Lung cancer

1.1.1.

Refer people using a suspected cancer pathway referral for lung cancer if they:

• have chest X-ray findings that suggest lung cancer or
• are aged 40 and over with unexplained haemoptysis. [2015]

1.1.2.

Offer an urgent chest X-ray (to be done within 2 weeks) to assess for lung cancer in people aged 40 and over if they have 2 or more of the following unexplained symptoms, or if they have ever smoked and have 1 or more of the following unexplained symptoms:

• cough
• fatigue
• shortness of breath
• chest pain
• weight loss
• appetite loss. [2015]

1.1.3.

Consider an urgent chest X-ray (to be done within 2 weeks) to assess for lung cancer in people aged 40 and over with any of the following:

• persistent or recurrent chest infection
• finger clubbing
• supraclavicular lymphadenopathy or persistent cervical lymphadenopathy
• chest signs consistent with lung cancer
• thrombocytosis. [2015]

Mesothelioma

1.1.4.

Refer people using a suspected cancer pathway referral for mesothelioma if they have chest X-ray findings that suggest mesothelioma. [2015]

1.1.5.

Offer an urgent chest X-ray (to be done within 2 weeks) to assess for mesothelioma in people aged 40 and over, if:

• they have 2 or more of the following unexplained symptoms, or
• they have 1 or more of the following unexplained symptoms and have ever smoked, or
• they have 1 or more of the following unexplained symptoms and have been exposed to asbestos:

  —

  cough

  —

  fatigue

  —

  shortness of breath

  —

  chest pain

  —

  weight loss

  —

  appetite loss. [2015]

1.1.6.

Consider an urgent chest X-ray (to be done within 2 weeks) to assess for mesothelioma in people aged 40 and over with either:

• finger clubbing or
• chest signs compatible with pleural disease. [2015]

Oesophageal cancer

1.2.1.

Offer urgent, direct access upper gastrointestinal endoscopy (to be done within 2 weeks) to assess for oesophageal cancer in people:

• with dysphagia or
• aged 55 and over with weight loss and any of the following:

  —

  upper abdominal pain

  —

  reflux

  —

  dyspepsia. [2015]

1.2.2.

Consider non-urgent, direct access upper gastrointestinal endoscopy to assess for oesophageal cancer in people with haematemesis. [2015]

1.2.3.

Consider non-urgent, direct access upper gastrointestinal endoscopy to assess for oesophageal cancer in people aged 55 or over with:

• treatment-resistant dyspepsia or
• upper abdominal pain with low haemoglobin levels or
• raised platelet count with any of the following:

  —

  nausea

  —

  vomiting

  —

  weight loss

  —

  reflux

  —

  dyspepsia

  —

  upper abdominal pain, or

• nausea or vomiting with any of the following:

  —

  weight loss

  —

  reflux

  —

  dyspepsia

  —

  upper abdominal pain. [2015]

Pancreatic cancer

1.2.4.

Refer people using a suspected cancer pathway referral for pancreatic cancer if they are aged 40 and over and have jaundice. [2015]

1.2.5.

Consider an urgent direct access CT scan (to be done within 2 weeks), or an urgent ultrasound scan if CT is not available, to assess for pancreatic cancer in people aged 60 and over with weight loss and any of the following:

• diarrhoea
• back pain
• abdominal pain
• nausea
• vomiting
• constipation
• new-onset diabetes. [2015]

Stomach cancer

1.2.6.

Consider a suspected cancer pathway referral for people with an upper abdominal mass consistent with stomach cancer. [2015]

1.2.7.

Offer urgent, direct access upper gastrointestinal endoscopy (to be done within 2 weeks) to assess for stomach cancer in people:

• with dysphagia or
• aged 55 and over with weight loss and any of the following:

  —

  upper abdominal pain

  —

  reflux

  —

  dyspepsia. [2015]

1.2.8.

Consider non-urgent, direct access upper gastrointestinal endoscopy to assess for stomach cancer in people with haematemesis. [2015]

1.2.9.

