Use Of Primary Androgen Deprivation Therapy Research Articles

National Trends in the Utilization of Androgen Deprivation Therapy for Very Low Risk Prostate Cancer

ObjectiveTo analyze national trends using the National Cancer Database (NCDB) in use of androgen deprivation therapy (ADT), outside of standard of care, in patients with very low risk prostate cancer. MethodsWe identified 52,797 men in the NCDB from 2010 to 2015 diagnosed with very low risk prostate cancer as defined (cT1cM0, PSA <10, Gleason ≤6, <3 biopsy cores positive). We evaluated the treatment trends and the proportion of men treated with ADT based on race, income, insurance status, treatment facility volume, and Charlson comorbidity. ResultsFrom 2010 to 2015, prevalence of primary ADT use in patients with very low risk prostate cancer remained 0.7%. Patients treated at low-volume facilities were more likely to receive primary ADT (hazard ratio [HR] 1.29, P <.001) as were black patients (HR 1.47, P <.001). When evaluated over time, the proportion of men treated with primary ADT who were white decreased while the proportion of men who were black increased. ConclusionThe use of primary ADT in men with very low risk prostate cancer has not changed over time, and may be over utilized, particularly among black men and those treated at low-volume facilities.

Trends in risk classification and primary therapy of Japanese patients with prostate cancer in Nara urological research and treatment group (NURTG) \u2013 comparison between 2004\u20132006, 2007\u20132009, and 2010\u20132012

BackgroundTo assess the trends in risk classification and primary therapy of Japanese prostate cancer patients who were diagnosed between 2004 and 2012.MethodsA total of 7768 patients who were newly diagnosed with prostate cancer at Nara Medical University and its 23 affiliated hospitals between 2004 and 2012 were enrolled. The trends in risk classification and primary therapy in 2004–2006 (prior period), 2007–2009 (middle period), and 2010–2012 (latter period) were compared.ResultsThe proportion of high-risk and worse patients significantly decreased in the latter period compared to the prior period (p < 0.001), while that of intermediate-risk patients significantly increased over the years (p < 0.001). The proportion of primary androgen deprivation therapy (PADT) was 50% in the prior period, 40% in the middle period, and 30% in the latter period, respectively. The proportions of radiation therapy and active surveillance significantly increased. The proportion of radical prostatectomy remained similar over these periods (30%). The primary therapy was significantly different between the three periods (p < 0.001).ConclusionsHigh-risk patients significantly decreased in the latter period. The use of PADT also significantly decreased, while radiation therapy and active surveillance significantly increased over these periods.

National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3+3=6, prostate-specific antigen level <10ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information.We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. ADT use in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions.

Treatment patterns for older veterans with localized prostate cancer

ObjectiveConcerns about over-treatment have led to practice guidelines discouraging active treatment of prostate cancer (PCa) in men with limited life expectancies and/or low-risk tumors. We evaluated treatment patterns for older veterans with localized PCa, particularly those with low-risk features. MethodsWe used VA Cancer Registry data to identify men aged 65+ diagnosed with clinically localized PCa between January 1st, 2003 and December 31st, 2008. We obtained baseline data on demographics, tumor characteristics, comorbidities, and initial treatment within 6 months of diagnosis: radical prostatectomy, radiotherapy, primary androgen-deprivation therapy (PADT), or no active treatment. National VA surveys provided facility data, including academic affiliation, availability of oncologic specialists, and distance to radiotherapy facilities. Multinomial regression analyses determined associations between patient and facility characteristics and cancer treatment for men with localized (stage<III) and low-risk PCa (stage≤IIa, PSA<10ng/mL, Gleason ≤6). Results17,206 veterans had localized PCa, 32% age 75+, 12% had comorbidity scores ≥3, and 33% had low-risk tumors. Overall, 39% received radiotherapy, 6% surgery, 20% PADT, and 35% no active treatment. For those with low-risk cancers, older men (RR=0.36, 95% CI 0.30–0.43) and sicker men (RR=0.75, 95% CI 0.62–0.90) were less likely to receive surgery or radiotherapy versus no active treatment. Over time, more of these men received no active treatment (from 41% to 57%, P<0.001) while fewer received PADT (from 11% to 4%, P<0.001). ConclusionVA treatment patterns followed evidence-based guidelines against treating older and sicker men with surgery or radiotherapy, for decreasing use of PADT, and for increasingly withholding active treatment, particularly for men with low-risk PCa.

