Supported exercise TrAining for Men wIth prostate caNcer on Androgen deprivation therapy (STAMINA): study protocol for a randomised controlled trial of the clinical and cost-effectiveness of the STAMINA lifestyle intervention compared with optimised usual care, including internal pilot and parallel process evaluation.

BACKGROUND: UK national clinical guidance recommends that men with prostate cancer on androgen deprivation therapy are offered twice weekly supervised aerobic and resistance exercise to address iatrogenic harm caused by treatment. Very few NHS trusts have established adequate provision of such services. Furthermore, interventions fail to demonstrate sustained behaviour change. The STAMINA lifestyle intervention offers a system-level change to clinical care delivery addressing barriers to long-term behaviour change and implementation of new prostate cancer care pathways. This trial aims to establish whether STAMINA is clinically and cost-effective in improving cancer-specific quality of life and/or reducing fatigue compared to optimised usual care. The process evaluation aims to inform the interpretation of results and, if the intervention is shown to benefit patients, to inform the implementation of the intervention into the NHS. METHODS: Men with prostate cancer on androgen deprivation therapy (n = 697) will be identified from a minimum of 12 UK NHS trusts to participate in a multi-centre, two-arm, individually randomised controlled trial. Consenting men will have a 'safety to exercise' check and be randomly allocated (5:4) to the STAMINA lifestyle intervention (n = 384) or optimised usual care (n = 313). Outcomes will be collected at baseline, 3-, 6- and 12-month post-randomisation. The two primary outcomes are cancer-specific quality of life and fatigue. The parallel process evaluation will follow a mixed-methods approach to explore recruitment and aspects of the intervention including, reach, fidelity, acceptability, and implementation. An economic evaluation will estimate the cost-effectiveness of the STAMINA lifestyle intervention versus optimised usual care and a discrete choice experiment will explore patient preferences. DISCUSSION: The STAMINA lifestyle intervention has the potential to improve quality of life and reduce fatigue in men on androgen deprivation therapy for prostate cancer. Embedding supervised exercise into prostate cancer care may also support long-term positive behaviour change and reduce adverse events caused by treatment. Findings will inform future clinical care and could provide a blueprint for the integration of supervised exercise and behavioural support into other cancer and/or clinical services. TRIAL REGISTRATION: ISRCTN 46385239, registered on 30/07/2020. Cancer Research UK 17002, retrospectively registered on 24/08/2022.

Androgen deprivation therapy-related fracture risk in prostate cancer: an insurance claims database study in Japan.

INTRODUCTION: Androgen deprivation therapy (ADT) is widely used for the treatment of prostate cancer. ADT is associated with reduced bone density leading to an increased risk of osteoporotic fracture. The objective of this retrospective cohort study was to quantify fracture risk in men treated with ADT for prostate cancer in real-world practice in Japan. MATERIALS AND METHODS: Data were extracted from the Japanese Medical Data Vision (MDV) database. Men initiating ADT for treatment of prostate cancer between April 2010 and March 2021 were identified and matched to a cohort of prostate cancer patients not taking ADT using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared between cohorts using a Cox cause-specific hazard model. Information was extracted on demographics, comorbidities and bone densitometry. RESULTS: 30,561 men with PC starting ADT were matched to 30,561 men with prostate cancer not treated with ADT. Following ADT initiation, <5% of men underwent bone densitometry. Prescription of ADT was associated with an increased fracture risk compared to not taking ADT (adjusted hazard ratio: 1.63 [95% CI 1.52-1.75]). CONCLUSION: ADT is associated with a 1.6-fold increase in the risk of osteoporotic fracture in men with prostate cancer. Densitometry in this population is infrequent and monitoring urgently needs to be improved in order to implement effective fracture prevention.

Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

Characterizing the real-world economic burden of metastatic castration-sensitive prostate cancer in the United States.