Consider non-urgent, direct access upper gastrointestinal endoscopy to assess for stomach cancer in people aged 55 or over with:

• treatment-resistant dyspepsia or
• upper abdominal pain with low haemoglobin levels or
• raised platelet count with any of the following:

  —

  nausea

  —

  vomiting

  —

  weight loss

  —

  reflux

  —

  dyspepsia

  —

  upper abdominal pain, or

• nausea or vomiting with any of the following:

  —

  weight loss

  —

  reflux

  —

  dyspepsia

  —

  upper abdominal pain. [2015]

Gall bladder cancer

1.2.10.

Consider an urgent direct access ultrasound scan (to be done within 2 weeks) to assess for gall bladder cancer in people with an upper abdominal mass consistent with an enlarged gall bladder. [2015]

Liver cancer

1.2.11.

Consider an urgent direct access ultrasound scan (to be done within 2 weeks) to assess for liver cancer in people with an upper abdominal mass consistent with an enlarged liver. [2015]

Colorectal cancer

1.3.1.

Offer quantitative faecal immunochemical testing (FIT) using HM-JACKarc or OC-Sensor to guide referral for suspected colorectal cancer in adults:

• with an abdominal mass, or
• with a change in bowel habit, or
• with iron-deficiency anaemia, or
• aged 40 and over with unexplained weight loss and abdominal pain, or
• aged under 50 with rectal bleeding and either of the following unexplained symptoms:

  —

  abdominal pain

  —

  weight loss, or

• aged 50 and over with any of the following unexplained symptoms:

  —

  rectal bleeding

  —

  abdominal pain

  —

  weight loss, or

• aged 60 and over with anaemia even in the absence of iron deficiency.
  FIT should be offered even if the person has previously had a negative FIT result through the NHS bowel cancer screening programme. People with a rectal mass, an unexplained anal mass or unexplained anal ulceration do not need to be offered FIT before referral is considered. [2023]

1.3.2.

Refer adults using a suspected cancer pathway referral for colorectal cancer if they have a FIT result of at least 10 micrograms of haemoglobin per gram of faeces. [2023]

1.3.3.

For people who have not returned a faecal sample or who have a FIT result below 10 micrograms of haemoglobin per gram of faeces:

• safety netting processes should be in place
• referral to an appropriate secondary care pathway should not be delayed if there is strong clinical concern of cancer because of ongoing unexplained symptoms (for example, abdominal mass). [2023]

1.3.4.

Clinicians should consider if people need additional help, information or support to return their sample. [2023]

1.3.5.

Consider a suspected cancer pathway referral for colorectal cancer in adults with a rectal mass. [2015, amended 2023]

Anal cancer

1.3.6.

Consider a suspected cancer pathway referral for anal cancer in people with an unexplained anal mass or unexplained anal ulceration. [2015]

Ovarian cancer

The recommendations in this section have been incorporated from NICE's guideline on ovarian cancer and have not been updated. The recommendations for ovarian cancer apply to women aged 18 and over.

1.5.1.

Make a referral to a gynaecological cancer service using a suspected cancer pathway referral if physical examination identifies ascites and/or a pelvic or abdominal mass (which is not obviously uterine fibroids). [2011, amended 2020]

1.5.2.

Carry out tests in primary care (see recommendations 1.5.6 to 1.5.9) if a woman (especially if aged 50 or over) reports having any of the following symptoms on a persistent or frequent basis – particularly more than 12 times per month:

• persistent abdominal distension (women often refer to this as 'bloating')
• feeling full (early satiety) and/or loss of appetite
• pelvic or abdominal pain
• increased urinary urgency and/or frequency. [2011]

1.5.3.

Consider carrying out tests in primary care (see recommendations 1.5.6 to 1.5.9) if a woman reports unexplained weight loss, fatigue or changes in bowel habit. [2011]

1.5.4.

