Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data

Abstract

SUMMARY Background To assess the use of circulating tumor cell (CTC) number as a continuous variable as a prognostic factor for survival, and for the clinical management of patients with progressive metastatic castration-resistant prostate cancer receiving first-line chemotherapy. Methods The study included 164 men with progressive metastatic castration-resistant prostate cancer. CTCs were isolated by immunomagnetic capture from blood samples drawn at baseline and after the initiation of first-line chemotherapy. Baseline variables including CTC number, prostate-specific antigen (PSA), and lactate dehydrogenase (LDH), and posttreatment variables (fold change in CTCs and PSA) were tested for association with survival using the Cox proportional hazards models. The concordance probability estimate was used to gauge the discriminatory strength of the informative factors in separating low- and high-risk patients. Findings At baseline, variables associated with increased risk of death were a high LDH (hazard ratio [HR] 6.44), CTC number (HR 1.58), and PSA (HR 1.26), low albumin (HR 0.10), and low hemoglobin (HR 0.72) (all p<0.001). At 4, 8, and 12 weeks posttreatment, changes in CTC number were strongly associated with risk (all p≤0.001), while changes in PSA were modestly associated (p=0.04 to 0.8). The combination of factors most predictive of survival were LDH and CTC number (concordance probability estimate 0.72–0.75). Time to CTC progression was modestly associated with time to death. Interpretation CTC number, analyzed as a continuous variable, was more predictive of survival than PSA at baseline and during patient follow-up, and can be used to monitor disease status. A model including baseline and posttreatment CTC, independent of discrete cutoff values, and baseline LDH was most predictive. The prospective evaluation of CTC number as an intermediate endpoint of survival in randomized prospective clinical trials is warranted. Funding The Prostate Cancer Foundation.