Toxicity Analysis of Patients with Prostate Cancer Treated with 3D-Conformal Compared to Intensity Modulated Radiotherapy: Secondary Analysis of RTOG 0126 and RTOG 0415

Abstract

<h3>Purpose/Objective(s)</h3> Patients with low- (LR) and intermediate-risk (IR) prostate cancer (PC) have excellent control rates following definitive radiation therapy (RT), but may experience treatment morbidity that impacts quality-of-life. To decrease normal tissue toxicity, modern techniques such as intensity modulated (IM) RT have largely replaced 3D-Conformal (3D-C) RT for PC. The objective of our study was to describe the comparative benefit of IMRT over 3D-CRT for patients undergoing prostate RT across different RT dosing and fractionation schemes. <h3>Materials/Methods</h3> We performed a post-hoc analysis of patients enrolled on RTOG 0126 and RTOG 0415. RTOG 0126 randomized to dose escalated (DE), conventionally fractionated (CF) RT (79.2 Gy/44 Fx) or standard dose (SD) CF RT (70.2 Gy/39 Fx). RTOG 0415 randomized to hypofractionated (HF) RT (70 Gy/28 Fx) or SD CF RT (73.8 Gy/41 Fx). Treatment with 3D-CRT and IMRT was at the discretion of the treating physician; target OAR dose constraints were the same irrespective of RT modality. We performed a logistic regression analysis of RT modality and acute and late grade 2+ gastrointestinal (GI) or genitourinary (GU) toxicity as per CTCAE criteria across the different dose regimens. <h3>Results</h3> A total of 2,590 patients treated in both studies were included in our analysis. The median patient age was 69 and median follow up was 6.9 years. On RTOG 0126, 66.3% and 33.7% were treated with 3DCRT and IMRT respectively, while 20.6% and 78.2% were treated with 3DCRT and IMRT on RTOG 0415, respectively. On both studies combined, the overall rate of acute grade 2+ GI and GU toxicity was 7.7% and 20.9%, respectively; the rate of late grade 2+ GI and GU toxicity was 18.2% and 17.5%, respectively. There was no significant difference in acute grade 2+ GI or GU toxicity between those treated with either RT modality across the different dosing regimens. For patients receiving DE CF RT, IMRT resulted in improved late grade 2+ GI toxicity compared to 3D-CRT (16.8% vs. 23.4%, OR=0.65, 95% CI 0.44-0.96, p=0.03). There was also a significant improvement in late grade 2+ GU toxicity with the use of IMRT compared to 3D-CRT (9.4% vs. 16.1%, OR=0.53, 95% CI 0.32-0.86, p=0.01). However, there was no significant difference in toxicity rates between IMRT and 3D-CRT for late GI or GU toxicity when using SD CF RT or HF RT. <h3>Conclusion</h3> Patients undergoing CF dose-escalated RT benefit from IMRT, while patients receiving CF SD (70.2Gy or 73.8 Gy) RT or HF RT did not show a difference in toxicity based on RT modality. These data provide a framework to compare the relative benefit of modern RT techniques (e.g., proton, SBRT, MR-guided RT) to IMRT in future studies.