Renal Cell Carcinoma Research Sheds New Light on Advanced Disease

In a recent study, UCSF researchers found that renal cell carcinoma (RCC) with venous tumor thrombus (VTT) does not always signify metastatic disease with poor prognosis. These findings provide insight into the development of advanced RCC and may help to better inform surveillance regimens and treatment decisions and, ultimately, improve clinical outcomes.

“This study shows that if patients have VTT, it does not mean they have or will have metastases,” said Maxwell Meng, MD, urologic cancer surgeon and chief of urologic oncology at UCSF. “That’s why we treat these patients very aggressively surgically at UCSF.”

Research driven by clinical observations

RCC with VTT arising from the primary tumor occurs in approximately 10% of cases and has been thought to represent advanced disease due to the intravascular nature of VTT. However, little is known regarding the origin of these tumors with VTT and how they may differ from RCC with distant spread.

“This study grew out of our clinical observations,” Meng said. “Patients with VTT are a unique subset of those with kidney cancer. After having cared for a lot of these patients, we wanted to investigate how and why these tumors arise. We found that VTT is biologically different from metastatic kidney cancer.”

The study included 16 patients with RCC with VTT. Meng and the research team performed whole-exome and RNA sequencing on multiple tumor regions, including at least one VTT region from each patient and one metastatic region from eight patients.

While the researchers found no specific genomic alterations associated with VTT, copy-number alterations were linked with metastasis and disease recurrence, and secondary driver alterations accumulated in metastatic lineages. Mismatch repair mutational signatures occurred in most tumors, suggesting a role for intracellular DNA damage in RCC.

Study finds VTT and metastasis occur independently

After analyzing the phylogenetic timing, the researchers found that in most patients, metastasis emerged before VTT, with the earliest metastases predicted to begin years before diagnosis.

These results suggest that the development of VTT and metastasis occur independently, with different molecular pathways, and that VTT presence alone does not necessarily imply distant disease with inevitably poor prognosis. Estimating the timing of metastasis in RCC and understanding the biological pathways that contribute to metastasis help to inform treatment decisions and improve patient outcomes.

Team approach to research and treatment

“Surgical treatment for patients with VTT is quite complex,” Meng said. “At UCSF, we have a lot of experience with these surgeries. We work together with vascular, transplant and cardiac surgeons as well as with the anesthesiologists. It’s a team effort. Our approach to care for patients with RCC is multidisciplinary and includes medical and radiation oncology, diagnostic and interventional radiology, pathology and cancer genetics.

“Our research is also very collaborative and high yield,” he continued. “From our clinical observations, we’re working to understand the biology of RCC with VTT and answer unique clinical questions with basic science. We are fortunate to have amazing colleagues here at UCSF as well as at Genentech.”

Cancer research and treatment take place within the UCSF Helen Diller Family Comprehensive Cancer Center.

 

To learn more

UCSF Urologic Surgical Oncology Clinic

Phone: (415) 353-7171 | Fax: (415) 353-7093

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