Fifteen-year survival outcomes following primary androgen-deprivation therapy for localized prostate cancer.

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. To determine the long-term survival impact of primary ADT in older men with localized (T1/T2) prostate cancer. 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. Prostate cancer-specific survival and overall survival. 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%). 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.

Prostate cancer: primary ADT monotherapy not suitable for localized disease.

Although current guidelines do not endorse the use of primary androgen deprivation therapy (PADT) as monotherapy for localized prostate cancer, many patients continue to receive this treatment. New outcomes research confirms that there is no clear reason for use of PADT in men with localized prostate cancer.

Trends of risk classification and primary therapy for Japanese patients with prostate cancer in Nara Uro-Oncological Research Group (NUORG)–a comparison between 2004-2006 and 2007-2009

BackgroundTo assess the trends of risk classification and primary therapy in Japanese patients who were diagnosed with prostate cancer between 2004-2006 and 2007-2009.MethodsA total of 4752 patients who were newly diagnosed with prostate cancer at Nara Medical University and its 23 affiliated hospitals between 2004 and 2009 were enrolled. The differences in risk classification and primary therapy were compared in patients who were newly diagnosed between 2004-2006 (prior period) and 2007-2009 (latter period).ResultsThe proportion of patients with a high or greater risk significantly decreased in the latter period compared to the prior period (p < 0.001). The proportion of primary androgen deprivation therapy (PADT) was 50% in the prior period, and 40% in the latter period. On the other hand, the proportion of radiation therapy was 14% in the prior period, but 24% in the latter period. The proportion of radical prostatectomy was the same in the two periods (30%). The primary therapy was significantly different between the two periods (p < 0.001).ConclusionsHigher risk patients significantly decreased in the latter period compared to the prior period. The use of PADT also significantly decreased in the latter period. However, there were still higher risk patients in Japan, and the use of PADT was still common in patients with localized prostate cancer or locally advanced prostate cancer in Japan.

