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Frank A Schumacher,1 Irene B Helenowski,1 Laura B Oswald,2 Brian D Gonzalez,2 James T Benning,1 Alicia K Morgans1 1Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 2Program of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USACorrespondence: Frank A SchumacherFeinberg School of Medicine, Northwestern University, 1835 W Thomas St, Apt 2F, Chicago, IL, 60622, USATel +1 314 640-2883Email frank.schumacher@northwestern.eduBackground: Multiple treatments for metastatic prostate cancer have similar efficacy, leaving patients with complicated treatment choices. Shared decision-making can facilitate difficult treatment decisions, but the extent to which this is used for metastatic prostate cancer is unknown. We assessed patient, caregiver, and physician perceptions of decision locus of control (shared decision-making vs physician- or patient-directed decisions) and the degree of agreement between groups.Methods: Triads of patients, caregivers, and physicians completed surveys of decision-making practices after a clinic visit in which a decision occurred. To evaluate the degree of agreement for decision locus of control, we used the quadratic-weighted kappa coefficient (κ). We used relative frequencies to evaluate which knowledge learned and treatment factors were most strongly endorsed by patients as informing and influencing their treatment decision-making, respectively.Results: Fifty triads participated, with median patient age of 72 years. A majority of patients, caregivers, and physicians reported shared decision-making (66%, 56%, and 52%, respectively). Patients and physicians demonstrated minimal agreement about decision locus of control (44%, κ=0.35 [SD = 0.52]), but caregiver reports were not statistically significantly associated with physician and patient reports (38%, κ=0.23, [SD = 0.28]), p=0.055; 44%, κ=0.34 [SD = 1.98], p=0.14). Treatment efficacy was the most common patient-reported factor influencing treatment decisions (44%).Conclusion: This study characterized metastatic prostate cancer patients’, caregivers’, and physicians’ experiences and communication preferences for treatment decision-making. Patients and physicians had greater agreement in decision locus of control compared with caregivers, yet patient-physician agreement was minimal. Metastatic prostate cancer patients report being influenced by information about treatment efficacy and clear next steps, and a desire for patient-friendly language and an invitation to be as involved in decision making at their preferred level. Emphasizing these may increase agreement in decision locus of control between all participants in the decision-making process.Keywords: prostate cancer, decision making, shared decision making, treatment decisions, cancer survivorship

Laura B Oswald,1 Frank A Schumacher,2 Brian D Gonzalez,1 Kelvin A Moses,3 David F Penson,3,4 Alicia K Morgans2 1Health Outcomes and Behavior Program, Moffitt Cancer Center, Tampa, FL, USA; 2Department of Medicine (Hematology and Oncology), Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA; 4Department of Urology, VA Tennessee Valley Geriatric Research, Education, and Clinical Center (GRECC), Nashville, TN, USACorrespondence: Alicia K MorgansNorthwestern University Feinberg School of Medicine, 676 N. Saint Clair, Suite 850., Chicago, IL 60611, USATel +1312-695-2381Email Alicia.Morgans@northwestern.eduObjective: Metastatic prostate cancer (mPCa) patients often make complicated treatment decisions, yet decision aids to facilitate shared decision-making for mPCa are uncommon. To inform the development of patient-centered mPCa decision aids, we examined what mPCa survivors considered most important when making treatment decisions.Methods: Using an exploratory sequential approach, we conducted three focus groups with 14 advanced prostate cancer survivors (n=5, n=3, n=6 in each group) to identify considerations for making treatment decisions. Focus groups were audio-recorded and transcribed, and we identified qualitative themes. We then developed a quantitative survey to assess the importance of each theme and administered the survey to mPCa survivors (N=100). We used relative frequencies to determine the most strongly endorsed items and chi-squared and Fisher’s exact tests to assess associations with participant characteristics.Results: Focus groups yielded 11 themes, and the resulting survey included 20 items. The most strongly endorsed mPCa treatment considerations were: relying on physician’s treatment recommendations (79% strongly agree); wanting to feel well enough to spend quality time with loved ones (72% strongly agree); the importance of dying in a manner consistent with one’s wishes (70% strongly agree); hoping to eliminate cancer completely (68% strongly agree); and optimizing treatment efficacy (65% strongly agree). Age, race, marital status, employment status, and self-reported health were related to how strongly men endorsed various considerations for mPCa treatment decision-making.Conclusion: We identified multiple considerations that mPCa survivors appraised when making treatment decisions. These data may inform the development of patient-centered decision aids for mPCa.Keywords: decision-making, focus groups, metastasis, prostate cancer, quality of life

