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      Time Trends and Local Variation in Primary Treatment of Localized Prostate Cancer

      1 , 1 , 1
      Journal of Clinical Oncology
      American Society of Clinical Oncology (ASCO)

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          Abstract

          Purpose

          In the absence of high-level evidence or clinical guidelines supporting any given active treatment approach over another for localized prostate cancer, clinician and patient preferences may lead to substantial variation in treatment use.

          Methods

          Data were analyzed from 36 clinical sites that contributed data to the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Distribution of primary treatment use was measured over time. Prostate cancer risk was assessed using the D'Amico risk groups and the Cancer of the Prostate Risk Assessment (CAPRA) score. Descriptive analyses were performed, and a hierarchical model was constructed that controlled for year of diagnosis, cancer risk variables, and other patient factors to estimate the proportion of variation in primary treatment selection explicable by practice site.

          Results

          Among 11,892 men analyzed, 6.8% elected surveillance, 49.9% prostatectomy, 11.6% external-beam radiation, 13.3% brachytherapy, 4.0% cryoablation, and 14.4% androgen deprivation monotherapy. Prostate cancer risk drives treatment selection, but the data suggest both overtreatment of low-risk disease and undertreatment of high-risk disease. The former trend appears to be improving over time, while the latter is worsening. Treatment varies with age, comorbidity, and socioeconomic status. However, treatment patterns vary markedly across clinical sites, and this variation is not explained by case-mix variability or known patient factors. Practice site explains a proportion of this variation ranging from 13% for androgen deprivation monotherapy to 74% for cryoablation.

          Conclusion

          Substantial variation exists in management of localized prostate cancer that is not explained by measurable factors. A critical need exists for high-quality comparative effectiveness research in localized prostate cancer to help guide treatment decision making.

          Related collections

          Most cited references18

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          Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer.

          The comparative effectiveness of localized prostate cancer treatments is largely unknown. To compare the effectiveness and harms of treatments for localized prostate cancer. MEDLINE (through September 2007), the Cochrane Library (through Issue 3, 2007), and the Cochrane Review Group in Prostate Diseases and Urologic Malignancies registry (through November 2007). Randomized, controlled trials (RCTs) published in any language and observational studies published in English that evaluated treatments and reported clinical or biochemical outcomes in localized prostate cancer. 2 researchers extracted information on study design, sample characteristics, interventions, and outcomes. 18 RCTs and 473 observational studies met inclusion criteria. One [one randomized controlled trial] [corrected] RCT enrolled mostly men without prostate-specific antigen (PSA)-detected disease and reported that, compared with watchful waiting, radical prostatectomy reduced crude [corrected] all-cause mortality (24% vs. 30%; P = 0.04) and prostate cancer-specific mortality (10% [corrected] vs. 15% [corrected]; P = 0.01) at 10 years [corrected] Effectiveness was limited to men younger than age 65 years but was not associated with Gleason score or baseline PSA level. An older, smaller trial found no significant overall survival differences between radical prostatectomy and watchful waiting (risk difference, 0% [95% CI, -19% to 18%]). Radical prostatectomy reduced disease recurrence at 5 years compared with external-beam radiation therapy in 1 small, older trial (14% vs. 39%; risk difference, 21%; P = 0.04). No external-beam radiation regimen was superior to another in reducing mortality. No randomized trials evaluated primary androgen deprivation. Androgen deprivation used adjuvant to radical prostatectomy did not improve biochemical progression compared with radical prostatectomy alone (risk difference, 0% [CI, -7% to 7%]). No randomized trial evaluated brachytherapy, cryotherapy, robotic radical prostatectomy, or photon-beam or intensity-modulated radiation therapy. Observational studies showed wide and overlapping effectiveness estimates within and between treatments. Adverse event definitions and severity varied widely. The Prostate Cancer Outcomes Study reported that urinary leakage (> or =1 event/d) was more common with radical prostatectomy (35%) than with radiation therapy (12%) or androgen deprivation (11%). Bowel urgency occurred more often with radiation (3%) or androgen deprivation (3%) than with radical prostatectomy (1%). Erectile dysfunction occurred frequently after all treatments (radical prostatectomy, 58%; radiation therapy, 43%; androgen deprivation, 86%). A higher risk score incorporating histologic grade, PSA level, and tumor stage was associated with increased risk for disease progression or recurrence regardless of treatment. Only 3 randomized trials compared effectiveness between primary treatments. No trial enrolled patients with prostate cancer primarily detected with PSA testing. Assessment of the comparative effectiveness and harms of localized prostate cancer treatments is difficult because of limitations in the evidence.
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            Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis.