724 TRANS-PACIFIC VARIATION IN OUTCOMES FOR MEN TREATED WITH PRIMARY ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced (I)1 Apr 2013724 TRANS-PACIFIC VARIATION IN OUTCOMES FOR MEN TREATED WITH PRIMARY ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER Matthew Cooperberg, Shiro Hinotsu, Mikio Namiki, Peter Carroll, and Hideyuki Akaza Matthew CooperbergMatthew Cooperberg San Francisco, CA More articles by this author , Shiro HinotsuShiro Hinotsu Kyoto, Japan More articles by this author , Mikio NamikiMikio Namiki Kanazawa, Japan More articles by this author , Peter CarrollPeter Carroll San Francisco, CA More articles by this author , and Hideyuki AkazaHideyuki Akaza Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.283AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Primary androgen deprivation therapy (PADT) is endorsed as an option for monotherapy for localized prostate cancer by guidelines in Asia but not in the United States (US) or Europe. PADT use is common, however, in both the US and Japan. Prior studies on either side of the Pacific have reported disparate outcomes for PADT; we aimed to explore these differences in a direct comparison study. METHODS Data were drawn from the US community-based CaPSURE registry and from J-CaP, comprising men in Japan treated with PADT. 1934 men treated with PADT were included from CaPSURE, and 16,300 treated in J-CaP. Risk adjustment was based on the validated Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score. Cox propor-tional hazards regression was used to assess prostate cancer-specific mortality (CSM), adjusting for age, J-CAPRA, year of diagnosis, and treatment type (combined androgen blockade [CAB] vs. castration (medical or surgical) monotherapy). RESULTS Men treated with PADT in J-CaP were older than those in CaPSURE (mean age 75.0 vs. 72.7, p<0.001), and had higher risk disease (mean J-CAPRA score 3.0 vs. 2.1, p<0.001). They were more likely to be treated with CAB: 67.1% vs. 44.5% (p<0.001). In the Cox model, the hazard ratio (HR) for PCSM was 0.31 for J-CaP compared to CaPSURE, 95% CI 0.25?0.40. In J-CaP, CAB improved survival compared to castration alone (HR 0.81, 95% CI 0.66?1.0), but this effect was not observed in CaPSURE (HR 0.96, 95% CI 0.69?1.34). For all-cause mortality, the HR for J-CaP was 0.27 (95% CI 0.24?0.30). CONCLUSIONS Adjusting for multiple factors including disease risk and type of androgen ablation, men treated with PADT in Japan compared to the US have more than 3-fold lower CSM and 4-fold better overall survival. CAB improved outcomes compared to castration alone in J-CaP but not in CaPSURE. These findings support existing guidelines both encouraging PADT in Asia and discouraging its use in the West. The reasons for these substantial differences likely include both genetic and dietary/environmental factors, as well as potential confounding variables such as comorbidities. Such factors may explain varying biology of prostate cancer on both sides of the Pacific. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e297 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Cooperberg San Francisco, CA More articles by this author Shiro Hinotsu Kyoto, Japan More articles by this author Mikio Namiki Kanazawa, Japan More articles by this author Peter Carroll San Francisco, CA More articles by this author Hideyuki Akaza Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Trans-Pacific variation in outcomes for men treated with primary androgen deprivation therapy for localized prostate cancer.

92 Background: Primary androgen deprivation therapy (PADT) is endorsed as an option for monotherapy for localized prostate cancer by guidelines in Asia but not in the United States (US) or Europe. PADT use is common, however, in both the US and Japan. Prior studies on either side of the Pacific have reported disparate outcomes for PADT; we aimed to explore these differences in a direct comparison study. Methods: Data were drawn from the US community-based CaPSURE registry and from J-CaP, comprising men in Japan treated with PADT. 1934 men treated with PADT were included from CaPSURE, and 16,300 treated in J-CaP. Risk adjustment was based on the validated Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score. Cox proportional hazards regression was used to assess prostate cancer-specific mortality (CSM), adjusting for age, J-CAPRA, year of diagnosis, and treatment type (combined androgen blockade [CAB] vs. castration (medical or surgical) monotherapy). Results: Men treated with PADT in J-CaP were older than those in CaPSURE (mean age 75.0 vs. 72.7, p&lt;0.001), and had higher risk disease (mean J-CAPRA score 3.0 vs. 2.1, p&lt;0.001). They were more likely to be treated with CAB: 67.1% vs. 44.5% (p&lt;0.001). In the Cox model, the hazard ratio (HR) for PCSM was 0.31 for J-CaP compared to CaPSURE, 95% CI 0.25–0.40. In J-CaP, CAB improved survival compared to castration alone (HR 0.81, 95% CI 0.66–1.0), but this effect was not observed in CaPSURE (HR 0.96, 95% CI 0.69–1.34). For all-cause mortality, the HR for J-CaP was 0.27 (95% CI 0.24–0.30). Conclusions: Adjusting for multiple factors including disease risk and type of androgen ablation, men treated with PADT in Japan compared to the US have more than 3-fold lower CSM and 4-fold better overall survival. CAB improved outcomes compared to castration alone in J-CaP but not in CaPSURE. These findings support existing guidelines both encouraging PADT in Asia and discouraging its use in the West. The reasons for these substantial differences likely include both genetic and dietary/environmental factors, as well as potential confounding variables such as comorbidities. Such factors may explain varying biology of prostate cancer on both sides of the Pacific.

