LBA 05 - Androgen Deprivation Therapy (ADT) and High Dose Definitive Radiotherapy (RT) +/- Whole Pelvic RT in Patients with Unfavorable Intermediate or Favorable High-Risk Prostate Cancer: Early Results of a Phase III Randomized Controlled Trial
Presenter(s)
M. Roach III1, T. G. Karrison2, H. T. Chung3, A. J. Chang4, L. G. Gomella5, I. C. J. Hsu6, G. Morton3, R. E. Wallace7, B. Movsas8, D. W. Bruner9, A. P. Dicker10, D. E. Citrin11, I. Kauffman12, J. M. Michalski13, E. Vigneault14, M. A. Papagikos15, D. E. Spratt16, A. Jani17, T. Johnson18, and H. M. Sandler7; 1UCSF HDFCCC, San Francisco, CA, 2NRG Oncology SDMC, Philadelphia, PA, 3Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 4Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, 5Department of Urology, Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, 6University of California San Francisco, Department of Radiation Oncology, San Francisco, CA, 7Cedars-Sinai Medical Center, Los Angeles, CA, 8Department of Radiation Oncology, Henry Ford Health, Detroit, MI, 9Emory University, Atlanta, GA, 10Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, 11Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 12Wayne State University/Karmanos Cancer Institute, Detroit, MI, 13Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 14CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ), Quebec, QC, Canada, 15Coastal Carolina Radiation Oncology, Wilmington, NC, 16Department of Radiation Oncology, University Hospitals Cleveland Medical Center/ Seidman Cancer Center, Cleveland, OH, 17Department of Radiation Oncology, Emory University, Atlanta, GA, 18NRG, Philadelphia, PA
Purpose/Objective(s): Assess whether prophylactic whole pelvic radiotherapy (WPRT) improves overall survival (OS) compared to prostate only dose escalated radiotherapy (PORT) in patients with protocol defined unfavorable intermediate risk (UIR) or favorable high risk (FHR) prostate cancer (PC).
Materials/Methods: Eligible patients had localized prostate cancer with an estimated risk of lymph node involvement of > 15% (Roach equation), and UIR or FHR (PSA <50 ng/ml clinical T1-2b, i.e., no T3’s) PC and a Zubrod of 0 or 1. Patients were stratified by the risk group, RT boost: brachytherapy (BT) vs intensity modulated RT (IMRT) to 79.2 Gy, and duration of ADT (4 to 6 vs 32 months) and randomized to PORT or WPRT (superior border at the L4-5 interspace), arms 1, and 2 respectively, with the primary endpoint OS. Staging and treatment were based on conventional imaging.
Results:
From July 2011, thru June 24, 2019, 2473 (UIR=1130; FHR=1343) eligible and evaluable patients were accrued (median age 69 years). Approximately 30% of patients received long term ADT, 21% received a BT boost, 16% had a PSA > 20ng/mL, while 98% had a Gleason score of 7-10. At the planned interim analysis, WPRT did not improve OS, therefore the Data Safety Monitoring Committee released the data, with a median follow-up was 7.3 years (IQR 6.1-9.2), and 64 patients followed beyond 12 years. The 10-year OS was 68% (hazard ratio [HR]=1.01, 95% CI: 0.85-1.20, one-sided p=0.54), and PC specific survival (PCS) 98%, on both arms. The cumulative incidence of biochemical failure (BF) by the Phoenix definition at 10 years was 17% and 13% for arms 1 and 2, respectively (cause-specific HR=0.82, 95% CI: 0.65-1.03, one-sided p=0.045), but there was no difference in the risk of distant metastases (cause-specific HR=1.05, 95% CI: 0.73-1.50, one-sided p=0.60). The maximum gastrointestinal (GI) grade 2 (CTCAE version 4) adverse event rate was 14.7% on the PORT arm vs 18.7% on the WPRT arm (p=0.0035, one-sided). However, there was no difference in grade >3 GI adverse events being 3.4% on the PORT vs 3.3% on the WPRT arm. The reported rate of grade 2 and > 3 urinary frequency was 24.8 and 0.5% on the PORT arm respectively, vs 26.5 and 0.7% on the WPRT arm.
Conclusion:
At 10 years, WPRT did not improve OS in men with UIR or FHR PC. However, the follow-up is relatively short, with most cancer related deaths expected beyond 10 years. Additional follow-up is warranted to determine whether the early trends in BF ultimately translate into differences in OS or metastases. The high PCS rate and relatively low morbidity (by physician report) confirms that ADT + PORT appears to represent an excellent treatment option for men with UIR or FHR PC. Future studies incorporating biomarkers may help us determine whether there are subsets of patients who would benefit from WPRT.