Sites of metastasis differ by histologic variant of renal cell carcinoma (RCC) and, importantly, relate to overall survival (OS), according to new research.

Using the International mRCC Database Consortium (IMDC) of patients with metastatic RCC starting systemic treatment (median age 60 years; 72.4% male), investigators identified 9252 patients (92%) with clear cell RCC (ccRCC), 667 (7%) with papillary RCC (pRCC), and 186 (2%) with chromophobe RCC (chrRCC). (Patients with mixed histology were excluded.) Patients had a median of 2 metastatic sites. The vast majority of patients in the overall cohort (84.5%) underwent nephrectomy.

Lung (70%), adrenal gland (10%), brain (8%), and pancreatic (5%) metastases were more frequent in ccRCC, whereas lymph node (69%) and peritoneum (5%) involvement was more common in pRCC and liver metastases (34%) were more frequent in chrRCC.

Patients with pRCC tended to have lower OS than patients with ccRCC, regardless of metastatic site, Daniel Heng, MD, MPH, of the University of Calgary in Alberta, Canada, and colleagues reported in JAMA Network Open. The investigators could not distinguish type 1 and 2 pRCC.


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For patients with ccRCC, median OS varied by metastasis site, ranging from less than 18 months for the pleura, liver, and brain to 50 months for the pancreas.

In addition, median OS was significantly worse in pRCC than ccRCC among patients with metastases in the lung (15.6 vs 25.1 months), lymph nodes (14.3 vs 21.4 months), and bone (11.0 vs 19.4 months). In contrast, OS was significantly better in chrRCC than ccRCC among patients with metastases to the lymph nodes (28.1 vs 21.4 months) and bone (26.7 vs 19.4 months), but OS was significantly worse with lung involvement (14.1 vs 25.1 months). Some sites of metastasis were not captured in the database, including soft tissue, parotid gland, and perinephric locoregional sites, which is a study limitation.

“These data highlight the clinical and biological variability between histologic subtypes of mRCC,” according to Dr Heng’s team. “Metastases to endocrine organs are infrequent but are associated with the longest median OS, whereas metastases to pleura, brain, liver, and bone are associated with poor OS.

“These benchmark values are useful for patient counseling and study design.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Dudani S, de Velasco G, ConnorWells J, et al. Evaluation of clear cell, papillary, and chromophobe renal cell carcinoma metastasis sites and association with survival. JAMA Netw Open. 2021;4(1):e2021869. doi:10.1001/jamanetworkopen.2020.21869