title: Phase 1 trial of neoadjuvant radiation therapy before prostatectomy for high-risk prostate cancer.
abstract: OBJECTIVE
  To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer.
  
  
  METHODS
  Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes.
  
  
  RESULTS
  No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors.
  
  
  CONCLUSIONS
  Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.
authors.affiliation: Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina, USA. Bridget.Koontz@duke.edu
authors.forename: Bridget F
authors.initials: BF
authors.lastname: Koontz
authors.forename: Brian P
authors.initials: BP
authors.lastname: Quaranta
authors.forename: John A
authors.initials: JA
authors.lastname: Pura
authors.forename: W R
authors.initials: WR
authors.lastname: Lee
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Leah
authors.initials: L
authors.lastname: Gerber
authors.forename: Michael
authors.initials: M
authors.lastname: Haake
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Anscher
authors.forename: Cary N
authors.initials: CN
authors.lastname: Robertson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Polascik
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D015182:Lymphatic Irradiation / Q000379:methods; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D010388:Pelvis; D011300:Preoperative Care; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D020266:Radiotherapy, Conformal; D014525:Urethral Stricture / Q000209:etiology; D014549:Urinary Incontinence / Q000209:etiology
chemical_list: D017430:Prostate-Specific Antigen