In a study reported in the Journal of Clinical Oncology, Susan Halabi, PhD, and colleagues validated an overall survival prognostic model for docetaxel-naive patients with metastatic castration-resistant prostate cancer.
As noted by the investigators, “We have previously developed and externally validated a prognostic model of overall survival in [patients] with metastatic castration-resistant prostate cancer treated with docetaxel. We sought to externally validate this model in a broader group of [patients] with docetaxel-naive metastatic castration-resistant prostate cancer.”
Susan Halabi, PhD
Study Details
The study used data from 8,083 docetaxel-naive patients from seven phase III trials. The prognostic model comprised: opioid analgesic use, Eastern Cooperative Oncology Group performance status, albumin, disease site (lymph node only, bone metastases with no visceral involvement, or any visceral metastases), lactate dehydrogenase greater than upper limit of normal, hemoglobin, prostate-specific antigen, and alkaline phosphatase. The predictive performance of the model was assessed by the time-dependent area under the receiver operating characteristic curve (tAUC), and tested in low-, intermediate-, and high-risk groups based on model scoring.
Key Findings
The overall model tAUC was 0.74 (95% confidence interval [CI] = 0.73–0.75). In analysis adjusting for first-line androgen receptor inhibitor trial status, the tAUC was 0.75 (95% CI = 0.74–0.76). Similar results were observed across racial, age, and treatment subgroups.
In patients enrolled in first-line androgen receptor inhibitor trials, 60.8%, 30.1%, and 9.1% were in the low-, intermediate-, and high-risk groups, respectively. Median overall survival was 43.3 months (95% CI = 40.7–45.8 months), 27.7 months (95% CI = 25.8–31.3 months), and 15.4 months (95% CI = 14.0–17.9 months) in the three groups, respectively. Compared with the low-risk group, hazard ratios were 4.3 (95% CI = 3.6–5.1, P < .0001) for the high-risk group and 1.9 (95% CI = 1.7–2.1, P < .0001) for the intermediate-risk group.
In patients in first-line non–androgen receptor inhibitor trials, 34.0%, 41.2%, and 24.8% were in the low-, intermediate-, and high-risk groups. Median overall survival was 32.5 months (95% CI = 30.8–34.2 months), 20.3 months (95% CI = 19.3–21.1 months), and 11.6 months (95% CI = 11.1–12.5 months) in the three groups, respectively. Compared with the low-risk group, hazard ratios were 4.7 (95% CI = 4.3–5.2, P < .0001) for the high-risk group and 2.2 (95% CI = 2.0–2.4, P < .0001) for the intermediate-risk group.
The investigators concluded, “This prognostic model for overall survival in docetaxel-naive [patients] with metastatic castration-resistant prostate cancer has been validated using data from seven trials and yields similar results overall and across race, age, and different treatment classes. The prognostic risk groups are robust and can be used to identify groups of patients for enrichment designs and for stratification in randomized clinical trials.”
Dr. Halabi, of Duke University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute, a U.S. Army Medical Research Award, and the Prostate Cancer Foundation. For full disclosures of the study authors, visit ascopubs.org.
