Home-based versus supervised group exercise in men with prostate cancer on androgen deprivation therapy: A randomized controlled trial and economic analysis.

INTRODUCTION: Differences between health outcomes, participation/adoption, and cost-effectiveness of home-based (HOME) interventions and supervised group-based training (GROUP) in men with prostate cancer (PC) on androgen deprivation therapy (ADT) are currently unknown. The objective of this study was to assess the clinical efficacy, adherence, and cost-effectiveness of HOME versus GROUP in men on ADT for PC. MATERIALS AND METHODS: This was a multicentre, 2-arm non-inferiority randomized controlled trial and companion cost-effectiveness analysis. Men with PC on ADT were recruited from August 2016 to March 2020 from four Canadian centres and randomized 1:1 to GROUP or HOME. All study participants engaged in aerobic and resistance training four to five days weekly for six months. Fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F)] and functional endurance [6-min walk test (6MWT)] at six months were the co-primary outcomes. Secondary outcomes included quality of life, physical fitness, body composition, blood markers, sedentary behaviour, and adherence. Between-group differences in primary outcomes were compared to margins of 3 points for FACT-F and 40 m for 6MWT using a Bayesian analysis of covariance (ANCOVA). Secondary outcomes were compared with ANCOVA, Costs included Ministry of Health costs, program costs, patient out-of-pocket, and time costs. TRIAL REGISTRATION: #NCT02834416. RESULTS: Thirty-eight participants (mean [standard deviation (SD)] age, 70 [9.0] years) were enrolled (GROUP n = 20; HOME n = 18). There was an 89.8% probability that HOME was non-inferior to GROUP for both fatigue and functional endurance and a 9.5% probability that HOME reduced fatigue compared to GROUP (mean [SD] change, 12.1 [8.1] vs 3.6 [6.1]; p = 0.040) at six months. Adherence was similar among study arms. HOME was cost-saving (mean difference: -$4122) relative to GROUP. DISCUSSION: A HOME exercise intervention appears non-inferior to GROUP for fatigue and functional endurance and requires fewer resources to implement. HOME appears to ameliorate fatigue more than GROUP, but has comparable effects on other clinically relevant outcomes. Although limited by sample size and attrition, these results support further assessment of home-based programs.

The STAMPEDE2 Trial: a Site Survey of Current Patterns of Care, Access to Imaging and Treatment of Metastatic Prostate Cancer.

AIMS: The forthcoming STAMPEDE2 trial has three comparisons in metastatic hormone-sensitive prostate cancer. We aim to determine clinical practices among STAMPEDE trial investigators for access to imaging and therapeutic choices and explore their interest in participation in STAMPEDE2. MATERIALS AND METHODS: The survey was developed and distributed online to 120 UK STAMPEDE trial sites. Recipients were invited to complete the survey between 16 and 30 May 2022. The survey consisted of 30 questions in five sections on access to stereotactic ablative body radiotherapy (SABR), 177lutetium-prostate-specific membrane antigen-617 (177Lu-PSMA-617), choice of systemic therapies and use of positron emission tomography/computerised tomography and whole-body magnetic resonance imaging. RESULTS: From 58/120 (48%) sites, 64 respondents completed the survey: 55/64 (86%) respondents were interested to participate in SABR, 44/64 (69%) in 177Lu-PSMA-617 and 56/64 (87.5%) in niraparib with abiraterone comparisons; 45/64 (70%) respondents had access to bone, spine and lymph node metastases SABR delivery and 7/64 (11%) to 177Lu-PSMA-617. In addition to androgen deprivation therapy, 60/64 (94%) respondents used androgen receptor signalling inhibitors and 46/64 (72%) used docetaxel; 29/64 (45%) respondents would consider triplet therapy with androgen deprivation therapy, androgen receptor signalling inhibitors and docetaxel. Positron emission tomography/computerised tomography was available to 62/64 (97%) respondents and requested by 45/64 (70%) respondents for disease uncertainty on conventional imaging and 39/64 (61%) at disease relapse. Whole-body magnetic resonance imaging was available to 24/64 (38%) respondents and requested by 13/64 (20%) respondents in highly selected patients. In low-volume disease, 38/64 (59%) respondents requested scans at baseline and disease relapse. In high-volume disease, 29/64 (45%) respondents requested scans at baseline, best response (at prostate-specific antigen nadir) and disease relapse; 54/64 (84%) respondents requested computerised tomography and bone scan for best response assessment. CONCLUSION: There is noteworthy disparity in clinical practice across current study sites, however most have expressed an interest in participation in the forthcoming STAMPEDE2 trial.

