title: Postoperative radiation therapy for patients at high-risk of recurrence after radical prostatectomy: does timing matter?
abstract: OBJECTIVE
  To evaluate among radical prostatectomy (RP) patients at high-risk of recurrence whether the timing of postoperative radiation therapy (RT) (adjuvant, early salvage with detectable post-RP prostate-specific antigen [PSA], or 'late' salvage with a PSA level of >1.0 ng/mL) is significantly associated with overall survival (OS), prostate-cancer specific survival or metastasis-free survival, in a longitudinal cohort.
  
  
  METHODS
  Of 6 176 RP patients in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 305 patients with high-risk pathological features (margin positivity, Gleason score 8-10, or pT3-4) who underwent postoperative RT were examined, either in the adjuvant (≤6 months after RP with undetectable PSA levels, 76 patients) or salvage setting (>6 months after RP or pre-RT PSA level of >0.1 ng/mL, 229 patients). Early (PSA level of ≤1.0 ng/mL, 180 patients) or late salvage RT (PSA level >1.0 ng/mL, 49 patients) was based on post-RP, pre-RT PSA level. Multivariable Cox regression examined associations with all-cause mortality and prostate cancer-specific mortality and/or metastases (PCSMM).
  
  
  RESULTS
  After a median of 74 months after RP, 65 men had died (with 37 events of PCSMM). Adjuvant and salvage RT patients had comparable high-risk features. Compared with adjuvant, salvage RT (early or late) had an increased association with all-cause mortality (hazard ratio [HR] 2.7, P = 0.018) and with PCSMM (HR 4.0, P = 0.015). PCSMM-free survival differed by further stratification of timing, with 10-year estimates of 88%, 84%, and 71% for adjuvant, early salvage, and late salvage RT, respectively (P = 0.026). For PCSMM-free survival and OS, compared with adjuvant RT, late salvage RT had statistically significantly increased risk; however, early salvage RT did not.
  
  
  CONCLUSIONS
  This analysis suggests that patients who underwent early salvage RT with PSA levels of <1.0 ng/mL may have comparable metastasis-free survival and OS compared with adjuvant RT; however, late salvage RT with a PSA level of >1.0 ng/mL is associated with worse clinical outcomes.
authors.affiliation: Department of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.|Department of Radiation Oncology, College of Medicine, University of Arizona, Tucson, AZ.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Paciorek
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cooperberg
authors.affiliation: Department of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Mack
authors.initials: M
authors.lastname: Roach
authors.affiliation: Department of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: I-Chow J
authors.initials: IC
authors.lastname: Hsu
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
mesh_terms: D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D011184:Postoperative Period; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000401:mortality; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016879:Salvage Therapy; D013997:Time Factors
chemical_list: D017430:Prostate-Specific Antigen
keywords: CaPSURE; adjuvant; postoperative; prostate; radiation therapy; salvage