AUA 2022: Not All Adverse Pathology Features Are Equal: Identifying Optimal Candidates For Adjuvant Radiotherapy Among Patients With Adverse Pathology at Radical Prostatectomy

( In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Mazzone presented an analysis aimed at identifying subgroups of patients with adverse pathology at the time of radical prostatectomy who may benefit from adjuvant radiotherapy. While an adjuvant radiotherapy approach for patients with adverse pathological findings at the time of radical prostatectomy was guideline recommended for many years, it was infrequently utilized in part due to concerns for overtreatment and treatment-related toxicity. More recently, randomized data have supported the role of early salvage radiotherapy, rather than adjuvant radiotherapy, though the role of adjuvant radiotherapy is still debated due to the low rate of enrolment of patients with adverse features in these RCTs.

To evaluate this further, the authors examined a cohort of 8,362 patients treated with radical prostatectomy at a single center between 1987 and 2020. Among these 8,362 men, 1,328 had adverse pathology features (i.e. Gleason Grade [GG] 4-5 with ≥pT3a stage and/or lymph node invasion [LNI]). The authors further restricted their analytic cohort to patients with follow-up >36 months, absence of PSA persistence following surgery, and ≤6 positive nodes were included (n=682). Patients were stratified according to treatment with adjuvant RT vs. observation with or without salvage RT. The primary endpoint was overall mortality (OM) and the authors used multivariable Cox regression models to assess the association between adverse pathology features on OM. Based on Cox-derived coefficients, a score was assigned to each adverse pathology feature (1 point for pT3b; 2 for GG 5 or 1-2 positive nodes; 3 for >2 positive nodes). Patients were stratified in low (0-1 points), intermediate (2-3 points) and high (4-5 points) risk groups. The probability of receiving adjuvant RT was weighted using an inverse-probability of treatment weighting propensity score adjusted for the presence of positive surgical margins, PSA, year of surgery and age. The resulting weight was used as propensity adjustment in multivariable Cox regression models examining the impact of adjuvant RT on OM after adjusting for age, salvage RT and adjuvant or salvage hormonal therapy (HT), with each risk group tested independently.

Among the 682 patients comprising the analytic cohort, 438 (64%) received adjuvant radiotherapy, 79 (12%) received salvage radiotherapy, and 167 (24%) received observation. The median follow-up for survivors was 116 months and 65 patients died during follow-up. The overall 10-year OM-free survival (ie. overall survival) rate was 90%.

Based on multivariable Cox regression models, the presence of >2 positive nodes was the strongest predictor of OM (HR 2.8, p<0.001). After stratification according to risk groups, 75 (11%) patients were classified as low-risk, 434 (63%) as intermediate-risk, and 175 (26%) as high-risk.


Cox-derived Kaplan Meier analyses demonstrated no differences in 10-year OM-free survival between low and intermediate risk patients (all p=0.2) who were treated with adjuvant RT or observation with or without salvage RT. However, in the high-risk group, use of adjuvant RT was associated with significant improvement in 10-year OM-free survival compared to observation +/- salvage RT (86 vs 73%, p=0.04). 

Thus, the authors conclude that, among patients with adverse pathology features, they were able to identify three subclassification of risk. Only among those with high-risk characteristics did an adjuvant RT approach appear to provide a survival benefit compared to observation with or without salvage RT.

Presented by: Elio Mazzone, PhD, San Raffaele Scientific Institute, Milan, Italy

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.



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