Dataset Information

Survival following primary androgen deprivation therapy among men with localized prostate cancer.

ABSTRACT:

Context

Despite a lack of data, increasing numbers of patients are receiving primary androgen deprivation therapy (PADT) as an alternative to surgery, radiation, or conservative management for the treatment of localized prostate cancer.

Objective

To evaluate the association between PADT and survival in elderly men with localized prostate cancer.

Design, setting, and patients

A population-based cohort study of 19,271 men aged 66 years or older receiving Medicare who did not receive definitive local therapy for clinical stage T1-T2 prostate cancer. These patients were diagnosed in 1992-2002 within predefined US geographical areas, with follow-up through December 31, 2006, for all-cause mortality and through December 31, 2004, for prostate cancer-specific mortality. Instrumental variable analysis was used to address potential biases associated with unmeasured confounding variables.

Main outcome measures

Prostate cancer-specific survival and overall survival.

Results

Among patients with localized prostate cancer (median age, 77 years), 7867 (41%) received PADT, and 11,404 were treated with conservative management, not including PADT. During the follow-up period, there were 1560 prostate cancer deaths and 11,045 deaths from all causes. Primary androgen deprivation therapy was associated with lower 10-year prostate cancer-specific survival (80.1% vs 82.6%; hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.03-1.33) and no increase in 10-year overall survival (30.2% vs 30.3%; HR, 1.00; 95% CI, 0.96-1.05) compared with conservative management. However, in a prespecified subset analysis, PADT use in men with poorly differentiated cancer was associated with improved prostate cancer-specific survival (59.8% vs 54.3%; HR, 0.84; 95% CI, 0.70-1.00; P = .049) but not overall survival (17.3% vs 15.3%; HR, 0.92; 95% CI, 0.84-1.01).

Conclusion

Primary androgen deprivation therapy is not associated with improved survival among the majority of elderly men with localized prostate cancer when compared with conservative management.

SUBMITTER: Lu-Yao GL

PROVIDER: S-EPMC2645653 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IMPORTANCE:One in 6 American men will be diagnosed as having prostate cancer during their lifetime. Although there are no data to support the use of primary androgen-deprivation therapy (ADT) for early-stage prostate cancer, primary ADT has been widely used for localized prostate cancer, especially among older patients. OBJECTIVE:To determine the long-term survival impact of primary ADT in older men with localized (T1/T2) prostate cancer. DESIGN, SETTING, AND PARTICIPANTS:This was a population-based cohort study of 66,717 Medicare patients 66 years or older diagnosed from 1992 through 2009 who received no definitive local therapy within 180 days of prostate cancer diagnosis. The study was conducted in predefined US geographical areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program. Instrumental variable analysis was used to assess the impact of primary ADT and control for potential biases associated with unmeasured confounding variables. The instrumental variable comprised combined health services areas with various usage rates of primary ADT. The analysis compared survival outcomes in the top tertile areas with those in the bottom tertile areas. MAIN OUTCOMES AND MEASURES:Prostate cancer-specific survival and overall survival. RESULTS:With a median follow-up of 110 months, primary ADT was not associated with improved 15-year overall or prostate cancer-specific survival following the diagnosis of localized prostate cancer. Among patients with moderately differentiated cancers, the 15-year overall survival was 20.0% in areas with high primary ADT use vs 20.8% in areas with low use (difference: 95% CI, -2.2% to 0.4%), and the 15-year prostate cancer survival was 90.6% in both high- and low-use areas (difference: 95% CI, -1.1% to 1.2%). Among patients with poorly differentiated cancers, the 15-year cancer-specific survival was 78.6% in high-use areas vs 78.5%, in low-use areas (difference: 95% CI, -1.8% to 2.4%), and the 15-year overall survival was 8.6% in high-use areas vs 9.2% in low-use areas (difference: 95% CI, -1.5% to 0.4%). CONCLUSIONS AND RELEVANCE:Primary ADT is not associated with improved long-term overall or disease-specific survival for men with localized prostate cancer. Primary ADT should be used only to palliate symptoms of disease or prevent imminent symptoms associated with disease progression.