AIMS: To describe healthcare resource utilization (HRU) and costs of patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: Linked data from Flatiron Metastatic PC Core Registry and Komodo's Healthcare Map were evaluated (01/2016-12/2021). Patients with chart-confirmed diagnoses for metastatic PC without confirmed castration resistance in Flatiron who initiated androgen deprivation therapy (ADT) monotherapy or advanced therapy for mCSPC in 2017 or later (index date) with a corresponding pharmacy or medical claim in Komodo Health were included. Advanced therapies considered were androgen-receptor signaling inhibitors, chemotherapies, estrogens, immunotherapies, poly ADP-ribose polymerase inhibitors, and radiopharmaceuticals. Patients with <12 months of continuous insurance eligibility before index were excluded. Per-patient-per-month (PPPM) all-cause and PC-related HRU and costs (medical and pharmacy; from a payer's perspective in 2022 $USD) were described in the 12-month baseline period and follow-up period (from the index date to castration resistance, end of continuous insurance eligibility, end of data availability, or death). RESULTS: Of 871 patients included (mean age: 70.6 years), 52% initiated ADT monotherapy as their index treatment without documented advanced therapy use. During baseline, 31% of patients had a PC-related inpatient admission and 94% had a PC-related outpatient visit; mean all-cause costs were $2551 PPPM and PC-related costs were $839 PPPM with $787 PPPM attributable to medical costs. Patients had a mean follow-up of 15 months, during which 38% had a PC-related inpatient admission and 98% had a PC-related outpatient visit; mean all-cause costs were $5950 PPPM with PC-related total costs of $4363 PPPM, including medical costs of $2012 PPPM. LIMITATIONS: All analyses were descriptive; statistical testing was not performed. Treatment effectiveness and clinical outcomes were not assessed. CONCLUSION: This real-world study demonstrated a significant economic burden in mCSPC patients, and a propensity to use ADT monotherapy in clinical practice despite the availability and guideline recommendations of advanced life-prolonging therapies.

Cost-Effectiveness Analysis of Systemic Therapy for Intensification of Treatment in Metastatic Hormone-Sensitive Prostate Cancer in India.

BACKGROUND AND OBJECTIVE: Androgen-deprivation therapy is the mainstay of treatment for patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). However, the intensification of treatment with either docetaxel or novel anti-androgens (abiraterone-acetate plus prednisone [AAP], enzalutamide, and apalutamide) is being recommended based on the improved clinical outcomes and quality of life among patients. This study aimed to determine the most cost-effective drug for treatment intensification for patients with mHSPC in India. METHODS: A Markov model was developed with four health states: progression-free survival, progressive disease, best supportive care, and death. Lifetime costs and consequences were estimated for four treatment sequences: AAP-first, enzalutamide-first, apalutamide-first, and docetaxel-first. Incremental cost per quality-adjusted life-year (QALY) gained with a given treatment option was compared against the next best alternative and assessed for cost effectiveness using a willingness to pay threshold of 1 × per capita gross domestic product in India. RESULTS: We estimated that the total lifetime cost per patient was ₹1,367,454 (US$17,487), ₹2,168,885 (US$27,735), ₹7,678,501 (US$98,190), and ₹1,358,746 (US$17,375) in the AAP-first, enzalutamide-first, apalutamide-first, and docetaxel-first treatment sequence, respectively. The mean quality-adjusted life-years lived per patient were 4.78, 5.03, 3.22, and 2.61, respectively. The AAP-first sequence incurs an incremental cost of ₹4014 (US$51) per quality-adjusted life-year gained as compared with the docetaxel-first sequence, with a 87% probability of being cost effective at the willingness-to-pay threshold of 1 × per-capita gross domestic product of India. The use of AAP-first also incurs an incremental net monetary benefit of ₹396,491 (US$5070) as compared with the docetaxel-first treatment sequence. Nearly a 48% reduction in the price of enzalutamide is required to make it a cost-effective treatment sequence as compared with AAP-first in India. CONCLUSIONS: We concur with the inclusion of standard-dose AAP in India's publicly financed health insurance scheme for the intensification of treatment in mHSPC as it is the only cost-effective sequence among the various novel anti-androgens when compared with the docetaxel-first treatment sequence. Furthermore, a systematic reduction in the price of enzalutamide would further help to improve clinical outcomes among patients with mHSPC.

