Metastatic tropism of molecularly defined clear-cell renal cell carcinoma clusters.

BACKGROUNDThe relationship between molecular subgroups in clear-cell renal cell carcinoma (ccRCC) and metastatic tropism is poorly understood.METHODSWe analyzed over 5,000 metastatic sites from 305 treatment-naive ccRCC patients in the IMmotion150 phase II clinical trial, where patients were randomized to atezolizumab, atezolizumab/bevacizumab, or sunitinib.RESULTSAngiogenic tumors (clusters 1 and 2) had a higher rate of pancreatic (21% vs. 6.9%; P = 0.002) and lower absolute number of lymph node (2.5 vs. 4.2; P = 0.006) metastases. In contrast, proliferative tumors (clusters 4 and 5) exhibited a higher absolute number of lymph node metastases (5.5 vs. 3.5; P = 0.019). Patients with pancreatic metastases receiving sunitinib had higher odds of overall response (OR, 7.13; 95% CI, 1.81-28.07; P = 0.0049) and longer progression-free survival than those without pancreatic metastases (P = 0.02).CONCLUSIONccRCC metastatic tropism relates to molecular clusters that predict response to therapy for tumors that metastasize to the pancreas.TRIAL REGISTRATIONClinicalTrials.gov NCT01984242FUNDINGNIH grants R01CA154475 and P50CA196516.