title: A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902.
abstract: OBJECTIVE
  Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).
  
  
  METHODS
  Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05.
  
  
  RESULTS
  A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61).
  
  
  CONCLUSIONS
  NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa.
authors.affiliation: Radiation Oncology, Sutter Cancer Centers, Roseville, California. Electronic address: rosents@sutterhealth.org.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Rosenthal
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hunt
authors.affiliation: Tulane University Medical Center, New Orleans, Louisiana.
authors.forename: A Oliver
authors.initials: AO
authors.lastname: Sartor
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Leonard
authors.initials: L
authors.lastname: Gomella
authors.affiliation: Indiana University, Bloomington, Indiana.
authors.forename: David
authors.initials: D
authors.lastname: Grignon
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Raghu
authors.initials: R
authors.lastname: Rajan
authors.affiliation: Community Clinical Oncology Program, Southeast Cancer Control Consortium, Inc, Winston-Salem, North Carolina.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kerlin
authors.affiliation: Radiation Oncology, Sutter Cancer Centers, Roseville, California; Radiological Associates of Sacramento, Sacramento, California.
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.affiliation: University of Alabama at Birmingham Medical Center, Birmingham, Alabama.
authors.forename: Michael
authors.initials: M
authors.lastname: Dobelbower
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.affiliation: Albert Einstein Medical Center, Bronx, New York.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Zeitzer
authors.affiliation: University of Michigan Medical Center, Ann Arbor, Michigan.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.affiliation: Christiana Care Health Services, Inc, Wilmington, Delaware.
authors.forename: Viroon
authors.initials: V
authors.lastname: Donavanik
authors.affiliation: State University of New York Health Science Center-Brooklyn, Brooklyn, New York.
authors.forename: Marvin
authors.initials: M
authors.lastname: Rotman
authors.affiliation: Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Hartford
authors.affiliation: Washington University, St. Louis, Missouri.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Michalski
authors.affiliation: Akron City Hospital, Akron, Ohio.
authors.forename: Michael
authors.initials: M
authors.lastname: Seider
authors.affiliation: Wayne State University, Detroit, Michigan.
authors.forename: Harold
authors.initials: H
authors.lastname: Kim
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Kuban
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moughan
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Howard
authors.initials: H
authors.lastname: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D003131:Combined Modality Therapy / Q000379:methods; D018450:Disease Progression; D057239:Early Termination of Clinical Trials; D004961:Estramustine / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017239:Paclitaxel / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D013997:Time Factors
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D004961:Estramustine; D005047:Etoposide; D017430:Prostate-Specific Antigen; D017239:Paclitaxel