Emerging ADCs in the GU Cancers Space

Robert L. Ferris, MD, PhD, co-editor-in-chief of Targeted Therapies in Oncology highlights the transformative impact of antibody-drug conjugates (ADCs) in genitourinary cancers, particularly bladder cancer, marking a shift from traditional cytotoxic and checkpoint-based therapies toward precision-engineered, biomarker-driven treatment paradigms.

He emphasizes that enfortumab vedotin (EV) has become a new backbone in advanced urothelial carcinoma, with emerging data showing that combining EV with pembrolizumab may redefine neoadjuvant therapy for muscle-invasive bladder cancer. This combination leverages complementary mechanisms—cytotoxic payload delivery and immune activation—achieving unprecedented pathologic responses and offering an alternative to cisplatin-based regimens. Additionally, disitamab vedotin, a HER2-targeted ADC, demonstrates efficacy in both HER2-positive and HER2-low bladder cancers, broadening the actionable patient population and reinforcing the importance of nuanced biomarkers.

Beyond bladder cancer, Ferris notes converging breakthroughs across GU malignancies. In prostate cancer, darolutamide enhances PSMA expression to improve radioligand therapy sequencing. In renal cell carcinoma, nivolumab-based combinations and the HIF2-α inhibitor belzutifan plus lenvatinib show superior outcomes over standard therapies. Capivasertib addresses key resistance pathways in P10-loss prostate cancer.

Overall, Ferris describes a broader convergence of targeted payloads, immune modulation, and functional biomarkers, moving ADCs into earlier, curative settings. He urges clinicians to adopt molecular testing and biomarker-guided sequencing to keep pace with a field now rivaling lung and breast oncology in therapeutic evolution.