title: Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer.
abstract: OBJECTIVE
  To report the 5-year prostate-specific antigen (PSA) relapse-free survival outcome and incidence of long-term morbidity for patients with localized prostate cancer treated with CT-planned permanent I-125 prostate implantation using a transperineal technique (TPI).
  
  
  METHODS
  Between 1989-1996, 248 patients with clinically localized prostate cancer were treated with TPI. The median age was 65 years (range: 45-80 years). The clinical stage was T1c in 143 patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%) had Gleason scores <6, 158 patients (64%) had Gleason scores of 6, and 60 (24%) had scores >or =7. The median pretreatment PSA was 7 ng/mL (range: 1-58 ng/mL). The median prescribed implant dose was 150 Gy. Patients were characterized as having favorable risk disease if their pretreatment PSA level was < or =10.0 ng/mL and Gleason score < or = 6; those with one and two adverse prognostic features (PSA > 10 ng/mL and Gleason score >6) were classified as having intermediate and unfavorable risk disease, respectively. PSA relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was scored according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up was 48 months (range: 12-126 months).
  
  
  RESULTS
  Thirty-eight patients (15%) developed a PSA relapse, and the overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable-risk (n = 17) patients were 88%, 77%, and 38%, respectively (p < 0.0001). The 5-year PRFS rates among patients treated with a 2-month course of neoadjuvant androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified pretreatment PSA > 10 ng/mL and Gleason score >6 as independent predictors for biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2 urinary toxicity was 41%. The 5-year likelihood of urethral stricture development was 10%, and the median time to stricture development was 18 months. One patient (0. 4%) in the early phase of this clinical experience developed a Grade 4 urethral complication. The actuarial incidence of late Grade 2 rectal bleeding was 9%. One patient (0.4%) developed a Grade 4 rectal complication.
  
  
  CONCLUSIONS
  Especially for favorable risk disease, the 5-year biochemical outcome with this approach was excellent and appears to be comparable to other therapeutic interventions. Grade 2 urinary symptoms were common in these patients but gradually resolved in most. Improved treatment planning approaches that further constrain the urethral dose without compromising the target volume dose will likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. zelefskm@mskcc.org
authors.forename: M J
authors.initials: MJ
authors.lastname: Zelefsky
authors.forename: T
authors.initials: T
authors.lastname: Hollister
authors.forename: A
authors.initials: A
authors.lastname: Raben
authors.forename: S
authors.initials: S
authors.lastname: Matthews
authors.forename: K E
authors.initials: KE
authors.lastname: Wallner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D007172:Erectile Dysfunction / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy*; D011880:Radiotherapy Planning, Computer-Assisted; D012044:Regression Analysis; D014057:Tomography, X-Ray Computed
chemical_list: D017430:Prostate-Specific Antigen