title: Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.
abstract: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF).
  
  
  
  422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n=111), minimal residual disease (MRD) SRT (n=70) and SRT (n=83) were defined by PSA levels of <0.2, 0.2-0.49 and ⩾0.5 ng ml(-1), respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome.
  
  
  
  During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P<0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P=0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high.
  
  
  
  The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Ross
authors.affiliation: Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Den
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Yousefi
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Trock
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tosoian
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: EMMES Canada, Burnaby, BC, Canada.
authors.forename: D J S
authors.initials: DJ
authors.lastname: Thompson
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Choeurng
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Haddad
authors.affiliation: Department of Radiation Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Tran
authors.affiliation: Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Trabulsi
authors.affiliation: Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Gomella
authors.affiliation: Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Lallas
authors.affiliation: Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: F
authors.initials: F
authors.lastname: Abdollah
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: F Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: Department of Surgery, Division of Urology, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.|Surgery section, Durham Veteran Affairs Medical Center, Durham, NC, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Freedland
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Urology, Northwestern University, Evanston, IL, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Schaeffer
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011184:Postoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000532:radiotherapy* / Q000601:surgery; D018714:Radiotherapy, Adjuvant
chemical_list: D014408:Biomarkers, Tumor