Cost-effectiveness analysis of 7 treatments in metastatic hormone-sensitive prostate cancer: a public-payer perspective.

BACKGROUND: Recently, several new treatment regimens have been approved for treating metastatic hormone-sensitive prostate cancer, building on androgen deprivation therapy alone. These include docetaxel androgen deprivation therapy, abiraterone acetate-prednisone androgen deprivation therapy, apalutamide androgen deprivation therapy, enzalutamide androgen deprivation therapy, darolutamide-docetaxel androgen deprivation therapy, and abiraterone-prednisone androgen deprivation therapy with docetaxel. There are no validated predictive biomarkers for choosing a specific regimen. The goal of this study was to conduct a health economic outcome evaluation to determine the optimal treatment from the US public sector (Veterans Affairs). METHODS: We developed a partitioned survival model in which metastatic hormone-sensitive prostate cancer patients transitioned between 3 health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a Bayesian network meta-analysis of 7 clinical trials (7208 patients). The effectiveness outcome in our model was quality-adjusted life-years (QALYs). Cost input parameters included initial and subsequent treatment costs and costs for terminal care and for managing grade 3 or higher drug-related adverse events and were obtained from the Federal Supply Schedule and published literature. RESULTS: Average 10-year costs ranged from $34 349 (androgen deprivation therapy) to $658 928 (darolutamide-docetaxel androgen deprivation therapy) and mean QALYs ranged from 3.25 (androgen deprivation therapy) to 4.57 (enzalutamide androgen deprivation therapy). Treatment strategies docetaxel androgen deprivation therapy, enzalutamide androgen deprivation therapy docetaxel, apalutamide androgen deprivation therapy, and darolutamide-docetaxel androgen deprivation therapy were eliminated because of dominance (ie, they were more costly and less effective than other strategies). Of the remaining strategies, abiraterone acetate-prednisone androgen deprivation therapy was the most cost-effective strategy at a willingness-to-pay threshold of $100 000/QALY (incremental cost-effectiveness ratios = $21 247/QALY). CONCLUSIONS: Our simulation model found abiraterone acetate-prednisone androgen deprivation therapy to be an optimal first-line treatment for metastatic hormone-sensitive prostate cancer from a public (Veterans Affairs) payer perspective.

Cost-Utility Analysis of Darolutamide Combined with Androgen Deprivation Therapy for Patients with High-Risk Non-Metastatic Castration-Resistant Prostate Cancer in China.

INTRODUCTION: The increasing incidence of prostate cancer (PC) in China leads to a significant disease burden. Although three novel androgen inhibitors (darolutamide, apalutamide, and enzalutamide) have been approved for patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), the economic evaluation of these novel treatments in China remains unknown. In this study, we aimed to evaluate the cost-utility of darolutamide combined with androgen deprivation therapy (ADT), comparing with apalutamide + ADT and enzalutamide + ADT, in patients with high-risk nmCRPC from a healthcare system perspective in China. METHODS: A partitioned survival model was developed to capture time spent by patients in three health states: nmCRPC, metastatic CRPC (mCRPC), and death. Clinical outcomes from the ARAMIS, PROSPER, and SPARTAN studies were obtained. In the absence of head-to-head studies, indirect treatment comparisons were conducted to capture the comparative effectiveness between darolutamide + ADT, apalutamide + ADT, and enzalutamide + ADT. The prices of apalutamide and enzalutamide were assumed to be the same as the initial launch price of darolutamide, since post-negotiation prices after national reimbursement drug list (NRDL) inclusion remain confidential. Other health resources costs, baseline characteristics, treatment patterns, and utility were collected through literature or clinical expert interviews. Selected sensitivity analyses were also performed. RESULTS: For a 20-year time horizon, darolutamide + ADT was associated with lower cost per quality-adjusted life years (QALYs) than apalutamide + ADT and enzalutamide + ADT (202,897 Chinese yuan (CNY)/QALY vs. 228,998 CNY/QALY and 221,409 CNY/QALY, respectively) (exchange rate, 1 USD = 6.7871 CNY). Darolutamide + ADT had better health outcomes and lower total costs compared to both apalutamide + ADT (+ 0.22 QALYs and - 72,818 CNY) and enzalutamide + ADT (+ 0.09 QALYs and - 67,451 CNY). Across the modelled sensitivity analyses (including hazard ratios and drug costs), darolutamide + ADT remained dominant or cost-effective. CONCLUSIONS: This economic evaluation suggested that, in comparison with apalutamide + ADT and enzalutamide + ADT, darolutamide + ADT was a dominant or cost-effective treatment option for patients with high-risk nmCRPC in China.