            Although many tools for the assessment of prostate cancer risk have been published, most are designed to predict only biochemical recurrence, usually after a single specified treatment. We assessed the accuracy of the Cancer of the Prostate Risk Assessment (CAPRA) score, which was validated previously to predict pathological and biochemical outcomes after radical prostatectomy, to predict metastases, prostate cancer-specific mortality, and all-cause mortality. We studied 10 627 men with clinically localized prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor registry, who underwent primary radical prostatectomy, radiation therapy (external beam or interstitial), androgen deprivation monotherapy, or watchful waiting/active surveillance, and had at least 6 months of follow-up after treatment. CAPRA scores were calculated at diagnosis from the prostate-specific antigen level, Gleason score, percentage of biopsy cores that were positive for cancer, clinical tumor stage, and age at diagnosis. Survival was studied with Kaplan-Meier analyses. Associations between increasing CAPRA scores and bone metastasis, cancer-specific mortality, and all-cause mortality were examined by use of proportional hazards regression, with adjustment for primary treatment; for all-cause mortality, the analysis also included adjustment for age and comorbidity. Accuracy of the CAPRA score was assessed with the concordance (c)-index. Among the 10 627 patients, 311 (2.9%) men developed bone metastases, 251 (2.4%) died of prostate cancer, and 1582 (14.9%) died of other causes. Each single-point increase in the CAPRA score was associated with increased bone metastases (hazard ratio [HR] for bone metastases = 1.47, 95% confidence interval [CI] = 1.39 to 1.56), cancer-specific mortality (HR for prostate cancer death = 1.39, 95% CI = 1.31 to 1.48), and all-cause mortality (HR for death = 1.13, 95% CI = 1.10 to 1.16). The CAPRA score was accurate for predicting metastases (c-index = 0.78), cancer-specific mortality (c-index = 0.80), and all-cause mortality (c-index = 0.71). In a large cohort of patients with clinically localized prostate cancer who were managed with one of five primary modalities, the CAPRA score predicted clinical prostate cancer endpoints with good accuracy. These results support the value of the CAPRA score as a risk assessment and stratification tool for both research studies and clinical practice.
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              The changing face of low-risk prostate cancer: trends in clinical presentation and primary management.

              Early intervention for prostate cancer is associated with excellent long-term survival, but many affected men, especially those with low-risk disease characteristics, might not experience adverse impact to survival or quality of life were treatment deferred. We sought to characterize temporal trends in clinical presentation and primary disease management among patients with low-risk prostate cancer. Data were abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a disease registry of 8,685 men with various stages of prostate cancer. Included were 2,078 men who were diagnosed between 1989 and 2001 and had a serum prostate specific antigen

                Author and article information

                Journal
                Journal of Clinical Oncology
                JCO
                American Society of Clinical Oncology (ASCO)
                0732-183X
                1527-7755
                March 01 2010
                March 01 2010
                : 28
                : 7
                : 1117-1123
                Affiliations
                [1 ]From the Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco Veterans Affairs Medical Center, San Francisco, CA.
                Article
                10.1200/JCO.2009.26.0133
                2834465
                20124165
                57983420-01db-4a70-af7c-1ab7312d6fc5
                © 2010
                History

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