Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.
Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy.



We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival.



Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R2= 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R2= 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml).



The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials.
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Ahmed
A
Abugharib
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
William C
WC
Jackson
Department of Radiation Oncology, University of Texas Southwestern, Dallas, Texas.
Vasu
V
Tumati
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Robert T
RT
Dess
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Jae Y
JY
Lee
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Shuang G
SG
Zhao
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Moaaz
M
Soliman
Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
Zachary S
ZS
Zumsteg
Department of Pathology, University of Michigan, Ann Arbor, Michigan.
Rohit
R
Mehra
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiation Oncology, University of California-San Francisco, San Francisco, California.
Felix Y
FY
Feng
Department of Urology, University of Michigan, Ann Arbor, Michigan.
Todd M
TM
Morgan
Department of Radiation Oncology, University of Texas Southwestern, Dallas, Texas.
Neil
N
Desai
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. Electronic address: sprattda@med.umich.edu.
Daniel E
DE
Spratt
D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome
prostate-specific antigen; prostatectomy; prostatic neoplasms; radiotherapy; salvage therapy