The optimal biopsy strategy for patients with a clinical suspicion of prostate cancer remains an area of active investigation and refinement. Current areas of controversy in prostate cancer biopsy/diagnosis include (1) feasibility of omitting systematic (ie, non-MRI–targeted) biopsies, (2) methods of MRI-ultrasound fusion (eg, cognitive vs software-based fusion), and (3) biopsy technique (transrectal vs transperineal).

The ideal prostate biopsy technique is one that accurately identifies only those cancers for which treatment appropriately balances trade-offs in quality and quantity of life. For decades, prostate cancer was the only malignancy identified predominantly by random sampling. This approach was plagued by underdetection of clinically significant cancers and overdetection of clinically insignificant cancers. The incorporation of MRI into the diagnostic pathway of suspected prostate cancer has enabled targeting of suspicious lesions to increase the detection of clinically significant prostate cancer.

In the PRECISION trial, patients with clinical suspicion for prostate cancer and no history of prostate biopsy were randomized to undergo either a standard systematic transrectal ultrasound (TRUS) biopsy or to undergo an MRI; patients in whom the MRI demonstrated a suspicious lesion underwent targeted biopsy of the suspicious lesion alone without concurrent systematic biopsy. Patients who received an MRI upfront had greater detection of clinically significant cancer and lower detection of clinically insignificant cancer compared with those who underwent systematic biopsy alone.¹ In the PROMIS trial, multiparametric MRI and systematic TRUS biopsies were compared against a referent template prostate mapping biopsy. All patients were biopsy naïve, and each underwent MRI, TRUS biopsy, and template mapping biopsy. The sensitivity of MRI was greater than that of systematic TRUS biopsy (93% vs 48%, P < .0001), with the authors concluding that 27% of men might be able to avoid an initial systematic biopsy if MRI is used to triage men with suspicious lesions.²

However, other studies, both retrospective³ and prospective,^4-6 have reported that the most accurate approach to diagnose clinically significant prostate cancer is by combining MRI-targeted biopsies with standard systematic biopsies. In these studies, approximately 10% to 20% of clinically significant cancers may have been missed on targeted biopsy or systematic biopsy alone, with a combined approach also resulting in lower rates of upgrading on radical prostatectomy specimens.⁶ Table 1 summarizes key studies examining the roles of MRI targets and systematic prostate biopsies. Both the European Association of Urology and AUA guidelines support the use of MRI in the prostate biopsy pathway; however, the European Association of Urology recommends perilesional biopsy only in men with a positive MRI, whereas the AUA recommends at least 2 targeted biopsies alongside traditional systematic biopsy.

Table 1. Key Trials Evaluating Role of MRI and Systematic Biopsies in Prostate Cancer Detection

The fusion method by which MRI-identified lesions are targeted also remains debated. Three fusion techniques have been described: cognitive registration, software fusion, and MRI-in-bore. In-bore biopsy, which involves actively targeting a biopsy while in the MRI machine, is rare in the US. With cognitive registration, the operator mentally overlays the patient’s MRI while performing transrectal ultrasonography to obtain biopsy samples from the area of suspicion identified on MRI. With software fusion, the MRI image is fused with real-time ultrasound images to target the region of interest. The FUTURE trial randomized 234 patients with a prior negative systematic biopsy to software fusion biopsy, targeted biopsy performed with cognitive registration, or in-bore MRI-targeted biopsy. While the study was likely underpowered, no differences in detection of clinically significant prostate cancer were found among the 3 groups.⁷ A randomized trial is ongoing that will compare software and cognitive fusion in men undergoing MRI-targeted biopsy (clinicaltrials.gov, ID NCT06517901). Several software packages and platforms are available for software-based fusion with varying costs and specifications.

Finally, the path of the needle during prostate biopsy has recently been an area of contentious debate. Traditionally, prostate biopsy has been performed using a transrectal approach, where the needle passes directly through the rectal mucosa and into the prostate. During transperineal biopsy, on the other hand, the needle passes through the perineal skin and subcutaneous tissues on its way to the prostate, thereby avoiding the rectum altogether. Potential advantages of a transrectal approach include patient tolerance in an office-based setting and clinician familiarity with performance. Three key proposed advantages of the transperineal approach are (1) a reduction in infectious complications by avoiding the passage of the biopsy needle through the rectal wall and into the prostate, (2) improved antibiotic stewardship with the ability to omit prophylactic antibiotics altogether, and (3) easier access to sample anterior or apical tumors. Three randomized trials have been published recently to help better understand the transrectal and transperineal approaches. These studies include PREVENT 1 (2024),⁸ ProBE-PC (2024),^9,10 and PERFECT (2024).¹¹ PREVENT 1 and PERFECT included only biopsy-naïve patients, whereas ProBE-PC included all patients regardless of prior biopsy history. A meta-analysis of these 3 trials did not identify any statistically significant differences between the transperineal and transrectal approaches with respect to detection of clinically significant prostate cancer or complications.¹² Results of PREVENT 2 (clinicaltrials.gov ID NCT04815876), which will include men with prior negative biopsy and those on active surveillance, are eagerly awaited. Given the similar outcomes reported in these randomized trials, clinicians may rely on other perceived benefits of one approach over another. These may include surgeon comfort/ease of use, patient comfort, and ability to perform in an outpatient clinic setting. The population benefit of omitting prophylactic antibiotics when using the transperineal approach should not be underestimated given increasing antimicrobial resistance patterns. Table 2 summarizes the key prospective trials comparing transperineal and transrectal prostate biopsies.

Table 2. Key Trials Evaluating Transperineal or Transrectal Approach to Prostate Biopsy

The ideal prostate biopsy approach is one that balances detection of clinically significant prostate cancer, minimizes clinically insignificant prostate cancer diagnosis, reduces patient discomfort/complications, promotes responsible use of antibiotics, and remains mindful of health care costs/resources. Important work remains ongoing to identify strategies to optimize biopsy performance across these domains.