Metastasis-free survival is a strong Surrogate of overall survival in localized prostate cancer

Wanling Xie, Meredith M. Regan, Marc Buyse, Susan Halabi, Philip W. Kantoff, Oliver Sartor, Howard Soule, Noel W. Clarke, Laurence Collette, James J. Dignam, Karim Fizazi, Wendy R. Paruleker, Howard M. Sandler, Matthew R. Sydes, Bertrand Tombal, Scott G. Williams, Christopher J. Sweeney, Ove Andren, John Armstrong, Donald BerryMichel Bolla, Joseph Chin, Simon Chowdhury, Noel Clarke, Matthew Cooperberg, Jim Denham, James Dignam, Savino Mauro Di Stasi, Mario Eisenberger, Boris Freidlin, Silke Gillessen, Martin Gleave, Muriel Habibian, Nicholas James, Jonathan Jarow, Nancy Keating, Gary Keloff, Laurence Klotz, Himu Lukka, Malcolm Mason, Andrea Miyahira, Nicolas Mottet, Mari Nakabayashi, Wendy R. Parulekar, Meredith Regan, Howard Sandler, Peter Scardino, Howard Scher, Richard Simon, Jonathan Simons, Eric Small, Matthew Sydes, Catherine Tangen, Ian Thompson, Anders Widmark, Thomas Wiegel, Manfred Wirth, Eric Yeoh, Almudena Zapatero

Research output: Contribution to journalArticlepeer-review

178 Scopus citations


Purpose: Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods: By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasisfree survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage metaanalytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS. Results: Trials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall's π correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R2 was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effects-measured by log hazard ratios-for the surrogates and OS were well correlated (R2, 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS). Conclusion: MFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.

Original languageEnglish (US)
Pages (from-to)3097-3104
Number of pages8
JournalJournal of Clinical Oncology
Issue number27
StatePublished - Sep 20 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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