes in cognition or personality (symptomatic or noted by others)
• Changes in speech such as difficulty finding words or using the wrong words
• History of Human Immunodeficiency Virus (HIV) or cancer originating in other parts of the body (especially lung, breast, melanoma or renal)

Single clinical features alone are poorly predictive of brain cancers e.g. headache without other clinical features has a PPV of 0.1%^[22]. However, by the time of diagnosis, headache and cognitive symptoms co-occur with a PPV of 7.2%, supporting the importance of searching for “headache plus” other symptoms^[22]. At the early stages of disease, cognitive changes may be subtle or go unnoticed by patients and may only be apparent retrospectively.

Emergency (same day) Referral

Refer a person with two or more of the following as an emergency (same day):

• New headache
• New seizure
• Papilloedema
• New focal neurological deficit

Urgent Suspicion of Cancer (USC) Referral

Refer a person with a headache where there is concern about a brain/CNS cancer plus one or more of the following features:

• Cognitive change – symptomatic or noted by others
• Personality change
• History of cancer (especially lung, breast, melanoma or renal)
• History of HIV

Good Practice Points

Referral guidance:

Boards’ local pathways for referral of a headache which raises suspicion for brain cancer should be followed. If this includes direct access to imaging it must be delivered urgently to avoid a delay in diagnosis. Imaging should not be used in place of an emergency referral if that is more appropriate.

When referring to secondary care, a note should be made of any recent brain imaging as this may alter the urgency and the need for further radiology assessment.

Refer a person urgently to an optometrist for assessment if there is uncertainty about the presence of papilloedema or visual field loss. If papilloedema is confirmed, consideration should be given to same day referral to secondary care. A clear plan should be made as to who will be responsible for the follow-up of the results of an optometry assessment.

Headache management:

Many people presenting with headache will not fit into the referral guideline above. CfSD has published the National Headache Pathway to guide referral in other scenarios.

Assessing changes in cognition:

Changes in cognition may not be volunteered by a person presenting with signs and symptoms of a brain tumour and direct enquiry may have to be made. The Semantic Verbal Fluency Test (SVFT) is a quick test which can be done easily in practice and may indicate cognitive deficit if the score is reduced (i.e. less than 17 different animals named in one minute). A headache concerning for a brain tumour along with a reduced SVFT score has been shown to have a PPV higher than 5%^[23]. Please note that a SVFT score may be reduced in other conditions such as dementia, previous serious head injury, stroke, learning disabilities or for those whose first language is not English.

Breast Cancer

Breast cancer is the most common (non-skin) cancer in women in Scotland, with around 5,140 new cases each year. Breast cancer is much less likely in men, with approximately 40 cases per year in Scotland. Incidence rises from age 30 in women (more than 99.5% of new cases are aged 30 years or over) and from age 45 in men (more than 90% of new cases are aged 45 or over).

Most breast cancers are diagnosed at an early stage (1 or 2). In 2022, 38.0% of cases were diagnosed at stage 1, 46.5% at stage 2, 8.4% at stage 3, 4.8% at stage 4, and 2.2% were diagnosed at an unknown stage in Scotland^[5]. Women diagnosed at an earlier stage may have an improved chance of survival^[24]. Stage distribution differs by deprivation, with women living in more deprived areas being more likely to experience an advanced stage breast cancer diagnosis^[4].

There are several risk factors for breast cancer, including^[25]:

• Significant family history of breast cancer (see good practice section) or an inherited genetic alteration
• A previous diagnosis of breast cancer
• Early menarche (before age 11)
• Oral contraceptive use or hormone replacement therapy
• Older age at first giving birth (35 years or over)
• Nulliparity
• Not breastfeeding
• Older age at menopause (50 years or over)

The risk of breast cancer is also two to four times higher in women with previous false-positive breast screening results^[26].

Published data has shown that transgender women have a higher risk of breast cancer compared to men, and transgender men have a lower risk of breast cancer compared to women. In transgender women the risk of breast cancer is associated with hormone treatment^[27]. In cases of gender reassignment, it is important to provide sensitive and clinically appropriate care depending on individual circumstances and considering any hormone therapy involved.

Help-seeking behaviours and awareness of symptoms varies by demographic. There is evidence suggesting that first-generation Black African and Black Caribbean women in the UK who were diagnosed with symptomatic breast cancer had lower symptom awareness and faced barriers which resulted in delayed help-seeking^[28].

Assessment for Suspected Breast Cancer

Breast cancer is characterised by a narrow symptom signature, meaning that most people present with only a few specific symptoms such as a breast lump and typically have short diagnostic intervals.

Assessment of a person presenting with breast symptoms or signs should include examination to determine if any lump (discrete, palpable abnormality) or lesion (any abnormal tissue change) is within the breast tissue, or related to the skin and if there are any associated axillary lumps. If there is an axillary lump without other breast findings, examination for other lymphadenopathy should be performed.

It is helpful to document if any nipple discharge is spontaneous or expressed, is from a single duct, multiple ducts or bilateral and if there is any blood staining. It is also helpful to note if any nipple inversion is fixed or reversible.

Any pain should be assessed to determine if it is coming from the breast or the chest wall.

Ask about any family history of breast cancer or other cancers related to inherited genetic alterations (e.g. ovarian cancer). Also ask about past medical history including menopausal status, previous chest radiotherapy, and mammography or breast screening results, as patients with false-positive results have a higher risk of developing breast cancer.

Urgent Suspicion of Cancer (USC) Referral

Refer a person with any of the following to the Breast Service as a USC:

Lump:

• New breast lump in a person aged 30 years or over
• New breast lump in a person aged under 30 who also has other suspicious features such as an axillary lump, nipple or skin changes (as below) or a significant family history of breast cancer (see Appendix 5)
• New, unexplained axillary lump (2 cm or more in size, persisting for six weeks or more, or increasing in size)

Nipple changes:

• Nipple discharge that is serosanguinous (clear yellow liquid with or without red blood staining)
• New, unilateral and non-reversible nipple retraction
• Unilateral nipple eczema that is unresponsive to a two-week treatment with moderately potent topical steroids

Skin changes:

• Skin tethering
• Peau d’orange
• Unexplained, new breast ulceration

Inflammation:

• Mastitis or breast inflammation that does not settle or recurs after one course of antibiotics

Good Practice Points

Access CfSD breast pathways for support in managing a range of breast symptoms, including breast pain.

Breast lump:

Consider a non-USC referral for a person with:

• New asymmetrical breast nodularity (generalised unevenness or thickened areas rather than a discrete lump) that persists for three weeks or more
• A new breast lump under 30 years of age but with no other suspicious features (described above under USC referral)

Infection:

An acute breast abscess requires immediate discussion with the breast team or on-call surgical team for management.

Male breast cancer:

Breast cancer is much less common in men than women. Most men are diagnosed over the age of 60. It can be confused with gynaecomastia. Gynaecomastia is a benign enlargement of the male breast with firm tissue extending concentrically beyond the nipple. It may present as unilateral, bilateral, painful or asymptomatic. If a man presents with a new breast lump (not generalised breast tissue swelling or a skin lesion close to the breast) or other suspicious features as described above, they should be referred as a USC.

Breast pain:

Breast pain alone (no associated suspicious features described above under USC referral), is not associated with breast cancer – see CfSD pathway.

Skin and nipple changes:

Skin and nipple changes are common breast symptoms. Suspicious changes described above should be referred as a USC. Available guidelines on Right Decision Service (RDS) should be followed for other skin or nipple changes.

Axillary lumps:

Breast cancer rarely presents with axillary nodes alone. Consider other malignant or non-cancer causes of lymphadenopathy such as, connective tissue disease, eczema and HIV infection. Consider other causes of axillary lumps, for example, skin lesions or accessory breast tissue.

If axillary lymph node(s) are persisting with no obvious cause, the patient should be referred to secondary care. Further guidance on assessment of lymphadenopathy can be found in the Haematological Cancers Referral Guideline.

Breast implants:

In the context of breast implants, it is important to determine if the issue being described relates to the implant or the overlying breast tissue. If there is an implant issue rather than a breast issue, then please refer to the service that first inserted the implant (usually plastic surgery) or follow your local pathway.

Family history:

A family history of breast cancer increases the risk of developing breast cancer, however most women diagnosed will not have a family history. See Appendix 5 for advice on referral.

Recurrence of primary breast cancer:

Recurrence is when a breast cancer has come back, it is not a new breast cancer. If a patient has been discharged from follow-up they may present in primary care. For recurrence symptoms see the Breast Clinical Management Pathway.

Metastatic breast cancer:

Metastatic or secondary breast cancer is when breast cancer spreads to other parts of the body, such as the bones, liver, lungs or brain. For metastatic breast cancer symptoms please see the Breast Clinical Management Pathway and refer to the Non-Specific Cancer Referral Guideline.

Gynaecological Cancers

Gynaecological cancer is an umbrella term for ovarian, endometrial, cervical, vaginal and vulval cancers. These cancers tend to present with different symptoms and have different stage distributions and outcomes.

In 2021, 19.8% of corpus uteri cancers, 32.3% of cervix uteri cancers, and 39.8% of ovarian cancers were diagnosed at stage 3 or 4^[29].

Evidence has shown inequalities in cervical screening uptake, with those from areas of deprivation demonstrating lower uptake^[30]. Further research is required to understand the risk of reproductive cancers in transgender people and any barriers to timely recognition and referral in a symptomatic context.

Ovarian cancer:

Approximately 585 new cases of ovarian cancer are diagnosed in Scotland every year, more than 90% of which are in women aged 40 years or over. Family history (both maternal and paternal) of breast or ovarian cancer can be used to identify women who have a higher risk of developing ovarian cancer. See Appendix 5.

Endometrial cancer:

Approximately 800 new cases of endometrial cancer are diagnosed in Scotland each year^[31]. Fewer than 5% of cancers of the corpus uteri (which includes endometrial cancer) occur in women below the age of 45.

Risk factors for endometrial cancer include:

• Obesity
• Age over 45 years
• Nulliparity
• Exposure to unopposed oestrogens
• Tamoxifen usage
• Family history of endometrial or colon cancer

Thrombocytosis is a risk marker for underlying malignancy including endometrial cancer^[17]. There should be a higher index of suspicion for women with associated risk factors.

Cervical cancer:

Cervical cancer affects all adult age groups, with above 50% of cases occurring between the ages of 30 and 50 years. 40% of new cervical cancer cases in women of screening age (25-64 years) were screen detected in Scotland in 2022.

Taking a cervical sample in symptomatic individuals is not necessary before referral. Cervical sampling is intended to be used as a screening tool to detect pre-cancerous changes in asymptomatic people, not for diagnosing symptomatic cancers. A previous negative screening result is not a reason to delay referral.