Advise any woman who is not suspected of having ovarian cancer to return to her GP if her symptoms become more frequent and/or persistent. [2011]

1.5.5.

Carry out appropriate tests for ovarian cancer (see recommendations 1.5.6 to 1.5.9) in any woman aged 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS), because IBS rarely presents for the first time in women of this age. (See NICE's guideline on irritable bowel syndrome in adults). [2011]

1.5.6.

Measure serum CA125 in primary care in women with symptoms that suggest ovarian cancer (see recommendations 1.5.1 to 1.5.5). [2011]

1.5.7.

If serum CA125 is 35 IU/ml or greater, arrange an ultrasound scan of the abdomen and pelvis. [2011]

1.5.8.

If the ultrasound suggests ovarian cancer, make a referral to a gynaecological cancer service using a suspected cancer pathway referral. [2011, amended 2020]

1.5.9.

For any woman who has normal serum CA125 (less than 35 IU/ml), or CA125 of 35 IU/ml or greater but a normal ultrasound:

• assess her carefully for other clinical causes of her symptoms and investigate if appropriate
• if no other clinical cause is apparent, advise her to return to her GP if her symptoms become more frequent and/or persistent. [2011]

Endometrial cancer

1.5.10.

Refer women using a suspected cancer pathway referral for endometrial cancer if they are aged 55 and over with post-menopausal bleeding (unexplained vaginal bleeding more than 12 months after menstruation has stopped because of the menopause). [2015]

1.5.11.

Consider a suspected cancer pathway referral for endometrial cancer in women aged under 55 with post-menopausal bleeding. [2015]

1.5.12.

Consider a direct access ultrasound scan to assess for endometrial cancer in women aged 55 and over with:

• unexplained symptoms of vaginal discharge who:

  —

  are presenting with these symptoms for the first time or

  —

  have thrombocytosis or

  —

  report haematuria, or

• visible haematuria and:

  —

  low haemoglobin levels or

  —

  thrombocytosis, or

  —

  high blood glucose levels. [2015]

Cervical cancer

1.5.13.

Consider a suspected cancer pathway referral for women if, on examination, the appearance of their cervix is consistent with cervical cancer. [2015]

Vulval cancer

1.5.14.

Consider a suspected cancer pathway referral for vulval cancer in women with an unexplained vulval lump, ulceration or bleeding. [2015]

Vaginal cancer

1.5.15.

Consider a suspected cancer pathway referral for vaginal cancer in women with an unexplained palpable mass in or at the entrance to the vagina. [2015]

Prostate cancer

1.6.1.

Refer people using a suspected cancer pathway referral for prostate cancer if their prostate feels malignant on digital rectal examination. [2015]

1.6.2.

Consider a prostate-specific antigen (PSA) test and digital rectal examination to assess for prostate cancer in people with:

• any lower urinary tract symptoms, such as nocturia, urinary frequency, hesitancy, urgency or retention or
• erectile dysfunction or
• visible haematuria. [2015]

1.6.3.

Consider referring people with possible symptoms of prostate cancer, as specified in recommendation 1.6.2, using a suspected cancer pathway referral for prostate cancer if their PSA levels are above the threshold for their age in table 1. Take into account the person's preferences and any comorbidities when making the decision. [2021]

Table 1

Age-specific PSA thresholds for people with possible symptoms of prostate cancer.

Bladder cancer

1.6.4.

Refer people using a suspected cancer pathway referral for bladder cancer if they are:

• aged 45 and over and have:

  —

  unexplained visible haematuria without urinary tract infection or

  —

  visible haematuria that persists or recurs after successful treatment of urinary tract infection, or

• aged 60 and over and have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test. [2015]

1.6.5.

Consider non-urgent referral for bladder cancer in people aged 60 and over with recurrent or persistent unexplained urinary tract infection. [2015]

Renal cancer

1.6.6.

