337 - The Interplay between Acute and Late Toxicity among Patients Receiving Prostate Radiotherapy: A Pooled Analysis of 7 Randomized Trials

J. Nikitas¹, P. Jamshidian², A. Tree³, E. Hall³, D. Dearnaley⁴, J. M. Michalski⁵, W. R. Lee⁶, L. Incrocci⁷, W. Heemsbergen⁸, S. Roy⁹, S. Malone¹⁰, E. M. Horwitz¹¹, J. K. Wong¹¹, S. Arcangeli¹², G. Sanguineti¹³, M. L. Steinberg¹, J. B. Weidhaas¹, D. E. Spratt¹⁴, D. Telesca², and A. U. Kishan¹; ¹Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, ²Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, ³The Institute of Cancer Research, London, United Kingdom, ⁴The Institute of Cancer Research and Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, ⁵Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, ⁶Duke University Medical Center, Department of Radiation Oncology, Durham, NC, ⁷Department of Radiotherapy, Erasmus Medical Center, Rotterdam, Netherlands, ⁸Erasmus Medical Centre, Rotterdam, Netherlands, ⁹Rush University Medical Centre, Chicago, IL, ¹⁰The Ottawa Hospital Cancer Center, Ottawa, ON, Canada, ¹¹Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, ¹²University of Milan Bicocca - School of Medicine and Surgery, Milan, Italy, ¹³IRCCS Regina Elena National Cancer Institute, Radiation Oncology, Rome, Italy, ¹⁴Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH

Purpose/Objective(s): Both acute and late toxicity after prostate radiotherapy arise from normal tissue irradiation at the time of treatment. The association between acute toxicity and late toxicity remains poorly understood. We sought to characterize the relationship between acute and late genitourinary (GU) and gastrointestinal (GI) toxicity, both as scored by physicians and as reported by patients, among patients receiving radiotherapy for prostate cancer. Materials/

Methods: Individual patient data for trials that had acute and late GU and GI toxicity data were extracted from the MARCAP consortium. Physician-reported acute (=3 months from treatment) and late (>3 months from treatment) GU and GI toxicity were graded using Radiation Therapy Oncology Group criteria or Common Terminology Criteria. Urinary and bowel patient-reported quality of life (QOL) data from Expanded Prostate Cancer Index Composite (EPIC) questionnaires were used to identify late QOL decrements greater than twice the minimal clinically important difference (>2x MCID) at any time beyond 3 months post-treatment. MCID was defined as half of the standard deviation at baseline. Generalized linear mixed models were used to examine the relationship between acute grade =2 GU and GI toxicity and both late grade =2 GU and GI toxicity and late decrement >2x MCID in urinary and bowel QOL. These were adjusted for age, performance status, receipt of androgen deprivation therapy (ADT), use of intensity modulated radiotherapy (IMRT), and use of moderate hypofractionation.
Results: 6,349 patients from seven trials were included (conventional fractionation: n = 4,128; moderate hypofractionation: n = 2,221). Median follow-up was 76 months (interquartile range [IQR], 59-101 months). 71.3% received IMRT. Median equivalent dose (EQD2) was 74 Gy (IQR, 72-76 Gy). 51.8% received ADT. Rates of acute grade =2 GU and GI toxicity were 29.6% and 14.9%, respectively. Rates of late grade =2 GU and GI toxicity were 15.7% and 15.2%, respectively, while rates of urinary and bowel QOL decrement >2x MCID were 19% and 33%, respectively. Acute grade =2 GU toxicity was associated with late grade =2 GU toxicity (odds ratio [OR] 2.09, p<0.001), and acute grade =2 GI toxicity was associated with late grade =2 GI toxicity (OR 2.94, p<0.001). Similarly, acute grade =2 GU toxicity was associated with late urinary QOL decrement >2x MCID (OR 1.46, p=0.02), and acute grade =2 GI toxicity was associated with late bowel QOL decrement >2x MCID (OR 2.00, p<0.001).
Conclusion: Acute toxicity following conventionally fractionated or moderately hypofractionated prostate radiotherapy was significantly associated with late GU and GI toxicity as defined both by physician scoring and patient-reported QOL metrics. These data suggest that efforts to prevent acute toxicity may translate into reduced risks of late toxicity.