Vaginal cancer:

Vaginal cancer is rare and comprises of less than 1% of gynaecological cancers. It is most frequently diagnosed in women aged 60 years or over and is rare in women aged under 40. Approximately 30 new cases of vaginal cancer are diagnosed in Scotland every year.

Vulval cancer:

There are about 155 new cases of vulval cancer diagnosed every year in Scotland, approximately 60% of which are in women aged 65 years or over. Lichen sclerosis increases the risk of developing invasive squamous vulval cancer, but the overall risk remains low^[32].

Assessment for Suspected Gynaecological Cancers

Recognising gynaecological cancers in primary care can be challenging, as many symptoms (e.g. bloating, pelvic pain) are non-specific and are often caused by benign disease^[33]. There are different investigations required depending on the cancer suspected.

Ovarian cancer:

Presenting features often include non-specific abdominal symptoms that are persistent and frequent - there may be a palpable pelvic mass^[34].

An abdominal palpation should be undertaken, CA125 blood serum level measured, and a USC pelvic ultrasound scan (USS) arranged in:

• Women (especially those aged 50 or over) with one or more of the following unexplained symptoms occurring most days over the last four weeks:
• abdominal distension or persistent bloating
• feeling full quickly, difficulty eating or loss of appetite
• pelvic or abdominal pain
• increased urinary urgency and/or frequency
• change in bowel habit

• Women aged 50 or over who have experienced new symptoms within the last 12 months that suggest irritable bowel syndrome

CA125 is not raised in all cases of ovarian cancer and therefore this test should always be done in conjunction with a pelvic USS in those with symptoms or signs that are suspicious of ovarian cancer.

Endometrial, cervical and vaginal cancer:

Most women with endometrial cancer present with postmenopausal bleeding^[35]. For the purpose of this guideline we define postmenopausal bleeding as vaginal bleeding occurring 12 months or more after periods have stopped.

Typical symptoms of cervical cancer include vaginal discharge and abnormal vaginal bleeding.

A full pelvic examination, including speculum examination of the cervix, should be considered in women presenting with:

• Abnormal vaginal bleeding (including postmenopausal bleeding, post-coital bleeding and persistent intermenstrual bleeding)
• Unexplained vaginal discharge
• Pelvic pain

A woman presenting with a palpable abdominal or pelvic mass on examination that is not obviously uterine fibroids, gastrointestinal or urological in origin should be referred for a USC priority ultrasound scan.

Vulval cancer:

Women with vulval cancer usually present with bleeding, discomfort, an itch or a burning sensation^[36]. The majority of patients have a visible ‘tumour’ on clinical examination^[36]. Failure of treatment for ‘benign conditions’ should prompt consideration of further assessment or referral.

A vulval examination should be carried out for any woman with vulval symptoms.

Urgent Suspicion of Cancer (USC) Referral

Refer a woman with any of the following to the Gynaecology Service as a USC:

Ovarian cancer:

• An ultrasound scan (USS) suggesting ovarian cancer or abdominal/pelvic mass (not obviously uterine fibroids, gastrointestinal or urological in origin)
• A raised CA125 (a level of 35 International Units per millilitre (IU/ml) or greater)
• Unexplained ascites

Endometrial cancer:

• Postmenopausal bleeding in a person with an intact uterus who is:
• not taking hormone replacement therapy
• taking hormone replacement therapy and has risk factors for endometrial cancer – see British Menopause Society Guidance
• Abnormal vaginal bleeding in a person who currently takes or has a previously taken Tamoxifen
• A USS suggesting endometrial cancer

Cervical cancer:

• An abnormal cervical examination and symptoms suggestive of cervical cancer:
• vaginal discharge
• postmenopausal, postcoital or persistent intermenstrual bleeding
• pelvic pain

Vaginal cancer:

• A suspicious abnormality of the vagina

Vulval cancer:

• Unexplained vulval lump, bleeding or ulceration

Good Practice Points

Referral guidance:

If there is significant concern, awaiting the results of any investigation should not delay referral.

It is important to remember that transmen may still have female reproductive organs and, therefore, are still at risk of gynaecological cancers.

Ultrasound for assessing the pelvis:

Transvaginal USS is more sensitive for assessment of the female pelvis than transabdominal USS. It is important to request the correct test based on the information required. Local pathways should be followed when requesting a USS.

Abnormal vaginal bleeding:

Abnormal vaginal bleeding is a common presentation to primary care. Endometrial cancer is uncommon in pre-menopausal women. An urgent gynaecology referral or pelvic USS request should be considered for women with premenopausal abnormal vaginal bleeding that persists after medical management. A woman with abnormal vaginal bleeding on HRT should be assessed for endometrial cancer risk according to British Menopause Society Guidance.

CA125:

CA125 may be elevated in many physiological and pathological conditions (Raised CA125 – what we actually know), which may be gynaecological or non-gynaecological. The physiological causes include menstruation, so it is advisable to avoid sample taking during this time if possible. CA125 can be elevated in other cancers (e.g. pancreas, breast, lung and colon). If the person has a normal USS, then referral guidelines for other cancers or non-specific symptoms should also be considered.

Overlap with other pathways:

Patients with intra-abdominal cancer can present with symptoms that overlap. A Quantitative Faecal Immunochemical Test (qFIT) should be considered if there is a change in bowel habit – please see Upper and Lower Gastrointestinal Cancers and Kidney Cancers Guidelines.

Haematological Cancers

This Guideline is for adult cancer referrals. Please see the Cancer in Children and Young People Guideline for a person within that age range in whom there is concern about a possible haematological cancer.

Haematological cancer is an overarching term for three main groups of cancers: leukaemia, lymphoma and multiple myeloma. These are further divided into sub-types.

Route to diagnosis data for emergency presentations versus GP referrals for haematological cancers is not yet publicly available for Scotland. However, in England (2019 data) the highest proportion (40.0%) of haematological cancers are diagnosed following a GP referral, with emergency presentations accounting for 26.6% of all referrals^[19]. Survival for those diagnosed with a haematological cancer via an emergency route is significantly worse compared to other routes^[37]. There are differences in haematological cancer incidence based on ethnicity. For example, there is a higher incidence of myeloma in people of black ethnicity^[38].

Leukaemia (acute and chronic):

Approximately 670 people are diagnosed with leukaemia in Scotland each year. Although all ages can be affected, around 70% of new cases occur in people aged 60 years or over. The most common form of leukaemia in adults is Chronic Lymphocytic Leukaemia (CLL), which is often an indolent disease and an incidental finding.

Non-Hodgkin’s Lymphoma:

Approximately 1,050 new cases of Non-Hodgkin’s Lymphoma are diagnosed in Scotland each year. Although all ages can be affected, around 75% of cases occur in people aged 60 or over.

Hodgkin’s Lymphoma:

Approximately 180 new cases of Hodgkin’s Lymphoma are diagnosed in Scotland each year, with around 45% of new cases occurring in people under the age of 40.

Myeloma:

Approximately 510 new cases of multiple myeloma and malignant cell neoplasms are diagnosed in Scotland each year, with around 85% occurring in people aged 60 years or over.

The presence of an isolated paraprotein or Monoclonal Gammopathy of Unknown Significance (MGUS) is not a cancer and is a common incidental finding in the elderly (8.9% of people over 85 years of age)^[39]. MGUS can progress to myeloma or related lymphoplasmacytic malignancies at a rate of 1% per year^[39]. Monitoring of patients with MGUS should be considered after shared decision-making taking into account the risk, benefits, and limitations of further surveillance.

Assessment for Suspected Haematological Cancers

Leukaemia (acute and chronic):

Acute leukaemia often presents rapidly with clinical features of bone marrow failure such as fatigue, pallor, bruising, bleeding and infections which can be particularly severe. Due to extramedullary leukaemic infiltration there can be lymphadenopathy and/or hepatosplenomegaly.

Chronic myeloid leukaemia (CML) usually develops gradually and in the early chronic phase people are often asymptomatic. CML can progress to a more accelerated phase with symptoms arising from the accumulation of abnormal cells in the bone marrow and blood. Clinical features include, anaemia, low platelets, repeated infections, splenomegaly, drenching sweats and weight loss.

Chronic lymphocytic leukaemia (CLL) is an indolent haematological cancer that can be an incidental finding on a blood test or present with lymphadenopathy, splenomegaly, symptoms of associated cytopenia (breathlessness, fatigue, petechiae, infections) or B symptoms (weight loss, fever or drenching night sweats).

Consider urgent clinical assessment, including full blood count (FBC), of an adult patient with any of the following unexplained features:

• Pallor
• Bleeding, bruising or petechial haemorrhage
• Fatigue
• Breathlessness
• Recurrent infections
• Fever
• Drenching night sweats
• Lymphadenopathy (lymph node 2 cm or more in size, persisting for six weeks or more, or increasing in size, or generalised lymphadenopathy)
• Hepatomegaly and/or splenomegaly

Lymphoma:

Common presenting features include fatigue, weight loss, night sweats, lymphadenopathy and hepatomegaly and/or splenomegaly. 95% of people with Hodgkin’s Lymphoma present with lymph node involvement.

Consider full blood count, renal function, liver function, calcium, lactate dehydrogenase (LDH), serum protein electrophoresis and HIV serology, for an adult patient with any of the following unexplained features:

Lymphadenopathy (lymph node 2 cm or more in size, persisting for six weeks or more, or increasing in size, or generalised lymphadenopathy)

• Fatigue
• Drenching night sweats
• Fever
• Splenomegaly and/or hepatomegaly
• Breathlessness
• Pruritus
• Weight loss

Myeloma:

Clinical features at presentation include bone pain, symptoms of anaemia, renal impairment (e.g. fatigue, pruritus without rash) and symptoms of hypercalcaemia (e.g. constipation, confusion, polyuria, or polydipsia).

Consider FBC, plasma viscosity or Erythrocyte Sedimentation Rate (ESR), renal function and calcium blood tests for a person, particularly if aged 60 years or over, with any of the following unexplained features:

• Bone pain, particularly bony back pain
• Fractures (pathological or fragility), or bone x-rays reported as being suggestive of myeloma
• Fatigue
• Polyuria, polydipsia
• Peripheral neuropathy
• Recurrent infection (e.g. blood stream infection, pneumonia)

CRAB features of myeloma:

• Raised Calcium
• Renal impairment
• Anaemia
• Bone pain

Further testing should be done if there are suspicious abnormalities in these initial blood tests or ongoing clinical concern of a myeloma diagnosis. This should include serum immunoglobulins, serum protein electrophoresis, serum Free Light Chains (sFLC) or urinary Bence Jones Proteins if sFLC testing is not available.