Costs to Medicare of Nonrecommended Bone-Modifying Agent Use for Castration-Sensitive Prostate Cancer.

PURPOSE: Bone-modifying agents (BMAs) do not prevent skeletal-related events among patients with castration-sensitive prostate cancer (CSPC), but many patients receive BMAs unnecessarily. The costs to Medicare from overuse have not been assessed. METHODS: We used linked SEER-Medicare data 2011-2015 to measure the frequency and number of doses of zoledronic acid (ZA) and denosumab received during CSPC (between diagnosis and initiation of metastatic, castration resistant prostate cancer therapy). We estimated excess BMA among patients who received BMA therapy for CSPC and did not have an indication for osteoporosis fracture prevention. We used the Medicare fee schedule for drug prices and peer-reviewed sources to estimate adverse event frequencies and costs. RESULTS: Median CSPC duration was 387 days (IQR, 253-573), during which time 42% of patients received ≥one dose of denosumab (mean doses, 7) and 18% received ≥one dose of ZA (mean doses, 7). Thirty-eight percent of those receiving denosumab and 47% of those receiving ZA had a history of osteoporosis, osteopenia, spine or hip fracture, or hypercalcemia. The estimated, annual excess BMA cost to Medicare was $44,105,041 in US dollars (USD), composed of $43,303,078 USD and $45,512 USD in drug costs for denosumab and ZA, respectively, and $682,865 USD and $75,585 USD in adverse event costs, respectively. In one-way sensitivity analysis, the estimate was most sensitive to denosumab dosing frequency (estimate range, $28,469,237 USD-$98,830,351 USD) and duration of CSPC (estimate range, $36,823,311 USD-$99,015,908 USD). CONCLUSION: BMA overuse in CSPC incurs substantial cost to Medicare, largely because of denosumab drug costs. Excess costs may be reduced by greater adherence to guideline-concordant BMA use.

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.

Safety assessment, radioiodination and preclinical evaluation of antinuclear antibody as novel medication for prostate cancer in mouse xenograft model.

This study aims to provide in vitro and in vivo data to support the utilization of antinuclear antibodies (ANAs) as novel tools for the diagnosis and treatment of prostate cancers. The hematological, biochemical, and histological toxicities of ANAs were assessed at the doses of 5 and 50 µg per mouse. Radiolabeling study was then conducted with ANA and 131I using the chloramine T method, and the biodistribution and treatment efficacy were subsequently investigated in a PC3 xenograft model. No changes in clinical behavior or signs of intoxication, necrosis, or malignancy were observed in ANA-treated mice. 131I-ANA was obtained in very high yield and radiochemical purity, at 94.97 ± 0.98% and 98.56 ± 0.29%, respectively. They achieved immunoreactivity fraction of 0.841 ± 0.17% with PC-3 cells. Levels of radiolabeled ANAs were 1.15-10.14 times higher in tumor tissues than in other examined organs at 24 h post-injection. The tumor growth inhibition rates were 28.33 ± 5.01% in PC3 xenografts mice treated with 131I-ANAs compared with controls and a nearly twofold improvement in median survival was observed. These results demonstrate that radioimmunotherapy of radiolabeled natural ANAs may be an effective treatment for prostate tumors.

Cost-Effectiveness Analysis for Therapy Sequence in Advanced Cancer: A Microsimulation Approach with Application to Metastatic Prostate Cancer.