Cost-effectiveness analysis of androgen deprivation therapy with relugolix for the treatment of advanced prostate cancer.

BACKGROUND: Relugolix treatment of advanced prostate cancer (APC), like other gonadotropin-releasing hormone-antagonists, results in rapid decrease in testosterone concentrations without the risk of flare, as seen in leuprolide. Despite this benefit over leuprolide, no economic evaluation assessment to ascertain the cost-effectiveness of relugolix has been conducted. Therefore, this study aims to assess the cost-effectiveness of androgen deprivation therapy (ADT) with 120 mg relugolix against 7.5 mg leuprolide for the treatment of APC. METHODS: A Markov model was used to assess and compare the costs of APC treatment from a health care payer's perspective and the effectiveness of ADT with relugolix and leuprolide at the 3 lines of APC treatment among modified intent-to-treat patients. Relative progression-free (PFS) and overall survival (OS) rates were estimated. Outcomes measured in the analyses included costs of the drugs and therapies, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), cost-effectiveness acceptability, and probability curves. RESULTS: The cost-effectiveness analysis showed the ICER for ADT with relugolix to be US $49,571.1 per QALY. At the ICER value, the sensitivity analysis indicated that ADT with leuprolide was dominant in 100% of the simulations. ADT acceptance with relugolix was 100% when a willingness-to-pay threshold was set at US $100,000/QALY. At 5-years, the relative PFS and OS rates for relugolix at the first line of therapy were 72.7% and 86.0%, respectively, compared to 61.0% and 85.90% for leuprolide. CONCLUSION: Though the influence of adverse events was not considered in the analysis, ADT with relugolix was not a cost-effective choice for APC management. While the analysis revealed a slight chance of sustaining testosterone suppression with relugolix, ADT with relugolix provided no significant survival advantages over ADT with leuprolide. Therefore, this analysis confirms no need for further assessment of APC interventions to make informed decisions beneficial to the APC patients, oncologists, and other stakeholders.

Androgen Deprivation and Sleep Disturbance: A Mixed Methods Pilot Study of Remote Assessment and Intervention.

BACKGROUND: Men receiving androgen deprivation therapy (ADT) for prostate cancer (PC) are at risk for cardiovascular comorbidities and cognitive changes. Interventional research involves in-person assessment of physical fitness/activity and cognitive function, which has been negatively affected by the COVID-19 pandemic. Androgen deprivation therapy-related hot flashes and nocturia increase risk for insomnia. Insomnia is associated with fatigue and may exacerbate ADT-related cognitive changes. OBJECTIVES: The purpose of this mixed-methods pilot was to (1) determine feasibility/acceptability of remotely assessing physical fitness/activity, cognitive function, and sleep; (2) deliver telehealth cognitive behavioral training for insomnia (teleCBT-I) to improve sleep; and (3) garner qualitative feedback to refine remote procedures and teleCBT-I content. METHODS: Fifteen men with PC receiving ADT completed a 4-week teleCBT-I intervention. Videoconferencing was used to complete study assessments and deliver the weekly teleCBT-I intervention. RESULTS: Self-report of sleep quality improved ( P < .001) as did hot flash frequency ( P = .04) and bother ( P = .025). Minimal clinically important differences were detected for changes in insomnia severity and sleep quality. All sleep logs indicated improvement in sleep efficiency. Remote assessment of fitness/cognitive function was demonstrated for 100% of participants. Sufficient actigraph wear time allowed physical activity/sleep assessment for 80%. Sleep actigraphy did not demonstrate significant changes. CONCLUSIONS: Remote monitoring and teleCBT-I are feasible/acceptable to men with PC on ADT. Further research to confirm teleCBT-I efficacy is warranted in this population. IMPLICATIONS FOR PRACTICE: Preliminary efficacy for teleCBT-I interventions was demonstrated. Remote assessments of physical fitness/activity, sleep, and cognitive function may enhance clinical trial access for rural or economically disadvantaged PC survivors.

