PL 01 - Plenary Session
LBA5 - Short Term Androgen Deprivation Therapy Without or With Pelvic Lymph Node Treatment Added to Prostate Bed Only Salvage Radiotherapy: The NRG Oncology/RTOG 0534 SPPORT Trial
Monday, October 22
3:15 PM - 3:25 PM
Location: Stars at Night Ballroom
Alan Pollack, MD, PhD
University of Miami Sylvester Comprehensive Cancer Center
University of Miami Miller School of Medicine: Chair and Professor of Radiation Oncology: Employee; University of Miami School of Medicine: Chair and Professor of Radiation Oncology: Employee
City of Hope: Honoraria, Travel Expenses; Radiation Therapy Oncology Group: Research Grants, Travel Expenses; Varian: Research Grants; Varian Medical Systems: Research Grants
Short Term Androgen Deprivation Therapy Without or With Pelvic Lymph Node Treatment Added to Prostate Bed Only Salvage Radiotherapy: The NRG Oncology/RTOG 0534 SPPORT Trial
A. Pollack1, T. G. Karrison2, A. G. Balogh3, D. Low4, D. W. Bruner5, J. S. Wefel6, L. G. Gomella7, E. Vigneault8, J. M. Michalski9, S. Angyalfi10, H. Lukka11, S. L. Faria12, G. Rodrigues13, M. C. Beauchemin14, S. A. Seaward15, A. M. Allen16, D. C. Monitto17, W. Seiferheld2, and H. M. Sandler18; 1University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, 2NRG Oncology SDMC, Philadelphia, PA, 3University of Calgary, Calgary, AB, Canada, 4UCLA, Los Angeles, CA, 5Nell Hodgson Woodruff School of Nursing, and Winship Cancer Institute at Emory University, Atlanta, GA, 6University of Texas MD Anderson Cancer Center, Houston, TX, 7Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, 8CHU de Québec, University of Laval, Quebec, QC, Canada, 9Washington University School of Medicine, St. Louis, MO, 10Tom Baker Cancer Centre, Calgary, AB, Canada, 11McMaster University, Hamilton, ON, Canada, 12McGill University Health Centre, Montreal, QC, Canada, 13London Health Sciences Center, London, ON, Canada, 14Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada, 15Kaiser Permanente, Vallejo, CA, 16Davidoff Center, Rabin Medical Center, Tel Aviv, Israel, 17Spartanburg Regional Medical Center, Spartanburg, SC, 18Cedars Sinai Medical Center, Los Angeles, CA
To determine in a three-arm randomized trial whether there are incremental gains in freedom from progression (FFP) from the addition of 4-6 months of short term androgen deprivation therapy (STADT) using antiandrogen plus an LHRH agonist, without or with pelvic lymph node treatment (PLNRT), to prostate bed salvage radiotherapy (PBRT).
Materials/Methods: Patients were randomized to PBRT alone (Arm 1), PBRT + STAD (Arm 2), and PLNRT + PBRT + STAD (Arm 3). The FFP primary endpoint included PSA nadir+2, clinical failure, or death from any cause, with censoring for secondary salvage therapy initiated prior to these events. The sample size provided 90% statistical power to detect a 10% absolute FFP improvement at 5 yr in Arm 2 compared to Arm 1 and a 10% absolute improvement at 5 yr in Arm 3 compared to Arm 2 at an overall alpha level of 0.025. On the third planned interim analysis for efficacy and futility based on 1191 eligible patents with 5 yr minimum follow-up, the treatment arms were compared in a stepwise approach to determine if the Haybittle-Peto (HP) threshold boundary of p < 0.001 (one sided) was crossed. Futility evaluation tested the alternative hypotheses at p < 0.001. Adverse events were graded using CTCAEv3.0.
