A novel prognostic model predicting overall survival in patients with metastatic castration‐resistant prostate cancer receiving standard chemotherapy: A multi‐trial cohort analysis

Abstract

Purpose Generalizable, updated, and easy‐to‐use prognostic models for patients with metastatic castration‐resistant prostate cancer (mCRPC) are lacking. We developed a nomogram predicting the overall survival (OS) of mCRPC patients receiving standard chemotherapy using data from five randomized clinical trials (RCTs). Methods Patients enrolled in the control arm of five RCTs (ASCENT 2, VENICE, CELGENE/MAINSAIL, ENTHUSE 14, and ENTHUSE 33) were randomly split between training (n = 1636, 70%) and validation cohorts (n = 700, 30%). In the training cohort, Cox regression tested the prognostic significance of all available variables as a predictor of OS. Independent predictors of OS on multivariable analysis were used to construct a novel multivariable model (nomogram). The accuracy of this model was tested in the validation cohort using time‐dependent area under the curve (tAUC) and calibration curves. Results Most of the patients were aged 65–74 years (44.5%) and the median (interquartile range) follow‐up time was 13.9 (8.9–20.2) months. At multivariable analysis, the following were independent predictors of OS in mCRPC patients: sites of metastasis (visceral vs. bone metastasis, hazard ratio [HR]: 1.24), prostate‐specific antigen (HR: 1.00), aspartate transaminase (HR: 1.01), alkaline phosphatase (HR: 1.00), body mass index (HR: 0.97), and hemoglobin (≥13 g/dl vs. <11 g/dl, HR: 0.41; all p < 0.05). A nomogram based on these variables was developed and showed favorable discrimination (tAUC at 12 and 24 months: 73% and 72%, respectively) and calibration characteristics on external validation. Conclusion A new prognostic model to predict OS of patients with mCRPC undergoing first line chemotherapy was developed. This can help urologists/oncologists in counseling patients and might be useful to better stratify patients for future clinical trials.

Conditional survival does not improve over time in metastatic castration‐resistant prostate cancer patients undergoing docetaxel

“…Six‐month conditional overall survival (OS) assessed at 0, 6, 12, and 18 months of chemonaïve metastatic castration‐resistant prostate cancer patients undergoing docetaxel. Patients were stratified into a high‐ ( n = 299) and low‐risk ( n = 300) group, based on the median predicted 18‐month OS (64%; interquartile range: 52–71) estimated using the prognostic model developed by Halabi et al 17 [Color figure can be viewed at wileyonlinelibrary.com]…”

“…[14][15][16] To provide a riskbased prediction, we stratified our patients into a low-and highrisk groups, based on a previously described methodology. 17 Then, we calculated the 6-month conditional OS at 0, 6, 12, 18, and 24 months for the entire cohort, as well as for both risk (n = 599), as the other trials did not record these variables.…”

“…Then, we applied the multiplicative law of probability stratified to calculate the conditional OS of the overall population at 6 months 14–16 . To provide a risk‐based prediction, we stratified our patients into a low‐ and high‐risk groups, based on a previously described methodology 17 . Then, we calculated the 6‐month conditional OS at 0, 6, 12, 18, and 24 months for the entire cohort, as well as for both risk groups.…”

“…Several effective treatments are currently available, but the optimal therapeutic sequence to adopt is still a matter of study and debate. In this context, a reliable conditional survival estimate couldF I G U R E 417 [Color figure can be viewed at wileyonlinelibrary.com] help both oncologists and urologists' therapeutic decision-making, providing a rationale in selecting the most appropriate treatment sequence based on a more accurate life expectancy measure of the individual patient. Moreover, identifying the "true" high-risk patients can guide to a better adaptation of the patient-centered follow-up strategy.…”

The cost-effectiveness of germline BRCA testing-guided olaparib treatment in metastatic castration resistant prostate cancer

“…The cost-effectiveness analysis was performed from the Australian health system perspective. We used monthly cycles to estimate the costs and outcomes were expressed in quality-adjusted life-years (QALYs) gained over a 5-year time horizon, typical of the mCRPC population (43)(44)(45). The incremental cost effectiveness ratio (ICER) was calculated and in line with Australian guidelines (46), costs and outcomes were discounted at an annual discount rate of 5 percent.…”