Treatments for Metastatic Hormone-sensitive Prostate Cancer: Systematic Review, Network Meta-analysis, and Benefit-harm assessment.

CONTEXT: Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear. OBJECTIVE: To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments. EVIDENCE ACQUISITION: We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate. EVIDENCE SYNTHESIS: Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (>60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (<40%) to be beneficial. CONCLUSIONS: Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies. PATIENT SUMMARY: We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.

Cost-effectiveness of enzalutamide versus apalutamide versus androgen deprivation therapy alone for the treatment of metastatic castration-sensitive prostate cancer in Canada.

AIMS: There are no direct comparisons of the relative cost-effectiveness of second-generation anti-androgens (enzalutamide and apalutamide) used in managing metastatic castration-sensitive prostate cancer (mCSPC) in Canada. This study compared the cost-effectiveness of enzalutamide versus apalutamide versus androgen deprivation therapy (ADT) alone (standard of care) in patients with mCSPC from the Canadian public payer perspective using a Markov model with a 15-year time horizon. MATERIALS AND METHODS: Efficacy data for enzalutamide and ADT alone were informed by the ARCHES and ENZAMET clinical trials, while a Bayesian network meta-analysis enabled comparison with apalutamide and ADT alone. RESULTS: Over the 15-year period, enzalutamide achieved the highest number of life-years (LY, 7.6) and quality-adjusted life-years (QALY, 5.62) compared with apalutamide (LY, 6.1; QALY, 4.59) and ADTs (LY, 4.9; QALY, 3.61). Enzalutamide incurred the most costs ($349,345) compared with apalutamide ($294,349) and ADT ($162,550). Sequential analysis showed that enzalutamide lies on the cost-effectiveness frontier with ADT alone (incremental cost-effectiveness ratio: $92,868/QALY), with apalutamide extendedly dominated through enzalutamide and ADT alone. LIMITATIONS: Limitations include the heterogeneity of the studies included in the network meta-analysis and the validations for the treatment sequencing assumptions in the modeling. CONCLUSIONS: Enzalutamide was the most effective treatment option for mCSPC in the Canadian market, with the greatest LYs and QALYs, and incurred the most costs.

Association of Bone Mineral Density Testing With Risk of Major Osteoporotic Fractures Among Older Men Receiving Androgen Deprivation Therapy to Treat Localized or Regional Prostate Cancer.

