Impact of Tumor Location Within the Prostate on Prognostic Outcomes Following Radical Prostatectomy

Purpose: To evaluate whether tumor zonal origin is associated with clinical, pathological, and prognostic outcomes in patients with prostate cancer (PC) treated with radical prostatectomy (RP). Patients and Methods: This retrospective cohort study analyzed 488 patients who underwent RP at UNICAMP between 1997 and 2017. Tumor zonal origin was defined by the dominant (index) lesion, identified through standardized whole-mount pathological analysis based on the highest ISUP grade and largest tumor volume. The primary endpoint was a composite of biochemical recurrence and/or metastasis, selected to capture clinically significant disease relapse and ensure statistical robustness in a long-term cohort. Associations were assessed using the Mann–Whitney U -test and the Chi-square test. Multivariate logistic regression was performed to identify independent predictors of progression (p < 0.05). Results: The index tumor originated in the peripheral zone (PZ) in 79.9% of cases and in the transition zone (TZ) in 6.5%. During follow-up, 38.3% of patients experienced biochemical recurrence or metastasis. Tumor location was not significantly associated with biochemical recurrence or metastasis (p = 0.428). Independent predictors included clinical stage (risk classification), pathological ISUP grade, positive surgical margins, and extra prostatic extension. Notably, biopsy ISUP grade and lymph node status were not independently predictive. The limited representation of TZ tumors may have constrained the statistical power to detect subtle prognostic differences. Conclusion: Within the limitations of this cohort, tumor zonal origin was not independently associated with biochemical recurrence or metastasis following RP. Established pathological factors remain the primary determinants of disease progression. Plain Language Summary: In men treated with radical prostatectomy for prostate cancer, the area of the prostate where the main tumor begins does not appear to influence the risk of cancer recurrence or spread. Instead, well-established pathological features, such as risk classification, tumor grade, surgical margins, and extra prostatic extension, remain the most important predictors of outcome. These findings support the use of comprehensive pathological assessment to guide prognosis and treatment decisions. Keywords: prostate cancer, radical prostatectomy, zonal origin, transition zone, prognosis, biochemical recurrence