title: High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?
abstract: OBJECTIVE
  Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant).
  
  
  METHODS
  A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20.
  
  
  RESULTS
  With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis.
  
  
  CONCLUSIONS
  The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.
authors.affiliation: Policlinico A Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Numa
authors.initials: N
authors.lastname: Cellini
authors.forename: Luciano
authors.initials: L
authors.lastname: Pompei
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Fortuna
authors.forename: M Vittoria
authors.initials: MV
authors.lastname: Ammaturo
authors.forename: Ugo
authors.initials: U
authors.lastname: De Paula
authors.forename: Stefano
authors.initials: S
authors.lastname: Luzi
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Mattiucci
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Digesù
authors.forename: M Elena
authors.initials: ME
authors.lastname: Rosetto
authors.forename: Tiziana
authors.initials: T
authors.lastname: Palloni
authors.forename: M Grazia
authors.initials: MG
authors.lastname: Petrongari
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Gentile
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
mesh_terms: D000206:Actuarial Analysis; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009570:Nitriles; D018579:Patient Selection; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D016019:Survival Analysis; D014105:Tosyl Compounds; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; C053541:bicalutamide; D017430:Prostate-Specific Antigen