We addressed this gap by examining real-world outcomes among 86 men with PI-RADS 3–5 lesions and a negative index MRI-targeted biopsy at a tertiary referral center, focusing not only on whether cancer was eventually detected, but on how patients actually moved through follow-up pathways in routine care.
The central finding was reassuring. Only 4 cancers were detected during follow-up (4.7%): two on repeat biopsy, both ISUP grade group 1, and two incidentally in surgical specimens obtained during outlet obstruction treatment — including the only case of clinically significant prostate cancer. No cancers were observed in PI-RADS 3 lesions. Follow-up imaging reinforced this picture: stability or downgrading predominated on repeat MRI, and PSMA-PET suspicious findings were confined to PI-RADS 5 lesions. Taking together, these observations confirm that PI-RADS category retains meaningful prognostic information even after a negative biopsy, and that PI-RADS 3, 4, and 5 lesions should not be managed identically.
To make this actionable, we derived a simple risk score from three routinely available variables: PI-RADS category 5, PSA density, and abnormal digital rectal examination. A threshold of ≥2 points identified all subsequent cancers, yielding 100% sensitivity and negative predictive value while potentially avoiding 76.7–81.4% of repeat invasive procedures. With few cancer events and a single-center design, the score is hypothesis-generating and requires external validation — but the underlying principle is sound: a small amount of baseline clinical information may be sufficient to identify most men who can safely defer repeat biopsy.
Perhaps the most instructive finding was that half the detected cancers never emerged through repeat biopsy at all — both were incidental discoveries during surgery for outlet obstruction. This exposes a blind spot in any follow-up algorithm that treats repeat biopsy as the sole endpoint, and it reflects how prostate cancer is encountered in practice. That insight frames the broader ambition of this work: not to reduce interventions indiscriminately, but to calibrate their intensity to risk — observation for PI-RADS 3 with favorable features, selective repeat MRI with conditional biopsy for PI-RADS 4, and assertive reassessment for PI-RADS 5, abnormal DRE, or elevated PSA density.
The limitations of a small, retrospective, single-center cohort are real. What the data do establish, however, is that PI-RADS 3–5 lesions are not interchangeable after a negative biopsy. The clinical imperative is risk stratification precise enough to protect the men who need closer follow-up without burdening those who do not.
Written by: Horst Emanuel Lagos-Beitz, Gabriela Neri-Moguel, Jorge Augusto Alcacio-Mendoza, Gerardo Tena-González Méndez, Ricardo Alonso Castillejos Molina
- Department of Urology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.