PURPOSE: Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. We developed a general microsimulation framework to study therapy sequence and applied it to metastatic prostate cancer. METHODS: We constructed a discrete-time state transition model to study 2 lines of therapy. Using digitized published survival curves (progression-free survival, time to progression, and overall survival [OS]), we inferred event types (progression or death) and estimated transition probabilities using cumulative incidence functions with competing risks. We incorporated within-patient dependence over time; first-line therapy response informed subsequent event probabilities. Parameters governing within-patient dependence calibrated the model-based results to a target clinical trial. We applied these methods to 2 therapy sequences for metastatic prostate cancer, wherein both docetaxel (DCT) and abiraterone acetate (AA) are appropriate for either first- or second-line treatment. We assessed costs and quality-adjusted life-years (5-y QALYs) for 2 treatment strategies: DCT → AA versus AA → DCT. RESULTS: Models assuming within-patient independence overestimated OS time, which corrected with the calibration approach. With generic pricing, AA → DCT dominated DCT → AA, (higher 5-y QALYs and lower costs), consistent for all values of calibration parameters (including no correction). Model calibration increased the difference in 5-y QALYs between treatment strategies (0.07 uncorrected v. 0.15 with base-case correction). Applying the correction decreased the estimated difference in cost (-$5,360 uncorrected v. -$3,066 corrected). Results were strongly affected by the cost of AA. Under a lifetime horizon, AA → DCT was no longer dominant but still cost-effective (incremental cost-effectiveness ratio: $19,463). CONCLUSIONS: We demonstrate a microsimulation approach to study the cost-effectiveness of therapy sequences for advanced prostate cancer, taking care to account for within-patient dependence. HIGHLIGHTS: We developed a discrete-time state transition model for studying therapy sequence in advanced cancers.Results are sensitive to dependence within patients.A calibration approach can introduce dependence across lines of therapy and closely match simulation outcomes to target trial outcomes.

In-office dispensing of oral targeted agents by urology practices in men with advanced prostate cancer.

BACKGROUND: Management of men with advanced prostate cancer has evolved to include urologists, made possible by oral targeted agents (eg, abiraterone or enzalutamide) that can be dispensed directly to patients in the office. We sought to investigate whether this increasingly common model improves access to these agents, especially for Black men who are historically undertreated. METHODS: We used 20% national Medicare data to perform a retrospective cohort study of men with advanced prostate cancer from 2011 through 2019, managed by urology practices with and without in-office dispensing. Using a difference-in-difference framework, generalized estimating equations were used to measure the effect of in-office dispensing on prescriptions for abiraterone and/or enzalutamide, adjusting for differences between patients, including race. RESULTS: New prescription fills for oral targeted agents increased after the adoption of in-office dispensing (+4.4%, 95% confidence interval [CI] = 3.4% to 5.4%) relative to that for men managed by practices without dispensing (+2.4%, 95% CI = 1.4% to 3.4%). The increase in the postintervention period (difference-in-difference estimate) was 2% higher (95% CI = 0.6% to 3.4%) for men managed by practices adopting dispensing relative to men managed by practices without dispensing. The effect was strongest for practices adopting dispensing in 2015 (difference-in-difference estimate: +4.2%, 95% CI = 2.3% to 6.2%). The effect of dispensing adoption did not differ by race. CONCLUSION: Adoption of in-office dispensing by urology practices increased prescription fills for oral targeted agents in men with advanced prostate cancer. This model of delivery may improve access to this important class of medications.

Estimating the Impact of the Inflation Reduction Act on the Out-of-Pocket Costs for Medicare Beneficiaries With Advanced Prostate Cancer.

