title: Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408.
abstract: OBJECTIVE
  The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer.
  
  
  METHODS
  Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤ 20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeat prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes.
  
  
  RESULTS
  A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥ 7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35).
  
  
  CONCLUSIONS
  Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall survival in patients with high-grade tumors.
authors.affiliation: Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan. Electronic address: dkrauss@beaumont.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Krauss
authors.affiliation: NRG Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.affiliation: Centre Hospitalier de l'Université de Montréal-Notre Dame, Montreal, Quebec, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gore
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Susan Maria Jacinta
authors.initials: SM
authors.lastname: Chafe
authors.affiliation: Sutter General Hospital, Sacramento, California.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Leibenhaut
authors.affiliation: Michigan Cancer Research Consortium CCOP.
authors.forename: Samir
authors.initials: S
authors.lastname: Narayan
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Javier
authors.initials: J
authors.lastname: Torres-Roca
authors.affiliation: Washington University, St. Louis, Missouri.
authors.forename: Jeff
authors.initials: J
authors.lastname: Michalski
authors.affiliation: Albert Einstein Medical Center, Bronx, New York, New York.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Zeitzer
authors.affiliation: Christiana Care Health Services Inc CCOP, Newark, Delaware.
authors.forename: Viroon
authors.initials: V
authors.lastname: Donavanik
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Howard
authors.initials: H
authors.lastname: Sandler
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: McGowan
authors.affiliation: Sutter General Hospital, Sacramento, California.
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001706:Biopsy / Q000379:methods; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005485:Flutamide / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D005485:Flutamide; D017430:Prostate-Specific Antigen