Prostate Biopsy

Prostate biopsy takes small cores of tissue from the prostate gland to diagnose prostate cancer. It is done when a raised prostate specific antigen (PSA), an abnormal digital rectal examination, or an abnormal MRI suggests cancer. It also gives the grade of the tumour, which is a key part of risk assessment.

There are three main approaches. A systematic biopsy takes 10 to 12 cores from set regions of the gland under ultrasound control. A targeted biopsy takes cores from MRI-identified suspicious areas, either by cognitive registration, software fusion with ultrasound, or in the MRI scanner. In a combined approach, targeted and systematic cores are taken together, which gives the highest yield.

The route is transrectal (through the rectal wall) or transperineal (through the skin between the scrotum and anus). The transperineal route has a lower risk of infection because it avoids the rectum.

The procedure takes 15 to 30 minutes, with local anaesthetic around the prostate (a periprostatic block) or a general anaesthetic for transperineal mapping. About 25 to 30% of men with a raised PSA have cancer on biopsy. MRI-targeted biopsy finds about 10 to 20% more clinically significant cancers than systematic biopsy alone, and it avoids biopsy in about 25 to 30% of men with a normal MRI. Systematic biopsy misses significant cancer in about 20 to 30% of cases.

Indications.

• Raised PSA, or rising PSA, with an age adjusted risk, usually after repeat measurement and exclusion of infection.
• Abnormal digital rectal examination (hard nodule or asymmetry).
• MRI showing a suspicious lesion (a high score on the structured MRI scale).
• Persistently suspicious findings after a negative first biopsy.
• Active surveillance of known low risk cancer, for confirmation and monitoring.
• Confirmation of cancer before treatment, and assessment after treatment in selected cases.

Not indicated when the man has a limited life expectancy and no symptoms, or when the result would not change management.

Contraindications and precautions.

• Active urinary tract infection or acute prostatitis: biopsy is delayed.
• Bleeding disorder, low platelets, and anticoagulant or antiplatelet treatment: managed with the prescriber. Aspirin at low dose is often continued.
• Painful anal conditions, rectal disease, or an artificial heart valve or joint (infection risk), where the transperineal route is preferred.
• Recent urinary instrumentation or catheterisation, and recent fluoroquinolone use or travel to regions with resistant organisms, which raise the risk of infection after a transrectal biopsy.
• Immunosuppression and diabetes: higher infection risk.
• Patients who cannot lie in the position needed.

Preparation and technique.

The patient has a negative urine culture, a recent PSA, and in most cases a prostate MRI done before biopsy. Antibiotic prophylaxis is given (targeted to the rectal flora in transrectal biopsy), and a rectal swab culture is used in some centres to select the drug. For transrectal biopsy, an enema may be given. The patient lies on his left side, or in lithotomy for a transperineal approach.

Using ultrasound, the prostate volume is measured and the biopsy plan is made. Local anaesthetic is given, and spring loaded needle cores are taken. Cores are placed in separate, labelled containers or by region, with MRI targets identified, and sent in formalin.

Normal appearances.

Benign prostate tissue shows glands lined by a two layer epithelium (basal and secretory cells), with surrounding stroma. A benign result means no cancer was found in the cores, and it does not exclude cancer outside the sampled areas.

Interpretation.

• Adenocarcinoma: the report gives the number of positive cores, the percentage or length of tumour in each core, and the grade (a score from the two most common patterns, converted into a grade group from 1 to 5). Grade group 1 is low risk, 2 to 3 intermediate, and 4 to 5 high risk.
• Perineural invasion, extraprostatic extension, and seminal vesicle invasion, when seen, are reported.
• Intraductal carcinoma and cribriform pattern: indicate more aggressive disease and are reported.
• Atypical small acinar proliferation (ASAP): suspicious, but not diagnostic. Repeat biopsy is needed in about 40% of men.
• High grade prostatic intraepithelial neoplasia: not a cancer, and the risk of cancer on repeat biopsy is only slightly higher than baseline.
• Prostatitis and benign hyperplasia are common benign findings and can explain a high PSA.
• Risk grouping combines the grade group, PSA and the clinical and MRI stage, and it directs whether surveillance or treatment is needed.

Critical values and findings needing immediate action.

• Fever, rigors, hypotension or confusion within 1 to 3 days after biopsy: urgent assessment for sepsis, cultures, and intravenous antibiotics (post-biopsy sepsis is about 1 to 3% with the transrectal route, and under 0.5% transperineal).
• Acute urinary retention: catheterisation.
• Heavy rectal bleeding or large haematuria with clots: assessment and control of bleeding.
• High grade cancer found: prompt referral to a urologic oncology team for staging.

Limitations and artefacts.

• Sampling error: biopsy takes less than 1% of the gland, and cancers in the anterior gland, the apex or the transition zone can be missed. Repeat biopsy is needed if suspicion remains.
• Systematic biopsy can both miss significant cancer and find insignificant cancer, leading to overdiagnosis and overtreatment.
• Biopsy grade may be lower than the final grade in the whole gland in about 20 to 30% of men.
• Inflammation, recent biopsy, haemorrhage and an enlarged gland affect MRI and PSA.
• Fragmented cores, crush artefact and poor orientation make the reading difficult.
• PSA is raised by prostatitis, urinary retention, instrumentation, ejaculation and a recent biopsy, and the test is timed accordingly.
• A normal MRI reduces but does not exclude clinically significant cancer.

Complications.

• Haematuria (up to 50%), rectal bleeding, and blood in the semen (up to 90% for weeks), which are usually self-limiting.
• Infection: urinary tract infection or prostatitis (up to 5%) and sepsis (1 to 3% transrectal).
• Acute urinary retention (about 1 to 2%, higher in men with large prostates).
• Vasovagal reactions, pain, and erectile dysfunction that is usually short lived.
• Antibiotic resistant organisms in the rectal flora, which have increased the risk of sepsis in some regions.

Special groups.

• Men on active surveillance: repeat biopsy, usually targeted, at set intervals or when the MRI or PSA changes.
• Men with a previous negative biopsy and persistent suspicion: MRI-targeted or saturation biopsy.
• Men on anticoagulants: planning with the prescriber, and a transperineal approach reduces infection but not bleeding.
• Men with a history of resistant infection or recent travel: transperineal approach, or culture directed prophylaxis.
• Younger men with a family history or a BRCA variant: earlier and more careful assessment.
• Regions: prostate cancer is common in men of African ancestry, who present at younger ages and with higher grade disease. MRI is not widely available, and systematic transrectal biopsy under ultrasound is used. Biopsy directed by finger alone, without imaging, has a low yield. Infection control, and antibiotic choice based on local resistance, are important.

Follow up tests.

• Histology review, with a second pathologist opinion for difficult cases.
• Repeat PSA and PSA density, and MRI for lesion mapping and staging.
• Staging with CT, bone scan, or prostate specific membrane antigen imaging in higher risk disease.
• Germline testing in men with high risk or metastatic disease, or a family history.
• Repeat biopsy at planned intervals for surveillance.
• Urinalysis and culture if symptoms of infection develop.