Dr Wang on Testing for Molecular Alterations in Relapsed/Refractory Urothelial Carcinoma

Jue Wang, MD, professor, Department of Internal Medicine, member, Division of Hematology and Oncology, UT Southwestern Medical Center, discusses how to approach testing for molecular alterations in patients with relapsed or refractory urothelial carcinoma. 

Urothelial cancer is characterized by a high prevalence of genetic mutations; however, progress continues to unfold in the ongoing exploration of these genetic alterations within the framework of molecular and precision medicine, Wang begins. Importantly, agents targeting FGFR2/3 mutations have received regulatory approval, he explains, adding that tissue testing remains the cornerstone of accurate diagnosis and tailored treatment strategies. Wang emphasizes the importance of early testing and preparedness for the incorporation of targeted therapies.

Moreover, the emergence of liquid biopsies for the assessment of circulating tumor cells has added another dimension to the ability to identify genetic mutations and guide therapeutic decisions in urothelial cancer, Wang emphasizes. In the context of real-world clinical practice, oncologists have harnessed the wealth of existing tissue samples from previous biopsies, he expands. The dynamic nature of cancer, marked by its evolving processes, presents challenges for molecular testing because of variability in sample preparation, isolated DNA, and complex clinical scenarios, he explains. Oncologists’experience in caring for patients with urothelial carcinoma confirms the gradual evolution of molecular events over time, Wang says. 

Presently, the urothelial cancer treatment paradigm is limited to a singular targeted therapy. However, it is essential to consider that when patients experience rapid deterioration, practicalities inherent in the real-world healthcare system, including the necessity of pre-authorization for specific treatments, must be navigated, Wang continues. Therefore, oncologists continue to advocate for patients, particularly those with refractory disease, to receive the opportunity to undergo molecular profiling as an integral component of their care, he says. This proactive approach can be seamlessly integrated into the standard of care, ensuring a more comprehensive understanding of the disease and facilitating the timely application of personalized therapies, ultimately offering potential avenues for improved patient outcomes, Wang concludes.