Upstaging of Patients Diagnosed with Favorable Intermediate-Risk Prostate Cancer—Is Active Surveillance Really a Suitable Approach for All These Patients?

BACKGROUND & OBJECTIVES: Current guidelines recognize a subgroup of favorable intermediate-risk (FIR) ISUP grade group (GG) 2 prostate cancer (PCa) that may be eligible for active surveillance (AS). However, upgrading and upstaging to more aggressive disease are frequently observed. We aimed to identify risk factors for adverse pathology in this cohort to better define clinical scenarios where AS may need to be reconsidered. METHODS: We retrospectively analyzed 170 patients diagnosed with ISUP GG2 PCa by multiparametric MRI (mpMRI)/TRUS fusion biopsy, all treated with radical prostatectomy (RP). Patients with FIR disease were evaluated for upstaging to ≥pT3 or upgrading to ISUP GG of ≥3 at RP. Multivariable logistic regression identified predictors of adverse pathology. Key Findings and Limitations: Among 170 FIR patients, median PSA was 5.6 ng/mL. Most had PI-RADS 4 (57%) or 5 (20%) lesions; 13% were diagnosed by systematic biopsy only. At RP, 28% showed adverse pathology, including 5 patients (2.9%) with lymph node metastases. Independent predictors were a PI-RADS Score of ≥4, PSA of >7 ng/mL, and clinical T-stage on digital rectal examination. CONCLUSIONS AND CLINICAL IMPLICATIONS: Nearly 1/3 of FIR PCa patients were upstaged to high-risk PCa at RP. Based on these findings, AS in clinical practice should only be considered after thorough patient counseling and performed using a stringent follow-up and staging regimen to minimize the risk of further disease progression. A key limitation is the lack of the percentage of Gleason pattern 4.