Is the PROTEUS trial practice-changing? Or should we be more cautious? For the first time, a phase III trial demonstrated that perioperative treatment with apalutamide plus androgen deprivation therapy improves pathological response and metastasis-free survival in men with high-risk localized prostate cancer undergoing radical prostatectomy. Some key reflections: 🔹 A landmark study. PROTEUS provides proof of concept that intensified perioperative systemic therapy can modify the biology of localized prostate cancer and potentially reshape future treatment paradigms. 🔹 A modest absolute benefit. While statistically significant, the absolute improvement in 5-year metastasis-free survival was relatively small. This highlights the need to carefully balance efficacy against toxicity, cost, and the risk of overtreatment. 🔹 An innovative but challenging endpoint. PROTEUS is the first randomized phase III trial to include PSMA-PET-detected metastases within its primary metastasis-free survival endpoint. This reflects modern imaging practice, but PSMA-PET-based MFS has not yet been validated as a surrogate for overall survival. As our imaging becomes more sensitive, we must ensure that our clinical endpoints remain meaningful for patients. 🔹 Patient selection remains the key question. High-risk prostate cancer is not a single disease. The future lies in identifying the patients who truly benefit from treatment intensification through better biological and molecular stratification, rather than applying a “one-size-fits-all” approach. PROTEUS is undoubtedly a landmark trial. However, its greatest contribution may not simply be demonstrating that “more treatment is better,” but rather opening the door to a more nuanced discussion about who should receive intensified therapy, how we should measure success, and how we can personalize treatment for patients with high-risk localized prostate cancer. euoncology.europeanurology.c… #ProstateCancer #Urology @GiuliaMarvaso84 @CMercinelli @GGandaglia @PBlanchardMD @roodvdb @GGiannarini @MRoupret @EurUrolOncol @Lara__Rodriguez @foxal72

A productive weekend working on PIONEER and real-world data in localized prostate cancer. We used the study-a-thon to define a focused research portfolio using broad real-world datasets: baseline characteristics, first-line treatment, subsequent treatment, metastasis after primary therapy, adverse events, and overall survival. The potential research lines include treatment patterns, disease trajectory, outcomes in elderly and frail patients, post-primary treatment sequencing, adverse-event burden, and long-term survivorship. We also aligned on key endpoints: metastasis-free survival, ADT-free survival, local-treatment-free survival, time to first subsequent local or systemic treatment, and overall survival. Most excitingly, we have identified more than 500,000 patients with localized prostate cancer across our datasets. But beyond the numbers, this weekend was also a reminder that bringing the right people together, clinicians, researchers, data scientists, and collaborators, is what turns ideas into projects and projects into impact. This is a huge opportunity to generate meaningful real-world evidence in prostate cancer. Big data is coming, stay tuned 🤞 @NICOLETTIRosse1 @Sevans_axelsson @dr_rajwa @Uroweb @CMercinelli #PIONEER #ProstateCancer #RealWorldData