Low Utilization of Androgen Deprivation Therapy Among Men Receiving Stereotactic Body Radiotherapy for Localized Prostate Cancer in the United States.
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SUBMITTER: Royce TJ
PROVIDER: S-EPMC7775872 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer.In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures.At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups.Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.)
| S-EPMC3038121 | biostudies-literature
Project description:ContextDespite 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.ObjectiveTo evaluate the association between PADT and survival in elderly men with localized prostate cancer.Design, setting, and patientsA 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 measuresProstate cancer-specific survival and overall survival.ResultsAmong 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).ConclusionPrimary androgen deprivation therapy is not associated with improved survival among the majority of elderly men with localized prostate cancer when compared with conservative management.
| S-EPMC2645653 | biostudies-literature
Project description:IntroductionAndrogen deprivation therapy (ADT) and radiotherapy (RT) increase survival in selected patients with prostate cancer. Nevertheless, the side effects of these therapies are associated with an increased risk of accidental falls and fractures and a decreased quality of life. Preliminary evidence suggests that physical exercise can be a valid strategy to reduce the side effects of ADT and RT in men with prostate cancer. Despite this knowledge, most patients with prostate cancer are insufficiently active, and there is a lack of data on the safety and adherence to the recommended dose of physical exercise. This study protocol is designed to examine the feasibility and safety of a multicomponent experimental physical exercise intervention targeting psychophysical and cognitive functions and the quality of life in this population.Methods and analysisThis is a pilot feasibility study. Twenty-five men currently treated with ADT and RT for prostate cancer will be invited to participate in a 20-week, multicomponent physical exercise intervention, including supervised and unsupervised exercise sessions and meeting the current recommendation for exercise in cancer. The primary outcomes are physical exercise feasibility (recruitment, adherence and drop-out rates) and safety (adverse events related and unrelated to the intervention). The secondary outcomes are muscle strength, balance, fatigue, symptoms of anxiety and depression, cognitive function, quality of life, and patient satisfaction. We will also record the number of accidental falls and fractures occurring during the intervention and at 1 year of follow-up.Ethics and disseminationThe study has received ethics approval from The Area Vasta Nord Local Ethics Committee (Province of Reggio Emilia, 23 June 2020, Number 520/2020/SPER/IRCCSRE). Recruitment began in September 2020 and will be completed in September 2021. The results will be disseminated through scientific journals and conference presentations.Trial registration numberNCT04500080.
| S-EPMC8928322 | biostudies-literature
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.
| S-EPMC4543371 | biostudies-literature
Project description:BackgroundAndrogen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT.Methods/designA 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data.DiscussionMusculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical function, and ultimately improving the health-related quality of life in men with prostate cancer receiving ADT.Trial registrationClinicalTrials.gov: NCT00834392.
| S-EPMC3352294 | biostudies-literature
Project description:PurposeAndrogen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period.Materials and methodsIn this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes.ResultsThe 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI -1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p <0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p <0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups.ConclusionsToremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles.
| S-EPMC3047407 | biostudies-literature
Project description:BackgroundIn men with node-positive prostate cancer after radical prostatectomy there are limited data on the value of adding androgen deprivation therapy (ADT) to postoperative radiotherapy.ObjectiveTo determine whether there is a clear oncologic benefit to ADT in the setting of node-positive prostate cancer treated with postoperative radiotherapy.MethodsWe analyzed data for 372 prostate cancer patients treated at San Raffaele Hospital with postoperative radiotherapy for node-positive disease after radical prostatectomy, 272 received both ADT and radiotherapy. Eighty-six men were followed without an event for more than 10 years.ResultsPatients who received postoperative radiotherapy + ADT had more aggressive disease, with higher preoperative PSA level, higher rate of ISUP grade 5, pT3b-T4 tumors and ≥3 positive nodes. At multivariable Cox regression, the comparison between men treated by postoperative radiotherapy + ADT vs. radiotherapy alone did not show a significant difference for overall (hazards ratio: 0.91; 95% confidence interval: 0.45, 1.84; P = 0.8) and cancer-specific survival (hazards ratio: 5.39; 95% confidence intervalI: 0.70, 41.39; P = 0.11). These results remained consistent in a number of sensitivity analyses, including propensity score matching. Consideration of 95% CIs suggests that a clinically significant benefit of ADT in node-positive patients receiving radiotherapy after surgery is unlikely.ConclusionsWe can exclude the sort of large survival benefit that would be required to justify the risks and toxicities of ADT in men with node-positive disease receiving postoperative radiotherapy. Awaiting larger and more powered studies on this topic, men with pN+ prostate cancer treated with postoperative radiotherapy should not receive ADT outside well-controlled clinical trials.
