Prognostic role of circulating tumor cells-CTCs in metastatic renal cell carcinoma.

Abstract

4568 Background: CTCs can be isolated in peripheral blood of cancer pts and have demonstrated to have prognostic role in several metastatic tumors such as breast, colorectal and prostate cancer. Few data are available for Renal Cell Carcinoma-RCC. Methods: We designed a multicenter prospective observational trial aiming to assess the association between CTC counts and PFS of RCC pts treated with an antiangiogenic tyrosine-kinase inhibitors as a first-line regimen for metastatic disease. OS and response rate were secondary objectives. Both basal and sequential counts were enumerated by Cellsearch system at 4 time points: day 0 of treatment, +1 mo, +3 mo, at progression or 12 mo in the absence of progression. Ethics Committee approval was obtained. Results: Among 246 pts, 195 are eligible for the present analysis, 71.4% males, median age 69 yrs (range, 27 to 91), 81% with previous partial/total nephrectomy. Treatment was sunitinib (77.5%), pazopanib (21%) or sorafenib (1.5%). According to Heng criteria there were 24.6% good, 62.6% intermediate and 24.6% poor prognosis pts. After a median follow-up of 31.5 mo, median PFS is 13.6 mo (23% censored), 49.2% of pts are still alive. Investigator-assessed best response was 3.8% complete, 37.3% partial response, 33% stable, 25.9% progression. At baseline 91 pts had 1 or more CTCs, median 2, range 1 to 263. Pts with at least 1 CTC had a significantly shorter PFS compared to negative pts (8.8 vs 16.6 mo, p = 0.03), HR = 1.41 (95%CI 1.02-1.9). Thirty pts had > = 3 CTCs, with a median PFS of 5.8 vs 15 mo in the remaining pts (p = 0.002), HR = 1.99 (CI 1.28-3.03). Percentage of pts with > = 3 CTCs increased from 6.6% of good, 18.4% intermediate and 38.9% poor Heng score pts (p = 0.042). Pts with > = 3 CTCs had a shorter estimated OS of 13.8 mo vs 52.8 mo (p = 0.003), HR = 1.99 (CI 1,17-3.2). Correlation between CTC positivity and response rate was not significant. Conclusions: In this robust multicenter prospective cohort of first-line metastatic RCC pts, the presence of 3 or more CTCs predicts a significantly shorter PFS and OS. Further analyses are ongoing on apoptotic markers of CTCs and concomitant counts of endothelial cells collected in the same cohort.