Genitourinary Cancer

SS 08 - GU 2 - Long-Term Updates of Prospective Prostate Cancer Clinical Trials

62 - Long-Term Update of NRG Oncology RTOG 94-08

Monday, October 22
8:15 AM - 8:25 AM
Location: Room 214 C/D

Long-Term Update of NRG Oncology RTOG 94-08
C. U. Jones1, S. Pugh2, H. M. Sandler3, M. P. Chetner4, M. Amin5, J. A. Efstathiou6, R. B. Den7, M. H. Leibenhaut1, J. M. Longo8, J. P. Bahary9, S. A. Rosenthal1, L. Souhami10, J. M. Michalski11, A. C. Hartford12, P. P. Amin13, M. Roach III14, D. Yee15, J. Rodgers2, and W. U. Shipley6; 1Sutter Medical Group and Cancer Center, Sacramento, CA, 2NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 3Cedars-Sinai Medical Center, Los Angeles, CA, 4University of Alberta, Edmonton, AB, Canada, 5University of Tennessee Health Science Center, Memphis, TN, 6Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Sidney Kimmel Medical College at Thomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia, PA, 8Medical College of Wisconsin, Milwaukee, WI, 9Centre Hospitalier de L'Universite de Montreal, Montreal, QC, Canada, 10McGill University Health Centre, Montreal, QC, Canada, 11Washington University School of Medicine, St. Louis, MO, 12Dartmouth-Hitchcock Medical Center, Lebanon, NH, 13University of Maryland Medical Center/Greenebaum Cancer Center, Baltimore, MD, 14Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 15Division of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada

Purpose/Objective(s): RTOG 9408 demonstrated that the addition of 4 months of androgen-deprivation therapy (ADT) before and during radiation therapy (RT) improved 10-year overall survival (OS), disease-specific mortality (DSM), biochemical failure (BF), incidence of distant metastases (DM) and local progression (LP) in patients with early, localized prostate adenocarcinoma. The long term update is presented.

Materials/Methods: Patients (pts) with AJCC 4th edition T1b, T1c, T2a or T2b prostate adenocarcinoma and PSA ≤ 20 ng/mL were randomly assigned to RT alone (990 pts) or RT + 4 months of ADT (984 pts). The RT dose was 66.6 Gy administered in 1.8 Gy fractions. The restricted mean log-rank test was used to test the primary endpoint of OS and secondary endpoints of DSM, BF (Phoenix Definition), DM and LP. Due to the non-proportionality of the hazards for OS, a time-varying treatment effect was used in the Cox proportional hazards model. Subset analyses by risk group, race, and age were conducted. Low risk was defined as Gleason score 2-6, PSA ≤ 10 and stage ≤T2a; Intermediate risk was Gleason score 7 or Gleason score 2-6 with either PSA between 10 and 20 or clinical T2b; High risk was Gleason score 8-10.

Results: From 1994 through 2001, 1974 eligible pts were enrolled. The median age at study entry was 71 years. The median follow-up for alive pts was 14.8 years. 194 pts were at risk at 18 years. The incidence of late grade 3, 4 and 5 genitourinary toxicity was 6.2%, 1.4% and 0.1% in the ADT+RT arm and 5.3%, 0.1% and 0 in the RT alone arm. Late grade 3, 4 and 5 gastrointestinal toxicity incidence was 2.5%, 0.2% and 0 for ADT+RT and 1.2%, 0.1% and 0.2% for RT alone. Efficacy results are as follows:
RT+ADT (at 10 years) RT alone (at 10 years) RT+ADT (at 18 years) RT alone (at 18 years) Hazard Ratio (HR) p-value
OS (1974 pts) 63% 56% 23% 23% 0.94 0.28
Low Risk (703 pts) 69% 62% 26% 31% 1.01 0.93
Int. Risk (1086 pts) 60% 53% 21% 20% 0.92 0.22
High Risk (185 pts) 55% 52% 19% 16% 0.88 0.48
Age<=70 (972 pts) 71% 64% 35% 34% 0.93 0.37
Age>70 (1002 pts) 55% 49% 11% 14% 0.99 0.89
BF 32% 46% 37% 51% 0.66 <0.01
DM 5% 8% 8% 12% 0.66 0.01
LP 11% 16% 12% 18% 0.68 <0.01
In model adjusted for age, baseline PSA, Gleason score, T-stage, N-Stage, and race, OS for RT + ADT was superior to RT alone prior to 10.4 years (HR=1.20, p=0.014) while RT alone was superior after 10.4 years (HR=0.80, p=0.010). OS rates in the ADT+RT and RT alone arms were 62.8% and 55.8% at 10 years and 22.6% and 23.4% at 18 years, respectively.

