Subsequent Detection of Clinically Significant Prostate Cancer After Suspicious MRI and an Initial Biopsy Negative for csPCa: A Longitudinal Subgroup Analysis of the MULTIPROS Trial

Background: Management after suspicious multiparametric MRI (mpMRI; PI-RADS ≥ 3) and an initial biopsy negative for clinically significant prostate cancer (csPCa) remains uncertain. We described the frequency of subsequent csPCa detection and explored baseline factors. Methods: This post hoc longitudinal analysis of MULTIPROS trial data included 153 men with PI-RADS ≥ 3 lesions and no csPCa detected on baseline transrectal systematic biopsy, with or without targeted biopsy. Participants contributed follow-up from the date of the initial mpMRI until csPCa detection or their last available clinical follow-up, with records reviewed through May 2025. Follow-up was not protocol-mandated, and repeat biopsy was guided by clinical findings. The primary outcome was time to histological csPCa detection. Kaplan–Meier and multivariable logistic regression analyses were exploratory. Results: Over a median observed time to csPCa detection or censoring of 64 months, csPCa was detected in 37/153 men (24.2%). Of these, 28/37 (75.7%) were detected within 6 months, and the median time to detection was 3 months. This early clustering was compatible with possible baseline sampling limitations, although timing alone could not establish this mechanism. Overall, 84/153 men underwent repeat biopsy and 69/153 did not; 69/116 men without detected csPCa lacked repeat histological confirmation. The between-group Kaplan–Meier comparison was not significant (p = 0.210) and was difficult to interpret because repeat-biopsy rates differed. Transition-zone location, anterior fibromuscular stroma location, and atypical small acinar proliferation were associated with detection. The hypothesis-generating model had moderate apparent discrimination (AUC 0.756) but low sensitivity at a 0.50 threshold (24.3%). Conclusions: Most detections occurred early, a pattern compatible with possible baseline sampling limitations, although the biological timing of disease onset cannot be established from these data. Selective follow-up limits the interpretation of the detection proportion and between-group comparison. The identified associations require external validation, and the model should not be used clinically.