Importance: Bone health screening is recommended for patients with prostate cancer who are initiating treatment with androgen deprivation therapy (ADT); however, bone mineral density screening rates in the US and their association with fracture prevention are unknown. Objective: To assess dual-energy x-ray absorptiometry (DXA) screening rates and their association with fracture rates among older men with prostate cancer initiating treatment with androgen deprivation therapy. Design, Setting, and Participants: This retrospective nationwide population-based cohort study used data from the Surveillance, Epidemiology, and End Results database and the Texas Cancer Registry linked with Medicare claims. Participants comprised 54 953 men 66 years or older with prostate cancer diagnosed between January 2005 and December 2015 who initiated treatment with ADT. Data were censored at last enrollment in Medicare and analyzed from January 1 to September 30, 2021. Exposures: Dual-energy x-ray absorptiometry screening within 12 months before and 6 months after the first ADT claim. Main Outcomes and Measures: Frequencies of DXA screening and fracture (any fracture and major osteoporotic fracture) and overall survival were calculated. The association between DXA screening and fracture was evaluated using a multivariable Cox proportional hazards model with propensity score adjustment. Results: Among 54 953 men (median age, 74 years; range, 66-99 years) with prostate cancer, 4689 (8.5%) were Hispanic, 6075 (11.1%) were non-Hispanic Black, 41 453 (75.4%) were non-Hispanic White, and 2736 (5.0%) were of other races and/or ethnicities (including 121 [0.2%] who were American Indian or Alaska Native; 1347 [2.5%] who were Asian, Hawaiian, or Pacific Islander; and 1268 [2.3%] who were of unknown race/ethnicity). Only 4362 men (7.9%) received DXA screening. The DXA screening rate increased from 6.8% in 2005 to 8.4% in 2015. Lower screening rates were associated with being single (odds ratio [OR], 0.89; 95% CI, 0.81-0.97; P = .01) and non-Hispanic Black (OR, 0.80; 95% CI, 0.70-0.91; P < .001), living in small urban areas (OR, 0.77; 95% CI, 0.66-0.90; P = .001) and areas with lower educational levels (OR, 0.75; 95% CI, 0.67-0.83; P < .001), and receiving nonsteroidal androgens (OR, 0.57; 95% CI, 0.39-0.84; P = .004). Overall, 9365 patients (17.5%) developed fractures after initial receipt of ADT. The median time to first fracture was 31 months (IQR, 15-56 months). In the multivariable model with propensity score adjustment, DXA screening was not associated with fracture risk at any site (hazard ratio [HR], 0.96; 95% CI, 0.89-1.04; P = .32) among men without previous fractures before receipt of ADT. However, previous DXA screening was associated with a decreased risk of major fractures (HR, 0.91; 95% CI, 0.83-1.00; P = .05) after propensity score adjustment. Conclusions and Relevance: In this study, low DXA screening rates were observed among older men with localized or regional prostate cancer after initiation of treatment with ADT. Despite low rates of screening, evaluation of bone mineral density with a DXA scan was associated with lower risk of major fractures. These findings suggest that DXA screening is important for the prevention of major fractures among older men with prostate cancer and that implementation strategies are needed to adopt bone health screening guidelines in clinical practice.

Enzalutamida para adenocarcinoma de próstata metastásico en primera línea de tratamiento / Enzalutamide for metastatic prostate adenocarcinoma in first-line treatment

DESCRIPCIÓN DEL PROBLEMA DE SALUD: El cáncer de próstata es el segundo diagnóstico de cáncer más frecuente en hombres y la quinta causa principal de muerte en todo el mundo. El cáncer de próstata puede ser asintomático en la etapa inicial y, a menudo, tiene un curso indolente que puede requerir solo una vigilancia activa. Según las estimaciones de GLOBOCAN 2018, en 2018 se notificaron 1.276.106 nuevos casos de cáncer de próstata en todo el mundo, con una mayor prevalencia en los países desarrollados. Las diferencias en las tasas de incidencia en todo el mundo reflejan diferencias en el uso de pruebas de diagnóstico. Las tasas de incidencia y mortalidad del cáncer de próstata están estrechamente relacionadas con la edad y la incidencia más alta se observa en hombres de edad avanzada (> 65 años). Los hombres afroamericanos tienen las tasas de incidencia más altas y el tipo de cáncer de próstata más agresivo en comparación con los hombres blancos. Aún no hay evidencia sobre cómo prevenir el cáncer de próstata; sin embargo, Es posible reducir el riesgo limitando los alimentos ricos en grasas, aumentando la ingesta de verduras y frutas y realizando más ejercicio. Se recomienda encarecidamente la detección a los 45 años para hombres con antecedentes familiares y hombres afroamericanos. Las estadísticas actualizadas sobre la aparición y los resultados del cáncer de próstata, junto con una mejor comprensión de la etiología y los factores de riesgo causales, son esenciales para la prevención primaria de esta enfermedad. TRATAMIENTO ACTUAL/ COMPARADOR: El comparador es considerado como el procedimiento con mayor probabilidad de ser reemplazado en la práctica clínica de la intervención solicitada enzalutamida, para lo cual el comparador actual acorde a las guías de tratamiento internacionales es abiraterona y docetaxel. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas Se filtró la búsqueda a Estudios Clínicos fase III, controlados randomizados, Revisiones Sistemáticas, Metaanálisis, Guías de Práctica Clínica, además se limitó la búsqueda estudios en humanos. También se realizó búsqueda manual en otras bases de datos bibliográficas (Cochrane, NIH, TRIP DATABASE), en buscadores genéricos de internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, meta-análisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnología sanitaria, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. CONCLUSIONES: Eficacia: No existe estudios que compare la eficacia de Enzalutamida Vs Abiraterona o Vs Docetaxel en relación a la sobrevida global o calidad de vida ganada. Los datos de sobrevida global en estudios contra placebo son similares para Enzalutamida y Abiraterona. Seguridad: El perfil de seguridad de Enzalutamida es similar al de abiraterona, sin embargo presenta ventajas con respecto a la terapia con Docetaxel. Conveniencia: Enzalutamida no requiere el uso concomitante de esteroides y al igual que abiraterona es uso por vía oral a diferencia de la terapia con docetaxel. COSTO: El costo de Enzalutamida es -3,205% mayor que la terapia con abiraterona y -126,928% en comparación con docetaxel.

