title: Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?
abstract: BACKGROUND
  The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear.
  
  
  METHODS
  We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively.
  
  
  RESULTS
  During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival.
  
  
  CONCLUSIONS
  No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL.
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Taguchi
authors.affiliation: Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. hfukuhara-jua@umin.ac.jp.
authors.forename: Hiroshi
authors.identifier: http://orcid.org/0000-0002-5404-600X
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Naito
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kakutani
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Takeshima
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000368:Aged; D001918:Brachytherapy; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000532:radiotherapy*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000601:surgery*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D013997:Time Factors
chemical_list: D017430:Prostate-Specific Antigen
keywords: Biochemical recurrence; Prostate cancer; Prostatectomy; Radiation; Radiotherapy; Salvage