(UroToday.com) The 2026 European Association of Urology (EAU) annual meeting featured a game changer session and a discussant presentation by Dr. Markus Graefen discussing the results from a phase II, randomized, controlled trial of best systemic therapy versus best systemic therapy with definitive treatment of the primary tumor in metastatic prostate cancer. In this randomized clinical trial, there was no benefit in progression free survival or overall survival for the addition of local therapy to best standard therapy in men with de novo M1 prostate cancer. One specific feature of this study was that patients and treating physicians could choose the type of local therapy after randomization to the local therapy group.
There are several important pieces of information that this study adds, including:
- The existing results of prospective trials evaluating the role of local treatment in metastatic hormone sensitive prostate cancer (mHSPC) remain controversial
- Dr. Graefen notes that we need to better identify those men who, in the era of modern systemic treatment benefit from local therapy
- Not all men need local therapy, but there is probably a group of men who do
- Men who do not need local therapy are likely those with high volume metastatic burden (of note, the STAMPEDE data,1 were not published in 2013)
How do we better select patients for local therapy? Improved identification of patients could be achieved by better understanding the biology of M1 disease beyond just counting the number of metastases. A new feature of this study is the identification of the aggressive variant prostate cancer signature as a potential biomarker of prognostic value in the metastatic population, which is a good example for such an approach.
Do we have to rethink the endpoints of local therapy in de novo M1 disease? The future role for local therapy may be that it will be applied to prevent symptomatic local progression, but not under the assumption of prolonging life. Our goal should be to identify those who are at risk for local progression and to treat only those locally, since they are not at risk. Potential factors for selection include pre-existing symptoms and disease extension, tumor biology, as well as local disease changes (ie. in follow-up MRIs).
Dr. Graefen concluded his discussant presentation by highlighting who may in the future be a good candidate for local therapy in de novo M1 prostate cancer:
Further insights are ahead, including SWOG S1802, which is a phase III randomized trial of standard systemic therapy versus standard systemic therapy + definitive treatment (surgery or radiation) of the primary tumor in metastatic prostate cancer. This trial is now 79% accrued.
Presented by: Markus Graefen, MD, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 European Association of Urology (EAU) Annual Meeting, London, United Kingdom, Fri, Mar 13 – Mon, Mar 16, 2026.
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