title: Neoadjuvant LHRH analog plus estramustine phosphate combined with three-dimensional conformal radiotherapy for intermediate- to high-risk prostate cancer: a randomized study.
abstract: OBJECTIVE
  The objective of this study is to assess the safety and efficacy of a treatment regimen comprising neoadjuvant conventional androgen deprivation therapy (ADT) plus estramustine phosphate (EMP) combined with three-dimensional conformal radiotherapy (3D-CRT) for patients with intermediate- to high-risk prostate cancer.
  
  
  METHODS
  Thirty-nine patients with intermediate- to high-risk prostate cancer classified according to the NCCN practice guidelines recurrence risk group were randomly allocated into two groups: neoadjuvant LHRH agonist plus EMP for 6 months until completion of the 3D-CRT (EMP group, n = 20), or neoadjuvant LHRH agonist alone (LHRH group, n = 19). Both groups received 3D-CRT in daily fractions of 2 Gy for a total dose of 70 Gy. PSA relapse was defined according to the Phoenix definition.
  
  
  RESULTS
  The median duration of follow-up was 27.1 months. None of the patients died during the follow-up period, but three patients in the LHRH group developed distant metastasis. The 4-year PSA relapse-free survival outcomes for the EMP group and LHRH group were 61.2 and 49.4%, respectively (P = 0.04). Multivariate Cox regression model analyses of the pretreatment PSA level (>20 ng/ml n = 16 vs. < or =20 ng/ml n = 23), grade (G8 or more n = 11 vs. G7 or less n = 28) and modality (LHRH group n = 19 vs. EMP group n = 20) revealed these factors to be independent predictors of PSA relapse after treatment: pretreatment PSA had a relative risk of 3.84 (95% CI: 1.003-14.722), grade had a relative risk of 4.29 (95% CI: 1.093-16.824), and modality had a relative risk of 8.01 (95% CI: 1.867-34.361). No severe toxicities were observed in either group.
  
  
  CONCLUSIONS
  The present results indicate that the combination of neoadjuvant ADT plus EMP combined with 3D-CRT sustains freedom from PSA relapse in patients with intermediate- to high-risk prostate cancer. However, this regimen is insufficient for preventing biochemical failure, and an additional intervention such as adjuvant ADT, radiation dose escalation, or both, is required, especially for patients with a pretreatment PSA level of more than 20 ng/ml and high-grade cancer.
authors.affiliation: Department of Urology, Nihon University School of Medicine, 30-1 Ooyaguchi Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan. byd04561@nifty.com
authors.forename: Daisaku
authors.initials: D
authors.lastname: Hirano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nagane
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Satoh
authors.forename: Junichi
authors.initials: J
authors.lastname: Mochida
authors.forename: Shuji
authors.initials: S
authors.lastname: Sugimoto
authors.forename: Taketo
authors.initials: T
authors.lastname: Ichinose
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Maebayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Saitoh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004961:Estramustine / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D012307:Risk Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; D004961:Estramustine