Kristen R Scarpato,1 Alicia K Morgans,2 Kelvin A Moses11Department of Urologic Surgery, 2Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USAAbstract: Muscle-invasive bladder cancer is a complex disease requiring aggressive management. Patients are often older with comorbid conditions that impact treatment options. This review describes the available therapies for invasive urothelial carcinoma, including chemotherapy, radical extirpative surgery, and bladder-preserving strategies.Keywords: bladder cancer, urothelial carcinoma, neoadjuvant chemotherapy, radical cystectomy

Background Despite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time. Objective To evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart. Design, setting, and participants Patients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter. Outcome measurements and statistical analysis We performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies. Results and limitations The study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding. Conclusions Reporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations. Patient summary Patient reporting of urinary and sexual function has evolved and is likely contingent on continually changing societal norms. Recognizing the evolving nature of patient reporting is essential in efforts to conduct high-quality, impactful comparative effectiveness research.

While suppressing testosterone to castration levels is the aim of androgen deprivation therapy for the treatment of advanced prostate cancer, studies have shown that prolonged low testosterone levels can have negative effects on patients' overall health and quality of life. This podcast covers two recently published papers that examined testosterone recovery in different ways. One real-world study assessed the impact of delayed testosterone recovery on clinical outcomes in patients with prostate cancer. A second subgroup analysis of the HERO trial assessed rates of testosterone recovery in patients receiving the long-acting, injectable gonadotropin-releasing hormone receptor agonist, leuprolide or the oral, once-daily gonadotropin-releasing hormone receptor antagonist, relugolix.