Emergency (same day) Referral

Refer a person with any of the following as an emergency (same day):

• Blood count/film reported as suggestive of Acute Leukaemia or Chronic Myeloid Leukaemia (CML)
• Blood tests or imaging suggestive of myeloma with symptoms/signs of Malignant Spinal Cord Compression or acute kidney injury

Urgent Suspicion of Cancer (USC) Referral

Refer a person with any of the following to the Haematology Service as a USC:

• Lymphocyte count >5 x 10⁹/l and any of the following features:
  • weight loss, fever, or drenching night sweats
  • lymphadenopathy and/or splenomegaly
  • cytopenia (haemoglobin less than 100 g/l, neutrophils less than 1.0 x 10⁹/l, platelets less than 100 x 10⁹/l)

• Test results reported as suggestive of a diagnosis of myeloma (raised paraprotein concentrations, paraprotein bands, or abnormal sFLC or urinary Bence Jones proteins) with one or more CRAB criteria (Raised Calcium, Renal impairment, Anaemia, or Bone pain)
• Generalised lymphadenopathy particularly with systemic upset (e.g. drenching night sweats or unintentional weight loss) and/or hepatomegaly and/or splenomegaly

Refer the following for consideration of assessment and / or biopsy via local pathways as a USC:

• Unexplained isolated lymphadenopathy (2 cm or more in size, persisting for six weeks or more, or increasing in size)

Good Practice Points

Lymphocytosis or raised paraproteins:

Blood test results showing lymphocytosis or raised paraprotein levels without the additional features outlined in the referral criteria above, should not be referred as USC. Local guidelines should be followed for non-USC referral or primary care management.

Myeloma is a difficult cancer to identify, especially in its early stages as it often presents with vague symptoms which could also have many other alternative causes. If blood tests are normal, myeloma is unlikely and other causes of the symptoms should be considered, investigated or referred via non-specific pathways as appropriate^[40].

Detailed clinical information submitted at the time of request for a blood test helps to improve advice and onward referral for patients.

Safety netting:

Baseline tests and investigations should be repeated if a person’s condition remains concerning and unexplained following investigation for other causes. This should be combined with safety netting advice for the patient. For people presenting with non-specific symptoms, the clinician should always consider checking HIV status along with other routine investigations.

Splenomegaly:

Splenomegaly can be identified on imaging (e.g. USS or Computed Tomography (CT) abdomen). When assessing splenomegaly, the spleen size calculator could be a useful resource.

Rarer blood cancers:

Further information on blood cancers including rarer cancers such as myeloproliferative neoplasms and myelodysplastic syndromes can be found via Blood Cancer UK or Cancer Research UK resources.

Children and young people:

The SRG for haematological cancers in children and young people has different criteria than the adult guideline. Please check the relevant section when considering children and young people.

Head and Neck and Thyroid Cancers

Head and neck cancer:

This is an umbrella term encompassing multiple types of cancer including pharynx (oropharynx, hypopharynx, nasopharynx), larynx, oral cavity, nasal, paranasal, and salivary gland.

Approximately 1,400 head and neck cancers are diagnosed each year in Scotland. Incidence for head and neck cancer rises from the age of 35 (more than 99% of new cases are aged 35 years or over) and there are over twice as many cases in males compared with females.

Groups with worse outcomes and higher rates of emergency presentation include people from more deprived areas, those from ethnic minority groups, older people and those with multiple comorbidities^[41]-[44].

Risk factors for head and neck cancers include:

• Socio-economic deprivation
• Smoking and tobacco chewing habits (including betel, gutkha, snus and pan)
• Human Papilloma Virus (HPV) (increasing incidence of oropharyngeal cancer in a younger population)
• Excessive alcohol use
• Recreational drug use (especially opioids and cannabis)
• Poor diet
• Older age

HPV may be the only risk factor in younger groups (30-40 years), who may not present with typical risk factors (e.g. have never smoked or used drugs recreationally).

Thyroid cancer:

People with suspected thyroid cancer are referred to the Head and Neck Service. There are around 320 new cases of thyroid cancer a year in Scotland. Thyroid cancers can occur at any age and are more common in females and those with a history of neck irradiation^[1],[44].

Assessment for Suspected Head and Neck Cancers

Assessment of a person presenting with head and neck symptoms should include examination of the neck to ascertain the position, mobility and consistency of any neck lump. Lymph nodes felt behind the sternomastoid muscle are more likely to be reactive and less concerning than those found in front of it or below the angle of the jaw. Intradermal lumps, which are often sebaceous cysts and lipomas, are superficial and can be differentiated from deeper lumps by palpation. They are often found on the scalp and do not require referral on a head and neck pathway.

It is helpful to ask about drug use as well as smoking and alcohol intake as laryngeal cancer is seen in younger patients who use recreational drugs. It is also helpful to document any pain on swallowing which radiates to the ear (in the absence of any infection) as this can be a sign of malignancy.

Emergency (same day) Referral

Head and neck or thyroid cancer:

Refer any person presenting with upper airway compromise (e.g. stridor) as an emergency (same day).

Urgent Suspicion of Cancer (USC) Referral

Head and neck cancer:

Refer a person with any of the following unexplained clinical features lasting three weeks or more to the Head and Neck Service as a USC:

• Constant hoarseness (voice is never normal) in those aged 35 years or over
• Constant unilateral throat pain (not simply a feeling of something stuck in the throat - FOSSIT)
• Pain on swallowing (odynophagia)
• Red or mixed red and white patches of the oral mucosa (not oral thrush)
• Ulceration or swelling/induration of the oral mucosa
• Neck or parotid lump

Thyroid cancer:

Refer a person with a thyroid nodule, and one or more of the following features to the Head and Neck Service as a USC:

• Nodule rapidly increasing in size
• Associated unexplained hoarseness
• Associated cervical lymphadenopathy
• Previous neck irradiation
• Family history of endocrine tumours
• Person aged 16 years or under

Good Practice Points

Changing pattern of disease:

For head and neck cancers (not thyroid) there is a changing pattern of disease (in particular HPV associated cancers). Younger age and absence of smoking or alcohol history should not be barriers to referral if there are concerning features as described above.

Neck lumps:

It is crucial that a good description of any neck lump is given in the referral to secondary care. Key features to cover are the position, size, shape, consistency, mobility and overlying skin changes. Sebaceous cysts and lipomas do not require referral to head and neck services. Small, mobile and rubbery lumps are likely to be reactive lymph nodes and in the absence of the above concerning features can be followed up clinically or assessed by a neck USS in the first instance, where available.

Thyroid nodules that do not have the features described in the USC referral section above can be referred as non-USC for further assessment.

Symptom combinations:

The PPV for single symptoms in head and neck cancer are lower than the 3% threshold set as a baseline in this guide. Hoarseness is the only symptom that nears the threshold at 2.7% for laryngeal cancer.

Symptom clusters can be useful in identifying those at higher risk of head and cancer e.g. combination of hoarseness, dysphagia and pain on swallowing, especially if radiating to the ear is very suspicious of cancer in the upper airway.

A feeling of something stuck in the throat (FOSSIT) or globus sensation, is unlikely to be head and neck cancer. In the absence of any other concerning features this symptom can be managed in primary care or via non-USC referral.

Risk calculator:

A head and neck risk calculator^[46] can be used to triage in secondary care but has not been validated for use in primary care.

Overlap with other pathways:

There is overlap between lung cancer and head and neck cancer symptoms, particularly in those with hoarseness (caused by recurrent laryngeal nerve palsy in lung cancer). Please see the Lung and Pleural Cancers Referral Guideline for when to arrange a chest X-ray.

Dysphagia should be referred in line with the Upper Gastrointestinal Cancers Guideline in the absence of any of the symptoms above.

Dental practitioners:

Dentists play a key role in the identification of head and neck cancers. There should be systems in place for USC referral pathways for dentists. If there is any uncertainty about the significance of an abnormality in the mouth it may be appropriate to seek a General Dental Practitioner (GDP) opinion in the first instance. This should be done as quickly as possible, with a direct referral made for any significant concern.

Rare head and neck cancers:

Sinonasal and ear cancers are rare. The associated clinical features include progressive or new unilateral nasal obstruction in association with one or more of proptosis, epistaxis, dental pain or loosening dentures, cranial nerve palsy or nasal (not facial) pain. However, sinus and nasal symptoms are common presenting features in primary care and are frequently benign (e.g. rhinosinusitis or benign nasal polyps). If there is concern that there is a nasal or paranasal cancer a USC referral should be made to the Head and Neck Service.

Lower Gastrointestinal Cancers

Lower Gastrointestinal (GI) cancer includes cancers of the colon, rectum and anus.

Colorectal cancer is the fourth most common cancer in Scotland, accounting for 12% of all new cancer cases across 2021 and 2022, (when excluding non-melanoma skin cancer). Later stage at diagnosis is associated with limited treatment options and therefore worse survival.

The main pathway to diagnosis for colorectal cancer is following a symptomatic presentation in primary care. In addition, bowel screening is offered every two years to people aged 50 to 74. A negative bowel screening test should not prevent a USC referral for a person with symptoms outlined below.

There are inequalities in the diagnosis of colorectal cancer. Men, those aged 65 years or under, those from areas of greater deprivation and those from Asian, Black or mixed ethnic groups are less likely to complete or return a qFIT^[47]. Being diagnosed via the emergency route is associated with later stage at diagnosis and worse outcomes. Evidence has also found that those who are older^[48], or from areas of greater deprivation are more likely to present as an emergency^[49].

Assessment for Suspected Lower GI Cancers

Clinical features of colorectal cancer include:

• Rectal bleeding
• Change in bowel habit
• Weight loss
• Abdominal pain
• Rectal or abdominal mass
• Iron deficiency anaemia

Many of these are common presentations in primary care. The published data on positive predictive value (PPV) for symptoms of suspected colorectal cancer are included in the reference section.^{[15],[16],[50],[51]}

If lower GI cancer is suspected:

• Perform an abdominal and rectal examination
• Arrange blood tests for renal function, liver function and full blood count plus ferritin/iron studies if anaemic^[9]

Quantitative faecal immunochemical test (qFIT)

The qFIT detects human haemoglobin breakdown products in the stool. It should be used in people with clinical features of suspected colorectal cancer to identify those who are more likely to have cancer and therefore need investigation as a USC.

• qFIT should be arranged for a person with any of the following, using the local pathway:
• Repeated anorectal bleeding without an obvious anal cause
• Blood mixed through the stool
• Change in bowel habit for four weeks or more, particularly looser or more frequent stool
• Iron deficiency anaemia (haemoglobin below reference range and ferritin < 30 micrograms/l or confirmed on iron studies)

A Persistent abdominal pain (four weeks or more) and weight loss (5% or more of body weight or strong clinical suspicion)

A qFIT is not indicated for a rectal or abdominal mass or unexplained anal ulceration.

In the context of other symptoms, a qFIT should only be arranged in line with national guidelines: Quantitative Faecal Immunohistochemical Testing (qFIT) 2024.

