Investigators have identified molecular features that differentiate primary and metastatic sites in patients with renal cell carcinoma (RCC), according to a presentation at the ASCO Genitourinary Cancers Symposium 2022.
Previous studies have shown that the site of metastasis is prognostic for overall survival (OS) in patients with RCC, said Rana R. McKay, MD, of the University of California San Diego in La Jolla, when presenting this research at the meeting.
For example, one study showed that pancreas, bowel, adrenal, and lung metastases were associated with improved OS, whereas bone and brain metastases were associated with inferior OS.
“These data suggest that site of metastatic involvement may reflect divergent biologic underpinnings driving heterogeneous clinical behavior,” Dr McKay said.
With this in mind, Dr McKay and colleagues set out to characterize molecular features across metastatic sites using a commercial database of RCC tumors. The investigators used targeted gene and whole-exome sequencing to identify mutations and polymorphisms. They also performed whole-transcriptome sequencing and assessed PD-L1 expression.
A total of 657 samples from 654 patients were analyzed. The patients had a median age of 62 years, and 70.6% were men. The most common histology was clear cell RCC (77.3%), followed by papillary (9.6%), chromophobe (4.6%), medullary (1.2%), MIT translocation (1.2%), collecting duct (0.9%), and mixed (5.2%).
Roughly half (51.8%) of samples were derived from the kidney, and the rest were derived from metastatic sites. The most common sites were lung (10%), bone (7.6%), and soft tissue (6.1%).
Several genes, such as PBRM1 and KDM5C, were mutated at higher rates at selected metastatic sites compared with the kidney.
Mutation rates in the PBRM1 gene were 59.5% in the bone, 59.1% in endocrine glands, and 45.9% in the lung, compared with 33.8% in the kidney (P <.05).
For KDM5C, the mutation rates were 27.8% in the endocrine glands, 29.2% in the lymph nodes, and 35.3% in soft tissue, compared with 9.3% in the kidney (P <.05).
Compared with kidney specimens, bone metastases had a significantly higher proportion of tumors classified as “angio/stromal” (42.2% vs 15.4%; P <.0001), whereas liver metastases had a higher proportion of the “complement/Ώ-oxidation” subgroup (60.7% vs 14.1%; P <.0001).
The researchers also found that PD-L1 and PD-L2 expression were higher in lung, pleural, and bone metastases.
“These findings define molecular features that differentiate primary and distant metastatic sites of disease in patients with renal cell carcinoma,” Dr McKay concluded. “Understanding the molecular underpinning of organotropism will help inform personalized therapy strategies in patients with renal cell carcinoma.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
McKay RR, Barata PC, Elliott A, et al. Molecular alterations across sites of metastasis in patients with renal cell carcinoma (RCC). Presented at ASCO GU 2022; February 17-19, 2022. Abstract 287.
This article originally appeared on Cancer Therapy Advisor