INTRODUCTION: Combination systemic therapy for advanced prostate cancer has reduced mortality, but high out-of-pocket costs impose financial barriers for patients. The Inflation Reduction Act's $2,000 out-of-pocket spending cap for Medicare's prescription drug benefit (Part D) can potentially lower out-of-pocket spending for beneficiaries starting in 2025. This study aims to compare out-of-pocket spending for commonly prescribed regimens for advanced prostate cancer before and after implementation of the Inflation Reduction Act. METHODS: Medication regimens constructed to treat metastatic, hormone-sensitive prostate cancer consisted of baseline androgen deprivation therapy with traditional chemotherapy, androgen receptor inhibitors, and androgen biosynthesis inhibitors. Using 2023 Medicare Part B prices and the Medicare Part D plan finder, we estimated annual out-of-pocket costs under current law and under the Inflation Reduction Act's redesigned standard Part D benefit. RESULTS: Under current law, out-of-pocket costs for Part D drugs ranged from $464 to $11,336 per year. Under the Inflation Reduction Act, annual out-of-pocket costs for 2 regimens remained unchanged: androgen deprivation therapy with docetaxel and androgen deprivation therapy with abiraterone and prednisone. However, out-of-pocket costs for regimens using branded novel hormonal therapy were significantly lower under the 2025 law with potential savings estimated to be $9,336 (79.2%) for apalutamide, $9,036 (78.7%) for enzalutamide, and $8,480 (76.5%) for docetaxel and darolutamide. CONCLUSIONS: The $2,000 spending cap introduced by the Inflation Reduction Act may significantly decrease out-of-pocket costs and reduce financial toxicity associated with advanced prostate cancer treatment, impacting an estimated 25,000 Medicare beneficiaries.

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.

Pharmaceutical industry funding and chemotherapy trials for prostate cancer: A systematic review.

INTRODUCTION: Clinical trials are increasingly supported by industries while previous studies have shown that industry-supported studies have more favorable results than studies with other sources of funding. In the present study, we investigated the association of industrial funding on the results of clinical trials regarding chemotherapy in prostate cancer. METHODS: A systematic literature search was performed in the Cochrane Library, MEDLINE, and EMBASE to identify clinical trials comparing chemotherapy with treatments such as hormone therapy, surgery, radiotherapy, and placebo in patients with metastatic or non-metastatic prostate cancer. Data were extracted by two reviewers on the financial resources and the positive or negative results of chemotherapy in each study. The quality of articles was evaluated and compared based on Cochrane Critical Appraisal Tool. The trials were divided into two groups; industry funded and those not funded by industry. Association of industry funding and positive outcome was presented as odds ratio. RESULTS: In this study, out of the 91 studies, 80.2% were funded by pharmaceutical companies and 19.8% were funded by government agencies. The end result of 61.6% of the studies funded by pharmaceutical companies was an increase in survival due to chemotherapy, whereas only 27.8% of the studies sponsored by government agencies reported positive results (P-value=0.010). In fact, industry-funded trials more often presented statistically significant positive results for survival (OR: 4.17; CI, 1.34-12.99). In general, there was no significant difference in the degree of bias between the two groups. CONCLUSION: According to this study, despite of the similar quality of studies funded by pharmaceutical companies and government agencies, positive results were more common in studies related to pharmaceutical companies. Therefore, this point should be taken into account when making a decision on the best treatment approach.

Out-of-Pocket Costs for Prostate Cancer Medications Substantially Vary by Medicare Part D Plan: An Online Tool Presents an Opportunity to Mitigate Financial Toxicity.

