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

ABSTRACT 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.