Refer people using a suspected cancer pathway referral for renal cancer if they are aged 45 and over and have:

• unexplained visible haematuria without urinary tract infection or
• visible haematuria that persists or recurs after successful treatment of urinary tract infection. [2015]

Testicular cancer

1.6.7.

Consider a suspected cancer pathway referral for testicular cancer in men if they have a non-painful enlargement or change in shape or texture of the testis. [2015]

1.6.8.

Consider a direct access ultrasound scan for testicular cancer in men with unexplained or persistent testicular symptoms. [2015]

Penile cancer

1.6.9.

Consider a suspected cancer pathway referral for penile cancer in men if they have:

• a penile mass or ulcerated lesion, when a sexually transmitted infection has been excluded as a cause, or
• a persistent penile lesion after treatment for a sexually transmitted infection has been completed. [2015]

1.6.10.

Consider a suspected cancer pathway referral for penile cancer in men with unexplained or persistent symptoms affecting the foreskin or glans. [2015]

Malignant melanoma of the skin

1.7.1.

Refer people using a suspected cancer pathway referral for melanoma if they have a suspicious pigmented skin lesion with a weighted 7-point checklist score of 3 or more. [2015]

1.7.2.

Refer people using a suspected cancer pathway referral if dermoscopy suggests melanoma of the skin. [2015]

1.7.3.

Consider a suspected cancer pathway referral for melanoma in people with a pigmented or non-pigmented skin lesion that suggests nodular melanoma. [2015]

1.8. Head and neck cancers

1.9. Brain and central nervous system cancers

1.10. Haematological cancers

Hodgkin's lymphoma

Separate recommendations have been made for adults and for children and young people to reflect that there are different referral pathways. In practice young people (aged 16 to 24) may be referred using either pathway depending on their age and local arrangements.

Adults

1.10.10.

Consider a suspected cancer pathway referral for Hodgkin's lymphoma in adults presenting with unexplained lymphadenopathy. When considering referral, take into account any associated symptoms, particularly fever, night sweats, shortness of breath, pruritus, weight loss or alcohol-induced lymph node pain. [2015]

Children and young people

1.10.11.

Consider a very urgent referral (for an appointment within 48 hours) for specialist assessment for Hodgkin's lymphoma in children and young people presenting with unexplained lymphadenopathy. When considering referral, take into account any associated symptoms, particularly fever, night sweats, shortness of breath, pruritus or weight loss. [2015]

Bone sarcoma in adults

1.11.1.

Consider a suspected cancer pathway referral for adults if an X-ray suggests the possibility of bone sarcoma. [2015]

Bone sarcoma in children and young people

1.11.2.

Consider a very urgent referral (for an appointment within 48 hours) for specialist assessment for children and young people if an X-ray suggests the possibility of bone sarcoma. [2015]

1.11.3.

Consider a very urgent direct access X-ray (to be done within 48 hours) to assess for bone sarcoma in children and young people with unexplained bone swelling or pain. [2015]

Soft tissue sarcoma in adults

1.11.4.

Consider an urgent, direct access ultrasound scan (to be done within 2 weeks) to assess for soft tissue sarcoma in adults with an unexplained lump that is increasing in size. [2015]

1.11.5.

Consider a suspected cancer pathway referral for adults if they have ultrasound scan findings that are suggestive of soft tissue sarcoma or if ultrasound findings are uncertain and clinical concern persists. [2015]

Soft tissue sarcoma in children and young people

1.11.6.

Consider a very urgent, direct access ultrasound scan (to be done within 48 hours) to assess for soft tissue sarcoma in children and young people with an unexplained lump that is increasing in size. [2015]

1.11.7.

Consider a very urgent referral (for an appointment within 48 hours) for children and young people if they have ultrasound scan findings that are suggestive of soft tissue sarcoma or if ultrasound findings are uncertain and clinical concern persists. [2015]

Neuroblastoma

1.12.1.

Consider very urgent referral (for an appointment within 48 hours) for specialist assessment for neuroblastoma in children with a palpable abdominal mass or unexplained enlarged abdominal organ. [2015]

Retinoblastoma

1.12.2.

