Incidence of significant prostate cancer after negative MRI and systematic biopsy in the FUTURE trial.

OBJECTIVES: To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow-up in patients with negative systematic biopsy (SB) followed by non-suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. PATIENTS AND METHODS: A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate-specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging-Reporting and Data System (PI-RADS) ≤2 on mpMRI entered biochemical follow-up. Follow-up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow-up compared to the expected number in the general population (standardized incidence ratio [SIR]). RESULTS: In total, 431 patients had non-suspicious mpMRI and entered biochemical follow-up. After a median (interquartile range) follow-up of 41 (23-57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3-7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI-RADS ≥3) were significant predictive factors for csPCa. CONCLUSION: After negative prior biopsy and non-suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image-guided risk-adapted diagnostic surveillance strategies is warranted.

Is There Still a Need for Repeated Systematic Biopsies in Patients with Previous Negative Biopsies in the Era of Magnetic Resonance Imaging-targeted Biopsies of the Prostate?

BACKGROUND: The role of targeted prostate biopsies (TBs) in patients with cancer suspicious lesions on multiparametric magnetic resonance imaging (mpMRI) following negative systematic biopsies (SBs) is undebated. However, whether they should be combined with repeated SBs remains unclear. OBJECTIVE: To evaluate the value of repeated SBs in addition to TBs in patients with a prior negative SB and a persistent suspicion of prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A prospective study as part of a multicenter randomized controlled trial conducted between 2014 and 2017, including 665 men with a prior negative SB and a persistent suspicion of PCa (suspicious digital rectal examination and/or prostate-specific antigen >4.0ng/ml). INTERVENTION: All patients underwent 3T mpMRI according to Prostate Imaging Reporting and Data System (PI-RADS) v2. Patients with PI-RADS ≥3 were randomized 1:1:1 for three TB techniques: MRI-TRUS fusion TB (FUS-TB), cognitive registration fusion TB (COG-TB), or in-bore MRI TB. FUS-TB and COG-TB were combined with repeated SBs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinically significant prostate cancer (csPCa) was defined as Gleason ≥3+4. Differences in detection rates of csPCa, clinically insignificant PCa (cisPCa), and overall PCa between TBs (FUS-TB and COG-TB) and repeated SBs were compared using McNemar's test. RESULTS AND LIMITATIONS: In the 152 patients who underwent both TB and SB, PCa was detected by TB in 47% and by SB in 32% (p<0.001, 95% confidence interval [CI]: 6.0-22%). TB detected significantly more csPCa than SB (32% vs 16%; p<0.001, 95% CI: 11-25%). Clinically significant PCa was missed by TB in 1.3% (2/152). Combining SB and TB resulted in detection rate differences of 6.0% for PCa, 5.0% for cisPCa, and 1.0% for csPCa compared with TB alone. CONCLUSIONS: In case of a persistent suspicion of PCa following a negative SB, TB detected significantly more csPCa cases than SB. The additional value of SB was limited, and only 1.3% of csPCa would have been missed when SB had been omitted. PATIENT SUMMARY: We evaluated the role of systematic biopsies and magnetic resonance imaging (MRI)-targeted biopsies for the diagnosis of prostate cancer in patients with prior negative systematic biopsies. MRI-targeted biopsies perform better in detecting prostate cancer in these patients. The value of repeated systematic biopsies is limited.