Genomic Landscape and Outcomes of Renal Cell Carcinoma With Metastases to the Pancreas.

Abstract

Renal cell carcinoma (RCC) that metastasizes to the pancreas (RCC-PM) is a rare but known phenomenon. These patients have been described to have indolent disease and longer overall survival than patients with metastasis to other sites. We investigated the genomic landscape and outcomes for patients with RCC-PM. We used two cohorts for this study: (1) a Tempus cohort (TC) to investigate the genomic landscape and (2) a Stanford cohort (SC) where we include disease course and outcomes in addition to the genomic landscape. All patients included underwent testing with commercial next-generation sequencing (NGS) platform (Tempus AI, Inc, Chicago, IL.). For the TC, we compared the genomic landscape based on tissue samples that underwent molecular analysis (DNA and RNA sequencing and immune cell subtypes) from RCC tumors metastatic to the pancreas, liver, lung, or brain. For SC, patients from 2000 to 2024 with RCC-PM had a tumor tissue sample undergo NGS testing, and we report baseline characteristics, NGS, treatment history, and outcomes. Between the TC and SC, we identified 83 patients with RCC-PM. Compared with other sites of metastasis, RCC-PM had enrichment in <i>PBRM1</i> mutations, similar tumor mutational burden but lower rates of infiltrating B cells and PD-L1 positivity compared with other metastatic sites. In the SC, patients demonstrated long and indolent disease courses, but without clear genomic predictors of benefit to tyrosine kinase inhibitors or immunotherapies. Our study furthers RCC with pancreatic metastasis as a good clinical prognostic marker. We also identified enrichment of angiogenic signatures, such as <i>PBRM1</i> mutations and potential suppression of an immunogenic environment. However, despite these findings, no systemic treatment strategy had significantly better outcomes.