Consider referral for ophthalmological assessment for retinoblastoma in children with an absent red reflex. If there is new-onset squint that occurs together with an absent red reflex, see the recommendation on new-onset squint with loss of red reflex in NICE's guideline on suspected neurological conditions. [2015]

Wilms' tumour

1.12.3.

Consider very urgent referral (for an appointment within 48 hours) for specialist assessment for Wilms' tumour in children with any of the following:

• a palpable abdominal mass
• an unexplained enlarged abdominal organ
• unexplained visible haematuria. [2015]

Symptoms of concern in children and young people

1.13.1.

Take into account the insight and knowledge of parents and carers when considering making a referral for suspected cancer in a child or young person. Consider referral for children if their parent or carer has persistent concern or anxiety about the child's symptoms, even if the symptoms are most likely to have a benign cause. [2015]

Symptoms of concern in adults

1.13.2.

For people with unexplained weight loss, which is a symptom of several cancers including colorectal, gastro-oesophageal, lung, prostate, pancreatic and urological cancer:

• carry out an assessment for additional symptoms, signs or findings that may help to clarify which cancer is most likely and
• offer urgent investigation or a suspected cancer pathway referral. [2015]

1.13.3.

For people with unexplained appetite loss, which is a symptom of several cancers including lung, oesophageal, stomach, colorectal, pancreatic, bladder and renal cancer:

• carry out an assessment for additional symptoms, signs or findings that may help to clarify which cancer is most likely and
• offer urgent investigation or a suspected cancer pathway referral. [2015]

1.13.4.

For people with deep vein thrombosis, which is associated with several cancers including urogenital, breast, colorectal and lung cancer:

• carry out an assessment for additional symptoms, signs or findings that may help to clarify which cancer is most likely and
• consider urgent investigation or a suspected cancer pathway referral. [2015]

Abdominal distension

Abdominal examination findings

Abdominal, pelvic or rectal mass or enlarged abdominal organ

Abdominal or pelvic pain

Change in bowel habit

Dyspepsia

Dysphagia

Nausea or vomiting

Rectal examination findings

Reflux

Bleeding, bruising or petechiae

Haematemesis

Haemoptysis

Post-menopausal bleeding

Post-menopausal bleeding is unexplained vaginal bleeding more than 12 months after menstruation has stopped because of the menopause.

Rectal bleeding

Vulval bleeding

Gynaecological examination findings

Vaginal symptoms

Vulval symptoms

Lumps and masses

See also the section on abdominal symptoms for abdominal, anal, pelvic and rectal lumps or masses.

Lymphadenopathy

Oral lesions

Neurological symptoms in adults

Pain

Chest infection

Chest pain

Cough

Hoarseness

Respiratory examination findings

Shortness of breath

Back pain

Bone pain

Fracture

Skin or surface symptoms

Dysuria

Erectile dysfunction

Haematuria

Testicular symptoms

Other urinary tract symptoms

Appetite loss or early satiety

Deep vein thrombosis

Diabetes

Fatigue

Fever

See also the section on respiratory symptoms for chest infection.

Infection

Night sweats

Pallor

Pruritus

Weight loss

Blood test findings

Dermoscopy findings

Digital rectal examination findings

Faecal tests

Imaging tests

Jaundice

Urine test findings

Abdominal symptoms

Bleeding, bruising or rashes

Lumps or masses

See also the section on abdominal symptoms for abdominal mass or unexplained enlarged abdominal organ, splenomegaly and hepatosplenomegaly.

Neurological symptoms

Respiratory symptoms

Skeletal symptoms

Skin or surface symptoms

Urological symptoms

Non-specific features of cancer

Ocular examination

Parental concern

Primary care investigations

1. Age thresholds in cancer

Longitudinal studies should be carried out to identify and quantify factors in adults that are associated with development of specific cancers at a younger age than the norm. They should be designed to inform age thresholds in clinical guidance. The primary outcome should be likelihood ratios and positive predictive values for cancer occurring in younger age groups.