Androgen deprivation therapy: further confirmation of known harms

Androgen deprivation therapy (ADT) has been an established and effective treatment for men with asymptomatic metastatic prostate cancer for decades. Randomized trials have shown significant survival benefits when ADT is used, coupled with radiotherapy, for patients with locally advanced disease; however it is often used in patients where the benefits are less clear, such as for a rising serum PSA level after radical prostatectomy, and among patients who elect to take a more conservative approach to treatment for low-risk disease. In addition to the absence of data proving benefit, there are a number of adverse consequences attached to androgen deprivation which should be given serious consideration before beginning treatment. Most of the side effects of ADT are linked to its induced hypo-androgenic, and consequently hypo-oestrogenic, state. These include fatigue, vasomotor flushing, loss of muscle mass, weight gain, hyperlipidaemia and insulin resistance 1. Osteoporosis and fracture are additional known consequences of ADT with a trend toward greater fracture risk with a higher number of doses of a GnRH agonist and/or longer duration of use 2, 3. Studies indicate that men with non-metastatic prostate cancer treated with ADT experience an annual loss in bone mineral density of up to nine times that of men in the general population 4. The use of intermittent ADT, as opposed to continuous use, as a strategy to reduce the negative cardiometabolic and osteoporotic effects is unresolved; however, a report indicating that more recent treatment was associated with a greater risk of fracture, irrespective of cumulative dose, suggests the potential for some reversibility in bone loss post-treatment 5. In the present issue of the BJU International, Lu-Yao et al. 6add to the literature in this area. In a study of nearly 76 000 men with prostate cancer, using data gathered as part of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) cancer registry linked to Medicare claims data, the authors reported that patients at high risk for skeletal complications were, not surprisingly, more likely to experience a fracture associated with ADT use over a 12-year period compared with patients receiving ADT but at low risk for developing such complications. Furthermore, men who experienced a fracture were 40% more likely to die during follow-up than those without fracture. Patients were sorted into risk groups using an index which summed the number of known risk factors for incident fracture identified from Medicare claims in the 12 months before their prostate cancer diagnosis. Unfortunately, owing to the relatively small number of patients with more than one risk factor, the study was limited in its ability to establish a dose – response relationship between the baseline index and fracture risk. SEER-Medicare is an excellent resource to investigate both outcomes and treatment-related expense associated with cancer diagnoses in the USA; however, in this particular study, the reliability of behaviours included in the baseline index (i.e. smoking) is questionable as it would require both patient report of tobacco use as well as physician documentation as a billable claim. Still, one might argue that the heaviest smokers, whose behaviour would most likely be captured as part of a claim, would also be the most important group to capture in an index intended to predict fracture risk. Interestingly, it was reported that patients at high risk for skeletal complications were significantly more likely to receive ADT than patients at low risk. This was driven in part by the use of primary ADT among elderly men (aged ≥80 years) with prostate cancer and consistent with the notion that when curative treatment is contraindicated (i.e. older patients and those with pre-existing comorbidities) treatment with ADT is more common. Lastly, these findings do not suggest any modification of fracture risk associated with ADT according to baseline risk index, which is consistent with reports of the impact of comorbid conditions and ADT on the risk of incident diabetes and cardiovascular events 7. This is an important observation in that it says, there is no group that is immune to the adverse effects of ADT – all men are at risk. In absolute terms, however, the men at the greatest risk of an ADT side effect (i.e. a fracture or diabetes) are the men who are at greatest risk of having that side effect even if they were not receiving ADT. The findings of Lu-Yao et al. reinforce the need for careful monitoring of all men receiving ADT. Moreover, when these data are combined with an earlier study 8 that showed that primary ADT was associated with poorer survival than that for men with low-risk prostate cancer who were managed conservatively with observation alone, it should be a wake-up call for us to stop treating non-lethal cancer with lethal and toxic treatments, including ADT. None declared.

