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Metastasis-free survival is strongly linked to general survival of males handled for prostate most cancers

Analysis of the Phase III NRG oncology clinical trial RTOG 9601 in men who received salvage radiation therapy (SRT) after prostatectomy for recurrent prostate cancer found that while biochemical failure (BF) was not a strong surrogate endpoint for the determination overall survival (OS) was, however, metastasis-free survival (MFS) was present in this patient population.

These results are consistent with the data in the cessation of primary radiation with an intact prostate. The analysis results were presented at the virtual edition of the American Society for Radiation Oncology (ASTRO) annual meeting in October 2020.

Previously, the Intermediate Clinical Endpoints in Prostate Cancer (ICECaP) group identified MFS as a valid substitute for OS in men treated with localized prostate cancer. However, only 8% of men treated with prostatectomy in the ICECaP analysis did not include any studies with SRT.

Prior to analysis of NRG-RTOG 9601, the performance of intermediate clinical endpoints (ICEs) as surrogate endpoints in an SRT environment was unknown. The NRG-RTOG 9601 analysis examined two types of BF, including PSA-Nadir + 0.3-0.5 ng / ml or the start of salvage hormone therapy according to the NRG-RTOG 9601 study and PSA-Nadir + 2 ng / ml according to NRG-RTOG 0534 study.

The researchers also assessed DM and MFS endpoints. All endpoints were examined for surrogacy using two approaches. the Prentice criteria; and a two-tier meta-analytical approach that required two conditions for surrogacy to be met, including the ICE had to be correlated with the OS and the treatment effect on the ICE and the OS had to be correlated.

Although BF, MFS, and Distant Metastasis (DM) each met the four Prentice criteria for OS, there were differences from the two-condition approach that was used to determine surrogacy. In the two-stage meta-analytical approach, MFS correlated strongly with OS (τ = 0.86). Other endpoints were not significantly related to the operating system.

DM correlated only moderately with OS (τ = 0.66) and BF correlated weakly with OS on both the RTOG 9601-defined BF (τ = 0.25) and the RTOG 0534-defined BF endpoints (τ = 0, 40). The biochemical failure was considered prognostic in this analysis. However, PSA-based ICEs and the treatment effect of anti-androgen therapy correlated only weakly with the OS and were therefore regarded as poor substitute endpoints.

From this analysis, we believe that researchers should exercise caution in concluding the clinical utility of studies that use biochemical failure as a substitute for overall survival. These results underscore that the two-step meta-analytical approach should be the preferred method in assessing surrogacy. “

William Jackson, MD, University of Michigan

Jackson is the lead author of the NRG-RTOG 9601 Analysis Abstract.

These results can be further validated as data from current, ongoing salvage radiation therapy studies are being collected in this patient population.

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