title: Improved local control and survival for surgically staged patients with locally advanced prostate cancer treated with up-front low dose rate iridium-192 prostate implantation and external beam irradiation.
abstract: OBJECTIVE
  In an effort to improve upon the historically poor local control and survival rates for locally advanced prostate carcinoma, a prospective multidisciplinary clinical trial was initiated using low dose rate Iridium-192 prostate implantation and external beam irradiation.
  
  
  METHODS
  Between January 1983 and September 1989, 57 patients with newly diagnosed bulky prostatic carcinoma (5 Stage B2, 52 Stage C) were treated at the Mayo Clinic (34 patients) and William Beaumont Hospital (23 patients) with (a) 5 Gy delivered preoperatively in one fraction, (b) pelvic lymphadenectomy with interstitial implantation of the prostate using Iridium-192 seeds via a perineal template to 30-35 Gy, and (c) 30.6 Gy external irradiation to prostate only in 17 fractions.
  
  
  RESULTS
  After lymphadenectomy, 30/57 (53%) patients had pathologically confirmed positive lymph nodes or "D1" disease. Thirty-four patients (60%) had Gleason scores > or = 7. Mean age at diagnosis was 63.3 years. Median overall follow-up was 72 months. The 5-year actuarial survival rate was 85% and disease-free survival was 63%. The 5-year survival for patients with negative nodes was 93% and with positive nodes was 79%. The corresponding survival for patients with Gleason scores < or = 6 was 96% and > or = 7 was 78%. Multivariate analysis demonstrated that of all covariates considered, only Gleason score had prognostic significance for disease-free survival (p < 0.05) and no covariates were statistically significant for overall survival. Thirty-nine of the 57 patients had a prostatic re-biopsy performed at 18 months. Pathologically confirmed local control was ultimately achieved in 31/39 (79.5%). There was no difference in survival in patients with positive re-biopsies vs. those with negative results. The 5-year actuarial rate of clinical local control was 94%. Three patients clinically failed locally and 21 demonstrated distant progression. The median time to progression was 34 months. Nineteen percent received some form of hormonal manipulation at the time of their treatment course and an additional 42% were treated with hormones during their follow-up period, primarily after distant failure. The grade 4 rectal ulceration rate decreased to 4.5% with modification of the brachytherapy technique. Three patients experienced grade 4 urinary incontinence and three patients experienced grades 3 or 4 chronic perineal pain.
  
  
  CONCLUSIONS
  These results indicate that bulky prostate carcinoma can be successfully controlled locally by this novel and aggressive approach with moderate toxicity and improved survival.
authors.affiliation: Dept. of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073.
authors.forename: J
authors.initials: J
authors.lastname: Stromberg
authors.forename: A
authors.initials: A
authors.lastname: Martinez
authors.forename: R
authors.initials: R
authors.lastname: Benson
authors.forename: G
authors.initials: G
authors.lastname: Garton
authors.forename: A
authors.initials: A
authors.lastname: Diokno
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez
authors.forename: H
authors.initials: H
authors.lastname: Zincke
authors.forename: M
authors.initials: M
authors.lastname: Schray
authors.forename: G
authors.initials: G
authors.lastname: Edmundson
authors.forename: D
authors.initials: D
authors.lastname: Brabbins
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D001918:Brachytherapy; D005500:Follow-Up Studies; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control*; D009367:Neoplasm Staging; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D007496:Iridium Radioisotopes