BACKGROUND: Dose escalation and hypofractionation may have a role in postprostatectomy radiotherapy (RT), but at the risk of increasing urinary toxicity.
OBJECTIVE: To address predictors of severe (Grade ≥3) late urinary toxicities (LGUTOX3) after postoperative irradiation.
DESIGN, SETTING, AND PARTICIPANTS: A single-institution cohort of 1176 patients treated between 1993 and 2010 with adjuvant or salvage RT was analyzed. A total of 929 patients underwent conventionally fractionated (CF) RT (1.8Gy per fraction; median dose to the prostatic bed: 70.2Gy) with nonconformal RT (n=169), three-dimensional conformal RT (n=657), or intensity-modulated RT (n=103) technique, while 247 patients received hypofractionated helical TomoTherapy (median: 2.50Gy per fraction) at the following doses: 117 patients at 65.8Gy (2.35Gy in 28 fractions), 80 patients at a median of 71.4Gy (2.5-2.6Gy in 28 fractions), and 50 patients at 58Gy in 20 fractions. Total doses were converted into 2 Gy-equivalent doses (EQD2) following the linear quadratic model taking α/β=5.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression models tested the relationship between clinicodosimetric variables and the risk of LGUTOX3 retrospectively, graded according to Common Terminology Criteria for Adverse Events v.4.0.
RESULTS AND LIMITATIONS: After a median follow-up of 98 mo, the 5-yr risk of LGUTOX3 was 6.9% and 18.1% in the CF and hypofractionated cohorts, respectively. At univariable analysis, the risk of LGUTOX3 was predicted by dose per fraction (hazard ratio [HR]: 2.96), acute Grade ≥2 toxicity (HR: 2.37), EQD2, pT4, and year of irradiation. At multivariable analyses, acute Grade ≥2 toxicity and dose per fraction independently predicted LGUTOX3 in the population, while an interaction analysis indicated a predictive role of hypertension in the hypofractionated cohort only. These findings are limited by their retrospective nature.
CONCLUSIONS: In the postprostatectomy setting, the logistic convenience of hypofractionation should be carefully balanced against the risk of severe late urinary sequelae.
PATIENT SUMMARY: This study investigated the causes of urinary adverse effects after postprostatectomy radiotherapy. Hypofractionation resulted in an increased risk of severe urinary toxicities.
Written by:
Cozzarini C, Fiorino C, Deantoni C, Briganti A, Fodor A, La Macchia M, Noris Chiorda B, Rancoita PM, Suardi N, Zerbetto F, Calandrino R, Montorsi F, Di Muzio N. Are you the author?
Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy; 2Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy; Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Centre of Statistics for the Biomedical Sciences, Università Vita Salute San Raffaele, Milan, Italy.
Reference: Eur Urol. 2014 Jun 27. pii: S0302-2838(14)00533-8.
doi: 10.1016/j.eururo.2014.06.012
PubMed Abstract
PMID: 24985964
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