Background and Objective: It is unclear whether "total therapy" (androgen deprivation therapy [ADT] with or without an androgen receptor pathway inhibitor [ARPI], metastasis-directed therapy, and local therapy to the prostate if de novo) may lead to long-term durable remission in oligometastatic hormone-sensitive prostate cancer (omHSPC). This study aims to evaluate the outcomes after the completion of total therapy in patients with omHSPC., Methods: A retrospective single-institution cohort of consecutive patients with omHSPC identified on conventional or molecular imaging treated with total therapy was assembled. All patients had prostate-specific antigen ≤0.1 ng/ml at the completion of systemic therapy. Kaplan-Meier and Cox regression models were used to evaluate the key outcomes of interest: clinical progression-free survival (cPFS), eugonadal progression-free survival (PFS), and time to restart of ADT (TTrADT)., Key Findings and Limitations: Eighty-nine patients were included, of whom 23 were with de novo omHSPC; the median number of metastases was 1, and detection of disease by molecular imaging was performed in 43 patients (48%). Forty-nine patients (55%) received ADT + ARPI doublet and 40 (45%) received ADT alone. At a median follow-up of 37 mo, there were 46 cPFS events; 3-yr cPFS rate was 45% (95% confidence interval 33-56) and the median eugonadal PFS was 12 mo. The median TTrADT was 47 mo, and 60% had not restarted ADT at 3 yr. Duration of systemic therapy ≥12 mo was the only significant predictor of better outcomes., Conclusions and Clinical Implications: Of the patients receiving total therapy for omHSPC, 45% remained progression free at 3 yr after completing therapy, hinting at the potential for long-term remission and possible cure with this strategy in a subset of patients with omHSPC. Prospective trials evaluating this approach are needed., Patient Summary: In this report, we looked at outcomes in men who had received a fixed duration of hormonal therapy along with radiotherapy to metastatic sites (and prostate radiotherapy or surgery in those with newly diagnosed disease) for oligometastatic prostate cancer. We found that nearly half of the patients had no evidence of cancer recurrence at 3 yr after completing therapy, and 60% had not resumed any therapy at this time point., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Androgen receptor inhibitors (ARIs) are approved for the treatment of advanced prostate cancer; however, some patients may experience symptoms and side effects that hinder their physical functioning. The Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests are used to assess physical functioning in older adults and are recommended assessments for patients with prostate cancer, despite lacking validation in this setting., Methods: DaroAct (NCT04157088) was an open-label, multicenter, phase 2b study designed to evaluate the effects of the ARI darolutamide (lead-in phase) and darolutamide vs enzalutamide (randomized phase) on physical functioning in men with castration-resistant prostate cancer (CRPC). Only the lead-in phase, in which participants received darolutamide 600 mg twice daily, was completed. The TUG and SPPB tests were used to assess physical functioning., Results: The lead-in phase enrolled 30 participants. During 24 weeks of treatment, 8 (32.0%) of 25 evaluable participants exhibited clinically meaningful worsening in TUG from baseline (primary endpoint). At the week 24 visit, 5 (21.7%) of 23 participants had worsening in TUG time, and 8 (33.3%) of 24 participants had worsening in SPPB score. Because only 48% of participants had the same outcome on the TUG and SPPB tests, the study was terminated without initiating the randomized comparison., Conclusion: Most participants showed no clinically meaningful worsening in physical functioning after 24 weeks of darolutamide treatment, but poor agreement between tests was observed. Tools to accurately and consistently measure the impact of ARIs on physical functioning in patients with CRPC are needed., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Novel therapies for metastatic castration-resistant prostate cancer (mCRPC) have improved patient outcomes. However, there is uncertainty on the optimal selection of therapeutic agents for subsequent lines of therapy., Methods: We conducted a comprehensive review of published evidence from pivotal clinical trials and recent guidelines for the treatment of mCRPC. We further identify gaps in knowledge and areas for future research., Results: Key considerations to help guide treatment selection for patients with mCRPC include personal treatment history, individual clinical characteristics, symptoms, prognosis, availability of clinical trials, and other patient-specific factors. Genetic testing and prostate-specific membrane antigen-targeted imaging are important tools to evaluate candidacy for newer therapeutic options such as poly (ADP-ribose) polymerase inhibitors, alone or in combination with androgen receptor pathway inhibitors, and [ 177 Lu]Lu-PSMA-617., Conclusion: This article provides an overview of the evolving treatment landscape of mCRPC, discussing guideline-recommended treatment options and data from key clinical trials, while highlighting ongoing trials that may impact the future treatment landscape. Recommendations for optimal treatment sequencing based on individual patient factors are provided., (© 2024. The Author(s).)