Project description:BACKGROUND:Androgen deprivation therapy (ADT) remains a primary treatment for localized prostate cancer (PCa) even though there is no evidence that its use is beneficial in the absence of curative treatment. METHODS:Men aged ?70?years (n?=?16,534) diagnosed with localized PCa from 1985 to 2014 and managed either with primary observation or ADT in the absence of curative treatment were included. The cases were identified from the population-based Finnish Cancer Registry. We estimated the standardized mortality ratios (SMR) for overall mortality by treatment group. We determined the relative risk (RR) of PCa-specific mortality (PCSM) and other-cause mortality between the two treatment groups. Survival was determined using the life table method. Two age groups (70-79?years and???80?years) and three calendar time cohorts (1985-1994, 1995-2004, and 2005-2014) were compared following adjustment of propensity score matching between the treatment groups with four covariates (age, year of diagnosis, educational level, and hospital district). Follow-up continued until death or until December 31, 2015. RESULTS:Patients in the observation group had lower overall SMRs than those in the ADT group in both age cohorts over the entire study period. PCSM was higher in men aged 70-79?years undergoing primary ADT compared to those managed by observation only (RR: 1.70, 95% confidence interval [CI]: 1.29-2.23 [1985-1994]; RR 1.55, 95% CI: 1.35-1.84 [1995-2004]; and RR 2.71, 95% CI: 2.08-3.53 [2005-2014]); p?=?0.005 for periodic trend. A similar trend over time was also observed in men aged >?80?years; (p for age-period interaction?=?0.237). Overall survival was also higher among men in their 70's managed by observation compared to those undergoing ADT. CONCLUSIONS:Primary ADT within four months period from diagnosis is not associated with improved long-term overall survival or decreased PCSM compared to primary conservative management for men with localized PCa. However, this observational study's conclusions should be weighted with confounding factors related to cancer aggressiveness and comorbidities.

Project description:PurposeAndrogen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors.Materials and methodsWe conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses.ResultsDiabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38-1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction=0.008).ConclusionsPrimary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle interventions to reduce the risk of diabetes in men receiving androgen deprivation therapy.

Project description:PurposeAndrogen deprivation therapy is often used as salvage treatment in men with rising prostate specific antigen after initial radical prostatectomy or radiotherapy for clinically localized prostate cancer. Given the lack of evidence from general practice, we examined the association of salvage androgen deprivation therapy with mortality in an observational cohort study.Materials and methodsFrom 3 managed care organizations we assembled a retrospective cohort of all 5,804 men with newly diagnosed localized prostate cancer from 1995 to 2009 who had a prostate specific antigen increase (biochemical recurrence) after primary radical prostatectomy or radiotherapy. The main outcomes were all-cause and prostate cancer specific mortality. We used Cox proportional hazards models to estimate mortality with salvage androgen deprivation therapy as a time dependent predictor.ResultsOverall salvage androgen deprivation therapy was not associated with all-cause or prostate cancer specific mortality in the prostatectomy cohort (HR 0.97, 95% CI 0.70-1.35 or HR 1.18, 95% CI 0.68-2.07) or in the radiotherapy cohort (HR 0.84, 95% CI 0.70-1.01 or HR 1.06, 95% CI 0.80-1.40, respectively). Among men with prostate specific antigen doubling time less than 9 months after the prostate specific antigen rise, salvage androgen deprivation therapy was statistically significantly associated with a decreased risk of all-cause and prostate cancer specific mortality in the prostatectomy cohort (HR 0.35, 95% CI 0.20-0.63 and HR 0.43, 95% CI 0.21-0.91) and in the radiotherapy cohort (HR 0.62, 95% CI 0.48-0.80 and HR 0.65, 95% CI 0.47-0.90, respectively).ConclusionsWe found no association of salvage androgen deprivation therapy with all-cause or cause specific mortality in most men with biochemical recurrence after primary radical prostatectomy or radiotherapy for clinically localized prostate cancer. Men with quickly progressed disease may derive a clinical benefit from salvage androgen deprivation therapy.