SUO 2017: Metastasis-Free Survival Endpoint

Washington, DC ( Dr. Sweeney discusses the use of metastasis free survival as a clinical endpoint. He began his talk by stating that preventing relapse after definitive local therapy is the most viable way in the near future to decrease the death rate from prostate cancer. With the discovery of PSA/early detection and multimodality therapy, we have already began doing this since the 1990s, with a clear evident decrease in the death rate beginning in that period. A good example for this is the famous Bolla paper published in the New England Journal of Medicine in 1997, demonstrating 40% decrease in the risk of dying from prostate cancer by adding 3 years of androgen deprivation therapy (ADT) to radiotherapy for high risk prostate cancer.

Dr. Sweeney proposes to increase the intensity/efficacy of therapy for patients with localized disease, resulting in a decrease of the death rate from prostate cancer. If we decrease the deaths by a 1/3 after local therapy, this will result in decrease of prostate cancer deaths from 26000 to 20000 a year in the US. Dr. Sweeney hopes to bring treatments effective for highly resistant incurable CRPC earlier to eradicate curable micrometastatic disease. 

However, we need to be aware that adjuvant therapy studies take longer than a decade to complete, entailing too much money, time and resources. For this reason, in 2013 the ICECaP working group was convened with “start-up” funding from the prostate cancer foundation. The goal was to develop an intermediate clinical endpoint (ICE) which accurately reflects the improvement in overall survival/cure rate, and accelerate conduction of adjuvant trials. The process for finding an ICE involves acquiring individual patient data of all randomized trials, systematic review and meta-analysis approach to identify trials, and meta-analysis of RCT individual patient data to identify validated surrogate endpoint of overall survival (OS). A repository was formed with individual patient data from 28 trials, encompassing 22825 patients managed with different types of treatment. By using the surrogacy-threshold-effect (STH), we can recognize metastasis free survival (MFS) is not exactly identical to overall survival (OS) – that is not all metastatic patients die from prostate cancer. Moving forward, the statistical constructs for conducting clinical trials using MFS as an endpoint can be created. Other intermediate endpoint that can also be used, including disease free survival (DFS) and intermittent vs. continuous ADT. However, there is currently no data to support PSA as a validated surrogate for radical prostatectomy trials.

Presented by: Christopher Sweeney, MBBS, is a Medical Oncologist at the Dana-Farber Cancer Institute.  He is a member of the American Society of Clinical Oncology, the Eastern Cooperative Oncology Group, and the American Association for Cancer Research. Dr. Sweeney’s primary research interest is drug discovery and development. His academic focus is management of genitourinary malignancies, including prostate, bladder, testis and renal cell cancer. 

Written by: Hanan Goldberg, MD @GoldbergHanan Society of Urologic Oncology Fellow University of Toronto, Princess Margaret Cancer Centre at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC