312 - Genomic Stratification of Benefit from Short-Term Androgen Deprivation with Dose-Escalated Radiotherapy in Intermediate-Risk Prostate Cancer: An Ancillary Study of NRG/RTOG 0815

03:55pm - 04:05pm ET

Room 210

Presenter(s)

Angela Jia, MD, PhD - University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH

A. Y. Jia¹, M. Johnson², J. Proudfoot³, E. Davicioni³, Z. H. Rana⁴, T. M. Seibert⁵, D. E. Spratt⁶, J. Simko⁷, D. E. Citrin⁸, A. A. Martinez⁹, E. M. Gore¹⁰, A. El-Gayed¹¹, J. M. Michalski¹², A. Raben¹³, S. P. H. Lee¹⁴, J. A. Efstathiou¹⁵, T. G. Karrison¹⁶, T. Johnson¹⁷, P. T. Tran¹⁸, and D. J. Krauss¹⁹; ¹Department of Radiation Oncology, University Hospitals Cleveland Medical Center/ Seidman Cancer Center, Cleveland, OH, ²Vercyte, San Diego, CA, ³Veracyte, Inc., South San Francisco, CA, ⁴University of Maryland Medical Center, Baltimore, MD, ⁵Research Service, VA San Diego Healthcare System, San Diego, CA, ⁶University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, ⁷UCSF, San Franscico, CA, ⁸Center for Cancer Research at the National Cancer Institute, Bethesda, MD, ⁹GenesisCare USA, Fort Myers, FL, ¹⁰Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, ¹¹Saskatoon Cancer Centre, Saskatoon, SK, Canada, ¹²Washington University School of Medicine, St. Louis, MO, ¹³Christiana Care Health System, Newark, DE, ¹⁴VA Long Beach Healthcare System, Long Beach, CA, ¹⁵Massachusetts General Hospital, Boston, MA, ¹⁶NRG Oncology SDMC, Philadelphia, PA, ¹⁷American College of Radiology, Philadelphia, PA, ¹⁸Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ¹⁹Department of Radiation Oncology, Corewell Health Beaumont University Hospital, Royal Oak, MI

Purpose/Objective(s):

NRG/RTOG 0815 is a phase 3 randomized trial of dose-escalated radiotherapy (RT) with or without 6 months of short-term androgen deprivation therapy (STAD). We aimed to validate the potential prognostic and predictive ability of the 22-gene genomic classifier (GC) on long-term outcomes in the NRG/RTOG 0815 trial.

Materials/Methods:

After National Cancer Institute approval of a prespecified analysis plan, archived prostate biopsy specimens from NRG/RTOG 0815 were profiled using a locked, clinical-grade Decipher GC assay (Veracyte, San Diego). Genomic risk was analyzed as a continuous variable and by prespecified score categories: low (GC < 0.45), intermediate (GC 0.45-0.6), and high (GC > 0.6). Linkage of GC data to updated clinical outcomes with extended follow-up was performed. The primary endpoint of this study was distant metastasis (DM). Secondary endpoints included biochemical failure (BF), metastasis-free survival (MFS), prostate cancer–specific mortality (PCSM), and overall survival (OS). Cox and Fine-Gray competing risk multivariable analysis (MVA) models adjusted for age, race, clinical risk factors, comorbidity score, and RT modality.

Results:

GC scores were successfully obtained for 395 patients of 856 patients with available tissue. Baseline characteristics were balanced between arms with 10.2 years (IQR 8.4-11.4) median follow-up. There were 91 BF, 139 MFS, 16 DM, 134 OS and 7 PCSM events. On MVA, a higher GC score (int/high vs low) was independently prognostic for BF (sHR 2.19, 95% CI 1.36-3.53, p<0.001) and for DM (sHR 4.89, 95% CI 0.98-24.3, p=0.05). A significant GC-STAD interaction was observed for DM (p-interaction <0.001) and PCSM (p-interaction <0.001). Patients with low-GC scores (44% of cohort) derived no clinically meaningful benefit from STAD (10-year DM absolute difference of 1%), whereas patients with high-GC (32% of cohort) scores had a significant DM reduction with STAD (10-year DM absolute benefit of 11%).

Conclusion:

In intermediate-risk prostate cancer treated with dose-escalated RT, the 22-gene GC is independently prognostic and predictive of DM benefit from STAD. Patients with low GC scores have favorable long-term outcomes with no clear benefit from treatment intensification with STAD. In contrast, patients with higher GC scores treated with RT alone had unacceptably high long-term DM rates, which were significantly improved with STAD. NRG GU010 will serve as prospective validation and build on these findings.