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    Localized prostate cancer survival outcomes better with radical prostatectomy than radiation therapy in large study

    Overall, disease-specific mortality lower with surgery at 15-year follow-up


    David F. Penson
    Atlanta—Analyses of data from the Prostate Cancer Outcomes Study (PCOS) show that among men with localized prostate cancer, treatment by radical prostatectomy results in significantly better 15-year overall and disease-specific survival outcomes compared with external beam radiotherapy (EBRT).

    In addition, the benefits of surgery are greatest in younger men, healthier men, and those with high-risk disease, reported senior author David F. Penson, MD, MPH, at the AUA annual meeting in Atlanta.

    "We undertook this analysis because to date there are no completed, adequately sized randomized controlled trials comparing RP to radiotherapy for treatment of localized prostate cancer. While PCOS is not randomized, our methods included appropriate techniques for risk adjustment, and we also undertook analyses of selected subgroups identified a priori to see if we could identify features to inform clinical decisions," said Dr. Penson, professor of urologic surgery, Vanderbilt University Medical Center, Nashville, TN.

    "We acknowledge that the findings of our study could be due to residual confounding and that radiation therapy for men in this study was performed using older techniques with lower doses and underutilization of adjuvant androgen deprivation therapy, especially in high-risk patients. However, we think it is also possible that surgery is truly more effective than radiation in prolonging survival for men with localized prostate cancer."

    PCOS is a population-based longitudinal study of patients from six Surveillance, Epidemiology, and End Results tumor registries enrolled between October 1994 and October 1995. The analyses presented by Dr. Penson included data from 1,655 men ages 55 to 74 years at diagnosis who had clinically localized disease (T1 or T2) and primary therapy with prostatectomy (1,164 men) or EBRT (491 men). They were identified from an initial 50% random sample of the entire PCOS population of 11,344 men.

    A propensity score analysis was performed to control for treatment selection bias, and a multivariate Cox regression model, including baseline measures and propensity score as covariates, was used to compare the two treatment groups for 15-year overall and disease-specific survival rates. At baseline, the two treatment groups were comparable for clinical stage, PSA, and biopsy Gleason score, but there were significant differences between the groups in age at diagnosis, race/ethnicity, percent with comorbidities, insurance status, and by region.


    UT Figure: EBRT vs. RP: 15-year overall mortality*
    "We tried to control for treatment selection bias by restricting the age range of patients selected for the study and using the propensity score analysis to adjust for differences at baseline. However, it is important to state that the propensity score analysis, which adjusted for certain known confounders, likely cannot account for all selection bias due to unmeasured confounding," Dr. Penson said.

    EBRT mortality rate nearly double that of RP

    In an unadjusted survival curve analysis, the 15-year overall mortality rate was nearly twice as high for the EBRT patients than for the surgery group (51% vs. 28%, respectively), and there was a threefold difference in the 15-year disease-specific mortality rate (12% vs. 4%, respectively).

    In the adjusted analysis, risks of overall mortality and disease-specific mortality were significantly lower (40% and 65%, respectively) in the surgery patients compared with the EBRT group. Overall mortality and disease-specific mortality rates determined in sensitivity analyses using other multivariate statistical approaches conducted to confirm the validity of the propensity score were essentially the same. Age, number of comorbidities, Gleason score, stage, log PSA, propensity score, education, Hispanic race, and registry were also independent predictors of overall mortality. Gleason score, stage, and log PSA independently predicted disease-specific mortality in the adjusted analysis.

    Planned subgroup analyses compared outcomes after prostatectomy and EBRT for men stratified by age (55-64 years and 65-74 years), risk group (low and high), and comorbidity status (none and any). In the analysis of the high-risk subgroup, EBRT patients were only included if they received androgen deprivation therapy.

    In all of the subgroups except the low-risk cohort, surgery significantly reduced the risks of overall mortality by between 21% and 54% and disease-specific mortality by between 46% and 82%; the 82% reduced risk of cancer-specific mortality was observed both among younger men (ages 55 to 64 years) and those with no reported comorbidities.

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