provides the distribution of risk factors for each study. Eighteen percent of S9346 patients, 38% of men from S8894 and 16% of men from S8494 were excluded from these analyses due to missing risk factors, primarily due to missing PSA and Gleason scores for the two more recent trials leaving 509 men from S8494, 791 men from S8894 and 1796 men from S9346. There was more extensive disease, higher prevalence of bone pain, higher PSA values, more African Americans and fewer obese men in the earlier study, S8894 compared to S9346 in the multivariate analysis.
Patient and Disease Factors for Eligible Patients with Complete Data from Each Trial
illustrates the survival curves stratified by clinical trial. The median survival in S8494 is 30 months, 33 months in S8894 and 49 months for S9346. The hazard ratio (HR) of 0.70 indicates a 30 percent reduced risk of death in the more recent S9346 compared to the older S8894 (95% CI 0.64, 0.77, p < 0.001). If all data from all eligible men from both trials are used regardless of completeness of risk factor information, the survival HR remains 0.70, suggesting that those with complete risk factor data are representative of both trials.
Kaplan-Meier survival curves stratified by clinical trial
provides the corresponding multivariate adjusted analysis of all-cause mortality. Factors associated with increased risk of death include extensive disease (versus minimal), presence of bone pain, older age, African American versus other race, BMI < 25, a performance status of 2 or 3, and a Gleason score of 8–10 (versus 2–6). PSA at study entry and a Gleason score of 7 (versus ≤6) were not significantly (p<0.05) associated with survival. After adjusting for these factors, S9346 has a lower risk of death compared to S8894 (HR=0.78; 95% CI 0.70, 0.87, p < 0.001). Adjustment for risk factors explained some of the difference in survival between the two trials, but not completely. There was still a 22 percent lower risk of death on S9346 compared to S8894.
Results of Multivariate Proportional Hazards Modeling of Survival Adjustment for All Risk Factors (n=2587) for S8894 and S9346**
The interaction of each risk factor with clinical trial was assessed. The interaction test evaluates whether the prognostic significance of a risk factor with survival is different for the two trials. Only the interaction with African American (AA) patient is statistically significant (p=0.008). AA patients have worse survival compared to non-AA patients in the S8894 trial after risk factor adjustment, but the disparity does not persist in S9346. provides the unadjusted survival curves stratified by clinical trial and African American status. Patterns of survival are similar for the two pre-PSA trials. Both racial groups show improvement over time when compared to S9346, but the AA group’s survival improvement is greater than non-AA (median increase of 21 months versus 14–15 months, respectively). For S9346 the AA and non-AA patients have survival curves that overlap, indicating that racial group is not a significant predictor of survival in patients with M1 prostate cancer in the post-PSA era trial. We chose to include the non-white, non-AA patients (n=2 S8494, n=14 S8894, n=68 S9346) in the non-AA category. When excluded from the analysis, the results remain unchanged.
Survival curves stratified by clinical trial and African American status
provides a comparison of patient and disease characteristics for AA patients in the three trials. There was a higher prevalence of extensive disease and bone pain in the earlier trials, and PSA values were also substantially higher in S8894 compared to S9346. Age was comparable, but there was more obesity in the more recent trial, S9346.
Distribution of Risk Factors among African Americans (AA) Stratified by Clinical Trial