Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival
Abstract
Purpose:
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.
Materials and Methods:
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.
Results:
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).
Conclusions:
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.
References
- 1 : A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol2016; 69: 428. Google Scholar
- 2 : Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol2009; 27: 2924. Google Scholar
- 3 : Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet2012; 380: 2018. Google Scholar
- 4 : Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA2006; 296: 2329. Google Scholar
- 5 : Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol2013; 190: 441. Link, Google Scholar
- 6 : Adjuvant and salvage radiotherapy after prostatectomy: American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol2014; 32: 3892. Google Scholar
- 7 : Variation in the use of postoperative radiotherapy among high-risk patients following radical prostatectomy. Prostate Cancer Prostatic Dis2016; 19: 216. Google Scholar
- 8 : Adjuvant versus salvage post-prostatectomy radiation therapy: a critical review of the evidence. J Urol2013; 190: 450. Link, Google Scholar
- 9 : Adjuvant versus salvage radiotherapy after prostatectomy: the apple versus the orange. Int J Radiat Oncol Biol Phys2012; 82: 1045. Google Scholar
- 10 : Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis. Eur Urol2012; 62: 472. Google Scholar
- 11 : Radiotherapy and androgen deprivation in combination after local surgery (RADICALS): a new Medical Research Council/National Cancer Institute of Canada phase III trial of adjuvant treatment after radical prostatectomy. BJU Int2007; 99: 1376. Google Scholar
- 12 : A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: background and rationale of the Radiotherapy-Adjuvant Versus Early Salvage (RAVES) trial. BJU Int2014; 113: 7. Google Scholar
- 13 : Quality assurance of the EORTC 22043-30041 trial in post-operative radiotherapy in prostate cancer: results of the Dummy Run procedure. Radiother Oncol2013; 107: 346. Google Scholar
- 14 : Improved metastasis-free and survival outcomes with early salvage radiotherapy in men with detectable prostate-specific antigen after prostatectomy for prostate cancer. J Clin Oncol2016; 34: 3864. Google Scholar
- 15 : Adjuvant radiotherapy following radical prostatectomy for prostate cancer. Cochrane Database Syst Rev2011; : CD007234. Google Scholar
- 16 : Salvage radiotherapy after prostatectomy: two sides of the coin. Eur Urol2016;
10.1016/j.eururo.2016.03.022 . Crossref, Google Scholar - 17 : The effect of salvage radiotherapy and its timing on the health-related quality of
life of prostate cancer patients. Eur Urol2016;
10.1016/j.eururo.2016.03.010 . Crossref, Google Scholar - 18 : Androgen receptor upregulation mediates radioresistance after ionizing radiation. Cancer Res2015; 75: 4688. Google Scholar
- 19 : Androgen receptor signaling regulates DNA repair in prostate cancers. Cancer Discov2013; 3: 1245. Google Scholar
- 20 : A hormone-DNA repair circuit governs the response to genotoxic insult. Cancer Discov2013; 3: 1254. Google Scholar
