gms | German Medical Science

Introduction: Current NCCN and EAU guidelines define a subgroup of favorable intermediate-risk (FIR) ISUP grade group (GG) 2 prostate cancer (PCa), in which active surveillance (AS) can be considered a suitable course of action. Defined per NCCN guidelines, these patients may be diagnosed with up to three biopsies positive for ISUP grade 2 PCa and overall PCa detection in less than 50% of all biopsy cores, cT2a disease, and a prostate-specific antigen (PSA) of <10 ng/ml. However, upstaging and upgrading to unfavorable intermediate or high-risk PCa can be observed regularly in daily clinical practice. Therefore, this study aimed to examine the exact histopathologic grade and stage of this specific subgroup of patients and the proportion of patients harboring unfavorable intermediate-risk or high-risk PCa at the time of surgery.

Material and methods: We retrospectively analyzed a prospectively collected institutional dataset of 473 patients diagnosed with ISUP GG 2 PCa by MRI/TRUS fusion targeted and systematic biopsy (07/2021–10/2023) who underwent RP (09/2021–09/2024). We examined the proportion of patients diagnosed with FIR PCa harboring either unfavorable intermediate- or high-risk PCa (defined as upstaging to pT3 or upgrading to Gleason Grade ³4+3) at the time of RP and used multivariable logistic regression analysis to calculate the odds of upstaging accounting for pre-biopsy multiparametric MRI results, pre-operative PSA, clinical T-stage, prostate volume, and proportion of positive biopsies.

Results: Of 473 patients diagnosed with ISUP GG 2 PCa, 170 (37%) were classified as FIR PCa. Most patients were found to have PI-RADS 4 (n=98; 55%) or PI-RADS 5 (n=39; 22%) lesions at pre-biopsy mpMRI, while 12% (n=21) of these patients had negative mpMRI and were identified by systematic biopsy alone. The median time to surgery was 73 days (IQR 56; 92 days). At the time of RP, 29% of cases (n=52) were upstaged to high-risk PCa. There were no patients classified as unfavorable intermediate-risk PCa. Six patients (3.4%) were found to have lymph node-positive disease. On multivariable analysis, a PI-RADS lesion >3 (Odds ratio(OR) 3.07, 95% Confidence interval (CI) 1.14–8.27, p=0.027), an increasing PSA (OR 1.23, 95% CI 1.01–1.49, p=0.036) and a pathologic clinical T-stage (i.e., cT2a vs. cT1c) (OR 3.99, 95% CI 1.78–8.95, p=0.001) were associated with upstaging at the time of surgery in FIR PCa.

Conclusion: In this cohort of patients undergoing RP for FIR PCa, upstaging to high-risk PCa could be observed in more than a quarter of patients. Based on these findings, AS should only be considered after thorough patient counseling and should only be performed using a stringent follow-up and staging regimen to minimize the risk of further disease.