Circulating Tumor Cell Count and Early Change in Count Are Prognostic for Survival in First-Line Docetaxel Treatment of Prostate Cancer
As reported in the Journal of Clinical Oncology, Goldkorn et al assessed the prognostic value of circulating tumor cell counts in patients with metastatic castration-resistant prostate cancer receiving standard first-line docetaxel plus prednisone with or without atrasentan in the SWOG S0421 trial. They found that baseline circulating tumor cell counts were prognostic for treatment response and survival and that rising circulating tumor cell count at 3 weeks was significantly associated with poorer survival. The findings could affect early treatment decisions.
Study Details
In SWOG S0421, patients with metastatic castration-resistant prostate cancer involving bone received docetaxel at 75 mg/m2 every 3 weeks with daily prednisone with or without the endothelin 1 receptor antagonist atrasentan. The primary endpoints were overall survival and progression-free survival.
Since there was no significant difference in outcomes with or without atrasentan, the results of the current circulating tumor count correlatives study are for the combined treatment arms. The study involved 238 patient specimens evaluable at day 0 and 232 specimens evaluable at day 21, prior to the second cycle of study treatment.
Prognostic Performance of Baseline Circulating Tumor Cell Count
Median circulating tumor cell count at day 0 was 5 cells/7.5 mL (range, 0–5,916/7.5 mL). At baseline, patients with circulating tumor cell count ≥ 5 vs < 5/7.5 mL had significantly worse bone pain, higher prostate-specific antigen (PSA), more liver disease, lower hemoglobin, and higher alkaline phosphatase (all P < .05). Baseline circulating tumor cell count ≥ 5/7.5 mL was associated with lower PSA response rate (44% vs 63%, P = .01) and lower objective response rate (14% vs 31%, P = .05).
Median overall survival was 13 vs 26 months. On regression analysis adjusting for other clinical variables (PSA, hemoglobin, alkaline phosphatase, liver disease, age, black race, performance status, PSA-only progression, worst pain, and minimal vs extensive disease), the lower circulating tumor cell count was associated with significantly greater risk of death (hazard ratio [HR] = 2.74, P < .001).
Receiver operating characteristic curves predicting 2-year overall survival had higher areas under the curve for baseline circulating tumor cell count (0.781) than for PSA (0.655) and integrated discrimination improvement analysis indicated that adding day 0 circulating tumor cell counts to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. A regression-tree analysis for baseline circulating tumor cell count as a continuous variable indicated that circulating tumor cell cut points of 0, 1 to 5, 6 to 53, and ≥ 54/7.5 mL were associated with median overall survival of 28, 23, 14, and 11 months, respectively.
Prognostic Value of Increased and Decreased Circulating Tumor Cell Counts
On regression analysis adjusting for other clinical variables, any increase in circulating tumor cell count as a continuous variable from day 0 to 21 was associated with significantly reduced overall survival (HR = 2.55, P = .041). Decreases in circulating tumor cell count as a continuous variable at day 21 were not associated with survival. However, among patients with circulating tumor cell count ≥ 5/7.5 mL at baseline, a decrease in count of > 50% at day 21 was associated with borderline significant improvement in overall survival (HR = 0.53, P = .071). In patients with a baseline count < 5/7.5 mL, an increase in count at day 21 was associated with significantly worse overall survival (HR = 6.47, P = .002).
The investigators concluded, “These data validate the prognostic utility of [circulating tumor cell] enumeration in a large docetaxel-based prospective cohort. Baseline [circulating tumor cell] counts were prognostic, and rising [circulating tumor cells] at 3 weeks heralded significantly worse [overall survival], potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.”
Amir Goldkorn, MD, of University of Southern California School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the National Cancer Institute, the Hope Foundation, and by Abbott Laboratories and sanofi-aventis. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