PCN8 Primary Androgen Deprivation Therapy Versus Radical Prostatectomy in Seer-Medicare Dataset: A Comparative Effectiveness Analysis of Retrospective Cohorts

To examine the comparative effectiveness of primary androgen deprivation therapy (PADT) and radical prostatectomy (RP). Male patients with localized prostate cancer (T1-T2, N0, M0) were identified in the SEER-Medicare database from January 1998 to December 2007. Patients were 66-74 years old, without other documented cancers, and had PADT initiation or RP within 6 months after the first recorded diagnosis of prostate cancer in the dataset. PADT-treated patients were 1:1 matched to the RP-treated patients via propensity score (PS) matching. The overall survival from diagnosis to death was analyzed using Cox proportional hazard models; prostate cancer specific survival examined using Fine and Gray competing risk modeling. The independent regression variables included age at diagnosis, race, marital status, census regions, urban residence, clinical cancer stage, Gleason score, prostate specific antigen level, Charlson comorbidity index, calendar year at diagnosis, and hospitalization (yes or no), surgery (yes or no) and outpatient visit (yes or no) during one year baseline period. The PS-matched sample size was 3432 with mean age of 66.0 years. The baseline characteristics were comparable between the two cohorts (all p-values>0.05). During median follow-up of 2.95 years, the cumulative incidence of death was 304 (17.72%) among 1716 PADT patients and 94 (5.48%) among 1716 RP patients; 66 (3.85%) and 2 (0.12%) for prostate cancer specific deaths, respectively. The PADT group had nearly 4 times higher overall mortality risk compared to those using RP (odds ratio (OR)=3.534, 95% confidence interval (CI)=2.801-4.464, p<0.001). Furthermore, patients who received PADT had significantly higher prostate cancer specific mortality compared to those using RP (OR=30.875, 95% CI=7.535-126.506, p<0.001). Overall mortality and prostate cancer specific mortality following PADT were significantly higher compared to those following RP among localized prostate cancer patients. These data do not support the use of PADT in men with clinically localized prostate cancer.

Does Primary Androgen-Deprivation Therapy Delay the Receipt of Secondary Cancer Therapy for Localized Prostate Cancer?

BackgroundDespite evidence that shows no survival advantage, many older patients receive primary androgen-deprivation therapy (PADT) shortly after the diagnosis of localized prostate cancer (PCa). ObjectiveThis study evaluates whether the early use of PADT affects the subsequent receipt of additional palliative cancer treatments such as chemotherapy, palliative radiation therapy, or intervention for spinal cord compression or bladder outlet obstruction. Design, setting, and participantsThis longitudinal population-based cohort study consists of Medicare patients aged ≥66 yr diagnosed with localized PCa from 1992 to 2006 in areas covered by the Surveillance Epidemiology and End Results (SEER) program. SEER-Medicare linked data through 2009 were used to identify the use of PADT and palliative cancer therapy. Outcome measurements and statistical analysisInstrumental variable analysis methods were used to minimize confounding effects. Confidence intervals were derived from the bootstrap estimates. Results and limitationsThis study includes 29 775 men who did not receive local therapy for T1–T2 PCa within the first year of cancer diagnosis. Among low-risk patients (Gleason score 2–7 in 1992–2002 and Gleason score 2–6 in 2003–2006) with a median age of 78 yr and a median follow-up of 10.3 yr, PADT was associated with a 25% higher use of chemotherapy (hazard ratio [HR]: 1.25; 95% confidence interval [CI], 1.08–1.44) and a borderline higher use of any palliative cancer treatment (HR: 1.07; 95% CI, 0.97–1.19) within 10 yr of diagnosis in regions with high PADT use compared with regions with low PADT use. Because this study was limited to men >65 yr, the results may not be applicable to younger patients. ConclusionsEarly treatment of low-risk, localized PCa with PADT does not delay the receipt of subsequent palliative therapies and is associated with an increased use of chemotherapy.

