Radical Prostatectomy vs. Radiotherapy in Prostate Cancer
Radical Prostatectomy vs. Radiotherapy in Prostate Cancer
Objective To compare the survival outcomes of patients treated with surgery or radiotherapy for prostate cancer.
Design Observational study.
Setting Sweden, 1996-2010.
Participants 34 515 men primarily treated for prostate cancer with surgery (n=21 533) or radiotherapy (n=12 982). Patients were categorised by risk group (low, intermediate, high, and metastatic), age, and Charlson comorbidity score.
Main outcome measures Cumulative incidence of mortality from prostate cancer and other causes. Competing risks regression hazard ratios for radiotherapy versus surgery were computed without adjustment and after propensity score and traditional (multivariable) adjustments, as well as after propensity score matching. Several sensitivity analyses were performed.
Results Prostate cancer mortality became a larger proportion of overall mortality as risk group increased for both the surgery and the radiotherapy cohorts. Among patients with non-metastatic prostate cancer the adjusted subdistribution hazard ratio for prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to 2.08, for radiotherapy v prostatectomy), whereas there was no discernible difference in treatment effect among men with metastatic disease. Subgroup analyses indicated more clear benefits of surgery among younger and fitter men with intermediate and high risk disease. Sensitivity analyses confirmed the main findings.
Conclusions This large observational study with follow-up to 15 years suggests that for most men with non-metastatic prostate cancer, surgery leads to better survival than does radiotherapy. Younger men and those with less comorbidity who have intermediate or high risk localised prostate cancer might have a greater benefit from surgery.
Prostate cancer is the commonest non-dermatological cancer and the second leading cause of cancer related death in men in the Western world. In more than 90% of cases the cancer is localised, and radical prostatectomy, radiotherapy, and active surveillance represent the main treatment options. The landmark Scandinavian Prostate Cancer Group (SPCG)-4 trial has shown a definite survival advantage for surgery over watchful waiting, at a median follow-up of 12.8 years, although the more recent randomised controlled trial, the Prostate Intervention Versus Observation Trial (PIVOT), has indicated that the benefit from surgery might be confined to intermediate and high risk tumours. Only one recent randomised controlled trial examined the comparative effectiveness of different treatment modalities, the ProtecT study, the results of which will not be available for at least the next two years. Furthermore, the results of randomised controlled trials may have limited generalisability because of differences between the enrolled population and community populations, who are likely to be more heterogeneous for comorbidities and socioeconomic characteristics. Hence the importance of using observational data from actual medical practice in comparative effectiveness studies to complement the evidence from randomised controlled trials. In the specialty of prostate cancer, however, most such studies have evaluated biochemical recurrence as the endpoint, and have shown conflicting results. The definition of biochemical recurrence varies between surgical and radiotherapy cohorts, and even between individual radiotherapy series, and thus comparing biochemical recurrence across treatment modalities is problematic. Furthermore, the median time to death after biochemical recurrence has been shown to be as long as 13 years in a surgical series, and not all men who experience recurrence will develop clinical disease. Hence, death remains the most valid endpoint for comparative studies in prostate cancer.
In this nationwide population based cohort study we assessed prostate cancer related mortality in patients in the Swedish national prostate cancer registry, who underwent radical prostatectomy or radiotherapy as their primary treatment. Linkage with other healthcare and demographic databases enabled reduction of potential confounding through statistical techniques as well as adjustment for competing risks of mortality, as many men with prostate cancer are known to die of other causes. We hypothesised that survival differences would vary by treatment, and that age and the burden from comorbidities would have an impact on survival.
Abstract and Introduction
Abstract
Objective To compare the survival outcomes of patients treated with surgery or radiotherapy for prostate cancer.
Design Observational study.
Setting Sweden, 1996-2010.
Participants 34 515 men primarily treated for prostate cancer with surgery (n=21 533) or radiotherapy (n=12 982). Patients were categorised by risk group (low, intermediate, high, and metastatic), age, and Charlson comorbidity score.
Main outcome measures Cumulative incidence of mortality from prostate cancer and other causes. Competing risks regression hazard ratios for radiotherapy versus surgery were computed without adjustment and after propensity score and traditional (multivariable) adjustments, as well as after propensity score matching. Several sensitivity analyses were performed.
Results Prostate cancer mortality became a larger proportion of overall mortality as risk group increased for both the surgery and the radiotherapy cohorts. Among patients with non-metastatic prostate cancer the adjusted subdistribution hazard ratio for prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to 2.08, for radiotherapy v prostatectomy), whereas there was no discernible difference in treatment effect among men with metastatic disease. Subgroup analyses indicated more clear benefits of surgery among younger and fitter men with intermediate and high risk disease. Sensitivity analyses confirmed the main findings.
Conclusions This large observational study with follow-up to 15 years suggests that for most men with non-metastatic prostate cancer, surgery leads to better survival than does radiotherapy. Younger men and those with less comorbidity who have intermediate or high risk localised prostate cancer might have a greater benefit from surgery.
Introduction
Prostate cancer is the commonest non-dermatological cancer and the second leading cause of cancer related death in men in the Western world. In more than 90% of cases the cancer is localised, and radical prostatectomy, radiotherapy, and active surveillance represent the main treatment options. The landmark Scandinavian Prostate Cancer Group (SPCG)-4 trial has shown a definite survival advantage for surgery over watchful waiting, at a median follow-up of 12.8 years, although the more recent randomised controlled trial, the Prostate Intervention Versus Observation Trial (PIVOT), has indicated that the benefit from surgery might be confined to intermediate and high risk tumours. Only one recent randomised controlled trial examined the comparative effectiveness of different treatment modalities, the ProtecT study, the results of which will not be available for at least the next two years. Furthermore, the results of randomised controlled trials may have limited generalisability because of differences between the enrolled population and community populations, who are likely to be more heterogeneous for comorbidities and socioeconomic characteristics. Hence the importance of using observational data from actual medical practice in comparative effectiveness studies to complement the evidence from randomised controlled trials. In the specialty of prostate cancer, however, most such studies have evaluated biochemical recurrence as the endpoint, and have shown conflicting results. The definition of biochemical recurrence varies between surgical and radiotherapy cohorts, and even between individual radiotherapy series, and thus comparing biochemical recurrence across treatment modalities is problematic. Furthermore, the median time to death after biochemical recurrence has been shown to be as long as 13 years in a surgical series, and not all men who experience recurrence will develop clinical disease. Hence, death remains the most valid endpoint for comparative studies in prostate cancer.
In this nationwide population based cohort study we assessed prostate cancer related mortality in patients in the Swedish national prostate cancer registry, who underwent radical prostatectomy or radiotherapy as their primary treatment. Linkage with other healthcare and demographic databases enabled reduction of potential confounding through statistical techniques as well as adjustment for competing risks of mortality, as many men with prostate cancer are known to die of other causes. We hypothesised that survival differences would vary by treatment, and that age and the burden from comorbidities would have an impact on survival.
