Are circulating tumor cells (CTCs) a feasible tool for predicting disease recurrence and survival in nonmetastatic (M0) colorectal cancer (CRC)?

Abstract

650 Background: Based on the correlation between CTCs and clinical outcome of metastatic breast, prostatic and CRC cancer, CTCs might be an ideal model to investigate the individual risk to develop metastasis. On the other way, data on their significance in M0 CRC are still limited. In a previous study we investigated CRC cell death in the circulating compartment, finding high value of apoptotic CTCs (M30-positive) independently from the disease stage. Our aim was to evaluate the prognostic role of total and M30-positive CTCs in M0 CRC patients (pts). Methods: From January 2009 to December 2011, we prospectively enrolled 192 stage 0-III CRC pts (stage 0 identified rectal cancer pts with Tis or complete pathological response after neoadjuvant therapy). We used CellSearch assay to quantify total and M30-positive CTCs in peripheral blood of CRC pts candidate to curative resection at diagnosis, time of surgery and four months later. Multivariate survival analyses were conducted using a Cox-regression. Results: At baseline 81 out of 192 pts (43.3%) had at least 1 CTC/7.5 mL of peripheral blood, 40 pts (22.2%) had >2 cells and 20 pts (11.6%) had >3 cells. We found a weak association between OS and total CTCs number (p=0.069), a significant association with M30-positive CTCs (p=0.022) and no association between RFS and CTC status. Limiting the analysis to stage I-III (n=151), we found a strong association between OS and both CTCs number (p=0.021) and M30-positive cells (p=0.007). The multivariate analyses demonstrated a significant improvement of survival prediction adding baseline CTCs count to clinical and pathological characteristics (HR=1.51, 95% CI 1.16-1.96). Conclusions: We first demonstrated a significant association between OS and CTCs status in stage I-III CRC pts. This result is consistent with previous report in metastatic CRC. It highlights a potential advantage of CTCs count in stratifying CRC pts and identifying a subset of pts with a high metastatic risk that could benefit from an adjuvant therapy. Further studies are needed to explore this aspect, which might be particularly significant in stage II CRC where the indication for adjuvant therapy is still under debate.