Multidisciplinary Coordination and Limitations of Conventional TROP2 Testing

This segment focuses on the operational aspects of biomarker testing in NSCLC and highlights the critical role of multidisciplinary collaboration in ensuring timely and appropriate molecular evaluation. Dr. Wistuba emphasizes that optimal testing requires close coordination among medical oncologists, pathologists, molecular laboratories, and, when applicable, surgeons and pulmonologists. This team-based approach helps ensure that the right tests are performed based on available therapies and the patient’s clinical context.

Institutional workflows may vary, particularly regarding reflex testing. In some centers, pathology automatically initiates biomarker testing when a lung cancer diagnosis is made, streamlining the process and reducing delays. In others, ordering is clinician-driven, requiring oncologists or advanced practice providers to request testing. Regardless of the model, the key priority is implementing a system that reliably delivers comprehensive results in a timely manner to support treatment decisions.

The discussion shifts to the limitations of conventional IHC for assessing TROP2 expression. Traditional evaluation relies on pathologist interpretation of membrane staining intensity using categorical scoring (0 to 3+), sometimes combined with percentage of positive cells to generate an H-score. However, data from phase 1 and phase 3 clinical studies of TROP2-directed antibody-drug conjugates (ADCs) showed that neither intensity-based scoring nor H-score reliably predicts treatment response.

These findings reveal a key challenge: conventional, semi-quantitative IHC methods may not adequately capture the biologic features that determine target engagement and therapeutic efficacy. The segment concludes by introducing the need for more precise and quantitative approaches such as computational pathology.