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

## TL;DR

This study shows that nearly a third of patients with favorable intermediate-risk prostate cancer may have more aggressive disease, suggesting active surveillance should be used cautiously and with close monitoring.

## Contribution

The study identifies specific risk factors for upstaging in favorable intermediate-risk prostate cancer patients, aiding in better selection for active surveillance.

## Key findings

- 28% of favorable intermediate-risk prostate cancer patients were upstaged to higher-risk categories at radical prostatectomy.
- Pre-operative PSA levels, PI-RADS score ≥4, and clinical T-stage were significant predictors of adverse pathology.
- Five patients (2.9%) had lymph node metastases at radical prostatectomy.

## Abstract

AS is a recommended strategy for low-risk PCa and, more recently, FIR PCa as well. However, concerns remain about the safety of AS for FIR PCa, as some patients may habor more aggressive disease at the time of biopsy. This study analyzed 170 patients diagnosed with FIR PCa to identify predictors of adverse pathology at time of RP. We found that 28% of patients were upstaged to higher-risk categories, with pre-operative PSA levels, PI-RADS Score of ≥4, and clinical T-stage as significant predictors in this highly selective cohort of FIR PCa patients. Our results support AS for carefully selected FIR patients but highlight the need for thorough patient counseling and close follow-up to minimize progression risks. Further research is needed to refine AS criteria and incorporate advanced imaging tools like multiparametric MRI on a general basis.

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.