Mohammad Shaikh, MD, ScB
PV QA 1 - Poster Viewing Q&A 1
Purpose/Objective(s): Conduct a meta-analysis of the available retrospective match-control literature comparing adjuvant radiotherapy (ART) to early salvage radiotherapy (ESRT) strategy in pathologic T3 or margin-positive prostate cancer.
Materials/Methods: A comprehensive MEDLINE, clinicaltrials.gov, and Cochrane Library search for matched-pair studies of ART vs ESRT was performed. Studies including patients with pT3 or margin-positive, node-negative disease, post-prostatectomy that compared outcomes of ART vs ESRT. Studies included, defined undetectable PSA as <0.10 ng/mL or below the sensitivity of assay. ESRT was defined as salvage radiotherapy delivered at PSA recurrence to 0.1 ng/mL or higher, but less than or equal to 0.5 ng/mL. Post-RT biochemical failure was defined as PSA rise to 0.2 ng/mL or first rise above 0.2 ng/mL if post-RT nadir was greater than 0.2 ng/mL. Results were synthesized for biochemical progression-free (BPFS), metastasis-free (MFS), overall survival (OS), freedom from androgen depravation therapy (FFADT) and prostate cancer-specific survival (PCSS). When hazard ratios (HR) were not provided, Parmar (1998) method was used and proportional hazard was assumed. Either random-effects model (RE) or fixed-effect model (FE) were used based on the test of heterogeneity. A proportion of patients who receive ART would have been cured with prostatectomy alone, we performed a sensitivity analysis to estimate proportion who need to be cured with prostatectomy alone for BPFS benefit of ART to lose statistical significance over ESRT.
Results: Three retrospective match-control studies (Buscariollo et al, Hwang et al & Ost et al) were identified with 1106 patients (ART n=553, ESRT n=553). All studies reported on BPFS. Pooled analysis showed that ART resulted in greater BPFS (HR = 0.46; 95% CI: 0.37, 0.57; P < 0.00001, FE). Two studies reported on MFS and OS. Synthesis of data showed that ART improved MFS (HR = 0.45; 95% CI: 0.26, 0.75; P = 0.003, FE) as well as OS (HR = 0.57; 95% CI: 0.35, 0.92; P = 0.02, FE) compared with ESRT. One article reported on FFADT, which was significantly improved with ART (HR = 0.28; 95% CI: 0.15, 0.52; P < 0.00001, FE). One article reported on PCSS, which showed trend in favor of ART (HR = 0.16; 95% CI: 0.02, 1.36; P < 0.09, FE). A sensitivity analysis estimated that surgery alone would have to achieve freedom from biochemical recurrence in > 52% of the patients at 10 years before BPFS benefit of ART over ESRT would lose statistical significance. For comparison BPFS was achieved in only 26-41% of the patients at 10 years in the wait-and-see arms of the three adjuvant randomized trials (EORTC, SWOG, ARO96-02).
Conclusion: BPFS, MFS, FFADT and OS were significantly improved with ART compared to ESRT. These findings support use of ART as a preferred treatment strategy in pathologic T3, margin positive patients.
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