Biochemical recurrence (BCR) surrogacy for clinical outcomes after radiotherapy for adenocarcinoma of the prostate (BCRSCRAP): A meta-analysis from MARCAP Consortium.

Authors

null

Soumyajit Roy

Rush University Medical Center, Chicago, IL

Soumyajit Roy , Tahmineh Romero , Allison Steigler , James William Denham , David John Joseph , Jeff M. Michalski , Felix Y Feng , Michel Bolla , Theo M. de Reijke , Philippe Maingon , Matthew R. Sydes , David P. Dearnaley , Luca Incrocci , Wilma Heemsbergen , Abdenour Nabid , Luis Souhami , Almudena Zapatero , Yilun Sun , Daniel Eidelberg Spratt , Amar Upadhyaya Kishan

Organizations

Rush University Medical Center, Chicago, IL, University of California, Los Angeles, Los Angeles, CA, University of NewCastle, New South Wales, Australia, Calvary Mater Newcastle, Georgetown, NSW, Australia, 5D CLINICS, Claremont, Australia, Washington University School of Medicine, Saint Louis, MO, University of California, San Francisco, San Francisco, CA, Grenoble Alpes University, Centre Hospitalier Universitaire de Grenoble, Grenoble, France, University of Amsterdam, Amsterdam, Netherlands, Hôpital Pitié Salpétrière, Paris, France, Medical Research Council at UCL, London, United Kingdom, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, Erasmus MC Cancer Institute, Rotterdam, Netherlands, Erasmus University Medical Center, Erasmus, Netherlands, Centre Hospitalier de Sherbrooke, Sherbrooke, QC, Canada, McGill University Health Centre, Montréal, QC, Canada, Hospital Universitario de La Princesa, Madrid, Spain, Case Western Reserve University, Cleveland, OH, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, University of California Los Angeles, Los Angeles, CA

Research Funding

No funding received
None.

Background: Event-free survival, a PSA-driven endpoint, was shown to not be surrogate endpoint for overall survival (OS) in the ICECAP two-stage meta-analytic approach. However, time to biochemical recurrence (TTBCR) in NRG/RTOG 9202 met Prentice criteria for surrogacy. We performed an individual patient data (IPD) meta-analysis of 11 randomized controlled trials evaluating RT dose escalation, ADT use, and adjuvant ADT prolongation to evaluate the surrogacy of time to BCR (TTBCR), censoring for non-prostate cancer deaths, using both approaches to evaluate surrogacy. Methods: This individual patient level meta-analysis was performed using data from the MARCAP consortium, and 11 radiotherapy trials were included. TTBCR was defined as time to developing a BCR or experiencing prostate cancer-specific mortality (PCSM), with censoring at time of other-cause death or loss to follow-up. Landmark analyses were used to test the Prentice criteria for surrogacy. For patient level correlation between TTBCR and OS, we applied a bivariate Copula model to estimate the Kendall’s τ. For trial level correlation of the treatment effect on TTBCR and true endpoints, a weighted linear regression model was applied between the effects of treatment (natural log of hazard ratio [log-HR]) on OS versus TTBCR using a weightage that was inverse variance of BCR log-HR estimate. Results: Based on Prentice criteria, BCR at the landmark time point of 48 months was associated with increased risk of mortality in trials that compared treatment intensification with adjuvant ADT prolongation (HR 2.18 [95% CI 1.95-2.42]), the addition of ADT (HR 1.38 [1.25-1.54]), and RT dose escalation (HR 2.12 [1.83-2.46]) on uni- and multi-variable analyses. At the patient level, there was a low to moderate level correlation between BCR and OS with Kendall’s τ of 0.34 and a R2 of 0.55 for correlation of treatment effect on TTBCR and OS. At the trial level, there was a poor correlation between treatment effect on TTBCR and OS (R2=0.16). Conclusions: This IPD meta-analysis demonstrates that while BCR is prognostic, it is not a surrogate endpoint for OS in localized prostate cancer for patients treated with a diverse array of radiotherapeutic strategies. This highlights the importance of other cause mortality in prostate cancer. Our results highlight the differences in interpretability of Prentice criteria and the two-stage meta-analytic approach and suitability of endpoints for clinical trial design.

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Abstract Details

Meeting

2023 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer - Advanced,Prostate Cancer - Localized

Sub Track

Other

Citation

J Clin Oncol 41, 2023 (suppl 6; abstr 391)

DOI

10.1200/JCO.2023.41.6_suppl.391

Abstract #

391

Poster Bd #

P8

Abstract Disclosures

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