[COST ANALYSIS OF ANDROGEN DEPRIVATION THERAPY AND DRUGS FOR CASTRATION-RESISTANT PROSTATE CANCER].

(Purpose) Recently, new effective drugs for the treatment of castration-resistant prostate cancer (CRPC) have been developed. Although they are expected to prolong the survival time of patients with advanced prostate cancer, they may result in an economic burden. In this study, we determined the treatment results and the cost of CRPC drugs. (Methods) From 2014 to 2017, patients who were unfit for curative therapy were enrolled in this study. First, they received androgen deprivation therapy (ADT) by surgical or chemical castration. Once castration-sensitive cancer progressed to castration-resistant cancer, CRPC drugs, such as docetaxel, cabazitaxel, abiraterone and enzalutamide, were administered sequentially. In elderly or fragile patients, drug doses were often reduced to minimize their toxicity. The total costs of drugs for castration-sensitive and castration-resistant cancers were calculated, and the results were evaluated. (Results) Prostate biopsies detected prostate cancer in 257 patients. Eighty-one patients were treated with ADT, and 56 of the cancers were metastatic or showed a high prostate specific antigen level (>100 ng/ml). Thirty patients out of the 56 with advanced cancers developed CRPC, and the median time to CRPC was 10 months (range, 3-39). Drugs targeting CRPC were administered in 25 patients for a median duration of 20 months (range, 3-50). During the median observation period of 48 months (range, 13-75), 15 patients died of prostate cancer. The median annual cost of drugs for castration-sensitive cancer was 234,000 Japanese yen (2,187 US dollars) [range, 50,000-315,000 yen (467-2,943 US dollars) ]. In contrast, the median annual cost of drugs for CRPC was 2,041,000 yen (19,075 US dollars) [range, 346,000-5,017,000 yen (3,230-46,886 US dollars) ]. (Conclusions) Advanced prostate cancer tended to rapidly progress to CRPC, which required a sequence of expensive drugs for treatment. Early diagnosis preventing the development of advanced prostate cancer is desirable to reduce the economic burden for the health insurance system.

Treatment of Metastasized Prostate Cancer Beyond Progression After Upfront Docetaxel-A Real-world Data Assessment.

BACKGROUND: Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce. OBJECTIVE: To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model. RESULTS AND LIMITATIONS: Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature. CONCLUSIONS: In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer. PATIENT SUMMARY: We analyzed the efficacy of second-line therapy after docetaxel in hormone-dependent metastatic prostate cancer. Novel hormone therapy appears to be a preferable option for deferring progression optimally. Larger patient databases are eagerly awaited.

Trends and Patterns of Testosterone Therapy among U.S. Male Medicare Beneficiaries, 1999 to 2014.

