Kidney Cancer Destination Could Guide Treatment Decisions Moving Forward

Renal cell carcinoma (RCC) that metastasizes in the pancreas is characterized by a different biology than kidney cancers that metastasize elsewhere, heightened angiogenesis, and an uninflamed stroma, according to a study published in JCI Insight.^1-2

These characteristics are likely credited for RCC’s good prognosis, sensitivity to antiangiogenic therapies, and refractoriness to immune checkpoint inhibitors. Along with this, RCC also possesses characteristics that can influence successful treatment.

“Gene expression analyses revealed limited evolution and an angiogenic signature, which together with histopathological studies, provide a potential explanation for the differential treatment responsiveness,” wrote the researchers.¹“Overall, these findings suggest that tumors that metastasize to the pancreas represent a distinct clade of (clear cell renal cell carcinoma), even if concomitant metastases are found elsewhere.”

More, patients with pancreatic metastases had significantly better overall survival than those whose tumors metastasized in other areas. The median survival rate for patients with pancreatic metastases was 8.4 years compared to 2.9 years for patients with metastases in other areas. While immune checkpoint inhibitors did not work for patients with pancreatic metastases, these patients had great success with angiogenesis inhibitors.

The researchers collected samples and performed tests with a group of 31 patients with pancreatic metastases to better understand why cancers that spread to the pancreas have better prognoses for patients than tumors that do not spread to the pancreas. The researchers compared their data to a cohort of patients without pancreatic metastasis, evaluating “each patient’s survival, individual risk factors that might have influenced survival, and the treatments these patients received.”

When compared to tumors that had metastasized elsewhere, tumors that had spread to the pancreas expressed signs of low aggressiveness and the activation of genes related to the vasculature. While the location of the tumor metastases does not typically guide cancer treatment, the researchers explain that this could change for patients with pancreatic metastases in the future. 

“Our data show that tumors that metastasize to the pancreas are associated with improved outcomes irrespective of the current (international metastatic database consortium) model, and that this model has limited application in this setting,” wrote the researchers. “Further, we show that tumors with pancreatic metastases are associated with differential response to systemic therapy, and while they respond favorably to antiangiogenic drugs, they are resistant to nivolumab.”

Clear cell renal cell carcinoma is the most common type of kidney cancer and can metastasize in a number of unique areas. The study data is the most comprehensive examination of RCC to date, according to the researchers. 

The researchers hope this data can help further the understanding as to why patients with pancreatic metastases have better prognoses than patients with other cancer types. Even more, the researchers tried to characterize the clinical behavior, therapeutic implications, and underlying biology of pancreatic metastases.

“The idea that the cancer destination can tell you something about the biology of the cancer and how it should be treated is provocative,” lead study author James Brugarolas, MD, PhD, said in a press release.²

References:

1. Singla N, Xie Z, Zhang Z, et al. Pancreatic tropism of metastatic renal cell carcinoma. JCI Insight. https://doi.org/10.1172/jci. insight.134564.

2. Where cancers go could guide their treatment [news release]. Dallas, Texas. Published April 10, 2020. https://www.newswise.com/articles/where-cancers-go-could-guide-their-treatment?sc=dwhr&xy=10019792. Accessed April 21, 2020.