PSA velocity (rate of rise of PSA over time) is a more sensitive cancer indicator than a single PSA value — a PSA rise of more than 0.75 ng/mL/year (for a baseline PSA of 4-10 ng/mL) or more than 2 ng/mL/year (for a baseline PSA above 10 ng/mL) is associated with a significantly increased risk of prostate cancer, including high-grade disease. A single PSA result in isolation provides only a snapshot — the trajectory matters. In the GP record, documenting previous PSA values and calculating velocity at each test is a quality standard. A PSA that was 2.5 ng/mL two years ago and is now 5.0 ng/mL represents a velocity of 1.25 ng/mL/year — a significant doubling that warrants 2WW urology referral even though the absolute PSA value (5 ng/mL) might not trigger automatic referral in isolation for an older man.

The age-adjusted PSA thresholds for 2WW referral are an important update in NICE NG12 (2015, updated) — previously a single threshold of PSA >4 ng/mL was used for all ages, but this misclassified both young men (where PSA >2.5 is already elevated) and elderly men (where PSA of 5-6 is common from BPH alone). The current NHS England/NICE approach uses age-specific thresholds. Important practical considerations: a symptomatic man of any age with a rising PSA or any PSA above age-specific threshold who has urinary symptoms should be referred on the 2WW pathway — the PSA threshold is a guide, not a hard cut-off. A man aged 60 with PSA of 4.0 ng/mL (below the 4.5 threshold) but with a family history of prostate cancer and rising PSA velocity should still be referred. Clinical judgement supersedes threshold arithmetic.

The multiparametric MRI (mpMRI) pathway before prostate biopsy has transformed prostate cancer diagnosis since its adoption in NICE NG131 (2019) — mpMRI uses T2-weighted imaging (morphology), diffusion-weighted imaging (DWI — tissue cellularity), and dynamic contrast enhancement (DCE) to detect and characterise suspicious prostate lesions, graded using the PI-RADS v2.1 scoring system (1-5: 1 = very unlikely malignant; 3 = indeterminate; 4-5 = likely malignant). The clinical benefit: mpMRI before biopsy reduces the number of unnecessary biopsies (mpMRI PI-RADS 1-2: approximately 50% of men can safely avoid biopsy), reduces the detection of insignificant low-grade cancers (Gleason 3+3 — which would never cause harm and lead to overtreatment), and increases the detection of clinically significant high-grade cancers (Gleason ≥3+4). The PRECISE trial and PRECISION trial both confirmed that mpMRI-guided biopsy is significantly superior to standard systematic biopsy for detecting clinically significant cancer.

Active surveillance (AS) for low-risk prostate cancer is one of the most important patient communication challenges in primary care — many men (and their partners) instinctively find it difficult to accept 'watch and wait' when a cancer diagnosis has been made. The evidence base: the PROTECT trial (New England Journal of Medicine 2016, 10-year follow-up) showed that for men with low-risk localised prostate cancer (which accounts for approximately 50% of all diagnoses), 10-year prostate cancer-specific survival was approximately 99% whether treated with surgery, radiotherapy, or active monitoring. Metastasis-free survival was slightly lower in the AS group but overall mortality was identical. The GP's role in the AS conversation: reinforce the shared-decision making rationale, normalise the concept of monitoring a slow-growing cancer without immediate treatment, and ensure the monitoring programme is adhered to — PSA non-attendance is the most common reason for delayed detection of progression.

The DRE (digital rectal examination) remains a mandatory component of prostate cancer assessment despite the mpMRI pathway — a hard, irregular, or asymmetric prostate on DRE indicates clinical T3 or T4 disease and should trigger 2WW referral regardless of the PSA level. PSA can be low in poorly differentiated (high-grade) prostate cancer because dedifferentiated prostate cancer cells lose the ability to produce PSA — the 'PSA leak' is paradoxically reduced in some high-grade cancers. A man with a rock-hard, nodular prostate and a PSA of only 3 ng/mL should still be referred on the 2WW pathway. The clinical standard: DRE should be offered to all men presenting with LUTS, elevated PSA, or any concern about prostate pathology. GPs should be trained in prostate DRE as a core competency of the SCA curriculum.

The testosterone flare with LHRH agonist initiation is a critical prescribing safety principle for prostate cancer ADT — LHRH agonists (leuprorelin, goserelin, triptorelin) cause an initial surge of LH and testosterone in the first 1-2 weeks before receptor desensitisation produces testosterone suppression. In patients with bone metastases or obstructing locally advanced cancer, this testosterone surge can cause disease flare: worsening bone pain (and risk of pathological fractures), urinary retention, spinal cord compression, and hypercalcaemia. Prevention: prescribe an anti-androgen (bicalutamide 50-150 mg OD) starting 3-7 days BEFORE the LHRH agonist injection and continuing for at least 4 weeks after. Failing to co-prescribe bicalutamide with the first LHRH agonist injection in a patient with metastatic disease is a prescribing error with potentially serious consequences.

The cardiovascular risk associated with long-term ADT is a clinically important GP responsibility to monitor — ADT (androgen deprivation therapy) significantly increases cardiovascular risk in prostate cancer patients: retrospective cohort studies show approximately 15-30% increased risk of myocardial infarction, stroke, and cardiovascular mortality in men on long-term ADT. The mechanisms: testosterone suppression causes: increased body fat (visceral adiposity), reduced lean muscle mass, insulin resistance (approximately 44% increased risk of diabetes), dyslipidaemia (increased triglycerides, LDL), and direct vascular effects. The GP monitoring programme for men on long-term ADT should include: annual HbA1c and fasting lipid profile, blood pressure monitoring every 3-6 months, weight and BMI, and exercise prescription (150 min moderate aerobic exercise per week reduces metabolic side effects).

The PDE5 inhibitor (sildenafil, tadalafil) prescribing on the NHS for prostate cancer treatment-related ED is a quality standard — NHS England guidance confirms that erectile dysfunction caused by prostate cancer treatment (surgery, radiotherapy, or ADT) is a specific indication for NHS prescription of PDE5 inhibitors, distinct from the general ED prescribing restriction that applies in many STPs. GPs should not decline to prescribe sildenafil or tadalafil for prostate cancer treatment-related ED on grounds of cost or non-urgent status — this represents a failure to provide evidence-based care for a significant treatment-related morbidity. The prescription should be endorsed with the specific indication on the FP10.

The nadir PSA after radical prostatectomy should be undetectable (below the assay detection limit, typically <0.01-0.1 ng/mL depending on the assay used) within 4-6 weeks of surgery — because all PSA-producing prostate tissue should have been removed. A detectable PSA after radical prostatectomy (above the assay threshold) suggests either residual prostate tissue or persistent/recurrent disease. GPs monitoring post-prostatectomy patients must use an ultrasensitive PSA assay (detection limit <0.01-0.05 ng/mL) — a standard PSA assay with a detection limit of 0.1 ng/mL is inadequate for post-prostatectomy monitoring. The biochemical recurrence definition after prostatectomy: PSA >0.2 ng/mL on two consecutive measurements, at least 6 weeks after surgery.