Circulating tumor cells predict progression free survival and overall survival in patients with relapsed/recurrent advanced ovarian cancer

Abstract

Objective: Serial circulating tumor cell (CTC) counts have demonstrated predictive and prognostic value in patients with metastatic breast, colorectal, and prostate cancer. In a phase III study of pegylated liposomal doxorubicin (PLD) with trabectedin vs. PLD for relapsed ovarian cancer, we evaluated the correlation, if any, between numbers of CTCs and progression free survival, (PFS) and overall survival (OS). Methods: CTCs were isolated from peripheral blood (10 mL) using the CellSearch system and reagents (Veridex). A CTC is defined as EpCAM+, cytokeratin+, CD45-, and is positive for the nuclear stain DAPI. The normal reference range for CellSearch is < 2 CTC/7.5 mL of blood. Hazard ratios adjusted for known prognostic factors were estimated by Cox regression. Results: Two-hundred sixteen patients had baseline CTC measurements of which 111 (51.4%) were randomized to the trabectedin + PLD arm; 143/216 patients (66.2%) were platinum-sensitive. Thirty-one of 216 patients (14.4%) had 2 or more CTCs detected prior to the start of therapy (range 2-566). Univariate Cox regression analyses indicated that patients with ≥ 2 CTCs prior to therapy had 1.89- (p = 0.003) and 2.06-fold (p = 0.003) higher risk for progression and death respectively. Multivariate analyses that include baseline CA-125, platinum sensitivity status, largest diameter lesion, number of tumor lesions, ECOG PS, and tumor grade show that patients with elevated baseline CTC had 1.58- (p = 0.058) and 1.54-fold (p = 0.096) higher risk for progression and death respectively. Conclusions: Results from this study indicate that elevated numbers of CTCs impart an unfavorable prognosis for ovarian cancer patients. © 2011 Elsevier Inc.