INTRODUCTION: Patients with advanced prostate cancer are frequently prescribed enzalutamide or abiraterone, often requiring high out-of-pocket costs. Many of these patients are insured through Medicare and have an option to select among 54 different Part D drug plans. However, less than 30% of patients report comparing costs before selecting a plan. An online Part D plan navigator is publicly available and allows patients to compare estimated out-of-pocket prescriptions costs. In this study, we examine the variability of out-of-pocket costs based on available Part D drug plans for patients with prostate cancer and demonstrate how an online tool could save patients thousands of dollars. METHODS: We identified drug plans available for selection in 2023 using the online Medicare Part D Plan Finder. We sampled plan options for 12 different zip codes within the United States. A university-sponsored specialty cancer pharmacy and online mail-order pharmacy were included for comparison. We identified out-of-pocket costs for enzalutamide and abiraterone based on all Part D plans available for selection. RESULTS: On average, 24 Part D drug plans were available for each zip code. Median annual out-of-pocket costs were $11,626 for enzalutamide and $9,275 for abiraterone. The range of annual out-of-pocket costs were $9,854 to $13,061 for enzalutamide and $1,379 to $13,274 for abiraterone. Within certain zip codes, potential out-of-pocket cost savings were $2,512 for enzalutamide and $9,321 for abiraterone. Median difference of out-of-pocket cost between enzalutamide and abiraterone was $8,758. CONCLUSIONS: Out-of-pocket costs vary considerably across Part D drug plans. The Medicare Part D Plan Finder is a simple and effective tool to identify affordable drug plans. Guidance on plan selection could save patients thousands of dollars and help mitigate the financial toxicity of treatment. Comprehensive cancer centers could include plan navigators as an essential component of treatment.

Assessment of bone-targeting agents use in patients with bone metastasis from breast, lung or prostate cancer using structured and unstructured electronic health records from a regional UK-based hospital.

ObjectiveTo assess use of bone-targeting agents (BTA) in patients with confirmed bone metastases (BM) from breast cancer (BC), non-small cell lung cancer (NSCLC) or prostate cancer (PC). DESIGN: Retrospective cohort study. SETTING: Regional hospital-based oncology database of approximately 2 million patients in England. PARTICIPANTS: Patients aged ≥18 years with a diagnosis of BC, NSCLC or PC as well as BM between 1 January 2007 and 31 December 2018, with follow-up to 30 June 2020 or death; BM diagnosis ascertained from recorded medical codes and unstructured data using natural language processing (NLP). MAIN OUTCOMES MEASURES: Initiation or non-initiation of BTA following BM diagnosis, time from BM diagnosis to BTA initiation, time from first to last BTA, time from last BTA to death. RESULTS: This study included 559 BC, 894 NSCLC and 1013 PC with BM; median age (Q1-Q3) was 65 (52-76), 69 (62-77) and 75 (62-77) years, respectively. NLP identified BM diagnosis from unstructured data for 92% patients with BC, 92% patients with NSCLC and 95% patients with PC. Among patients with BC, NSCLC and PC with BM, 47%, 87% and 88% did not receive a BTA, and 53%, 13% and 12% received at least one BTA, starting a median 65 (27-167), 60 (28-162) and 610 (295-980) days after BM, respectively. Median (Q1-Q3) duration of BTA treatment was 481 (188-816), 89 (49-195) and 115 (53-193) days for patients with BC, NSCLC and PC. For those with a death record, median time from last BTA to death was 54 (26-109) for BC, 38 (17-98) for NSCLC and 112 (44-218) days for PC. CONCLUSION: In this study identifying BM diagnosis from both structured and unstructured data, a high proportion of patients did not receive a BTA. Unstructured data provide new insights on the real-world use of BTA.

Financial toxicity of oral therapies in advanced prostate cancer.

The treatment landscape of advanced prostate cancer (CaP) has evolved significantly over the past 20 years. As the number of oral anticancer treatment options continues to increase, so do the costs of these drugs. Furthermore, payment responsibility for these treatments is increasingly shifted from insurers to patients. In this narrative review, we sought to summarize existing assessments of financial toxicity (FT) associated with oral advanced CaP treatments, describe efforts targeted at limiting FT from these agents, and identify areas in need of further investigation. FT is understudied in advanced CaP. Oral treatment options are associated with significantly higher direct costs to patients compared to standard androgen deprivation therapy or chemotherapy. Financial assistance programs, Medicare low-income subsidies, and recent health policy changes help offset these costs for some patients. Physicians are reluctant to discuss treatment costs with patients and further work is needed to better understand best practices for inclusion of FT discussions in shared decision-making. Oral therapies for advanced CaP are associated with significantly higher patient out-of-pocket costs which may contribute to FT. Currently, little is known regarding the extent and severity of these costs on patients' lives. While recent policy changes have helped reduce these costs for some patients, more work is needed to better characterize FT in this population to inform interventions that improve access to care and lessen the harms associated with the cost of novel treatments.