Urgent Suspicion of Cancer (USC) Referral

Refer a person with any of the following to the Colorectal Service as a USC:

• qFIT test result of 20 or more micrograms of haemoglobin per gram of faeces (≥20µgHb/g faeces) in the presence of colorectal symptoms or iron deficiency anaemia
• Symptoms that qualify for a qFIT test and either:
  • the local pathway is secondary care qFIT testing or assessment
  • the person is unable or unwilling to complete a test
• Unexplained abdominal mass
• Palpable anorectal mass
• Unexplained anal ulceration

Good Practice Points

qFIT testing:

Quantitative Faecal Immunohistochemical Testing (qFIT) 2024 provides advice on qFIT testing for new colorectal symptoms, iron deficiency anaemia, thresholds for referral and when repeat testing is recommended. It also defines the clinical scenarios in which a qFIT is not indicated.

Where possible, the referrer should provide the numerical value of the qFIT when referring to secondary care to allow effective triage.

If a qFIT cannot be arranged but the patient is being referred as a USC to secondary care, the reason for the absence of a qFIT result should be included in the referral. It should be made clear on referral if the person is unable or unwilling to comply. There should be safety netting processes for those who do not return their qFIT as there is a similar colorectal cancer prevalence in this group compared with those who return their qFIT^[52].

A person with iron deficiency anaemia and a normal qFIT may still require investigation. Refer according to local pathways.

Hereditary colon cancer:

See Appendix 5 for people with hereditary colorectal cancer, Lynch Syndrome or polyposis.

Overlap with other pathways:

People with intra-abdominal cancer can present with symptoms that overlap. Please see Upper Gastrointestinal Cancers Guideline (including hepatopancreatobiliary cancer), Ovarian Cancers Guideline and Kidney Cancers Guideline. This is particularly important if a person presents with abdominal pain, bloating and/or weight loss but has a negative qFIT. In this case, consider alternative pathways (e.g. upper GI, ovarian or kidney cancer) or arrange imaging studies.

Thrombocytosis is a risk factor for cancer. If present, there should be clinical assessment for causes^[17]. See the section on thrombocytosis.

Anaemia that is not iron deficient should prompt assessment for alternative diagnoses and monitoring if required.

Calprotectin is a biomarker for inflammation and is used to differentiate between inflammatory bowel disease (IBD) and functional gastrointestinal disorders (e.g. irritable bowel syndrome). A calprotectin test should be considered for people with persistent loose stools. Please see the national guidelines: Inflammatory Bowel Disease (IBD) Pathway for further investigations and/or referral to secondary care.

Lung and Pleural Cancers

Lung cancer is the most common cause of cancer death in the UK^[52]. On average, in 2021-2022, 46% of lung cancer cases in Scotland were diagnosed at stage 4^[5]. Data from England demonstrates that emergency presentation is a common route to diagnosis, making up 32.5% of routes in 2019^[19]. Inequalities exist in those most likely to present as an emergency, including women, older age groups, those from areas of higher deprivation, and those with non-respiratory symptoms^[54],[55].

The most significant risk factor for lung cancer is smoking, although family and occupational history are relevant. In people with a history of asbestos exposure, mesothelioma, as well as lung cancer, should be considered. Across the UK, 95% of mesothelioma cases in men and 85% of cases in women are caused by asbestos exposure^[56].

Assessment for Suspected Lung or Pleural Cancers

USC chest x-ray should be requested if a person has:

• Unexplained haemoptysis
• Unexplained symptoms lasting three weeks or longer (one or more symptoms in an ever-smoker or a person exposed to asbestos, two or more symptoms for all other people):
  • new cough or a change in a cough
  • breathlessness
  • chest or shoulder pain
  • weight loss
  • loss of appetite
  • fatigue
  • hoarseness – constant with voice never normal
• Examination findings:
  • focal chest signs (e.g. rhonchi, reduced breath sounds or dullness to percussion)
  • new or not previously documented finger clubbing
  • supraclavicular lymphadenopathy
• A chest infection or exacerbation of airways disease that does not resolve after two courses of antibiotics
• Thrombocytosis where clinical features do not suggest another cause

Urgent Suspicion of Cancer (USC) Referral

Refer a person with any of the following to the Respiratory Service as a USC referral:

• Chest x-ray (or CT scan) that is concerning for lung or pleural cancer (including unilateral pleural effusion, pleural mass and slowly resolving consolidation)
• Unexplained haemoptysis (arrange a USC chest x-ray but no need to wait for the result)

If the chest X-ray is not suspicious for lung or pleural cancer a USC referral should still be considered particularly if there are concerning symptom combinations^[57].

In smokers:

• Breathlessness with weight loss or appetite loss
• Chest pain with weight loss, appetite loss or thrombocytosis
• Weight loss and appetite loss together*

In all people:

• Weight loss and thrombocytosis together*

*referral to a Rapid Cancer Diagnostic Service (RCDS) or GP direct access to CT is an appropriate alternative for this combination

Good Practice Points

Haemoptysis:

Haemoptysis is bleeding arising from below the glottis. In addition to lung cancer, there are a range of benign causes including infection, bronchiectasis, pulmonary embolism and vasculitis.

Referral guidance:

Please arrange bloods including a full blood count (FBC) and renal function if not done in the preceding three months to expedite any further imaging required.

If the chest x-ray shows consolidation, repeat imaging should be arranged six weeks later to confirm resolution. A USC referral to respiratory should be made if it remains abnormal.

Overlap with other pathways:

Head and neck cancer and lung cancer symptoms overlap (e.g. hoarseness and neck lumps). If the chest x-ray is normal, consider referring according to the Head and Neck and Thyroid Cancers Guideline.

Thrombocytosis:

Thrombocytosis is associated with a range of cancers including lung^[17]. If the chest x-ray is not concerning for cancer and there are no other features suggestive of lung cancer (see above), then consider a USC referral to an alternative cancer pathway if appropriate. Please see the section on cancer and thrombocytosis.

Sarcoma and Bone Cancers

This is a guideline for adult cancer referral. Please see the Cancer in Children and Young People Guideline for a younger person in whom there is concern about sarcoma or bone cancer.

Sarcomas and primary bone cancers are classed as rare cancers^[58], with bone and connective tissue cancers accounting for less than 1% of all new cancer cases in Scotland across 2021 and 2022.

Connective tissue sarcomas (soft tissue sarcomas):

These can occur at any age, but most often in middle aged and older adults. Around 80% of new cases are diagnosed in people aged 40 years or older.

Bone cancers:

Osteosarcoma is the most common type of primary bone cancer in adolescents but it can occur at any age. They typically present with persistent localised bone pain in the absence of another explanation (e.g. injury, infection or metabolic conditions). They can grow anywhere on the skeleton, although the most common sites are the thigh, upper shin and upper arm bones^[59].

Ewing’s Sarcoma is most common in children and adolescents and has predominant symptoms of persistent pain and swelling of the affected area. Ewing’s Sarcoma can occur in any bone but most commonly starts in the pelvis, ribs, thigh or shoulder bones. It is also possible to occur in the soft tissues of the body^[59].

Chondrosarcoma is found most often in adults aged 30 to 60 years. Clinical presentation is usually a bony mass with pain often as a late feature. Chondrosarcoma is a cancer of cartilage cells within the bone and most commonly occurs at the hips, ribs, upper thigh or shoulder bones^[59].

There is some evidence of inequalities in diagnosis for younger adult patients^[60] and those from more deprived backgrounds^[61]. Younger et al. (2018)^[60] found that young adult sarcoma patients may be more likely to experience delays to diagnosis through misattribution of symptoms and multiple consultations with their GP, whereas elderly patients were more likely to be referred for further investigation. Bacon et al. (2023)^[61] noted that young adults, elderly people and people from more deprived areas were more likely to present via emergency routes.

Assessment for Suspected Sarcoma and Bone Cancers

Connective tissue sarcoma:

The most common presenting feature is a lump or mass.

Assess for the following:

• Characteristics of the lump – size, change in size (including how quickly), consistency, fixation to other structures, associated skin changes/ulceration and position on the body
• Determine if the lump has arisen in the site of a previously excised lump (even if the prior pathology was benign) or area of the body previously exposed to radiotherapy. Both factors increase the risk of the lump being malignant
• Any genetic conditions predisposing to sarcoma – See Appendix 5 for advice on referral with such conditions

In some Health Boards, the next step in investigating a soft tissue lump of concern is a USS – please follow local pathways.

Bone cancer:

Request a USC X-ray of the appropriate body part for any person with unexplained bone pain or tenderness, which is:

• Persistent or worsening (over six weeks or more)
• Nocturnal or at rest
• Interfering with activities of daily living

Blood investigations may be helpful if bone cancer is suspected but should not delay X-ray investigation. Consider the following blood tests: full blood count, renal function, bone profile and myeloma screen. Thyroid, lung, breast, renal and prostate cancers all commonly metastasise to bone and are more common than primary bone cancer, so it may be helpful to consider these in any assessment and investigation of bone pain.

Sarcoma and bone cancers can be missed. It is important to consider further investigation of a person who presents two or more times with a concern about a lump or bone pain with a negative X-ray.

Urgent Suspicion of Cancer (USC) Referral

Refer a person with any of the following to the appropriate local secondary care team as a USC:

• A soft tissue mass with one or more of the following characteristics:
  • rapidly increasing in size (over weeks to months)
  • 5 cm or more in size (unless long standing – see good practice regarding lipoma)
  • deep, tethered, fixed or immobile
  • hard or craggy
  • fungating
  • occurring in the site of a previous lump excision or within a previous radiotherapy field
• USS suspicious for a soft tissue sarcoma
• X-ray suspicious for a primary bone tumour/sarcoma

If the X-ray suggests metastases, myeloma or lymphoma refer as USC to the appropriate local specialty dependent on the most likely primary cancer site. Urgent orthopaedic referral should be considered if there is impending or acute pathological fracture.

Good Practice Points

Clinical features of soft tissue lesions:

The majority of soft tissue lesions referred are benign on ultrasound scan (USS). Masses present for more than 1 year that are asymptomatic and not growing or changing do not require further investigation. Longstanding masses with new growth, pain or other symptoms/changes should be investigated.

Lumps occurring after an episode of definite or recalled trauma are usually self-resolving. Clinical review four to six weeks following the traumatic episode is reasonable, and patients can be discharged with safety netting if the lump is significantly improved or resolved. Persistent or non-resolving masses can be referred for assessment.

Lipoma:

A lipoma is a benign lump, which can affect up to 1% of the population and is most frequent in people aged 40 to 60 years^[62]. It has the following features:

• Dome-shaped or egg-shaped lump usually 2-10 cm in diameter
• May grow slowly over several years
• Feels soft and smooth and is easily moved under the skin with the fingers
• May have a rubbery or doughy consistency

A lipoma should not be referred based on size alone. A clinical review in four weeks is reasonable for larger lesions. A referral should be made as a USC if there is rapid change in size or development of the other concerning features for a soft tissue lump noted above.

