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2019 SUO Annual Meeting

SUO 2019: Systematic Review and Meta-Analysis of Trials Evaluating the Role of Adjuvant Radiation After Radical Prostatectomy for Prostate Cancer

Washington, DC (UroToday.com) Radical prostatectomy (RP) is curative for approximately two-thirds of patients undergoing surgery for prostate cancer1. However, patients with adverse pathologic findings experience up to a 60% risk of recurrence at 10 years and may require subsequent radiation therapy2. In three randomized controlled trials, adjuvant radiotherapy improved recurrence-free survival for men with adverse pathologic findings compared to a ‘watch-and-wait’ approach (SWOG S87943, EORTC 229114 and ARO 96-025). As a result, the American Urological Association (AUA) and American Society for Radiation Oncology (ASTRO) published guidelines recommending adjuvant radiotherapy for these patients2. The effect on survival outcomes, however, is less clear. Further, there is concern for significant overtreatment, thus, there remains interest in better defining the patients who are most likely to benefit from adjuvant radiotherapy. Recently, the FINNPROST study provided additional data on this topic. Thus, in a poster presentation at the Society of Urologic Oncology meeting, Dr. Wallis and colleagues performed a systematic review and meta-analysis to assess survival outcomes in patients undergoing adjuvant radiotherapy.

The authors identified all published randomized controlled trials comparing adjuvant radiotherapy to observation in patients following radical prostatectomy. They assessed the primary outcome of overall survival (OS) and secondary outcomes of metastasis-free survival (MFS), locoregional recurrence-free survival (RFS), biochemical progression-free survival (bPFS), and adverse events.

They identified 4 randomized trials that enrolled 2068 patients and followed them for a median follow-up of 8.7 to 12.6 years. While data were not available for each outcome from each trial, there was no evidence of overall survival benefit to adjuvant radiotherapy (see figure below). There were significant benefits in biochemical and locoregional recurrence-free survival, with minimal heterogeneity between studies for these outcomes. Metastasis-free survival was non-significantly improved by adjuvant radiotherapy.

Forest Plot Comparing Adjuvant RT

The authors also performed subgroup analyses in an attempt to identify patients who are most likely to benefit from adjuvant radiotherapy. These results are summarized in the following table:

Subgroup Analyses Using Biochemical PFS Endpoint

Additionally, the authors demonstrated that adjuvant radiotherapy is associated with a moderate risk of overtreatment, with 35-60% of patients being biochemical recurrence-free with observation alone, and of adverse events.

Obviously, since this analysis has been performed, new randomized controlled trials have been published comparing adjuvant to early salvage radiotherapy. In an analysis from the same authors, there was a significantly lower benefit to adjuvant radiotherapy when compared to early salvage radiotherapy versus observation6. Thus, taken together, there is a diminishing role for adjuvant radiotherapy and the authors failed to identify subgroups of patients who are particularly likely to benefit from adjuvant radiotherapy.

Presented by: Christopher J.D. Wallis, MD, PhD, FRCSC, Department of Urologic Surgery, Vanderbilt University, Nashville, Tennesee

Co-authors: Bimal Bhindi, Zachary Klaassen, Soum Lokeshwar, Laurence Klotz

Written by: Christopher J.D. Wallis, MD, PhD, FRCSC, Twitter: @WallisCJD at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC

References:

1. Bianco FJ, Jr., Scardino PT, Eastham JA. Radical prostatectomy: long-term cancer control and recovery of sexual and urinary function ("trifecta"). Urology 2005; 66(5 Suppl): 83-94.

2. Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. The Journal of urology 2013; 190(2): 441-9.

3. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. The Journal of urology 2009; 181(3): 956-62.

4. Bolla M, van Poppel H, Tombal B, et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012; 380(9858): 2018-27.

5. Wiegel T, Bartkowiak D, Bottke D, et al. Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 trial. European urology 2014; 66(2): 243-50.

6. Wallis CJD, Klaassen Z, Luckenbaugh AN, Laviana AA, Bhindi B. Adjuvant Versus Salvage Radiotherapy Following Radical Prostatectomy: Meta-analysis of the Effect of Comparator Salvage Approach on Study Conclusions. European urology 2019.