Reducing Bias in the Assessment of Treatment Effectiveness

Indication bias is the major challenge in assessing treatment effectiveness in observational studies. We explored the potential advantages of using an instrumental variable approach in the context of primary androgen deprivation therapy (ADT) for prostate cancer. We identified 31,930 men in the linked Surveillance, Epidemiology, and End Results-Medicare database with a diagnosis of prostate cancer who were not treated definitively with radical prostatectomy or radiation in the years 1992 through 2002, with follow-up through 2005. The association between use of primary ADT and overall, prostate cancer-specific, and nonprostate cancer survival was assessed using multivariable regression and instrumental variable methods. Two instrumental variables, based on region and urologist prescribing preference, were constructed and analyzed using exogenous probit models. Prespecified subgroup analyses in patients with lower-risk and higher-risk prostate tumors were also carried out. In the overall cohort, standard multivariable regression analyses showed a significantly increased risk of prostate cancer-related death, whereas the instrumental variable approaches showed a protective effect of primary ADT, which was significant for the urologist preference instrument (hazard ratio: 0.74; 95% confidence interval, 0.60-0.93). In the high-risk subgroup, using urologist preference for primary ADT as the instrument, there was a significant reduction in overall mortality (hazard ratio: 0.75; 95% confidence interval, 0.57-0.99), driven by a large reduction in prostate cancer-specific mortality. Instrumental variable analysis appears to provide better control of bias when assessing the effectiveness of primary ADT for prostate cancer, although the results may be more applicable to policy rather than to clinical decisions.

High-risk prostate cancer: is androgen deprivation monotherapy still appropriate?

High-risk prostate cancer: is androgen deprivation monotherapy still appropriate?

345 CONTEMPORARY NATIONALLY-REPRESENTATIVE TRENDS IN TREATMENT FOR LOCALIZED PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Primary treatment trends for localized prostate cancer, including substantial local variation, have previously been documented among selected community-based U.S. practices. We aimed to determine whether these trends are confirmed in larger, more broadly representative databases. METHODS: We analyzed treatments in two national administrative datasets including men covered by Medicare in 1998–2006 and by private insurance (i3 database) in 2002–2006. Treatment distributions were determined in each year among watchful waiting/active surveillance (WW), radical prostatectomy (RP), radiation therapy (RT), cryotherapy, and primary androgen deprivation therapy (PADT). Trends in specific modalities were further examined within RP and RT. County-level variation was assessed, and treatment predictors were determined using multinomial regression. RESULTS: Among 54,322 Medicare patients (mean age at diagnosis 75), WW use fell from 30% in 1998 to 22% in 2002 and remained low. PADT use peaked at 24% in 2002 and fell to 17% by 2006. RP use varied between 11% and 13% during the study period, while RT use rose from 35 to 44%. Laparoscopic/robot-assisted RP (LRRP) and intensity-modulated radiation therapy (IMRT) were both first reported in 1999, and rose to 35% of RP and 53% of RT cases, respectively, by 2006. Among 16,161 privately insured patients (mean age 65), WW and PADT fell steadily from 25% and 12% in 2002, respectively, to 12% and 7% in 2006. RT use varied between 30 and 32%, while RP use rose from 33 to 48%. LRRP and IMRT use rose from 1% and 15% of RP and RT cases, respectively, in 2002 to 41% and 48% in 2006. Use of neoadjuvant androgen deprivation therapy (NADT) declined among RP and brachytherapy patients, to 6 and 25%, respectively, among Medicare patients and to 2% and 22% among private insurance patients by 2006. Use of NADT rose to 41% and fell to 37% among external-beam RT patients with Medicare and private insurance, respectively. There was considerable geographic variation in treatment selection. Across counties, use of WW, PADT, RP, and RT ranged, respectively, from 3 to 55%, 0 to 48%, 0 to 50%, and 15 to 71%. Comorbidity, age, income, year of diagnosis, and county-level sociodemographic variables predicted treatment. CONCLUSIONS: These trends echo those documented in prior studies in smaller datasets, and these data confirm extensive geographic variation. In both databases, there is rapid, ongoing adoption of high-cost technologies among both RP and RT patients. These findings underscore the urgent need for high-quality cost-effectiveness research comparing these treatments.