Bone cancers:

Bone cancers of the long bones are usually excluded by normal X-ray, but further investigation may be required for spine, pelvis, ribs or scapula.

Consideration should be given to referral if bone symptoms persist, but the X-ray is normal.

Other considerations:

Treatment for childhood cancer has been shown to increase the risk of subsequent cancers^[63],[64]. Specific regimes that increase the risk of sarcoma include those in which there is exposure to alkylating agents (e.g. Cyclophosphamide). Prior treatment should be noted where applicable.

Skin Cancers

The main types of skin cancer are basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC) and melanoma. There are also several much rarer skin cancer types.

BCC is the most common type of skin cancer (around 75% of all skin cancers diagnosed)^[65]. It develops from basal cells, found in the deepest part of the outer layer of the skin (the epidermis). It is rare for basal cell skin cancer to metastasise.

SCC begin in cells called keratinocytes which are found in the epidermis. SCC is faster growing than basal cell cancers. It is unlikely to metastasise (research suggests metastases are found in 1.2-5% of cases)^[66]. Around 23% of skin cancers are SCCs⁶⁵.

Melanoma accounts for around 1% of diagnosed skin cancers^[65]. Melanoma skin cancer typically starts in skin cells called melanocytes.

In England there are more USC referrals for skin cancer than for any other site, with referral rates increasing more than threefold between 2009/2010 and 2022/2023, while conversion rates have fallen^[67],[68]. PHS plans to publish data on USC referrals once data quality issues have been resolved.

Risk factors for all skin cancer types include:

• Excessive sunlight exposure and sun bed use and is highest in people with fair skin colour and a susceptibility to sunburn

Risk factors for melanoma include:

• Large number of benign melanocytic naevi (greater than 100 naevi has been shown to increase the relative risk of developing melanoma approximately sevenfold compared with 15 or less naevi)^[69]
• A family history of melanoma

Risk factors for SCC include:

• Multiple small actinic keratoses
• High levels of previous UV-A photochemotherapy
• Being immunocompromised

Skin cancers are very infrequent in those aged under 15 years of age.

Skin cancer can affect people of all skin colours, including those with brown and black skin. Skin cancer on darker skin often occurs on areas that get little sun exposure, like the palms of hands, soles of feet, and under/around the nails. People of colour have a higher risk of a late diagnosis and poorer prognosis as skin cancer may be less noticeable or less expected in their skin.

Assessment for Suspected Skin Cancers

The lesion should be examined and, if available, assessed using a dermatoscope. The dermatoscope is a useful tool for distinguishing benign pigmented lesions (e.g. seborrheic keratosis) from melanoma, potentially reducing unnecessary referrals. The Right Decision Service contains useful CfSD resources to aid in the assessment of skin lesions.

If the lesion is suspicious of cancer, a full medical history should be documented and the entire skin surface should be examined. History should include drugs, conditions that cause immuno-compromise, prior personal and family history of skin cancer.

Melanoma:

Suspect this if there is:

• A mole* with any of the following features (ABCDE criteria):
  • Asymmetry
  • Border (irregular, scalloped or poorly defined)
  • Colour (irregularity or darkening)
  • Diameter more than 6 millimetres (they can be smaller)
  • Evolution in shape, size, or colour (especially if quickly)
• A mole which stands out from those around it (the ‘ugly duckling’ sign)
• A new mole developing in a person aged 40 or over

*See good practice section below for the assessment of pigmented lesions

Subungual melanoma:

Suspect this if there is:

• Nail pigmentation which evolves but remains in contact with and/or involves the nail fold (fold of skin that borders the bottom and sides of the nail)

Squamous cell carcinoma (SCC):

Suspect this if a person with a skin lesion has one or more of the following features:

• Hyperkeratotic (scaly) nodule or indurated (thickened) lesion
• Ulcerated nodule that may bleed easily
• Lesion is painful or tender on palpation
• Lesion grows over weeks to a few months
• There is background of actinic keratosis

Squamous cell carcinoma (SCC) of the nail apparatus:

Suspect this if there is:

• A lesion growing underneath the nail that may be associated with local tissue destruction
• A change such as a nodule growing in an established periungual wart

Basal cell carcinoma (BCC):

Suspect this if a skin lesion has one or more of the following characteristics:

• Ulcer with a raised rolled edge, a nodule on the skin (waxy or pearly), a reddish plaque, scar-like with tethering or contraction
• Prominent fine blood vessels within the lesion
• History of spontaneous bleeding
• May contain pigmented areas
• Rarely painful

Other skin lesions that are concerning for malignancy:

The following skin changes should raise concern for a malignant lesion (including Merkel’s tumour, sarcoma, or amelanotic melanoma):

• Nodule grows quickly (over weeks)
• A new change (growth, pigmentation, or pain) in a long-standing ulcer, scar, traumatic or inflamed area of skin
• Non-healing and/or destructive atypical ulcer
• Progressive unexplained scar-like area
• An unexplained skin lesion with loco-regional lymphadenopathy

Urgent Suspicion of Cancer (USC) Referral

Refer a person with any of the following according to the local skin cancer pathway as a USC:

• Skin or nail lesion suspicious for melanoma
• Skin or nail lesion suspicious for SCC
• Skin lesion suspicious for a BCC invading a potentially dangerous area e.g. peri-ocular, auditory meatus, nerve, or major blood vessel
• Skin lesion whose features raise concern for malignancy (see – other skin lesions that are concerning for malignancy)
• Unexplained or concerning skin lesion in an immunocompromised person
• A biopsy proven melanoma, SCC, or high-risk BCC (infiltrative, micronodular, or basosquamous)

Good Practice Points

Pigmented lesions:

Not all pigmented skin lesions are melanomas. Seborrheic keratoses are common, benign, pigmented lesions that can change in colour, size, and shape. They have a classical ‘stuck on’ appearance and can easily be distinguished with a dermatoscope. It is important to recognise these benign lesions as application of the ABCDE criteria may result in over-referral for suspected melanomas. Lesions which are suspicious for melanoma should not be removed in primary care.

Subungual melanoma:

This is rare compared with other causes of nail discolouration and change including fungal infection and haematoma. A subungual haematoma will grow out distally resulting in normal nail proximally between the nail pigmentation and the nail fold.

Other considerations:

• Any skin lesion removed should be sent for pathological examination
• Referrals should be accompanied by an accurate description of the lesion – including size (with measurements), pain and tenderness
• A photograph of the lesion should be sent with the referral to secondary care wherever possible. This allows for accurate and timely triage increasing the efficiency of care for patients with skin cancer. Please follow local pathways
• Please visit the Right Decision Service for CfSD primary care management of skin lesions not referred as a USC
• GPs with a special interest in dermatology can often safely manage SCCs and BCCs in primary care, including excision
• Dentists play a key role in the identification of cancers on the skin, in particular of the face and neck. There should be systems in place for USC referral pathways for dentists

Upper Gastrointestinal Cancers

Upper gastrointestinal (GI) cancer is an umbrella term for multiple different cancer types, including oesophageal, stomach, pancreatic, gallbladder and liver.

Upper GI cancers (excluding gallbladder due to data availability) accounted for around 9% of new cancer cases in Scotland in 2021 and 2022 (excluding non-melanoma skin cancer). Late stage diagnosis is common for upper GI cancers, with 25.0% of liver, 40.6% of stomach, 35.3% of oesophageal and 53.1% of pancreatic cancers being diagnosed at stage 4 in Scotland in 2021^[29]. Upper GI cancers (where incidence data is available in Scotland) have a higher incidence in those from more deprived areas^[4].

Oesophago-gastric (OG) cancer:

UK data (2017-2019) indicates the following risk factors^[70]-[72]:

• Increasing age (it is less likely under the age of 40)
• Two times greater risk in men than women
• Family history of OG cancer
• Lower socioeconomic status
• Smoking
• Excessive alcohol use
• Chronic gastro-oesophageal reflux
• Barrett’s oesophagus
• Obesity (e.g. greater than two-fold higher risk of oesophageal cancer if BMI greater than 30 compared with Body Mass Index (BMI) less than 25)^[73]
• Prior history of aero-digestive cancers

Hepato-pancreato-biliary (HPB) cancer:

Pancreatic cancer is less likely below the age of 40 with incidence rates rising steeply from age 60. Risk factors include:

• Smoking
• Excessive alcohol use
• Chronic pancreatitis
• Family history

Liver cancer is less common than pancreatic cancer. Risk factors include^[74]:

• Smoking
• Obesity
• Excessive alcohol use
• Chronic liver disease
• Viral hepatitis
• Haemachromatosis
• Family history of liver cancer

Assessment for Suspected Upper GI Cancers

Upper GI cancers often present with vague symptoms that are common complaints in primary care and, that on their own, have a low PPV for cancer^[75]. The exceptions are dysphagia for oesophago-gastric cancer and jaundice for pancreatic cancer.

The clinical features of upper GI cancers overlap^[76].

Clinical Feature	OG cancer	HPB cancer
Dysphagia	✓	X
Dyspepsia/reflux	✓	X
Nausea/vomiting	✓	✓
Upper abdominal pain	✓	✓
Early satiety (feeling full up after a small amount of food)	✓	✓
Abdominal mass	✓	✓
Unintentional weight loss	✓	✓
Jaundice	X	✓
Change in bowel habit	X	✓
New onset diabetes at older age - see USC referral	X	✓

The PPV for upper GI cancers can exceed 3% if there are combinations of symptoms:

• Oesophago-gastric cancer^[16],[77]:
  • weight loss with abdominal pain, reflux or nausea/vomiting
• Pancreatic cancer^[16]:
  • abdominal pain, with nausea/vomiting, constipation or weight loss

The PPVs are affected by age and this has been reflected in the referral criteria below.

If upper GI cancer is suspected:

• Perform an abdominal examination
• Arrange blood tests (full blood count to assess for anaemia and thrombocytosis, renal function, liver function tests and haemoglobin A1c)

Urgent Suspicion of Cancer (USC) Referral

Oesophago-gastric cancer:

Refer a person with any of the following to secondary care (follow local pathway) as a USC:

• Persistent or progressive dysphagia (not ‘feeling of something stuck in the throat’ - FOSSIT)
• Weight loss (5% or more of body weight or strong clinical suspicion) in a person aged 55 years or over with any of the following:
  • upper abdominal pain
  • early satiety
  • reflux
  • dyspepsia
  • nausea and/or vomiting

Hepato-pancreato-biliary cancer:

Refer a person with any of the following to secondary care (follow local pathway) as a USC:

• Painless obstructive jaundice in a person aged 40 years or over
• Weight loss (5% or more of body weight or strong clinical suspicion) in a person aged 55 years or over with any of the following:
  • change in bowel habit
  • back and/or abdominal pain
  • nausea and/or vomiting
  • new onset diabetes
• Abdominal pain in a person aged 55 years or over with any of the following:
  • nausea and/or vomiting
  • weight loss (5% or more of body weight or strong clinical suspicion)
  • constipation
• Palpable upper abdominal or epigastric mass
• Any abnormality in the hepatobiliary tract/pancreas found on imaging that is suspicious for HPB cancer

Good Practice Points

Referral guidance:

Referral to secondary care for USC assessment will vary by Health Board – please follow the local pathway.

