The results of an academic research project to which EORTC contributed data, were recently published in the Journal of Clinical Oncology. This project investigated surrogate endpoints and was the first to formally establish surrogacy for localized prostate cancer. Their thorough analyses showed that metastasis-free survival (MFS) could be considered a strong surrogate for overall survival (OS) in localized prostate cancer associated with a significant risk of death by cancer.
Each year, about 1.1 million new cases of prostate cancer are diagnosed with more than 300,000 deaths worldwide. It is known that treatment of intermediate and high risk localized cancer with adjuvant systemic therapy is associated with fewer prostate cancer deaths. Unfortunately, adjuvant prostate cancer clinical trials take more than a decade to reach the endpoint of OS. While disease-free survival (DFS) has proven to be a surrogate for OS and used as a primary endpoint in certain cancers, no intermediate clinical endpoint (ICE) is accepted up until now as a robust surrogate for OS in prostate cancer trials.
An ICE could serve as a good surrogate for OS when there is no curative salvage therapy for relapsed disease and/or a substantial risk of dying of cancer. In the current project, it was hypothesized that DFS and/or MFS could be surrogates for OS as they track more closely with prostate cancer death.
By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data (IPD) was collected from 28 trials comprising 28,905 patients. The DFS and MFS were determined for 21,140 (from 24 trials) and 12,712 (from 19 trials) patients, respectively. After a median follow-up of 10 years, 45% of 21,140 patients and 45% of 12,712 patients achieved a DFS and MFS event, respectively.
The use of IPD from many different trials and the international multi-disciplinary collaborations were critical in conducting this analysis and allowed a side-by-side comparison of DFS and MFS as surrogates for OS. The sensitivity analysis revealed that the MFS correlation with OS was maintained independently of type of local treatment.
These results showed that MFS was a strong surrogate for OS in clinically localized prostate cancer in a patient population with approximately 15% chance of dying of prostate cancer over 10 years despite potentially curative local therapy. The advantage of using a surrogate as MFS rather than OS is that the use of MFS allows an expeditious evaluation of a new therapy if it has a meaningful treatment effect.