196 - A Randomized, Parallel Phase II Trial of Hypofractionated Proton Therapy or IMRT for Recurrent, Oligometastatic Prostate Cancer with Pelvic and/or Para-aortic Lymph Node Involvement Following Primary Localized Treatment with Radiotherapy
Presenter(s)
B. J. Davis1, T. J. Wilhite2, B. J. Stish1, R. Phillips1, S. S. Park1, J. D. Cameron3, T. J. O'Byrne4, M. A. Timm4, J. L. Leenstra1, M. R. Waddle1, C. R. Choo1, J. M. Wilson1, D. Hillman5, F. J. Quevedo6, R. J. Karnes7, V. J. Lowe8, and E. D. Kwon7; 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 2Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 3Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, 4Mayo Clinic, Rochester, MN, 5Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, 6Mayo Clinic, Division of Medical Oncology, Rochester, MN, 7Department of Urology, Mayo Clinic, Rochester, MN, 8Department of Radiology, Mayo Clinic, Rochester, MN
Purpose/Objective(s): To determine if moderate hypofractionated (MHF) pelvic and/or para-aortic radiotherapy (RT) in the management of recurrent prostate cancer (PCa) pelvic and/or para-aortic nodal involvement does not increase patient (pt)-reported genitourinary (GU) or gastrointestinal (GI) toxicity over conventionally fractionated RT using either protons or intensity modulated radiation therapy (IMRT).
Materials/Methods: Eligibility criteria were: 1) Prior prostate or post RP bed RT with or without pelvic nodal RT for local/regional PCa, 2) Detectable PSA with pelvic and/or para-aortic nodal recurrence only diagnosed by prostate-specific PET scan with biopsy confirmation recommended, 3) castrate-sensitive disease. Pt stratification factors included proton RT or IMRT. Randomization was 2:1, MHF, 39 Gy/15 fractions (fx) to conventional (CF) 45 Gy/25 fx, with simultaneous integrated boost to PET avid nodal recurrences to a maximum of 48 Gy/15 fx or 56.25 Gy/25 fx. Pelvic nodal fields adhered to 2021 NRG guidelines. Concomitant androgen deprivation for 12 to 18 mos was prescribed. Primary endpoints: Early and Late (3, 24 mos) > grade (Gr) 3 GI and/or GU toxicity. Secondary endpoints: A. Late Gr > 2 GI and/or GU toxicities after RT completion. B. Acute Gr >3 GI and/or GU toxicities within 3 mos. C. Compare the rates of late = Gr 3 GI and/or GU toxicity between the 2 treatment schedules.
Results: 81 pts were accrued from 1/20 to 8/23 with 74 post-RP and 7 as post primary RT with median follow up of 38.5 mos (IQR: 30.3, 48.4). 54 pts (22 proton, 32 IMRT) were randomized to the MHF and 27 pts (12 proton, 15 IMRT) in the CF arm. Median ([IQR], [Range]) and mean (SD) PSA at baseline is 2.2 ng/mL ([0.9, 4.6], [0.19, 19.5]), and 3.9 (SD=4.4). 62 pts were treated to the pelvis only, 18 pts to the pelvis + para-aortics and 1 pt to the para-aortic region only. No pts in either arm developed Gr 3 GU or GI acute toxicity whereas rates of Gr 1+ and Gr 2+ acute GI/GU toxicity were 43.2% and 4.94% respectively. A significant difference was noted in the occurrence of Gr 1+ acute toxicities between proton vs IMRT within the MHF arm (p=0.04). No significant difference was noted in the occurrence of Gr 1+ acute toxicities between modalities within the CF arm (p=0.34), nor was there a significant difference in Gr 2+ acute toxicities between modalities in either the MHF or CF arms (p=0.14, p=0.36, respectively). Cause specific and relapse-free survival at 4 years was 97% (Std.Err=0.021), and 52% (Std.Err=0.075). Mean small bowel dose in the two cohorts was 4.45 Gy (SD=3.2 Gy) for protons and 14.3 Gy (SD=4.9 Gy) for IMRT in the MHF arm.
Conclusion: In this randomized parallel Phase II trial, moderate hypofractionation for treatment of oligorecurrent nodal PCa using modern RT techniques demonstrated acceptably low toxicity similar to conventional fractionation using either IMRT or protons. Based on these results, moderate hypofractionation serves as an acceptable salvage regimen in the management of prostate cancer pelvic and/or para-aortic nodal relapse.