Referrals will be triaged by secondary care clinicians. It is therefore important that when a person is referred, they are advised that they are being referred for assessment, not for a specific investigation (e.g. an endoscopy).

When making a referral for a person with dysphagia it is essential that the correct information is included in the referral form to allow the secondary care team to triage the referral. Please see CfSD’s Dysphagia Pathway for guidance.

Overlap with other pathways:

Patients with intra-abdominal cancer can present with symptoms that overlap. Please see Lower GI Cancers Guideline, Ovarian Cancers Guideline and Kidney Cancers Guideline.

A normal Oesophago-Gastro-Duodenoscopy (OGD) or CT alone may be insufficient to exclude an upper GI cancer. Consideration should be given to using both modalities where clinically indicated, depending on symptoms, age, sex and risk factors.

There may also be a role for referral to a local pathway for non-specific symptoms in which cancer is suspected such as GP direct access to CT or to a RCDS. See also the Non-Specific Symptoms of Cancer Guideline.

Iron deficiency anaemia (IDA) falls below the 3% threshold for upper GI cancer and is therefore not included in the above USC referral criteria. See Lower Gastrointestinal Cancers Guideline for initial investigation.

Thrombocytosis:

Evidence has identified thrombocytosis as a risk marker for malignancy^[17]. In cases of unexplained thrombocytosis, it is advisable to assess for any signs or symptoms of cancer and if appropriate refer to a tumour specific USC pathway. Please see the thrombocytosis section for more details.

Urological Cancers

Urological cancer is an umbrella term for multiple different cancer types, including prostate, bladder, kidney, testicular and penile.

Prostate cancer:

This is the most common cancer among men in Scotland, accounting for around 4,700 diagnoses each year. Risk factors include:

• Father or brother with prostate cancer
• Black or mixed black ethnicity (the lifetime risk of prostate cancer in black men is double that of white men)^[78]
• Carrying a BRCA gene variant

Bladder and kidney cancer:

There are around 860 new bladder and 1,150 new kidney cancers in Scotland each year. 98% of kidney cancer cases are aged 40 years or over and 99% of bladder cancer cases are aged 45 years or over at the time of diagnosis. Risk factors include:

• Male sex (crude rates of kidney cancer are 2 times higher and bladder 2.3 times higher in males)
• Smoking history
• Family history

Testicular cancer:

This cancer is relatively rare, with around 185 new cases per year, of which approximately 70% are in males aged 15 to 45 years.

Penile cancer:

This cancer is rare, with around 90 new cases each year in Scotland but its incidence is rising.

Assessment for Suspected Urological Cancers

Prostate cancer:

Early prostate cancer is often asymptomatic. Prostate cancer can present with lower urinary tract symptoms. Symptoms suggestive of advanced or metastatic prostate cancer include back pain, bone pain, fatigue, or weight loss (see Malignant Spinal Cord Compression (MSCC)).

For men aged 50 years and over, or aged 45 years and over with one or more risk factor(s)*, a Prostate Specific Antigen (PSA) test and a Digital Rectal Examination (DRE) should be considered if there are any of the following symptoms:

• Lower urinary tract symptoms (urgency, hesitancy, frequency, nocturia, retention)
• Unexplained visible haematuria
• Haematospermia
• Erectile dysfunction

*Risk factors: a first degree relative (brother or father) who has or had prostate cancer, are black or mixed black ethnicity or carry a BRCA gene variant

Do not perform a PSA test until at least six weeks after treatment for men with symptoms or signs of a Urinary Tract Infection (UTI), or who have been prescribed antibiotics for a confirmed or suspected UTI.

In men aged 80 years or over, prostate cancer is commonly found but may not be clinically significant. It is recommended that PSA testing should be reserved for men aged 80 years or over in the following scenarios:

A Clinical features suggestive of metastatic prostate cancer (e.g. new significant bone pain, unexplained weight loss or unexplained anaemia)

A The man wants a PSA test after shared decision-making. The potential benefits of diagnosing and treating prostate cancer are greater in those with a good functional status (Performance Status e.g. ECOG/WHO performance status and Clinical Frailty Scale) and a longer life expectancy (10 plus years).

Bladder and kidney cancer:

The presenting features of bladder and kidney cancer include:

• Visible haematuria – the most common
• Loin pain
• Renal masses
• Persistent non-visible haematuria
• Anaemia
• Weight loss
• Pyrexia

Testicular cancer:

Clinical features include:

• Swelling or lump in the testis or scrotum
• Dull ache in the abdomen or groin

Solid swellings affecting the body of the testis have a more than 50% chance of being cancer. Testicular cancers have the potential to progress rapidly.

Consider testicular examination for any male presenting with abdominal or groin pain, testicular pain or swelling.

Consider a testicular USS for men with unexplained or persistent symptoms despite a normal examination.

Penile cancer:

Sexually transmitted infection should be excluded and treated before considering referral.

Presenting features include:

• Swelling or irritation in the head of the penis
• Thickening of the skin of the foreskin or penis
• Changing skin colour of the foreskin or penis
• Lumps or sores on the penis which may bleed
• Discharge or bleeding from underneath the foreskin

Urgent Suspicion of Cancer (USC) Referral

Prostate cancer:

Refer a person with any of the following to the Urology Service as a USC:

• Raised PSA in the following age categories:
  • under 70: ≥3 ng/ml
  • 70-79: ≥5 ng/ml
  • 80 and above: ≥20 ng/ml - see good practice
• A DRE suspicious of prostate cancer (hard and/or irregular) – request an urgent PSA test in parallel to a referral.

Do not refer as a USC if the PSA is raised in men with symptoms or signs of a Urinary Tract Infection (UTI), or who have been treated for a UTI. Instead, repeat the PSA after six weeks of completing treatment for the UTI. If the PSA is still raised (see above thresholds) refer as USC.

• UTI does not need to be excluded prior to referral if there are no clinical features of infection.
• A repeat PSA test may be carried out by secondary care to allow triage but is not needed for referral from primary care if there is not a confirmed or suspected UTI.

Bladder and kidney cancer:

Refer a person with any of the following to the Urology Service as a USC:

• Unexplained Visible Haematuria:

Aged under 45 years:

• more than one episode without UTI (not limited to a time duration)
• recurs/persists after treatment of UTI

Aged 45 years and over:

• single episode without UTI
• recurs/persists after treatment of UTI
• Unexplained Non-Visible Haematuria

Aged 60 years and over:

• persistent blood on repeat urine dipstick (between two to six weeks apart) and has a negative urine culture
• abdominal mass identified on imaging that is thought to arise from the urinary tract

Testicular cancer:

Refer a person with any of the following to the Urology Service as a USC:

• Non-painful enlargement or change in shape or texture of the body of the testis
• Epididymo-orchitis not improving after two weeks of antibiotics
• USS suggestive of testicular cancer

Referral pathways can vary locally, and, in some areas, the first step may be USC ultrasound scan referral. Local referral pathways should be followed to avoid any delay in triage.

Penile cancer:

Refer a person with any of the following to the Urology Service as a USC:

• Unexplained bleeding or persistent discharge from underneath the foreskin
• Penile mass or ulcerated lesion, when a sexually transmitted infection has been excluded as a cause
• Persistent penile lesion after treatment for a sexually transmitted infection has been completed

Good Practice Points

Prostate cancer:

There is no agreed screening programme for prostate cancer in the United Kingdom. There is an informed choice programme called the Prostate Cancer Risk Management Programme (PCRMP). This supports clinicians to give balanced information to men without symptoms of prostate disease who ask about a PSA test. The PCRMP was updated in December 2024 to clarify that PSA testing for asymptomatic men is not exclusively available to those aged 50 and over. The documents contain reference to NICE NG12. This is not applicable for NHS Scotland and instead the Scottish Referral Guidelines for Suspected Cancer should be followed for the referral of suspected prostate cancer.

If a PSA is performed in this context the following apply:

• PSA thresholds described in the ‘Urgent Suspicion of Cancer Referral’ section above should be used to guide referral
• If the PSA is below these thresholds, the test should not be repeated within a 12-month period, if the person remains asymptomatic

Men between the ages of 80 and 85 who have a high PSA ≥10, but <20, can be referred as urgent for further assessment if they are fit and do not have multiple co-morbidities, in line with the principles of Realistic Medicine.

Urinary catheterisation or other invasive procedures such as prostate biopsy raise PSA, with 5- alpha reductase inhibitors such as finasteride potentially reducing PSA.

The following people have a prostate gland:

• Men
• Transgender women
• Non-binary people with male as their biological sex
• Some intersex people

If the prostate is felt to be abnormal (hard and/or irregular) on DRE, a PSA test should be requested. The result of the PSA test is used to support triage in secondary care. The PSA result should not alter the category of referral to secondary care – an abnormal DRE in the presence of a normal PSA should still be referred as a USC.

The prostate is not removed as part of genital reconstructive surgery. Transgender women and non-binary people whose biological sex is male can get prostate cancer. Taking feminising hormones, testosterone blockers or having the testicles removed reduces the risk of prostate cancer by lowering testosterone levels.

Lower urinary tract symptoms in Transgender women or non-binary people whose biological sex is male, especially if aged 50 years or over, should be assessed carefully and the possibility of prostate cancer considered. If vagino/vulvoplasty has been carried out the prostate can be examined via the anterior wall of the vagina.

Bladder and kidney:

A urine culture should be obtained if a person presents with haematuria (visible or non-visible).

Consider seeking urology advice if there are recurrent issues with haematuria in patients who have had recent (within six months) negative investigations for haematuria. This does not need to be a USC referral.

There is an online risk calculator for bladder cancer available.

A single episode of visible haematuria in those aged under 45, in the absence of a UTI, does not meet the criteria for a USC referral. Consideration should be given to imaging or referral to urology through an alternative pathway, based on local guidelines.

Evidence suggests that certain groups may be at an increased risk of diagnostic delays and missed diagnostic opportunities – this includes older women with UTIs^[79], those with recurrent UTIs^[80], and people presenting with non-haematuria symptoms^[81].

