Risk of repeat biopsy and prostate cancer detection after an initial extended negative biopsy: longitudinal follow-up from a prospective trial

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Even after a negative set of prostate biopsies, the risk of undetected prostate cancer remains clinically significant. Predictive markers of such a risk are undefined. In addition to PSA and PSAD, low prostate volume and %fPSA are interesting time-varying risk factors and are relevant in biopsy decision-making.

Objective: To assess prospectively the time-varying risk of rebiopsy and of prostate cancer (PCa) detection after an initial negative biopsy protocol.

Patients and methods: Over a period of 10 years, 1995 consecutive patients with initially negative biopsies were followed. Rebiopsies were performed in patients who had a persistent suspicion of PCa. Predictive factors for rebiopsy and for PCa detection were tested using univariate, multivariate and time-dependent models.

Results: A total of 617 men (31%) underwent at least one rebiopsy after a mean follow-up of 19 months. PCa detection rates during second, third, and fourth sets of biopsies were 16.7, 16.9 and 12.5%, respectively. The overall rate of detected PCa was 7.0%. The 5-year rebiopsy-free and PCa-free survival rates were 65.9 and 92.5%, respectively. Indications for rebiopsy were more frequently reported in patients having a high prostate-specific antigen (PSA) level (P = 0.006) or a high PSA density (PSAD; P < 0.001) and in younger patients (P = 0.008). The risk of PCa on rebiopsies was not correlated with age, but significantly increased more than twofold in cases of PSA >6 ng/mL, PSAD >0.15 ng/mL/g, free-to-total PSA ratio (%fPSA) <15, and/or prostate volume <50 mL. Time-dependent analyses were in line with these findings. The main study limitation was the lack of control of the absence of PCa and PSA kinetics in men not rebiopsied.

Conclusions: The overall risk of detected PCa after an initial negative biopsy was low. In addition to PSA and PSAD, which are well-used in rebiopsy indications, low prostate volume and %fPSA are interesting time-varying risk factors for PCa on rebiopsy and could be relevant in biopsy decision-making.