Tumour markers are among the most misused tests in primary care — they are frequently requested for screening in asymptomatic patients (where they have poor positive predictive value) and their elevated results cause significant patient anxiety and cascade investigations. The fundamental principle that GPs must understand: no tumour marker is sufficiently sensitive and specific to be used as a standalone screening test in asymptomatic patients. The positive predictive value of any tumour marker depends critically on the pre-test probability: a PSA of 4 ng/ml in a 40-year-old with no symptoms has very different implications than the same result in a 70-year-old with nocturia and DRE abnormality. The two appropriate contexts for tumour marker use in primary care are: (1) investigation of symptomatic patients where a specific malignancy is suspected (CA125 for bloating in a post-menopausal woman), and (2) monitoring known malignancy for recurrence (CEA for colorectal cancer surveillance). The single exception to the no-screening rule is PSA for prostate cancer — UK primary care has an informed decision-making framework (Prostate Cancer Risk Management Programme) for PSA in asymptomatic men over 50 who request it after receiving information about the benefits and limitations.

The PSA controversy in UK primary care is one of the most important clinical ethics issues in cancer screening — the NHS does not have a national prostate cancer screening programme (unlike bowel, breast, and cervical cancer) because the evidence for PSA screening reducing prostate cancer mortality is contested (the ERSPC trial showed a 21% reduction in prostate cancer mortality at 16 years, but the ProtecT trial showed that active monitoring, surgery, and radiotherapy had equivalent 10-year survival, suggesting many PSA-detected cancers are low-grade and non-lethal). The current UK position: GPs should follow the Prostate Cancer Risk Management Programme (PCRMP) — any man over 50 who asks about PSA testing should receive balanced information about: (1) the benefits (detecting cancer early, potentially curative treatment), (2) the limitations (false positives causing unnecessary biopsies with complications, overdiagnosis of slow-growing cancers that would never have caused symptoms, PSA elevated by benign conditions), and (3) the uncertainties (whether PSA screening genuinely saves lives in the UK population). After receiving this information, if the man wants a PSA test, the GP should arrange it. GPs should never refuse a PSA test to a man over 50 who has been appropriately counselled and requests it.

The 2WW referral for prostate cancer is straightforward for most GPs but the borderline PSA range (4–10 ng/ml with a normal DRE) is an area where clinical judgement and good documentation matter most — at PSA between 4–10 ng/ml with a normal DRE, the probability of cancer is approximately 20–25%. The appropriate response: if there are other clinical features (weight loss, bone pain, hard prostate, rising PSA velocity) → 2WW. If no additional risk features → repeat PSA in 4–6 weeks after excluding prostatitis and ensuring pre-test conditions were met. If the repeat PSA confirms elevation in the 4–10 range → 2WW for MRI-directed biopsy. The MRI prostate (mpMRI) is now the standard first investigation after referral for suspected prostate cancer in the UK — it stratifies patients by PIRADS score (1–5) and guides targeted biopsy, reducing detection of clinically insignificant low-grade cancer and reducing unnecessary biopsies. The GP's referral letter should include: PSA value and date, DRE findings, LUTS severity, family history, and medication history (finasteride halves PSA — double the result if the patient is on it).

The RMI calculation is a simple and validated tool that every GP should know for triaging a woman with an adnexal mass — it was developed by Jacobs et al. in 1990 and has been validated in multiple large studies showing that an RMI above 200–250 identifies approximately 70–85% of women with ovarian cancer while avoiding 75–80% of unnecessary referrals for benign masses. The GP's role in calculating the RMI: measure CA125 (blood test), arrange USS pelvis (which reports the U score), apply the M score based on menopausal status, and calculate RMI = U × M × CA125. If the USS pelvis hasn't been done yet, the GP can send the referral based on CA125 alone (CA125 >35 in a post-menopausal woman = 2WW USS + gynaecology). The critical point: CA125 and USS pelvis should be requested simultaneously for any post-menopausal woman with new pelvic symptoms — not sequentially. The median time from symptom onset to diagnosis of ovarian cancer in the UK is 9–12 months — most of this delay is at the primary care stage.