Overlap with other pathways:

Patients with intra-abdominal cancer can present with symptoms that overlap. Please see Upper and Lower GI Cancers Guidelines and Ovarian Cancers Guideline. Data shows a PPV of 5% for kidney cancer in men aged 60 or over with abdominal pain and microcytosis (low mean corpuscular volume without the additional need for anaemia)^[16].

Patients with abdominal pain would normally be assessed and referred using the Upper or Lower GI Cancers Guidelines. A USS of the abdomen including the kidneys, or a USC referral to urology, should be considered if no cause is found and the kidneys have not been imaged.

Non-Specific Symptoms of Cancer

‘Red flag’ or ‘alarm symptoms’ of cancer are usually associated with a higher predictive value for specific cancer types e.g. a breast lump (breast cancer) or haemoptysis (lung cancer). These symptoms are included in the SRGs under the relevant cancer type.

However, people can often present with non-specific symptoms of cancer including:

• Unexplained weight loss
• Fatigue
• Abdominal symptoms (pain, bloating)
• Nausea/vomiting
• Loss of appetite
• Non-specific pain

Unexpected blood results such as anaemia or thrombocytosis can also occur prior to a cancer diagnosis. Additionally, a GP may have an intuition about an underlying diagnosis of cancer despite a lack of specific clinical features – commonly referred to as GP ‘gut feeling’^[12],[13].

In these circumstances, a person may not meet the threshold for referral to a specific cancer pathway which has the potential to prolong diagnostic intervals and increase the risk of emergency presentation with possible worse outcomes^[82]. In addition, people with non-specific symptoms are more likely to have multiple GP attendances and tests in primary care^[82].

This Guideline is a new addition to the SRGs with the purpose of collating the current knowledge on non-specific clinical features concerning for cancer, to aid primary care referral. There are currently two clinical pathways for non-specific symptoms – RCDSs and GP direct access to CT^[83].

Rapid Cancer Diagnostic Services:

In Spring 2021, CfSD facilitated the implementation of early adopter RCDSs, with the aim of providing primary care clinicians with a new route to refer people with non-specific clinical features concerning for cancer. An independent evaluation report from the University of Strathclyde was published in December 2023^[84]. Over the two-year evaluation period 3,616 people were referred (58.5% female, median overall age of 70 years). Unexplained weight loss was the most described clinical feature.

11.9% of the people assessed were diagnosed with cancer. Older age, GP ‘gut feeling’ and unexpected blood results were the features most strongly associated with a cancer diagnosis.

CT scanning was the most frequently used diagnostic test. The most frequently diagnosed cancers were lung, upper gastro-intestinal and colorectal.

GP direct access to CT:

At the time of publishing these Guidelines, not all Health Boards in Scotland have a RCDS. An alternative pathway is GP direct access to CT scanning. This has been shown to perform as well as secondary care triage and testing in terms of cancer detection and diagnostic interval^[85].

Assessment for Suspected Cancer in a Person with Non-specific Clinical Features

Non-specific symptoms often lead to repeated GP visits and extended diagnostic intervals. Thorough initial assessments and adherence to referral pathways are critical to minimising delays and improving outcomes.

The selection of initial investigations should be guided by the clinical context and local pathways, avoiding unnecessary testing where symptoms strongly suggest an alternative diagnosis.

The following tests may be helpful in a person with non-specific symptoms where there is a concern about an underlying cancer diagnosis:

• Urinalysis (for haematuria see Urological Cancers Guideline)
• Full blood count
• ESR and/or C-Reactive Protein (CRP)
• Renal function (especially if considering a contrast enhanced CT)
• Liver function tests
• Thyroid function tests
• Glycosylated haemoglobin (HBA1c)
• Bone profile
• Blood borne virus screen
• CA125 (see Gynaecological cancer guidelines for who to test and thresholds for referral)
• PSA (see Urological cancer guidelines for who to test and thresholds for referral)
• Vitamin B12 levels, ferritin, and folate
• Chest x-ray (see Lung and Pleural Cancers Guideline)

The results of the tests may guide the need for referral to a non-specific pathway described above or may help to identify a concern about a site-specific cancer diagnosis (e.g. raised PSA and prostate cancer or raised CA125 and ovarian cancer).

Some pathways have tests that are required before referral – please see local guidelines. The above list is not intended as a minimum set of tests required for referral.

See Appendix 5 for advice on referral for genetic conditions that predispose to cancer.

Urgent Suspicion of Cancer (USC) Referral

Refer a person with any of the following to a non-specific symptom pathway (RCDS or GP direct access to CT) as a USC, especially if accompanied by GP ‘gut feeling’ of a cancer diagnosis:

• New unexplained weight loss (either documented 5% or more of body weight in three months or with strong clinical suspicion)
• New unexplained loss of appetite, fatigue, nausea, malaise, or bloating of four weeks or more (less if strong clinical suspicion)
• New unexplained, unexpected, or progressive pain, including bone pain, of four weeks or more

A person referred to a non-specific symptom pathway should not meet criteria for a site-specific pathway in this latest version of SRGs. However, if a person presents with symptom combinations which could indicate several different cancer types, referral to a RCDS or GP direct access to CT may be appropriate dependent on local referral pathways.

Good Practice Points

Referring for assessment:

If a person is being referred for investigation for a suspected cancer, it is critical this is made clear to them and documented in the referral. It is also especially important that the wishes of the person and their functional status (e.g. ECOG/WHO performance status and Clinical Frailty Scale) are considered. This may need to include a collateral history from a carer or relative. Frailty or poorer performance status should not prevent a referral to a RCDS or GP direct access to CT. However, the decision should be made with the person to ensure it aligns with their overall goals of care and that the benefits and risks of further diagnostic assessment are understood.

The most common modality used to assess those with non-specific symptoms which are a concern for cancer, is a CT scan. Therefore, this should be discussed with the relevant service and provision made for non-radiation exposing diagnostic tests (e.g. ultrasound) if referring a person who is pregnant.

Metastatic cancer can present with non-specific symptoms, so it is important to check for a previous cancer diagnosis and refer to the relevant tumour specific service, if appropriate.

Bone pain:

Any cancer can spread to the bones, but it is more common in prostate cancer, breast cancer, lung cancer, kidney cancer, thyroid cancer and myeloma. If vertebral bones are involved there is a risk of spinal cord compression. If malignant spinal cord compression is suspected, then guidelines on assessment and investigation should be accessed.

Rapid Cancer Diagnostic Services and GP direct access to CT:

Please follow local guidelines when referring to these services and note the tests that are required before referral. Please also reference available national guidelines for primary care on which service to use if both are available in your Health Board^[83]. For GP direct access, the referrer is responsible for the action taken regarding the findings of the CT, including a USC referral to another cancer pathway and assessing, treating, and referring any additional or incidental findings as appropriate.

Unprovoked deep venous thrombosis (DVT):

Data indicates that 3.9% of people had a new diagnosis of cancer in the year following a diagnosis of unprovoked DVT^[86]. It has therefore been suggested that investigation for cancer in this group would be beneficial. However, a randomised trial has shown that the addition of a CT abdomen and pelvis to standard assessment (history, examination, blood tests and routine screening for cancer) did not detect significantly more cancers or alter diagnostic intervals or cancer-related mortality^[6]. On this basis it is recommended that unprovoked DVT alone should not prompt referral for a CT through either pathway – RCDS or direct access.

Unexplained thrombocytosis:

In cases of unexplained thrombocytosis, it is advisable to assess for any signs or symptoms of cancer and then to refer on a tumour specific USC pathway if appropriate^[17].

If isolated unexplained thrombocytosis is found, it is recommended that a chest x-ray is considered. If there is unexplained thrombocytosis combined with non-specific symptoms such as significant weight loss, or if there is associated GP ‘gut feeling’, it may also be appropriate to refer for further investigation through either a RCDS or GP direct access to imaging pathway.

Cancer in Children and Young People

Cancer in Children and Young People (CYP) encompasses multiple distinct types of cancers diagnosed in those aged 0-24 years. Typically, childhood cancers are defined as cancers in those aged 0-14 years and young people’s cancers in those aged 15-24 years. However, be aware that age ranges for local referral pathways may vary.

Around 130 children (aged 0-14 years) and 180 young people (aged 15-24 years) are diagnosed with cancer in Scotland each year (average over 2018, 2019, 2021)^[87].

In Scotland, 31% of children aged 0-14 years with cancer were diagnosed with leukaemia, and 26% were diagnosed with brain/CNS tumours (2012 – 2021)^[87]. Survival for children with cancer is high, with 85% of children expected to live for five years or more after their diagnosis (over years of diagnosis 2011-2016)^[87].

23% of 15-19 year olds with cancer were diagnosed with lymphoma, 17% with carcinomas and a further 17% with CNS tumours (2012-2021)^[87].

25% of 20-24 year olds with cancer were diagnosed with carcinomas, 18% with lymphoma, and 16% with melanoma (2012-2021). Cancer survival among young people is high, with 90% expected to live for five years or more after their diagnosis (years of diagnosis 2011-2015)^[87].

Large variation is seen in diagnostic intervals by cancer type and it is common for patients to see a health professional three or more times before referral^[88]. Longer intervals may result from non-timely help seeking for symptoms and a lack of awareness of cancers in CYP^[89],[90].

As cancer in CYP is uncommon, health professionals may not always initially suspect cancer and investigate other benign causes first, potentially leading to pathway delays or emergency presentation. It is estimated that a UK General Practice with an average list size will diagnose cancer in a child or young person every 1.8 years^[91].

Types of Cancer in Children and Young People

Childhood cancers:

There are 76 distinct types of childhood cancer. They are broadly grouped into cancers affecting the blood and those that cause solid tumours. There are clear differences between most childhood and adult tumours, reflecting different biology. Many childhood tumours are of ‘embryonal’ origin or other ‘high grade’ malignancies, whilst carcinomas are uncommon. Childhood malignancies can progress very rapidly and a delay of even a few days may be associated with substantial clinical deterioration. Conversely, some childhood tumours can present in a more indolent way, including Hodgkin Lymphoma, and some low-grade intracranial tumours - malignancy cannot therefore be excluded solely based on a long history.

The main types of childhood cancer are leukaemia, brain and spinal tumours, lymphoma, soft tissue sarcomas, neuroblastoma, renal tumours, bone tumours, germ cell tumours, retinoblastomas, other carcinomas and melanomas, and liver tumours.

Leukaemia:

This is the most common type of childhood cancer, accounting for approximately one third of all cancers in children^[87]. It is a cancer of the white blood cells – white blood cell production and maturation gets out of control and the cells continue to divide.

Brain and central nervous system tumours:

These are the most common solid tumours in childhood. In Scotland, they account for 26% of all cancers and 51% of deaths in children aged 0 to 14^[87]. They are often identified later than other childhood cancers due to their varied and often initially subtle symptoms.

Lymphoma:

This is the third most common type of childhood cancer. It accounts for around 9% of childhood cancer diagnoses in Scotland (2012-2021)^[87] and is split into two main groups: Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma.