PURPOSE: We explored the Medicare database (1999 to 2014) to provide a comprehensive assessment of testosterone therapy patterns in the older U.S. male population. MATERIALS AND METHODS: We estimated annual age-standardized incidence (new users) and prevalence (existing users) of testosterone therapy according to demographic characteristics, comorbidities and potential indications. RESULTS: There were 392,698 incident testosterone therapy users during 88 million person-years. Testosterone therapy users were predominantly younger, white nonHispanic, and located in South and West U.S. Census regions. On average testosterone therapy use increased dramatically during 2007 to 2014 (average annual percent change 15.5%), despite a decrease in 2014. In 2014 the most common recorded potential indications for any testosterone therapy were hypogonadism (48%), fatigue (18%), erectile dysfunction (15%), depression (4%) and psychosexual dysfunction (1%). Laboratory tests to measure circulating testosterone concentrations for testosterone therapy were infrequent with 35% having had at least 1 testosterone test in the 120 days preceding testosterone therapy, 4% the recommended 2 pre-testosterone therapy tests, and 16% at least 1 pre-testosterone therapy test and at least 1 post-testosterone therapy test. CONCLUSIONS: Testosterone therapy remains common in the older U.S. male population, despite a recent decrease. Although testosterone therapy prescriptions are predominantly for hypogonadism, a substantial proportion appear to be for less specific conditions. Testosterone tests among men prescribed testosterone therapy appear to be infrequent.

Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): Design and implementation of a double-blind randomized controlled trial.

BACKGROUND: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). AIMS: To determine in a multi-centre, double-blinded placebo-controlled randomized trial whether testosterone treatment combined with lifestyle intervention (Weight Watchers) relative to lifestyle intervention alone reduces T2DM incidence and improves glucose tolerance at 2 years. STUDY POPULATION: Overweight or obese men aged 50-74 years with a serum testosterone of ≤14 nmol/L and IGT or newly diagnosed T2DM established by an oral glucose tolerance test (OGTT). SETTING, DRUG AND PROTOCOL: Six Australian capital city-based tertiary care centres. Participants were randomized 1:1 and injected with testosterone undecanoate (1000 mg/4 mL) or vehicle (4 mL castor oil), at baseline, 6 weeks and 3-monthly thereafter. PRIMARY ENDPOINTS: (a) Proportion of participants with 2-hour OGTT ≥11.1 mmol/L at 2 years, and (b) a difference at 2 years ≥0.6 mmol/L in the mean 2-hour OGTT glucose between treatments. SECONDARY ENDPOINTS: Fasting insulin, HbA1c, body composition, maximal handgrip strength; sexual function and lower urinary tract symptoms; serum sex steroids and sex hormone binding globulin; mood and psychosocial function; adherence to lifestyle intervention; and healthcare utilization and costs. SAFETY: Overseen by an Independent Data Safety Monitoring Committee. Haematocrit, lipids and prostate-specific antigen (PSA) are assessed 6-monthly and information relating to haematological, urological and cardiovascular adverse events from each clinic visit. SUB-STUDIES: (a) Changes in bone density and micro-architecture, (b) motivation and behaviour, (c) telomere length, (d) extended treatment up to 4 years, and (e) hypothalamo-pituitary testicular axis recovery at treatment end.

Specialist Advice Support for Management of Severe Hereditary Angioedema Attacks: A Multicenter Cluster-Randomized Controlled Trial.

STUDY OBJECTIVE: Hereditary angioedema is a rare disease associated with unpredictable, recurrent attacks of potentially life-threatening edema. Management of severe attacks is currently suboptimal because emergency medical teams are often unaware of new specific treatments. The objective of this trial is to test whether a dedicated national telephone care-management strategy would reduce resource use during severe hereditary angioedema attacks. METHODS: We conducted a cluster-randomized multicenter prospective trial of patients with a documented diagnosis of hereditary angioedema (type I, II or FXII hereditary angioedema). Participants were enrolled between March 2013 and June 2014 at 8 participating reference centers. The randomized units were the reference centers (clusters). Patients in the intervention arm were given a national free telephone number to call in the event of a severe attack. Emergency physicians in the SOS-hereditary angiœdema (SOS-HAE) call center were trained to advise or prescribe specific treatments. The primary outcome was number of admissions for angioedema attacks. Economic evaluation was also performed. RESULTS: We included 100 patients in the SOS-HAE group and 100 in the control group. During the 2 years, there were 2,368 hereditary angioedema attacks among 169 patients (85%). Mean number of hospital admissions per patient in the 2-year period was significantly greater in the usual-practice group (mean 0.16 [range 0 to 2] versus 0.03 [range 0 to 1]); patient risk difference was significant: -0.13 (95% confidence interval -0.22 to -0.04; P=.02). Probabilistic sensitivity graphic analysis indicated a trend toward increased quality-adjusted life-years in the SOS-HAE group. CONCLUSION: A national dedicated call center for management of severe hereditary angioedema attacks is associated with a decrease in hospital admissions and may be cost-effective if facilities and staff are available to deliver the intervention alongside existing services.

Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2DM: a meta-analysis of randomized controlled trials.

Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta-analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5 years, were included in this study. The pooled results of the meta-analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of -6.44 (95% CI: -11.82 to -1.06; I2  = 28%; p = 0.02) and -27.94 (95% CI: -52.33 to -3.54; I2  = 76%; p = 0.02). Subgroup analyses revealed that the heterogeneity (I2  = 76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2  = 45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL-C level in developing countries compared with the control group (MD = 2.79; 95% CI: 0.73 to 4.86; I2  = 0%; p = 0.008), but there was no improvement in developed countries (MD = 1.02; 95% CI: -4.55 to 6.60; I2  = 91%; p = 0.72). However, LDL-C levels were not improved consistently. Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.

Marketing and Testosterone Treatment in the USA: A Systematic Review.

CONTEXT: Testosterone replacement therapy (TRT) is currently approved by the Food and Drug Administration only for classic hypogonadism, although off-label indications have resulted in a dramatic expansion in prescriptions in the USA. Marketing may significantly affect prescriber behavior. OBJECTIVE: To systematically review all available evidence on marketing and TRT in the USA. EVIDENCE ACQUISITION: PubMed, Embase, and Scopus were searched up to July 2017 for all relevant publications reporting on assessments of the TRT market size, economic costs associated with hypogonadism, trends in TRT prescriptions, drug discontinuation rates, and advertising and sales efforts in the USA. EVIDENCE SYNTHESIS: Twenty retrospective studies were included in the final analysis. The market size for hypogonadism constitutes 5.6-76.8% of men in the USA, with the lower end of the range representing the strictest criteria for diagnosis. Men with a diagnosis of hypogonadism consume $14 118 in direct and indirect costs to the payer. Over the last 2 decades, TRT prescriptions have increased between 1.8- and 4-fold. After 1 yr, 80-85% of men discontinue TRT. There is an association between direct-to-consumer advertising and testosterone testing, TRT prescriptions, and TRT without testosterone testing. There is a high prevalence of misinformation on Internet advertising. CONCLUSIONS: Off-label indications have driven the dramatic expansion of TRT prescriptions over the last 2 decades. Direct-to-consumer advertising poses a unique challenge in the USA. Overtreatment can be avoided by applying strict diagnostic criteria for hypogonadism, which limits the addressable market for TRT. PATIENT SUMMARY: In this report, we reviewed the relationship between marketing and testosterone therapy in the USA. We found that many patients are prescribed testosterone without an appropriate diagnosis of hypogonadism, which may be related to the marketing efforts for off-label prescribing.

Pharmacoepidemiology of testosterone: Curbing off-label prescribing.

OBJECTIVES: To estimate the impact of the first year of new Pharmaceutical Benefits Scheme (PBS) prescribing criteria that dictate eligibility for national health scheme subsidy of testosterone prescribing. DESIGN: Analysis of cumulative PBS data. SETTING: Retrospective analysis of testosterone prescribing from PBS data. PARTICIPANTS: Nil MAIN OUTCOME MEASURES: PBS expenditure analysed by total expenditure, by state, and by product type as well as the age, indication, and prescriber type for new testosterone treatment. RESULTS: Total PBS expenditure continued to exceed $20 million in 2014 before declining from 2015 with changes that were uniform by state and product type. Prior to 2015, over 80% were for men aged over 40 years of age for low circulating testosterone in the absence of reproductive system disorders ("Low T") initiated by GPs. From 2015, these features were markedly reduced without changing the numbers of new prescriptions for pathological reproductive disorders or specialist initiations. CONCLUSIONS: The short-term impact of 2015 PBS criteria showed highly effective and well-targeted curbing of off-label testosterone prescribing. The findings indicate that the main driver for the recent upsurge in testosterone prescribing was treatment of middle-aged men for "Low T" initiated by GPs.