Prognostic Model Predicts Metastatic Castration-Resistant Prostate Cancer Survival in Second-Line Chemotherapy After Docetaxel
In a study reported in the Journal of the National Cancer Institute, Susan Halabi, MD, of Duke University Medical Center, and colleagues developed and validated a prognostic model predicting prostate cancer survival in patients receiving second-line chemotherapy for castration-resistant metastatic disease. The final model consisted of nine variables and was significantly predictive of survival in testing and validation cohorts.
Study Details
The study involved data from one phase III trial in men with metastatic castration-resistant prostate cancer who had developed progressive disease after first-line chemotherapy including docetaxel (TROPIC trial) and another including 488 men previously treated with docetaxel (SPARC trial). The TROPIC trial population was randomly divided into training (n = 507) and testing (n = 248) cohorts, and 488 SPARC patients made up the validation cohort. The two trial populations differed with regard to age, presence of visceral metastases and measurable disease, and median overall survival.
Adaptive least absolute shrinkage and selection operator penalty methods were used to select prognostic factors for inclusion in prognostic models, with a prognostic score being computed from regression coefficients. Models were assessed for predictive accuracy using time-dependent area under the curve (tAUC).
Discriminating Ability of Model
Nine prognostic variables were selected for the final model, consisting of Eastern Cooperative Oncology Group performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of hormone therapy use, hemoglobin, prostate-specific antigen level, and alkaline phosphatase level. In the training cohort, the tAUC was 0.76 (95% confidence interval [CI] = 0.75–0.77).
This model was evaluated with the risk score used as a continuous variable in a Cox model in the testing and validation cohorts. The risk score was highly predictive of overall survival (P <.001) in both cohorts, with tAUCs of 0.73 (95% CI = 0.72–0.74) in the testing cohort and 0.70 (95% CI = 0.68–0.72) in the validation cohort.
Overall Survival With Risk Discrimination
Using a risk score cutpoint of –1.25 resulted in discrimination of 93 high-risk and 102 low-risk patients in the testing cohort with respective median overall survival of 10.8 months and 16.2 months (hazard ratio [HR] = 2.34, P < .001) in the testing cohort and 166 high-risk and 253 low-risk patients in with respective median overall survival of 10.5 months and 20.1 months (HR = 2.00, P < .001) in the validation cohort.
Use of cutpoints of < –1.55 and ≥ –1.01 resulted in discrimination of 65 high-risk, 76 intermediate-risk, and 54 low-risk patients with respective median overall survival of 8.3, 14.9, and 23.7 months (P < .001) in the testing cohort and 112 high-risk, 118 intermediate-risk, and 189 low-risk patients with respective median overall survival of 9.7, 15.9, and 21.7 months (P < .001) in the validation cohort.
The investigators concluded, “A prognostic model of [overall survival] in the post-docetaxel, second-line chemotherapy, [metastatic castration-resistant prostate cancer] setting was developed and externally validated. This model incorporates novel prognostic factors and can be used to provide predicted probabilities for individual patients and to select patients to participate in clinical trials on the basis of their prognosis. Prospective validation is needed.”
The study was supported in part by a National Institutes of Health grant.
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®.