Soft tissue sarcoma:

The most common soft tissue sarcoma is rhabdomyosarcoma. Other types include fibrosarcomas, schwannomas and primitive neuroectodermal tumours.

Neuroblastoma:

This is a solid cancer that develops from cells called neuroblasts. They can occur anywhere in the body but usually start in the adrenal glands or in nerve tissue that runs alongside the spinal cord. In some cases, neuroblastoma can spread to other places in the body such as the bone marrow, lymph nodes, bone, liver and skin.

Renal tumours:

These arise from the kidney and are more common in younger children. Wilm’s tumours may be associated with underlying genetic conditions.

Bone tumours:

The most common types are Osteosarcoma and Ewing’s Sarcoma. Osteosarcoma can present at any age but has a peak incidence in the second and third decade of life^[94]. Most common sites are the femur, tibia and humerus. Ewing’s Sarcoma has a peak incidence between the ages of 10 and 15 years and rarely occurs under the age of five. Most common sites are the pelvis, femur, tibia, fibula, rib and humerus.

Germ cell tumours:

Germ cell tumours are growths that form from reproductive cells. They can develop at any age and usually originate in the ovaries or testes (gonadal germ cell tumours), but they can sometimes occur in other parts of the body as well (extragonadal germ cell tumours). Sites where extragonadal germ cell tumours most commonly occur are at the bottom of the spine (sacrococcygeal), the brain, chest and abdomen. There are several types of germ cell tumours including germinomas, yolk-sac tumours, embryonal carcinomas and teratomas.

Retinoblastoma:

This is a rare cancer of the retina. It is most common in very young children and infants, with the average age of diagnosis being around four months old. It can occur in just one eye or both. Approximately 40% of cases are inherited.

Liver tumours:

There are two main types of liver tumours - hepatoblastoma and hepatocellular carcinoma. Hepatoblastoma most commonly affects children under the age of five. Hepatocellular carcinoma is less common and affects older children.

Other:

Histiocytoses and Rhabdoid tumours are rare cancers of childhood.

Young people’s cancer:

Cancer is more commonly seen in young people than children, with a mixture of late presenting childhood cancers and early presenting adult cancers.

The main types of cancer in young people are:

• Lymphoma
• Carcinomas (cervical, melanoma, thyroid cancer)
• Germ cell tumours (testicular or ovarian)
• Brain tumours
• Bone cancers
• Soft tissue sarcoma
• Leukaemia

Assessment for Suspected Cancer in Children and Young People

Children:

Studies show that children with cancer may attend multiple consultations before diagnosis. However, it is important to recognise that frequent attendance is common in this age group and usually reflects benign or self-limiting conditions rather than serious pathology.

An unwell child may be unwilling to comply with examination or may disguise their impairment. Developmental regression is a significant finding and lack of evidence of normality may need to be escalated for investigation.

It is essential for clinicians to balance vigilance with the broader context of frequent attendance. A child should be examined if there is concern about cancer even if they look well, and clinicians should ask how many times they have been seen by a healthcare professional or have sought advice for the problem.

The following features raise suspicion for a childhood cancer:

• Attendance across any pathway (e.g. A&E, NHS 111, GP) three or more times
• Change in attendance rates e.g. a family that usually attend infrequently suddenly attending frequently
• Unusual or persistent symptoms (see good practice), that do not respond to simple interventions e.g. antibiotics, laxatives, or a short course of steroids
• Parents or carers have persistent concerns, even if symptoms are more likely to have a benign cause

Young people:

Young people most commonly attend their GP for infection, psychological support or contraceptive advice. A presentation with symptoms which are unexpected within this age group should lead to focused clinical examination, even if they appear otherwise well.

Symptoms due to cancer in young people can be misattributed, for example:

• Pain following sport, gym or muscle strain
• Fatigue due to social life, academic pressures, studying for exams, jobs while at university, anxiety, or mental health problems

Certain conditions, such as Neuro-Developmental Difference (NDD), can affect a young person’s ability to manage medical consultations, including describing symptoms, being compliant with a physical examination or the stress of the environment.

As with children, repeat presentation, including to other professionals (e.g. A&E, AHPs) should be considered a warning sign of a possible cancer.

It may be appropriate to organise urgent tests in primary care if a young person is well and there are single clinical features of concern. Examples include:

• A full blood count (FBC) if there is pallor, bruising, petechiae, infection, lymphadenopathy or generalised bone pain.
• USS for a soft tissue mass
• X-ray for unexplained localised bone pain

A referral to secondary care must not be delayed by waiting for test results if investigations are being arranged for a young person in which there is significant concern about cancer. Repeated attempts at tests (e.g. bloods) should also not delay a referral for assessment.

Urgent Suspicion of Cancer (USC) Referral

Children:

In most cases the first contact for children with suspected cancer is general paediatrics. This may take the form of a phone call for emergency and very urgent concerns. Local guidelines should be followed as referral pathways differ across Scotland.

Young people:

The referral pathway may be more complex for young people with suspected cancer. The person may need clear guidance to understand different appointments, to avoid missed scans/failed attendances. For some young people, consideration should be given to sharing information with parents/guardians. Adult guidelines should be followed, where appropriate, bearing in mind that the more common cancer types seen in this age group are different to those in older adults.

Clinical features that can be associated with cancer in children and young people:

While many CYP cancers present with non-specific symptoms, the majority of CYP presenting with these symptoms will not have cancer. The guidance aims to support clinicians in identifying those at higher risk while avoiding unnecessary investigations.

The following table is not an exhaustive list of clinical features – it is important to remember that children and young people can present atypically.^[91]-[93]

Leukaemia

• fever
• recurrent or persistent infection
• pallor
• fatigue generalised bone pain and/or limp
• hepatosplenomegaly
• lymphadenopathy
• bleeding
• petechiae
• any of the features found in NHL (see below)

Lymphoma: Hodgkin’s

• lymphadenopathy typically progressing over weeks-months
• fever sweats (drenching and at night)
• pruritus
• weight loss
• breathlessness

Lymphoma: Non-Hodgkin’s (NHL)

• lymphadenopathy (particularly cervical)
• splenomegaly
• abdominal distension
• sweats
• fever
• pruritus
• weight loss
• breathlessness

Lymphoma (either type)

Lymphoma can present with a mediastinal mass (see good practice) causing:

• airway compromise – wheeze, stridor, orthopnoea superior vena cava obstruction – breathing difficulty with facial swelling

Brain tumour

See – Better Safe Than Tumour – for age specific symptoms

• persistent/recurrent headache
• persistent/recurrent vomiting
• behaviour change, confusion, or lethargy
• developmental regression or reduced school performance
• seizures
• loss of balance
• papilloedema
• head tilt, wry neck, or stiff neck
• focal neurological deficit
• abnormal eye movements
• new squint
• blurred or loss of vision
• co-ordination or walking issues
• increasing head circumference crossing the centiles
• delayed or arrested puberty

Neuroblastoma

• abdominal mass
• unexplained neurological symptoms
• hypertension
• periorbital bruising
• Horner’s syndrome
• skin lesions in infants (‘blueberry muffin’ appearance)
• systemic symptoms (bone pain, pallor, bruising, fever, fatigue, irritability, lymphadenopathy)

Renal tumours (nephroblastoma)

• palpable abdominal mass (can be painful),
• haematuria (can be visible or persistent non-visible)
• hypertension
• associated fever

Soft tissue sarcoma

• soft tissue mass anywhere on the body (firm/hard, tethered, non-tender, enlarging)
• proptosis nasal or ear obstruction or discharge (persistent or recurrent, bloody/purulent)
• urinary retention
• scrotal swelling, vaginal discharge (blood stained)
• back pain, lower limb pain or weakness (see good practice for malignant spinal cord compression)
• can be associated with enlarged draining lymph nodes and weight loss

Bone tumours

• persistent localised bone pain (pain can be at rest)
• bony mass or swelling
• spontaneous or minor trauma fracture
• back pain including a painful scoliosis
• unexplained limp can cause malaise and fever

Liver tumours

• hepatomegaly
• abdominal pain
• systemic upset (fever, fatigue, loss of appetite)
• rarely jaundice

Retinoblastoma

• white or absent pupillary red reflex
• new onset squint

Germ cell tumours

• scrotal swelling (testis)
• abdominal mass (ovary)
• neurological symptoms (CNS involvement) can be associated with gynaecomastia, virilisation, and/or precocious puberty

Germ cell tumours (continued)

Germ cell tumours can present with a mediastinal mass (see good practice) causing:

• airway compromise – wheeze, stridor, orthopnoea;
• superior vena cava obstruction – breathing difficulty with facial swelling

Langerhans cell histiocytosis

• Bone (pain, swelling, multiple lesions on X-ray and can be lytic)
• posterior pituitary features (polydipsia/polyuria)
• skin (rash, which is unusual, fluctuant, persistent, can look like eczema unresponsive to treatment, severe cradle cap, persistent/recurrent otitis externa, anal excoriation)

Haemophagocytic lymphohistiocystosis

• systemic upset
• fever
• splenomegaly
• pallor
• fatigue
• bruising and/or bleeding

Good Practice Points

Persistent symptoms:

For this guideline, ‘persistent’ indicates the continuation of specified symptoms and/or signs beyond a period that would normally be associated with self-limiting problems. This should take into account what the parent/carer/young person considers unusually persistent for them and the child’s baseline and overall clinical picture. The precise period will vary depending on the severity or combination of symptoms/associated features, as assessed by the health professional.

Lymphadenopathy:

Lymph nodes in the neck that are under 2 cm in longest dimension may be reactive and can commonly be felt in slim young people. Other reassuring features could include a recent infection, masses which are reducing in size and those which are very tender. Neck nodes which are 2 cm or larger, nodes palpable in supraclavicular fossae, axillae and large nodes in the groin merit further assessment and consideration of cancer. If there is associated splenomegaly, night sweats, weight loss, bone pain, unexplained respiratory symptoms, or limp then this is concerning regardless of the size of nodes and should prompt a USC referral. It is important to note that rapidly enlarging malignant nodes can be tender and/or uncomfortable and so do not fit the classic “painless lymphadenopathy” scenario.

Emergency referral:

The following clinical scenarios are emergencies and must be referred immediately to secondary care:

• Malignant Spinal Cord Compression is a severe, often irreversible complication of para- or intra-spinal pathology. It is rare in paediatrics but not in children with cancer
• Mediastinal involvement with cancer (most frequently lymphoma or germ cell tumours) causing airway compromise (wheezing, orthopnoea, stridor) or superior vena cava compression (breathing difficulties, distended neck veins, facial swelling)

Thyroid cancer:

For the assessment of suspected thyroid cancer in children and young people, please see the Head and Neck and Thyroid Cancers Guideline.