Diversity, equity, and inclusion in genitourinary clinical trials leading to FDA novel drug approval: An assessment of the FDA center for drug evaluation and research drug trials snapshot.

To determine the distribution of race and ethnicity among genitourinary oncology trial participants leading to FDA approval of novel molecular entities/biologics. Secondarily, we evaluated whether the proportion of Black participants in clinical trials increased over time. We quired the FDA Center for Drug Evaluation and Research Drug Trials Snapshot (DTS) between 2015 and 2020 for urologic oncology clinical trials leading to FDA approval of novel drugs. Enrollment data was stratified by race and ethnicity. Cochran-Armitage Trend tests were used to examine changes in Black patient participation over years. Nine clinical trials were identified that led to FDA approval of 5 novel molecular entities for prostate and 4 molecular entities for urothelial carcinoma treatment. Trials for prostate cancer included 5202 participants of which 69.8% were White, 4.0% Black, 11.0% Asian, 3.6% Hispanic, <1% American Indian/Alaska Native or Native Hawaiian/Pacific Islander, 3% other. Trials in urothelial carcinoma had 704 participants of which 75.1% were male, 80.8% White, 2.3% Black, 2.4% Hispanic, <1% American Indian/Alaska Native or Native Hawaiian/Pacific Islander, 5% other. Black participation rates over time did not change for urothelial (P = 0.59) or the combined cancer cohort (P = 0.29). Prostate cancer enrollment trends among Black participant declined over time (P = 0.03). Participants in genitourinary clinical trials leading to FDA approval of novel drugs are overwhelmingly white. Involving stakeholders who represent the needs and interests of underrepresented populations in the design and implementation of clinical trials of novel agents may be a strategy to increase diversity, equity, and inclusion among genitourinary clinical trials.

Use of weight loss medications in relation with prostate, colorectal and male breast cancers among older men: SEER-Medicare 2007-2015.

BACKGROUND: The association of weight loss medications with prostate (PCa), colorectal (CRC) or male breast cancers, including assessment of these cancers combined (HRCs, hormone-associated cancers) remain poorly understood. Testosterone replacement therapy (TTh) is reported to be inversely associated with obesity, PCa and CRC, but it is unclear whether TTh modifies the association of weight loss medications with HRCs. METHODS: In 49,038 men (≥ 65 years) of SEER-Medicare, we identified 15,471 men diagnosed with PCa, 4836 with CRC, and 141 with male breast cancers. Pre-diagnostic prescription of weight loss medications and TTh was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards (mortality) models were conducted. RESULTS: We found an inverse association between use of weight loss medications and incident PCa (OR 0.59, 95% CI 0.57-0.62), CRC (OR 0.86, 95% CI 0.80-0.92), and HRCs (OR 0.65, 95% CI 0.62-0.68). Similar associations were observed for advanced stage at diagnosis of PCa and CRC. Effects of weight loss medications on PCa and HRC remained significant irrespective of the use of TTh but were only suggestive with CRC with positive TTh use. No associations were observed with male breast cancer and HRCs mortality. CONCLUSION: Pre-diagnostic use of weight loss medications reduced the incidence of PCa, CRC, and HRCs. These associations persisted in the same direction irrespective of the history of TTh use. Future studies are needed to confirm these findings and to identify underlying biological mechanisms of weight loss medications and TTh on the risk of cancer.