| S-EPMC8142939 | biostudies-literature
Project description:BackgroundTo evaluate the clinical outcomes of combination of androgen deprivation therapy (ADT), whole pelvic radiotherapy (WPRT), and stereotactic body radiotherapy (SBRT) boost in high-risk prostate cancer patients.MethodsThis prospective phase I/IIa study was conducted between 2016 and 2017. Following WPRT of 44 Gy in 20 fractions, patients were randomized to two boost doses, 18 Gy and 21 Gy, in 3 fractions using the Cyberknife system. Primary endpoints were incidences of acute toxicities and short-term biochemical recurrence-free survival (BCRFS). Secondary endpoints included late toxicities and short-term clinical progression-free survival (CPFS).ResultsA total of 26 patients were enrolled. Twelve patients received a boost dose of 18 Gy, and the rest received 21 Gy. The Median follow-up duration was 35 months. There were no grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicities. Sixty-one and 4% of patients experienced grade 1-2 acute GU and GI toxicities, respectively. There were 12% late grade 1-2 GU toxicities and 8% late grade 1-2 GI toxicities. Patient-reported outcomes of urinary symptoms were aggravated after WPRT and SBRT boost. However, they resolved at 1 month and returned to the baseline level at 4 months. Three-year BCRFS was 88.1%, and CPFS was 92.3%.ConclusionsThe present study protocol demonstrated that the combination of ADT, WPRT, and SBRT boosts for high-risk prostate cancer is safe and feasible, and may reduce total treatment time to 5 weeks. Boost dose of 21 Gy in 3 fractions seems appropriate.Trial registrationClinicalTrials.gov, ID; NCT03322020 - Retrospectively registered on 26 October 2017.
| S-EPMC7542889 | biostudies-literature
Project description:BACKGROUND:Ultrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown. METHODS:Men >?40?years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index. RESULTS:With a median follow up of 74?months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group. On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68-1.74, p?=?.72; HR: adjusted HR 0.93, 95% CI 0.76-1.14, p?=?.51). On sensitivity analyses, when confining the cohort to men treated with NCCN-preferred dose fractionations, with no comorbidities, or?<?65?years old, there remained no survival difference between treatment groups for both UIR and HR. CONCLUSION:Within study limitations, we found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HR PC. These results support recent NCCN guideline updates, which include SBRT as a non-preferred option for higher risk men. Prospective validation would further strengthen the evidence basis behind these recommendations.
| S-EPMC7493337 | biostudies-literature
Project description:The utilization of Androgen Deprivation Therapy (ADT) in conjunction with Stereotactic Body Radiotherapy (SBRT) and Brachytherapy (BT) boost in prostate cancer treatment is a subject of ongoing debate and evolving clinical practice. While contemporary trends lean towards underutilizing ADT with these modalities, existing evidence suggests that its omission may lead to potentially inferior oncologic outcomes. Recommendations for ADT use should be patient-centric, considering individual risk profiles and comorbidities, with a focus on achieving optimal oncologic outcomes while minimizing potential side effects. Ongoing clinical trials, such as PACE-C, SPA, SHIP 0804, and SHIP 36B, are anticipated to provide valuable insights into the optimal use and duration of ADT in both SBRT and BT settings. Until new evidence emerges, it is recommended to initiate ADT for unfavorable intermediate-risk and high-risk prostate cancer patients undergoing radiotherapy, with a minimum duration of 6 months for unfavorable intermediate-risk patients and at least 12 months for those with high-risk characteristics. The decision to incorporate ADT into these radiation therapy modalities should be individualized, acknowledging the unique needs of each patient and emphasizing a tailored approach to achieve the best possible oncologic outcomes.
| S-EPMC10844661 | biostudies-literature