2. Primary care testing

Diagnostic accuracy studies of tests accessible to primary care should be carried out for a given cancer in symptomatic people. Priority areas for research should include tests for people with cough, non-visible haematuria, suspected prostate cancer, suspected pancreatic cancer, suspected cancer in childhood and young people and other suspected rare cancers. Outcomes of interest are the performance characteristics of the test, particularly sensitivity, specificity and positive and negative predictive values.

3. Cancers insufficiently researched in primary care

Observational studies of symptomatic primary care patients should be used to estimate the positive predictive value of different symptoms for specific cancers. Priority areas for research are those where the evidence base is currently insufficient and should include prostate cancer, pancreatic cancer, cancer in childhood and young people and other rare cancers. Outcomes of interest are positive predictive values and likelihood ratios for cancer.

4. Patient experience

Qualitative studies are needed to assess the key issues in patient experience and patient information needs in the cancer diagnostic pathway, particularly in the interval between first presentation to primary care and first appointment in secondary care. Outcomes of interest are patient satisfaction, quality of life and patient perception of the quality of care and information.

5. Prostate-specific antigen testing

What is the diagnostic accuracy of using age-adjusted and fixed prostate-specific antigen thresholds for people with symptoms of prostate cancer, including those at high risk of developing prostate cancer (such as those with an African family background or a family history of prostate cancer)?

Why the committee made the recommendation

The evidence on the diagnostic accuracy of fixed and age-specific prostate-specific antigen (PSA) thresholds was very uncertain because all of the studies were based on a population that had already been referred to secondary care. The 2019 guideline recommended referral if PSA levels were above the age-specific reference range. The committee agreed that referral should be considered based on PSA thresholds, but did not make a stronger recommendation because of the uncertainty in the evidence and the likely low positive predictive value of the PSA test for prevalence estimates based on UK population data. The committee noted that many prostate cancers are slow growing and might never impact a person's life expectancy. Some people might choose not to be referred to secondary care to avoid invasive investigations and treatment that might not benefit them. Therefore, the committee agreed that a patient-centred approach to referral is important, and recommended that the person's preferences and any comorbidities should be taken into account.

The committee agreed that more research is needed in this area to better understand the most appropriate thresholds that should prompt referral to secondary care for each age group. The committee noted that ethnicity and family history are important factors that affect the risk of prostate cancer. Therefore, they recommended that the data from research be stratified by these factors to determine whether different PSA levels should prompt referral in these groups. Research in this area may also help to address health inequalities in prostate cancer diagnosis and outcomes in the UK.

There was no strong evidence to differentiate between using age-specific or fixed PSA thresholds. The committee also noted that no cost-effectiveness evidence comparing age-specific thresholds with fixed thresholds was identified. However, because PSA levels increase naturally with age, the committee agreed a lower fixed PSA threshold would detect more cases of prostate cancer but also lead to unnecessary biopsies and overtreatment in some age groups. This would also be likely to result in more referrals to secondary care and have a significant impact on NHS resources. The committee therefore recommended the use of age-specific thresholds, which are already established in current practice and were recommended in the previous version of the guideline. Because of regional variations in practice (particularly in the 50 to 69 age range), the committee decided to define the age-specific PSA thresholds. The committee agreed that the thresholds used in the reviewed studies on people with symptoms of possible prostate cancer should be used in the absence of evidence to support alternative values, because these studies were most applicable to the population that the recommendation applies to. No evidence was available specifically for people under 40 or over 79, and so the committee recommended that clinical judgement is used when deciding whether to refer people in these groups to secondary care.

How the recommendation might affect practice

Referral based on age-specific PSA thresholds is already recommended, so practice should not change significantly. Also, clarifying the age-specific thresholds will help standardise care. Taking into account patient preferences and comorbidities should also lead to a more patient-centred approach to referral.

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