Survival and Economic Impact of Rapid Prostate-Specific Antigen Doubling Time in Patients With Nonmetastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), prostate-specific antigen doubling time (PSADT) is associated with risk of metastasis and survival. This study evaluated the association of PSADT with clinical and economic outcomes in a real-world setting among patients with nmCRPC not receiving novel hormonal therapy (NHT), using 2-month PSADT thresholds. PATIENTS AND METHODS: We retrospectively identified Veterans Health Administration patients with nonmetastatic prostate cancer and ≥2 PSA increases after medical/surgical castration (2012-2016). The third measurement was the index (CRPC) date. Patients with ≥3 postindex PSA measurements, including index, were followed until death or ≥12 months until disenrollment, study end, or death, and grouped into 2-month cohorts based on postindex PSADT. Cox regression models assessed association between PSADT, time to metastasis, and death. Healthcare resource utilization and costs were evaluated. RESULTS: Among 2800 evaluable patients, median follow-up was 30 months and median PSADT was 17 months. Relative to the reference cohort (PSADT >12 months), all cohorts had significantly higher metastasis risk. PSADT ≤10-month cohorts had significantly greater mortality risk than the reference; hazard ratios (95% confidence intervals) ranged from 12.3 (9.2, 16.4) in the PSADT ≤2-month cohort to 1.3 (0.9, 2.0) in the >10 to ≤12-month cohort. Total costs were significantly higher for cohorts up to and including the PSADT >8 to ≤10-month cohort, than for the reference cohort. Mean per patient per month all-cause medical plus pharmacy costs were $6623, $4768, and $4049 in the PSADT ≤2-month, >2 to ≤4-month cohort, and >4 to ≤6-month cohorts, respectively, versus $1911 in the PSADT >12-month cohort (P <0.05). CONCLUSION: Most patients with nmCRPC have PSADT >12 months and a long natural history. For those with shorter PSADT, the risk of metastasis, death, and costs increased. These data can help select patients for NHT and conversely those who can safely delay NHT for nmCRPC.

Assessment of oligometastasis status of prostate cancer following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone using PSA percentage decline rate.

Objective: To compare the tumor control in prostate cancer patients with oligo-metastasis following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone based on total prostate-specific antigen (tPSA) assessment. Methods: Medical data of a total of 18 prostate cancer patients with oligometastasis administered in The First Affiliated Hospital of Nanchang University from March 2017 to March 2018 were prospectively collected. 10 patients received a combined therapy of robot-assisted radical prostatectomy and pharmaceutical androgen deprivation (RARP+ADT group), while 8 patients received pharmaceutical androgen deprivation therapy alone (ADT group). Then demographic characteristics, prostate volume, tumor characteristics and tPSA data were analysised and compared. Statistical analysis was performed using t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. Results: No significant difference was found in patients' age (p = 0.075), prostate volume (p = 0.134) and number of bone metastasis (p = 0.342). Pre-treatment Gleason score was significantly lower in RA group (p = 0.003). Patients in RARP+ADT group had significantly lower pre-treatment tPSA (p = 0.014), while no statistical difference was noted in reexamined tPSA (p = 0.140) on follow-up. No statistical difference was noted in tPSA decline rates (declined tPSA value per day) in RARP+ADT and ADT group (8.1 ± 4.7 verse 7.5 ± 8.0 ng/ml/d, p = 0.853). However, tPSA percentage decline rate (declined tPSA percentage per day) was significantly higher in RARP+ADT group (11.6 ± 1.5%/d verses 2.9 ± 2.2%/d, p< 0.001). Immediate urinary continence was achieved in 9 patients (90%) upon removal of urethral catheter on post-operative day 7 in RARP+ADT group. Conclusion: ADT alone and in combination with RARP both provide effective tumor control in patients suffering from prostate cancer with oligometastasis. ADT combined with RARP exhibited significant advantage in PSA percentage decline rate without compromising patients' urinary continence. Long-term tumor control requires further follow-up.