Radical Prostatectomy vs. Radiotherapy in Prostate Cancer
Table 2 shows the baseline clinical and tumour characteristics of the participants, stratified by treatment. Generally, the radiotherapy group had a greater proportion of high clinical stage and grade disease, with higher levels of prostate specific antigen than the radical prostatectomy group. This was also the case within each individual risk group. Patients who received radiotherapy were on average also older and had higher scores on the Charlson comorbidity index. Patients in the radical prostatectomy group on average received their diagnosis at a later date than patients in the radiotherapy group. Furthermore, the choice of treatment differed significantly by county of residence (data not shown), and the radiotherapy group had a greater proportion of patients of low educational level, low socioeconomic status, and unmarried status. In each non-metastatic risk group the demographic and clinical characteristics of the patients showed the same differences when stratified by treatment modality, albeit attenuated for the tumour covariates (as a result of the risk categorisation). In the metastatic risk group, some adverse prognostic criteria such as a higher Charlson comorbidity score, N+ stage, and M+ stage, were more common in the radical prostatectomy group, whereas others were more common in the radiotherapy cohort. By the end of the study, 339 prostate cancer related deaths and 1064 deaths from other causes occurred in the radical prostatectomy arm and 697 and 1127, respectively in the radiotherapy arm ( Table 3 ).
The mortality estimates in the radical prostatectomy group were lower for non-metastatic disease (risk groups 1-3) than in the radiotherapy group (Fig 1). This was the case for mortality from both prostate cancer and other causes, although as clinical risk increased prostate cancer related mortality became a larger proportion of the overall mortality. In metastatic cases (risk group 4), roughly half of all the men had died by 15 years, and over half of those deaths were due to prostate cancer, regardless of treatment type.
(Enlarge Image)
Figure 1.
Cumulative incidence function estimates of cancer specific and other cause mortality survival curves (n=34 515), stratified according to treatment type
Among men with non-metastatic prostate cancer, treatment with radiotherapy was associated with a significantly higher crude prostate cancer mortality than surgery (subdistribution hazard ratio 3.09, 95% confidence interval 2.69 to 3.56; Table 3 ). Both propensity score and traditional adjustment reduced the subdistribution hazard ratios consistently, but results remained in favour of surgery (1.76, 1.49 to 2.08 and 1.77, 1.49 to 2.09, respectively); the subdistribution hazard ratios for radiotherapy versus surgery did not differ significantly between risk groups (P for homogeneity, 0.17). Differences in survival outcomes were non-discernible between treatment modalities for patients with metastatic disease (crude subdistribution hazard ratio 1.04, 95% confidence interval 0.74 to 1.48; Table 3 ); lack of difference persisted even after the main statistical adjustments. Figure 2 is a forest plot examining whether surgery or radiotherapy leads to improved survival with prostate cancer, based on risk group, age, and Charlson comorbidity index, and after adjustment for propensity score. Among men without metastatic disease, the subdistribution hazard ratios consistently favoured radical prostatectomy over radiotherapy, with point estimates for surgery trending to be better in younger men (<65 years) and fitter (Charlson score 0) men with intermediate (risk group 2) and high risk (risk group 3) prostate cancer; no discernible differences can be seen between treatment modalities for patients with metastatic disease. Similar results to those in Figure 2 were obtained after traditional (multivariable) adjustment (data not shown). Propensity score matching also confirmed our main findings of cancer outcomes favouring surgery over radiotherapy for patients without metastatic prostate cancer with no significant differences for the metastatic group, albeit with attenuated point estimates ( Table 4 ).
(Enlarge Image)
Figure 2.
Forest plot depicting propensity score adjusted subdistribution hazard ratios (sHR) for radiotherapy versus radical prostatectomy for cancer specific mortality stratified by risk group, and substratified by age and Charlson comorbidity index score
Men without metastatic prostate cancer had lower survival from other causes of death after radiotherapy (crude subdistribution hazard ratio 1.77, 95% confidence interval 1.62 to 1.93, Table 3 ). After propensity score and traditional adjustments the results moved in the direction of the null but remained worse after radiotherapy (subdistribution hazard ratio 1.32, 95% confidence interval 1.18 to 1.42 and 1.28, 1.16 to 1.42, respectively). In men with metastatic prostate cancer, no differences were seen in other cause mortality between treatments with and without the main statistical adjustments. Again, these results were confirmed in the propensity score matched analyses ( Table 4 ).
Sensitivity analysis on the non-metastatic groups showed that the required subdistribution hazard ratio effect of an unmeasured confounder would have to be large (and in some cases, infinite), given varying the differential expression of the unmeasured confounder between the surgery and radiotherapy groups (always assuming higher confounder levels in the radiotherapy group), to produce the observed subdistribution hazard ratios for radiotherapy versus radical prostatectomy ( Table 5 ). Analyses stratified by year of diagnosis showed no discernible temporal trend in point estimates for treatment comparisons for any risk groups (see Appendix 1 ). Furthermore, inverse probability of treatment weight adjustments showed that cancer outcomes favoured surgery over radiotherapy for patients without metastatic prostate cancer, with no significant differences for the metastatic group, but as with the propensity score matched sample, the point estimates were attenuated (see Appendix 2 ).