Results: There were 1792 patients enrolled from 2008 – 2015. Median follow-up for those living is 5.4 yr. Ineligible patients included 18, 17, and 21 in Arms 1, 2, and 3. The patient and tumor characteristics for the 1736 eligible patients include a median age of 64 yr (range 39-84), black in 13%, baseline Zubrod status of 0 in 93%, seminal vesicle involvement in 15%, pre-radiotherapy PSA of ≤1.0 ng/ml in 89%, Gleason score < 8 in 83%, and pT2 margin positive or pT3 in 72%. Arms 1, 2, and 3 had 5 yr FFP rates of 71.1%, 82.7% and 89.1%. Arm 3 had the highest rate compared to Arm 1 (p < 0.0001), exceeding the HP boundary. The hazard ratio (HR) between arms 3 and 1 was 0.44 (95% CI: 0.32-0.59). Arm 3 was then compared to Arm 2, yielding a difference of 6.4% (p = 0.0063) and a HR of 0.71 (95% CI: 0.51-0.98). In all eligible patients followed for up to 8 years, there were 45, 38 and 25 patients who developed distant metastasis (DM) in Arms 1, 2 and 3. Without second salvage censoring, the DM hazard ratio for Arm 3 vs Arm 1 was 0.52 (95% CI: 0.32-0.85) and for Arm 3 vs. Arm 2 was 0.64 (95% CI: 0.39-1.06). With IMRT use in 87% of cases, highest late grade 3+ toxicity was observed in 4.3%, 4.9% and 6.0% for renal/genitourinary events and 0.7%, 0.4%, and 1.1% for gastrointestinal events in Arms 1, 2, and 3.
Conclusion: This is the first report of the primary endpoint and is the first randomized trial to show significant incremental improvements in FFP going from PBRT only to PBRT+STAD to PLNRT+PBRT+STAD. The addition of PLNRT resulted in early, meaningful, reductions in failure. Follow-up of patients will further elucidate the magnitude of the differences between arms 2 and 3.
Author Disclosure: A. Pollack: Research Grant; Varian. T.G. Karrison: None. A. Balogh: None. D. Low: Research Grant; Varian Medican Systems Inc, Siemens. Travel Expenses; ViewRay Inc. Stock; ViewRay. D.W. Bruner: Research Grant; Radiation Therapy Oncology Group. Travel Expenses; Radiation Therapy Oncology Group. Deputy Chair, Publications; NRG Oncology. member; RTOG Foundation Board, NCI Symptom Mgmt & HRQOL Comm, NCAB. J.S. Wefel: Consultant; Novocure, Juno. Advisory Board; Bayer. L.G. Gomella: Advisory Board; Pfizer, Janssen. Urology Chair; NRG Oncology. E. Vigneault: Independent Contractor; CHUQ L'Hotel Dieu de Québec. Honoraria; Abbvie. Advisory Board; Abbvie. J.M. Michalski: Independent Contractor; Sheila Michalski and Associates. Research Grant; NCI. https://medicine.wustl.edu/news/effort-improve-radiation-therapy-veterans-receives-nearly-4-million/; Veteran's Administration. Consultant; Veteran's Administration. Stock; ViewRay Inc. Chair Radiation Oncology Committee; NRG Oncology. Radiation Oncology Practice Assessment; Veterans Affairs. Co-chair GU Steering Committee; NCI. S. Angyalfi: None. H. Lukka: Research Grant; Abbvie, Sanofi. Honoraria; Astra Zeneca, Bayer, Sanofi, Abbvie, Astellas, Janssen, Ferring, Amgen. Stock; Vertex Pharma. Stock Options; Bausch Health Cos. Co-ordinator; GU radiation Oncologists of Canada. S.L. Faria: None. G. Rodrigues: Independent Contractor; George Rodrigues Medicine Professional Corporation. Stock; George Rodrigues Medicine Professional Corporation. Royalty; Demos Medical Publishing. S.A. Seaward: None. H.M. Sandler: Stock; Advanced Medical Isotope Corporation.