Local variation in primary treatment of localized prostate cancer

5126 Background: We aimed to characterize and quantify variation in the primary management of localized prostate cancer at the level of clinical practice sites. Methods: Data were abstracted from patients accrued to the CaPSURE national prostate cancer registry. Patients were accrued from the 36 clinical practice sites which contributed at least 30 patients to the registry, and represented all those diagnosed since 1990 with localized disease who received radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy, active surveillance / watchful waiting (WW), or primary androgen deprivation therapy (PADT) were included. Descriptive analyses were performed, and a random effects logit hierarchical model was constructed, controlling for year of diagnosis, age, comorbidity, PSA, Gleason score, clinical T stage, and percent of biopsy cores positive, to estimate the proportion of variation in primary treatment selection explicable by practice site. Analyses were conducted for all patients and for low-risk patients (Gleason score ≤6, PSA ≤10 ng/ml, clinical stage ≤T2a). Results: 10,080 men were analyzed. The distribution among primary treatments at each clinical practice site varied widely: use of RP, for example, ranged from 12% to 95% of enrolled patients. Patterns of treatment are not reliably explained by patient risk distribution at each site. The proportion of variation attributable to clinical practice sites was 10% for PADT, 19% for WW, 21% for EBRT, 28% for RP, 37% for brachytherapy, and 75% for cryotherapy. For low-risk patients only, this proportion was higher for all treatment types except brachytherapy and cryotherapy. Only a small amount of the variation attributable to practice site can be explained by measured sociodemographic factors such as ethnicity, income, education, and geographic region. There are significant trends in treatments over time, including more use of PADT for intermediate- and high-risk patients, and more use of RP and WW for low-risk patients. Conclusions: These data do not represent a random sampling of the United States population. However, the significant variation in practice patterns across individual clinical sites suggests that factors other than patient clinical and sociodemographic factors may be driving selection of primary treatment. [Table: see text]

Survival Following Primary Androgen Deprivation Therapy Among Men With Localized Prostate Cancer

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. To evaluate the association between PADT and survival in elderly men with localized prostate cancer. 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. Prostate cancer-specific survival and overall survival. 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). 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.

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

5014 Background: Despite a lack of data, increasing numbers of patients have turned to primary androgen deprivation therapy (PADT) as an alternative to surgery, radiation or active surveillance for the management of localized prostate cancer. We studied the impact of PADT on survival and use of secondary therapy in elderly men with localized prostate cancer. Methods: Medicare claims linked to Surveillance, Epidemiology and End Results (SEER) data were used to assemble a cohort of 19,271 men with T1-T2 prostate cancer without local therapy within 6 months of cancer diagnosis. Instrumental variable analysis was used to overcome potential overt and hidden biases associated with unmeasured confounding variables. Results: Even though 41% of the population received PADT (median age 77), PADT use was not associated with improved median overall survival (114 vs. 113 months, hazard ratio [HR] 1.00; 95% CI 0.95–1.05) or cumulative risk of receiving secondary cancer therapy (31% at 10 years, HR 0.95; 95% CI 0.88 - 1...

