title: RTOG 94-06: is the addition of neoadjuvant hormonal therapy to dose-escalated 3D conformal radiation therapy for prostate cancer associated with treatment toxicity?
abstract: OBJECTIVE
  This study determines the effect on toxicity of adding neoadjuvant hormonal therapy (NHT) to three-dimensional conformal radiation therapy (3D-CRT) in RTOG 94-06.
  
  
  METHODS
  Between August 1994 and February 2000, 583 eligible prostate cancer patients enrolled on the first 3 dose levels of RTOG 94-06, a Phase I/II dose escalation 3D-CRT trial. Two hundred and seven men initiated hormonal therapy (HT) between 2 to 3 months before 3D-CRT, and completed all HT no longer than 3 months after radiotherapy. Thirty-three patients receiving longer-duration HT were excluded. The 547 patients were treated at dose level I (68.4 Gy), level II (73.8 Gy), or level III (79.2 Gy). All dose prescriptions were to the minimum isodose surface encompassing the planning target volume (dose levels I and II) or the clinical target volume (dose level III). Men were stratified into three risk groups according to their relative risk of seminal vesicle invasion: <15% (Group 1) vs. >15% (Group 2), or to T stage (T1, 2 vs. T3 tumors [Group 3]). In Group 2 patients, there was a clinical target volume reduction to treat only the prostate after delivery of 55.8 Gy to a planning target volume including the seminal vesicles. All HT consisted of a luteinizing hormone-releasing hormone agonist with or without a nonsteroidal anti-androgen.
  
  
  RESULTS
  On univariate analysis, NHT significantly increased the likelihood of Grade 2 acute genitourinary (GU) complications (22% to 32%, p = 0.009). Hormonal therapy did not have a significant univariate effect on any other acute or late toxicity. On multivariate analysis, the percent of the bladder (< or =30% vs. >30%) receiving > or = the reference dose (68.4 Gy, 73.8 Gy, or 79.2 Gy) (p = 0.0009, relative risk = 2.07, confidence interval: 1.88-2.28) was a significant predictor of acute GU effects. Although NHT was not significant in itself, in the multivariate analysis its interaction with baseline urinary status was an important factor (p = 0.011, relative risk = 4.31, confidence interval: 1.68-5.29).
  
  
  CONCLUSIONS
  Neoadjuvant HT did not show an independent effect on the risk of side effects after 3D-CRT in patients treated on RTOG 94-06. However, this combined modality therapy significantly increased the risk of acute GU effects compared to 3D-CRT alone in men with poor baseline urinary function.
authors.affiliation: Department of Radiation Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Richard.Valicenti@mailtju.edu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Valicenti
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winter
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: Walter
authors.initials: W
authors.lastname: Bosch
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Vijayakumar
authors.forename: Jeff
authors.initials: J
authors.lastname: Michalski
authors.forename: James
authors.initials: J
authors.lastname: Purdy
mesh_terms: D000230:Adenocarcinoma; D000368:Aged; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000009:adverse effects*
chemical_list: D006728:Hormones; D017430:Prostate-Specific Antigen