title: Significant impact of biochemical recurrence on overall mortality in patients with high-risk prostate cancer after carbon-ion radiotherapy combined with androgen deprivation therapy.
abstract: BACKGROUND
  Whether biochemical recurrence (BR) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown. The aim of the current study was to investigate the relation between BR and overall mortality (OAM) in high-risk prostate cancer patients who were treated with carbon-ion radiotherapy (CIRT) and had long-term follow-up in 2 prospective trials.
  
  
  METHODS
  In the 2 phase 2 clinical trials, which involved 466 prostate cancer patients who received 63.0 to 66.0 Gy of CIRT (relative biological effect) in 20 fractions between 2000 and 2007, 324 patients who were deemed to be at high risk on the basis of the modified D'Amico classification criteria and received CIRT along with androgen-deprivation therapy (ADT) were examined. The OAM rate was adjusted for the ADT duration, and multivariate analyses using a Cox proportional hazards model were performed for OAM with BR as a time-dependent covariate.
  
  
  RESULTS
  The median follow-up period was 107.4 months, and the 5- and 10-year OAM rates after adjustments for the ADT duration were 7.0% (95% confidence interval [CI], 4.0%-9.4%) and 23.9% (95% CI, 16.4%-26.2%), respectively. A multivariate analysis revealed that the presence of BR (hazard ratio, 2.82; 95% Cl, 1.57-5.08; P = .001) was one of the predictive factors for OAM. On the other hand, the duration of ADT had no impact on OAM.
  
  
  CONCLUSIONS
  BR after CIRT combined with ADT is an independent predictive factor for OAM in high-risk prostate cancer patients. The results of this study could be applied to other high-dose radiation therapies. Cancer 2016;122:3225-31. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
authors.affiliation: Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Kasuya
authors.affiliation: Department of Radiation Oncology, Graduate School of Medicine, Tsukuba University Faculty of Medicine, Ibaraki, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan. h_tsuji@nirs.go.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuji
authors.affiliation: Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Nomiya
authors.affiliation: Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Makishima
authors.affiliation: Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kamada
authors.affiliation: Department of Urology, Japan Community Health Care Organization Tokyo Shinjuku Medical Center, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Akakura
authors.affiliation: Department of Urology, Toho University Sakura Medical Center, Chiba, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.affiliation: Department of Public Health, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Haruyama
authors.affiliation: Department of Public Health, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Kobashi
authors.affiliation: Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Tsujii
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D063193:Heavy Ion Radiotherapy / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000401:mortality*; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000726:Androgen Antagonists
keywords: Phoenix definition; biochemical recurrence; carbon-ion radiotherapy; high-risk prostate cancer; mortality; prostate-specific antigen (PSA); prostate-specific antigen failure