Predictors of overall and cancer-specific survival in patients with clinically localized prostate cancer (PC) treated with primary androgen deprivation therapy (PADT): Results from the Prostate Cancer Outcomes Study

4610 Background: Use of PADT as sole therapy for clinically localized PC is rapidly increasing, despite little evidence to support this approach. We examined predictors of overall survival (OS) and cancer-specific survival (CSS) using the data available from the Prostate Cancer Outcome Study (PCOS). Methods: PCOS recruited 5,672 patients between 1994 and 1995, within 6 months of PC diagnosis. Vital status was last updated in 12/02. 276 patients had clinically localized PC and received PADT. We examined the relationship between baseline demographic, socio-economic, and tumor factors and OS and CSS using Kaplan-Meier and Cox regression methods implemented in the SUDAAN software. Results: Of 276 patients, 148 patients have died, 35 from PC. The median age at diagnosis was 75 (50–88). The average follow-up of censored subjects was 7.6 yrs (1.1–8.1). 5-year OS was 66% (95% CI: 69–72), while the 5-year CSS was 91% (95% CI: 86–94). In the multivariate analysis (see Table), age, serum PSA at diagnosis, and Gleason score were the only independent predictors of OS. Abnormal DRE was marginally significant. The Gleason score (≥7) was the only independent predictor of CSS (HR 4.0, p = 0.04); PSA ≥ 20 (HR 2.38, p = 0.09) approached significance. This analysis was limited by a smaller number of deaths due to prostate cancer (n = 35). Conclusions: In an analysis that included a broad range of demographic and socio-economic factors, overall survival of patients with clinically localized prostate cancer treated with PADT was predicted by age and measures of tumor biology (Gleason score) and tumor mass (serum PSA). Thus, cancer remains an important contributor to overall mortality in these patients, particularly those with high Gleason score and high serum PSA. These data can be used to inform patients regarding their individual 5-year survival if they choose PADT for the treatment of their clinically localized prostate cancer. [Table: see text] No significant financial relationships to disclose.

National practice patterns and time trends in androgen ablation for localized prostate cancer.

Recent reports have suggested that growing numbers of patients with localized prostate cancer are receiving androgen deprivation therapy as primary or neoadjuvant treatment, yet sparse clinical evidence supports the use of such treatment except among patients with high-risk or locally advanced disease receiving external beam radiotherapy. We describe national trends in the use of androgen deprivation therapy for localized disease. CaPSURE is an observational database of 7195 patients with prostate cancer. This study included 3439 of these patients who were diagnosed since 1989, had clinical staging information available, and were treated with radical prostatectomy, radiation therapy, or primary androgen deprivation therapy (PADT). High-, intermediate-, and low-risk groups were defined by serum prostate-specific antigen level, Gleason score, and clinical tumor stage. Time trends in the use of PADT and neoadjuvant androgen deprivation therapy (NADT) were analyzed. All statistical tests were two-sided. Rates of PADT use rose sharply between 1989 and 2001, from 4.6% (95% confidence interval [CI] = 3.4% to 5.8%) to 14.2% (95% CI = 12.2% to 16.2%), from 8.9% (95% CI = 7.3% to 10.5%) to 19.7% (95% CI = 17.5% to 21.9%), and from 32.8% (95% CI = 29.9% to 35.7%) to 48.2% (95% CI = 45.1% to 51.3%) (all P<.001) in low-, intermediate-, and high-risk groups, respectively. NADT use also increased in association with radical prostatectomy (2.9% [95% CI = 2.1% to 3.7%] to 7.8% [95% CI = 6.5% to 9.1%] of patients, P =.003) and external beam radiotherapy (9.8% [95% CI = 7.5% to 12.1%] to 74.6% [95% CI = 70.8% to 78.4%], P<.001) across all risk levels combined. Rates of NADT use among patients treated with brachytherapy also increased but not statistically significantly (7.4% [95% CI = 3.5% to 11.3%] to 24.6% [95% CI = 18.2% to 31.0%], P =.100). Rates of both PADT and NADT are increasing across risk groups and treatment types. Future clinical trials must define more clearly the appropriate role of hormonal therapy in localized prostate cancer, and their results should shape updated practice guidelines.