and Kasra Saeb-Parsy3
The Whittington Hospital, London, UK
Department of Urology, The Whittington Hospital, London, UK
Department of Urology, Cambridge Addenbrookes, Cambridge University Hospitals NHS Foundation TRUST, Hills Road, Cambridge, CB2 0QQ, UK
TRUS guided prostate biopsy is the gold standard in the diagnosis of prostate cancer. It was originally performed under ‘finger guidance’ alone but has evolved with the introduction of transrectal ultrasound imaging by Wantabe and colleagues in the 1960s, sextant biopsy protocols by Hodge et al. in the 1980s and more recently fusion multiparametric MRI.
Indications for Prostate Biopsy
EAU and NICE guidelines recommend first prostate biopsy to be offered based on PSA level and DRE findings, taking into account the man’s co-morbities and age. Although cancer is generally regarded as unlikely if PSA is less than 4 ng/ml, studies such as PCPT have shown an overall cancer burden of 15% in this group of men . Many clinicians lower this threshold to 2.5 ng/ml and are mindful that high grade prostate cancer can occur with low PSA levels.
Clinicians may use PSA velocity and density to further stratify risk, with a PSA velocity >0.75 ng/ml/year or a density <25% in those with a range 4–10 ng/ml warranting biopsy. Conversely, if the suspicion of prostate cancer is high with evidence of bone metastases, histological confirmation with biopsy is not necessary unless in trial settings.
Repeat biopsy is indicated in patients with a persistently high or rising PSA after initial negative biopsy, abnormal DRE, ASAP, extensive HGPIN or cell atypia adjacent to HGPIN on previous biopsy. Those on an active surveillance protocol are usually offered re-biopsy at 12 months or if there is clinical concern about DRE, PSA or multiparametric MRI (Mp-MRI) findings.
Although systematic transrectal TRUS guided biopsies remain the gold standard for diagnosis, transperineal template biopsy is used in many centres. Template biopsies offer a higher diagnostic yield  increases core sampling and carries a smaller risk of sepsis. It offers improved scrutiny of the anterior gland and apex and is often favoured in active surveillance and focal therapy protocols.
Multiparametric MRI and Fusion Biopsy
The much anticipated PROMIS trial  was a multi centre paired cohort study of 576 biopsy naive men with a suspicion of prostate cancer who underwent Mp-MRI followed by both TRUS and template biopsies. Mp-MRI had a sensitivity of 93% and a negative predictive value of 89% in detecting prostate cancer when template biopsy was used as the reference test. Indeed the authors suggest that if Mp-MRI were used as a triage test, one quarter of men may safely avoid prostate biopsy. TRUS biopsy was shown to be 96% specific but had a sensitivity of only 48%. Thus if TRUS were used alone in the diagnosis of prostate cancer over half of such men would be falsely reassured they did not have prostate cancer.
A Danish population cohort study  of 27,181 men with initial benign TRUS showed a 14-year prostate cancer specific survival of 97%. Thus a small but appreciable number of men undergoing TRUS only as their detection method die from prostate cancer.
Mp-MRI can be utilized to target sampling of suspicious lesions using MRI-fusion TRUS or template biopsies. The Pinto group  is one of several who have published encouraging detection rates of medium and high risk prostate cancer whilst decreasing the detection of low risk prostate cancer when using the targeted approach. However, the notion that targeted biopsy alone may safely replace systematic biopsies remains contentious.
Current EAU guidelines state it is too early to make recommendations on routine use of Mp-MRI pre biopsy. It sites only moderate inter-reader reproducibility and low specificity as limiting its use outside of ‘specialist’ centres. Current EAU guidelines recommend the use of Mp-MRI in the repeat biopsy and active surveillance setting.
Contraindications, Consent and Complications
Patients with uncorrected coagulopathy or severe immunosuppression or anorectal pathology such as AP resection are not candidates for transrectal biopsy route. Clopidogrel should be stopped 7–10 days prior to biopsy and INR should be less than 1.5 for those on warfarin. Active UTI should be excluded prior to biopsy. The transperineal route may be an alternative in some patients. Informed consent should include the risk of infection (1/10), sepsis (1/50), blood in the urine, semen and stools with 1% needing admission for bleeding, vasovegal (1/20) urinary retention (1/100), and the possible need for further procedures. Transperineal biopsies carry a lower risk of sepsis (1/300) but up to 1/10 risk of urinary retention.