Prognostic value of circulating tumor cell enumeration for castration refractory prostate cancer

Abstract

Objective To investigating the prognostic value of the CellSearch CTC enumeration system for the castration resistant prostate cancer (CRPC) patients. Methods From January 2013 to June 2014, 92 CRPC patients' peripheral blood were collected and tested by CellSearch CTC detection system. The median age was 69 (range 53-85) years old and the median PSA was 19.1(range 2.6-273.0) ng/ml. The median serum hemoglobin was 124(69-156)g/L, the serum alkaline phosphatase was 87.0(29.0-2778.5)U/L, the serum lactate dehydrogenase was 207(114-2467)U/ L and the serum albumin was 44.0(32.3-52.2)g/L respectively. Among all the patients, 39.1%(36/92) was Gleason score below 8, 32.6% (30/92)was 8 and 28.3%(26/92) was over 8. 93.5% (86/92) of the patients were diagnosed as bone metastasis and 31.5%(29/92)as lymph node metastasis. Another 5 healthy volunteers with no evidence of tumor history were also tested as the control group. During the follow up, 42 patients were treated with docetaxel plus prednisone as their first-line therapeutic regimen, and the remaining 50 patients who were intolerant to or refused chemotherapy were treated with ketoconazole, estrogen or traditional Chinese medicine. For the survival analysis, Kaplan-Meier plots were generated based on CTC enumeration at baseline and Log-rank test was conducted for calculating the survival difference between the groups. The independent prognostic factors were analyzed by the univariate and multivariate Cox analysis. Results At the time of follow-up, 41 patients had died of prostate cancer with the median follow up of 16.2 months (range: 7.0-26.0 months). All the five patients were detected with no CTC. Ninety-two patients were divided into two groups based on CTC enumeration. Fifty-six patients were defined as favorable CTC counts group (CTC<5) with median follow up of 25 months and 36 as unfavorable CTC counts group(CTC≥5) with median follow up of 18 months. Unfavorable CTC enumerations were predictive of shorter overall survival (Log-rank P=0.00). In the univariate analysis, lactate dehydrogenase(P=0.02), hemoglobin(P=0.00), alkaline phosphatase(P=0.00), serum albumin(P=0.01), ECOG performance status(P=0.00) and CTC enumeration(P=0.00) were associated with prognosis of CRPC patients. A multivariate analysis indicated that only baseline serum alumin (P=0.01), ECOG performance status(P=0.01) and CTC enumeration(P=0.00) were independent prognostic factors for overall survival. Subgroup analysis still support the notion that CTC≥5 are indicative of poor prognosis regardless of receiving docetaxel plus prednisone as their first-line therapeutic regimen or not(P<0.05). Conclusions In the current study, we validated that CTC enumeration could provide a useful prognostic determinant for CRPC patients. Key words: Castration resistant prostate cancer; Circulating tumor cell; Prognosis