The GTD referral to a designated centre is an RCOG mandate — gestational trophoblastic disease (hydatidiform moles, invasive moles, choriocarcinoma) is a rare but highly treatable condition that requires specialist management at one of three UK GTD centres: Charing Cross Hospital (London), Sheffield Teaching Hospitals, and Dundee. The UK has the best GTD outcomes globally because of this centralised model of care — the cure rate for choriocarcinoma is approximately 95% with appropriate chemotherapy (methotrexate ± combination regimens). The beta-hCG monitoring programme after molar pregnancy (urine or blood hCG every 2 weeks until normal, then monthly) is managed by the GTD centres. GPs must refer any suspected molar pregnancy (ultrasound showing characteristic snowstorm appearance, very high beta-hCG, abnormal vaginal bleeding) to the GTD centre BEFORE surgical evacuation where possible, or immediately after, to register the patient in the national surveillance programme.

The AFP + USS liver HCC surveillance programme is a NICE and EASL guideline recommendation for cirrhotic patients and chronic hepatitis B carriers — the rationale is that HCC detected at an early stage (lesion <2 cm) by surveillance has a 5-year survival of approximately 70–80% with ablation or transplantation, compared to approximately 10–20% for HCC detected symptomatically (when it is typically large or multifocal). The surveillance interval is 6 months (not annually — HCC doubling times are approximately 3–6 months in aggressive tumours). The AFP threshold for triggering CT is not clearly established — any rising AFP in a cirrhotic patient or a value above 20 ng/ml that is new or increasing should prompt USS, and if USS is inconclusive, CT with contrast. GPs managing patients with known cirrhosis (from alcohol, NAFLD, hepatitis B/C) should ensure that 6-monthly AFP + USS is happening — it is frequently omitted in patients not engaged with hepatology. Adding it to the chronic liver disease template in the practice clinical record system ensures regular checking.

The MRC OV05/EORTC 55955 trial finding for ovarian cancer CA125 monitoring is one of the most important counter-intuitive results in oncology — the trial showed that treating ovarian cancer recurrence based solely on CA125 rise (before clinical symptoms) did not improve overall survival, quality of life, or any patient outcome compared to waiting for clinical recurrence. This means that routine CA125 monitoring for ovarian cancer recurrence, while standard practice, should not automatically trigger chemotherapy at the first sign of CA125 rise — the decision to restart treatment should be based on symptoms, quality of life, and a full discussion between the oncologist and the patient. GPs monitoring CA125 post-ovarian cancer treatment should: record the result, communicate it to the oncology team, but not alarm patients unnecessarily about a modest rise in CA125 — the decision to treat is a specialist oncology discussion, not an automatic protocol.

The NHS bowel cancer screening programme with FIT (faecal immunochemical test) is one of the most cost-effective cancer screening interventions in medicine — the programme detects approximately 50% of colorectal cancers at an earlier stage than they would otherwise be detected, resulting in significant mortality reduction. The current programme (FIT kit to all 50–75 year olds every 2 years) has a participation rate of approximately 60% — GPs can significantly improve this by: actively encouraging eligible non-participants at every consultation, removing barriers (explaining the test is simple and does not require dietary restriction), and following up missed invitations. The FIT threshold of 10 mcg Hb/g faeces has a sensitivity of approximately 75% for colorectal cancer and 25% for advanced adenomas — it is important to understand that a negative FIT does not exclude colorectal cancer in a symptomatic patient. Symptomatic patients with lower GI symptoms should be investigated clinically (quantitative FIT + clinical assessment) regardless of the result of their population screening FIT.

The medico-legal documentation principle for raised cancer markers is essential — a GP who identifies a raised CA125, PSA, AFP, or CEA and fails to act on it, or acts but does not document the action, is at significant medico-legal risk if a cancer is subsequently diagnosed at a late stage. The key documentation requirements: (1) record the abnormal result with date; (2) document the differential diagnosis considered and what prompted the test; (3) document the action taken (referral made, repeat test arranged, patient counselled); (4) document safety-netting given to the patient (what symptoms to return with, timeframe for review); and (5) document that the referral outcome was received and reviewed. A common error is making a 2WW referral but not checking whether the patient was seen and the outcome received — the GP has a continuing duty of care to ensure the referral was acted upon and the result reviewed. Electronic clinical systems should flag outstanding referral outcomes for review at a defined interval (e.g., 4 weeks).