Results
Table 2 shows the baseline clinical and tumour characteristics of the participants, stratified by treatment. Generally, the radiotherapy group had a greater proportion of high clinical stage and grade disease, with higher levels of prostate specific antigen than the radical prostatectomy group. This was also the case within each individual risk group. Patients who received radiotherapy were on average also older and had higher scores on the Charlson comorbidity index. Patients in the radical prostatectomy group on average received their diagnosis at a later date than patients in the radiotherapy group. Furthermore, the choice of treatment differed significantly by county of residence (data not shown), and the radiotherapy group had a greater proportion of patients of low educational level, low socioeconomic status, and unmarried status. In each non-metastatic risk group the demographic and clinical characteristics of the patients showed the same differences when stratified by treatment modality, albeit attenuated for the tumour covariates (as a result of the risk categorisation). In the metastatic risk group, some adverse prognostic criteria such as a higher Charlson comorbidity score, N+ stage, and M+ stage, were more common in the radical prostatectomy group, whereas others were more common in the radiotherapy cohort. By the end of the study, 339 prostate cancer related deaths and 1064 deaths from other causes occurred in the radical prostatectomy arm and 697 and 1127, respectively in the radiotherapy arm ( Table 3 ).
The mortality estimates in the radical prostatectomy group were lower for non-metastatic disease (risk groups 1-3) than in the radiotherapy group (Fig 1). This was the case for mortality from both prostate cancer and other causes, although as clinical risk increased prostate cancer related mortality became a larger proportion of the overall mortality. In metastatic cases (risk group 4), roughly half of all the men had died by 15 years, and over half of those deaths were due to prostate cancer, regardless of treatment type.
(Enlarge Image)
Figure 1.
Cumulative incidence function estimates of cancer specific and other cause mortality survival curves (n=34 515), stratified according to treatment type
Among men with non-metastatic prostate cancer, treatment with radiotherapy was associated with a significantly higher crude prostate cancer mortality than surgery (subdistribution hazard ratio 3.09, 95% confidence interval 2.69 to 3.56; Table 3 ). Both propensity score and traditional adjustment reduced the subdistribution hazard ratios consistently, but results remained in favour of surgery (1.76, 1.49 to 2.08 and 1.77, 1.49 to 2.09, respectively); the subdistribution hazard ratios for radiotherapy versus surgery did not differ significantly between risk groups (P for homogeneity, 0.17). Differences in survival outcomes were non-discernible between treatment modalities for patients with metastatic disease (crude subdistribution hazard ratio 1.04, 95% confidence interval 0.74 to 1.48; Table 3 ); lack of difference persisted even after the main statistical adjustments. Figure 2 is a forest plot examining whether surgery or radiotherapy leads to improved survival with prostate cancer, based on risk group, age, and Charlson comorbidity index, and after adjustment for propensity score. Among men without metastatic disease, the subdistribution hazard ratios consistently favoured radical prostatectomy over radiotherapy, with point estimates for surgery trending to be better in younger men (<65 years) and fitter (Charlson score 0) men with intermediate (risk group 2) and high risk (risk group 3) prostate cancer; no discernible differences can be seen between treatment modalities for patients with metastatic disease. Similar results to those in Figure 2 were obtained after traditional (multivariable) adjustment (data not shown). Propensity score matching also confirmed our main findings of cancer outcomes favouring surgery over radiotherapy for patients without metastatic prostate cancer with no significant differences for the metastatic group, albeit with attenuated point estimates ( Table 4 ).
(Enlarge Image)
Figure 2.
Forest plot depicting propensity score adjusted subdistribution hazard ratios (sHR) for radiotherapy versus radical prostatectomy for cancer specific mortality stratified by risk group, and substratified by age and Charlson comorbidity index score
Men without metastatic prostate cancer had lower survival from other causes of death after radiotherapy (crude subdistribution hazard ratio 1.77, 95% confidence interval 1.62 to 1.93, Table 3 ). After propensity score and traditional adjustments the results moved in the direction of the null but remained worse after radiotherapy (subdistribution hazard ratio 1.32, 95% confidence interval 1.18 to 1.42 and 1.28, 1.16 to 1.42, respectively). In men with metastatic prostate cancer, no differences were seen in other cause mortality between treatments with and without the main statistical adjustments. Again, these results were confirmed in the propensity score matched analyses ( Table 4 ).
Sensitivity analysis on the non-metastatic groups showed that the required subdistribution hazard ratio effect of an unmeasured confounder would have to be large (and in some cases, infinite), given varying the differential expression of the unmeasured confounder between the surgery and radiotherapy groups (always assuming higher confounder levels in the radiotherapy group), to produce the observed subdistribution hazard ratios for radiotherapy versus radical prostatectomy ( Table 5 ). Analyses stratified by year of diagnosis showed no discernible temporal trend in point estimates for treatment comparisons for any risk groups (see Appendix 1 ). Furthermore, inverse probability of treatment weight adjustments showed that cancer outcomes favoured surgery over radiotherapy for patients without metastatic prostate cancer, with no significant differences for the metastatic group, but as with the propensity score matched sample, the point estimates were attenuated (see Appendix 2 ).
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