Conclusion: The addition of short-term ADT to RT improved OS during the 1st 10 years of follow-up but this benefit diminished with long term follow-up. By 18 years, OS was no longer superior with the addition of ADT. BF, DM and LP, however, all continued to show a long-term benefit. Disease-specific mortality continues to be analyzed and will be presented at the meeting. Support: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP) from the National Cancer Institute (NCI)

Author Disclosure: C.U. Jones: None. S. Pugh: Research Grant; Millennium. H.M. Sandler: Research Grant; ACR-RTOG. Stock; Advanced Medical Isotope Corporation. Committee Chair; NRG Oncology. M.P. Chetner: None. M. Amin: None. J.A. Efstathiou: Consultant; BlueEarth Diagnostics, Taris Biomedical, Bayer Healthcare, EMD Serono, Genetech. GU Track Past-Chair; ASTRO. Board of Directors; Massachusetts Prostate Cancer Coalition. Co-chair; NCI, NRG Oncology. Member; NRG Oncology. R.B. Den: Research Grant; GenomeDx. Speaker's Bureau; Bayer. Advisory Board; Bayer, GenomeDx. M.H. Leibenhaut: Stock; Amgen. J. Bahary: Independent Contractor; centre hospitalier de l'université de montreal. vice chair for canadian affairs; NRG. S.A. Rosenthal: Chair, ACR Commission on Radiation Oncology; American College of Radiology (ACR). L. Souhami: Consultant; Varian, Jansenn, Bayer. 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. A.C. Hartford: Chair; Guidelines and Standards Committee, ACR. P.P. Amin: None. M. Roach: Honoraria; Ferring Pharma, Blue Earth, Myriad. Consultant; Ferring Pharma, Janssen Pharma, International Atomic Energy Agency. Advisory Board; Janssen Pharma, Tolmar, Bayer, Blue Earth, Myriad. Travel Expenses; Ferring Pharma, Janssen Pharma, International Atomic Energy Agency, Tolmar, Bayer, Blue Earth, Myriad. Stock; Abbott, Agilent, Altria, GSK, Hospira. Board Member; NCAB. D. Yee: None. W.U. Shipley: Stock; Pfizer. Co-Chair of RTOG FOUNDATION; also Co-Chair of GU D; RTOG.

Christopher Jones, MD

Disclosure:
Employment
Sutter Medical Group: Attending Radiation Oncologist: Employee

Biography:
Christopher U. Jones M.D. is an attending radiation oncologist with Sutter Medical Group in Sacramento, California. In 1986, he received his Doctorate in Medicine from Rush University in Chicago, IL after having earned a B.S. in Biology and a B.A. in Music at Stanford University, Stanford, CA. He completed his Residency at the Department of Radiation Medicine at the Massachusetts General Hospital, Harvard Medical School., Boston, MA in 1990. He worked as an Assistant Professor at the Medical College of Virginia, Richmond, VA until 1991 and has since worked as a community radiation oncologist in the Sacramento area. He has served as the RTOG Principal Investigator for Radiological Associates of Sacramento from 1997-2014 and has since served as the Principal Investigator for NRG Oncology for Sutter Cancer Research Consortium. In 2010, he became a Fellow of the American College of Radiology.

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