Dr García-Carbonero on Considerations for Poorly Differentiated GI Neuroendocrine Carcinoma

"There are now emerging targeted therapies for many of these alterations. We need to continue shifting the field toward a more molecularly driven approach, as I believe our patients will significantly benefit from it."

Rocío García-Carbonero, MD, a medical oncologist at Hospital Universitario 12 de Octubre and associate professor at Universidad Complutense of Madrid, highlighted key diagnostic and molecular considerations in the management of poorly differentiated gastrointestinal (GI) neuroendocrine carcinomas during a case-based discussion. These tumors are characterized by aggressive clinical behavior and poor prognosis, necessitating precise diagnostic strategies and a shift toward molecularly informed treatment approaches.

One critical diagnostic consideration addressed was the appropriate use of imaging modalities. Although 25% of audience participants indicated they would order a gallium PET scan for this case, García-Carbonero emphasized that this modality is inappropriate for poorly differentiated tumors. Gallium PET imaging evaluates somatostatin receptor expression and is reserved for well-differentiated neuroendocrine tumors, not those lacking receptor expression, as seen in poorly differentiated disease.

Additionally, García-Carbonero underscored the clinical utility of molecular profiling in this tumor subtype. Approximately 20% of poorly differentiated neuroendocrine carcinomas harbor potentially actionable molecular alterations. Identifying these alterations can inform the selection of targeted therapies, offering an alternative to conventional cytotoxic chemotherapy. In the presented case, a BRAF mutation was identified, illustrating the relevance of genetic analysis. Other possible genomic alterations include microsatellite instability-high status, high tumor mutational burden, and RAS mutations—each associated with emerging therapeutic options.

García-Carbonero advocated for broader adoption of molecular profiling to better personalize treatment for patients with this aggressive malignancy. As targeted therapies continue to evolve, integrating molecular diagnostics into routine clinical evaluation could optimize outcomes and expand treatment possibilities beyond standard chemotherapy regimens.