Metastasis-Free Survival as Surrogate for Overall Survival in Localized Prostate Cancer

Key Points

  • At the patient level, metastasis-free survival was highly correlated with overall survival in patients with localized prostate cancer.
  • Treatment effects for metastasis-free survival and overall survival were well correlated.

In a meta-analysis reported in the Journal of Clinical Oncology, Xie et al found that metastasis-free survival was a strong surrogate for overall survival in patients with localized prostate cancer, potentially providing a metric that could accelerate assessment of new adjuvant therapy approaches.

Study Details

Eligible trials for the meta-analysis included randomized controlled trials of local therapy in localized disease that were closed to accrual and conducted in Australia, New Zealand, Canada, Europe, or the United States. By June 2013, 102 completed or ongoing randomized trials that enrolled patients between 1987 and 2011 were identified, with individual patient data available from 28 trials with 28,905 patients. Data on disease-free survival were available for 21,140 patients from 24 trials, and data on metastasis-free survival were available for 12,712 patients from 19 trials.

Correlations With Overall Survival

After a median follow-up of 10 years, 45% of 21,140 men had experienced disease-free survival events and 45% of 12,712 had experienced metastasis-free survival events. In the disease-free survival and metastasis-free survival cohorts, 61% and 90% of patients were from radiation trials and 63% and 66% had high-risk disease, respectively.

At the patient level, Kendall’s τ correlation with overall survival was 0.85 (95% confidence interval [CI] = 0.85–0.86) for disease-free survival and 0.91 (95% CI = 0.91–0.91) for metastasis-free survival. At the trial level, R2 correlations were 0.86 (95% CI = 0.78–0.90) and 0.83 (95% CI = 0.71–0.88) from weighted linear regression of 8-year overall survival vs 5-year disease-free survival and metastasis-free survival. Correlations of treatment effects for overall survival were R2 =0.73 (95% CI = 0.53–0.82) for disease-free survival and R2 = 0.92 (95% CI = 0.81–0.95) for metastasis-free survival.

The investigators concluded: “[Metastasis-free survival] is a strong surrogate for [overall survival] for localized prostate cancer that is associated with a significant risk of death from prostate cancer.”

The study was funded by the Prostate Cancer Foundation Challenge Award and grants from Astellas Pharma, Medivation, Janssen Pharmaceuticals, Millennium Pharmaceuticals, Sotio, and Sanofi.

Christopher J. Sweeney, MBBS, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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