Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis

Laila A Gharzai; Ralph Jiang; David Wallington; Gavin Jones; Samuel Birer; Neil Jairath; Elizabeth M Jaworski; Matthew R McFarlane; Brandon A Mahal; Paul L Nguyen; Howard Sandler; Todd M Morgan; Zachery R Reichert; Joshi J Alumkal; Rohit Mehra; Amar U Kishan; Karim Fizazi; Susan Halabi; Edward M Schaeffer; Felix Y Feng; David Elliott; Robert T Dess; William C Jackson; Matthew J Schipper; Daniel E Spratt

doi:10.1016/S1470-2045(20)30730-0

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Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis

Journal article

Peer reviewed

Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis

Laila A Gharzai, Ralph Jiang, David Wallington, Gavin Jones, Samuel Birer, Neil Jairath, Elizabeth M Jaworski, Matthew R McFarlane, Brandon A Mahal, Paul L Nguyen, …

The lancet oncology, Vol.22(3), pp.402-410

2021-03

DOI: https://doi.org/10.1016/S1470-2045(20)30730-0

PMID: 33662287

Abstract

Prostatic Neoplasms - pathology

Prognosis

Follow-Up Studies

Humans

Neoplasm Recurrence, Local - therapy

Biomarkers - analysis

Male

Survival Rate

Combined Modality Therapy

Lymphatic Metastasis

Neoplasm Recurrence, Local - mortality

Prostatic Neoplasms - mortality

Prostatic Neoplasms - therapy

Neoplasm Recurrence, Local - pathology

Aged

The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer. For this meta-analysis, we searched PubMed for all trials in localised or biochemically recurrent prostate cancer published between Jan 1, 1970, and Jan 15, 2020. Eligible trials had to be randomised, therapeutic, reporting overall survival and at least one intermediate clinical endpoint, and with a sample size of at least 70 participants. Trials of metastatic disease were excluded. Intermediate clinical endpoints included biochemical failure, local failure, distant metastases, biochemical failure-free survival, progression-free survival, and metastasis-free survival. Candidacy for surrogacy was assessed using the second condition of the meta-analytical approach (ie, correlation of the treatment effect of the intermediate clinical endpoint and overall survival), using R weighted by the inverse variance of the log intermediate clinical endpoint hazard ratio. The intermediate clinical endpoint was deemed to be a surrogate for overall survival if R was 0·7 or greater. 75 trials (53 631 patients) were included in our analysis. Median follow-up was 9·1 years (IQR 5·7-10·6). Biochemical failure (R 0·38 [95% CI 0·11-0·64]), biochemical failure-free survival (R 0·12 [0·0030-0·33]), biochemical failure and clinical failure (R 0·28 [0·0045-0·65]), and local failure (R 0·085 [0·00-0·37]) correlated poorly with overall survival. Progression-free survival (R 0·46 [95% CI 0·22-0·67]) showed moderate correlation with overall survival, and metastasis-free survival (R 0·78 [0·59-0·89]) correlated strongly. Intermediate clinical endpoints based on biochemical and local failure did not meet the second condition of the meta-analytical approach and are not surrogate endpoints for overall survival in localised prostate cancer. Our findings validate metastasis-free survival as the only identified surrogate endpoint for overall survival to date. Prostate Cancer Foundation and National Institutes of Health.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.147 Prostate Cancer; 1.147.97 Prostate Cancer
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis
Creators: Laila A Gharzai - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Ralph Jiang - Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
David Wallington - Department of Radiation Oncology, Western Michigan University, Kalamazoo, MI, USA
Gavin Jones - Department of Radiation Oncology, University of Kentucky, Lexington, KY, USA
Samuel Birer - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Neil Jairath - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Elizabeth M Jaworski - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Matthew R McFarlane - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Brandon A Mahal - Department of Radiation Oncology, University of Miami, Miami, FL, USA
Paul L Nguyen - Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Howard Sandler - Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Todd M Morgan - Department of Urology, University of Michigan, Ann Arbor, MI, USA
Zachery R Reichert - Department of Medical Oncology, University of Michigan, Ann Arbor, MI, USA
Joshi J Alumkal - Department of Medical Oncology, University of Michigan, Ann Arbor, MI, USA
Rohit Mehra - Department of Pathology, University of Michigan, Ann Arbor, MI, USA
Amar U Kishan - Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA
Karim Fizazi - Department of Cancer Medicine, Institut Gustave-Roussy, Villejuif, France
Susan Halabi - Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA
Edward M Schaeffer - Department of Urology, Northwestern University, Chicago, IL, USA
Felix Y Feng - Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA
David Elliott - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Robert T Dess - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
William C Jackson - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Matthew J Schipper - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
Daniel E Spratt - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address: sprattda@med.umich.edu
Publication Details: The lancet oncology, Vol.22(3), pp.402-410
Grant note: R01 CA240991 / NCI NIH HHS P50 CA186786 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Dept of Radiation Oncology
Language: English
Resource Type: Journal article
PMID: 33662287
Record Identifier: 991031597641302976