TY - JOUR
T1 - Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer
T2 - a reanalysis of IMMC38 trial data
AU - Scher, Howard I.
AU - Jia, Xiaoyu
AU - de Bono, Johann S.
AU - Fleisher, Martin
AU - Pienta, Kenneth J.
AU - Raghavan, Derek
AU - Heller, Glenn
N1 - Funding Information:
Study data were provided by the study sponsor (Immunicon Corporation) for the independent analysis reported herein. Funding for the independent analysis was provided by the Prostate Cancer Foundation (Santa Monica, CA, USA). The sponsor had no role in the analysis, interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
PY - 2009/3
Y1 - 2009/3
N2 - Background: Intermediate or surrogate endpoints for survival can shorten time lines for drug approval. We aimed to assess circulating tumour cell (CTC) count as a prognostic factor for survival in patients with progressive, metastatic, castration-resistant prostate cancer receiving first-line chemotherapy. Methods: We identified patients with progressive metastatic castration-resistant prostate cancer starting first-line chemotherapy in the IMMC38 trial. CTCs were isolated by immunomagnetic capture from blood samples at baseline and after treatment. Baseline variables, including CTC count, titre of prostate-specific antigen (PSA), and concentration of lactate dehydrogenase (LDH), and post-treatment variables (change in CTCs and PSA) were tested for association with survival with Cox proportional hazards models. Concordance probability estimates were used to gauge discriminatory strength of the informative factors in identifying patients at low-risk and high-risk of survival. Findings: Variables associated with high risk of death were high LDH concentration (hazard ratio 6·44, 95% CI 4·24-9·79), high CTC count (1·58, 1·41-1·77), and high PSA titre (1·26, 1·10-1·45), low albumin (0·10, 0·03-0·39), and low haemoglobin (0·72, 0·64-0·81) at baseline. At 4 weeks, 8 weeks, and 12 weeks after treatment, changes in CTC number were strongly associated with risk, whereas changes in PSA titre were weakly or not associated (p>0·04). The most predictive factors for survival were LDH concentration and CTC counts (concordance probability estimate 0·72-0·75). Interpretation: CTC number, analysed as a continuous variable, can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials. Prospective recording of CTC number as an intermediate endpoint of survival in randomised clinical trials is warranted. Funding: The Prostate Cancer Foundation, Immunicon Corporation, Memorial Sloan-Kettering Cancer Center.
AB - Background: Intermediate or surrogate endpoints for survival can shorten time lines for drug approval. We aimed to assess circulating tumour cell (CTC) count as a prognostic factor for survival in patients with progressive, metastatic, castration-resistant prostate cancer receiving first-line chemotherapy. Methods: We identified patients with progressive metastatic castration-resistant prostate cancer starting first-line chemotherapy in the IMMC38 trial. CTCs were isolated by immunomagnetic capture from blood samples at baseline and after treatment. Baseline variables, including CTC count, titre of prostate-specific antigen (PSA), and concentration of lactate dehydrogenase (LDH), and post-treatment variables (change in CTCs and PSA) were tested for association with survival with Cox proportional hazards models. Concordance probability estimates were used to gauge discriminatory strength of the informative factors in identifying patients at low-risk and high-risk of survival. Findings: Variables associated with high risk of death were high LDH concentration (hazard ratio 6·44, 95% CI 4·24-9·79), high CTC count (1·58, 1·41-1·77), and high PSA titre (1·26, 1·10-1·45), low albumin (0·10, 0·03-0·39), and low haemoglobin (0·72, 0·64-0·81) at baseline. At 4 weeks, 8 weeks, and 12 weeks after treatment, changes in CTC number were strongly associated with risk, whereas changes in PSA titre were weakly or not associated (p>0·04). The most predictive factors for survival were LDH concentration and CTC counts (concordance probability estimate 0·72-0·75). Interpretation: CTC number, analysed as a continuous variable, can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials. Prospective recording of CTC number as an intermediate endpoint of survival in randomised clinical trials is warranted. Funding: The Prostate Cancer Foundation, Immunicon Corporation, Memorial Sloan-Kettering Cancer Center.
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UR - http://www.scopus.com/inward/citedby.url?scp=62849099048&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(08)70340-1
DO - 10.1016/S1470-2045(08)70340-1
M3 - Article
C2 - 19213602
AN - SCOPUS:62849099048
SN - 1470-2045
VL - 10
SP - 233
EP - 239
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 3
ER -