Predictors of 2-Year Incidence of Patient-Reported Urinary Incontinence After Post-prostatectomy Radiotherapy: Evidence of Dose and Fractionation Effects.

Objective: To investigate predictors of patient-reported urinary incontinence (PRUI) in the first 2 years after post-prostatectomy radiotherapy (PORT) with particular emphasis on possible dose-effect relationships. Patients and Methods: Two-hundred-thirteen patients, whose clinical and dosimetric data were prospectively collected within a registered multi-institutional cohort study, underwent PORT with adjuvant (n = 106) or salvage (n = 107) intent with conventional (n = 123, prescribed dose to the prostatic bed: 66.6-79.8Gy in 1.8-2.0Gy/fr) or moderately hypo- (n = 90, 65.8-76.8Gy in 2.1-2.7Gy/fr) fractionation during the period 2011-2017. PRUI was evaluated through the ICIQ-SF questionnaire filled in at baseline and every 6 months thereafter. The analysis focused on three ICIQ-based clinically relevant endpoints: (a) very frequent leakage (FREQUENCY, ICIQ3 score >3), (b) moderate to severe amount of urine loss (AMOUNT, ICIQ4>2) (c) objective severe symptoms (OBJECTIVE, ICIQ3+4>5). Predictors of the incidence within 2 years for the three endpoints were investigated focusing only on patients without endpoint symptoms at baseline. A uni-variable logistic regression analysis was performed in order to determine the best dose metrics describing PRUI risk in terms of 2-Gy equivalent dose (EQD2) calculated with different α/β values reported in the literature (0.8, 3, 5Gy), and to identify the most significant clinical variables. Variables showing p < 0.20 at uni-variable analysis were entered into a backward stepwise multi-variable logistic regression analysis. Lastly, the goodness of fit and model calibration were evaluated and internally validated. Results: Patients without symptoms at baseline experienced (a), (b), and/or (c) within 2 years in 41/130 (32%), 40/192 (21%), and 41/129 (32%) of the cases, respectively. EQD2 for α/β = 0.8Gy was the best dose metric associated with PRUI. Multi-variable analysis identified baseline incontinence levels as the strongest predictor for all endpoints (p < 0.006). Both FREQUENCY and OBJECTIVE were significantly influenced also by EQD2(α/β = 0.8Gy). The goodness of fit was excellent, as was the calibration; internal calibration confirmed apparent performance. Conclusion: Baseline mild urinary incontinence symptoms strongly modulate the 2-year risk of PRUI. In addition, FREQUENCY is characterized by a marked dose-effect relationship also influencing the trend of OBJECTIVE, with results more reliable than AMOUNT as an objective index. A strong impact of fractionation on severe PRUI after post-prostatectomy radiotherapy also emerged.

Frontiers in oncology. 2020 Jul 23*** epublish ***

Andrea Bresolin, Elisabetta Garibaldi, Adriana Faiella, Domenico Cante, Vittorio Vavassori, Justina Magdalena Waskiewicz, Giuseppe Girelli, Barbara Avuzzi, Elisa Villa, Alessandro Magli, Barbara Noris Chiorda, Fernando Munoz, Giuseppe Sanguineti, Pietro Gabriele, Marco Gatti, Tiziana Rancati, Riccardo Valdagni, Nadia Di Muzio, Claudio Fiorino, Cesare Cozzarini

IRCCS Istituto Scientifico Ospedale San Raffaele, Medical Physics, Milan, Italy., Istituto di Candiolo-Fondazione del Piemonte per l'Oncologia IRCCS, Radiotherapy, Turin, Italy., IRCCS Istituto Nazionale dei Tumori "Regina Elena," Radiotherapy, Rome, Italy., Ospedale di Ivrea, Radiotherapy, Ivrea, Italy., Cliniche Gavazzeni-Humanitas, Radiotherapy, Bergamo, Italy., Comprensorio Sanitario di Bolzano, Radiotherapy, Bolzano, Italy., Ospedale degli Infermi, Radiotherapy, Biella, Italy., Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy, Milan, Italy., Azienda Ospedaliero Universitaria S. Maria della Misericordia, Radiotherapy, Udine, Italy., Ospedale Regionale Parini-AUSL Valle d'Aosta, Radiotherapy, Aosta, Italy., Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate Cancer Program, Milan, Italy., Istituto Scientifico Ospedale San Raffaele, Radiotherapy, Milan, Italy.