Purpose: There is limited evidence of tobacco smoking's effect on cancer survivors' quality of life (QOL) and function. As the natural history of localized prostate cancer (PCa) is protracted, there is a need to identify modifiable risk factors that can influence PCa survivorship, such as tobacco smoking., Material and Methods: We used up to 10-year survey data from the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study, a prospective, population-based, observational study of patients diagnosed with localized PCa in 2011-2012. Survivors were categorized as never, former, and current smokers during survivorship. Adjusted multivariable linear regression models were used to assess the association between smoking and 5-year and 10-year scores on the 26-Item Expanded Prostate Index Composite (EPIC-26; PCa-specific domains) and 5-year scores on the Medical Outcomes Study 36-Item Short Form Survey (SF-36; general health domains)., Results: We included 2426 patients of whom 142 (6%) were current smokers, 1039 (43%) were former smokers, and 1245 (51%) were never smokers. Current smokers were more likely to be Black, low-income, and less formally educated (all p < 0.01). After adjustments, there was no association between smoking history with disease-specific functional outcomes (EPIC-26) at 5 years or 10 years (all p > 0.05). However, in adjusted analyses assessing general health domains (SF-36), compared to participants who never smoked, current smokers during survivorship had worse physical function (- 10.96, 95% CI - 16.37 to - 5.55, p < 0.01) at 5 years., Conclusion: PCa survivors who continue to smoke experience worse physical functioning though there is no significant independent effect on PCa-specific functional domains., Implications for Cancer Survivors: Prostate cancer survivors who continue to smoke experience worse physical functioning though there is no significant independent effect on PCa-specific functional domains. Smoking cessation may improve prostate cancer survivorship., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts on key questions in clinical management in order to supplement evidence-based guidelines. Here we present voting results for questions from APCCC 2024., Methods: Before the conference, a panel of 120 international PC experts used a modified Delphi process to develop 183 multiple-choice consensus questions on eight different topics. Before the conference, these questions were administered via a web-based survey to the voting panel members ("panellists")., Key Findings and Limitations: Consensus was a priori defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. The voting results show varying degrees of consensus, as discussed in this article and detailed in the Supplementary material. These findings do not include a formal literature review or meta-analysis., Conclusions and Clinical Implications: The voting results can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Diagnostic and treatment decisions should always be individualised on the basis of patient and cancer characteristics, and should incorporate current and emerging clinical evidence, guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2024 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Early recognition of hereditary urological cancers may influence diagnostic and therapeutic decision-making, and potentially alter the fate of patients and family members. Here, we introduce readers to the current knowledge on germline genetic testing and clinical practice in prostate, bladder, renal, and testicular carcinoma. Considering all urological cancer patients, routine inquiries about familial cancer history should become a standard practice in clinical settings. If suspicion arises, patients can opt for two avenues: referral to genetic counseling or undergoing genetic tests after consultation with the treating urologist., Patient Summary: Tumors of the urogenital tract (prostate, kidney, bladder, and testes) can sometimes be related to genetic mutations that are present in all the cells of the body. Such mutations can be inherited and run in families. Therefore, it is relevant to obtain information on the incidence of all cancers in the family history. The information obtained may initiate genetic testing, leading to the identification of mutations that are related to cancer in the current or next generation. In addition, these mutations may offer alternative treatment options for patients., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.)

Cancer-related cognitive impairment (CRCI) is a broad term encompassing subtle cognitive problems to more severe impairment. CRCI severity is influenced by host, disease, and treatment factors and affects patients prior to, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a Clinical Trial Planning Meeting (CTPM) to review the state of the science on CRCI and to develop both Phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non-central nervous system (CNS) disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors. Participants included experts in the field of CRCI, members of the SxQOL SC, patient advocates, representatives from all seven NCI Community Oncology Research Program (NCORP) Research Bases, and the NCI. Presentations focused on the following topics: measurement, lessons learned from pediatric and geriatric oncology, biomarker and mechanism endpoints, longitudinal study designs, and pharmacologic and behavioral intervention trials. Panel discussions provided guidance on priority cognitive assessments, considerations for remote assessments, inclusion of relevant biomarkers, and strategies for ensuring broad inclusion criteria. Three CTPM working groups (longitudinal studies and pharmacologic and behavioral intervention trials) convened for one year to discuss and report on top priorities and to design studies. The CTPM experts concluded sufficient data exist to advance Phase II/Phase III trials utilizing selected pharmacologic and behavioral interventions for the treatment of CRCI in the non-CNS setting with recommendations included herein., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Finite courses of androgen deprivation therapy (ADT) are often utilized in men undergoing treatment for prostate cancer. Previous evidence suggests that timing of testosterone (T) recovery can be variable after ADT. Recently, an oral gonadotropin releasing-hormone (GnRH) antagonist, relugolix, has demonstrated more rapid T recovery than injectable GnRH agonists such as leuprolide. In this study, we sought to evaluate patient characteristics associated with T recovery in patients undergoing ADT of defined duration., Materials and Methods: The Northwestern Enterprise Data Warehouse was queried for men with prostate cancer who completed a course of ADT and subsequently had a testosterone lab performed. Testosterone recovery was evaluated for levels that reached above castrate (T > 50 ng/dl), partial recovery (T > 150 ng/dl), and full recovery (T ≥ 300 ng/dl)., Results: 388 men who received finite courses of ADT were identified (348 receiving leuprolide, 36 receiving relugolix, and 4 receiving degarelix). In multivariable Cox regression analysis, men who were prescribed GnRH antagonists (HR = 3.74, CI = 2.53-5.53, P ≤ 0.001) and who were younger (HR for 1 year increase in age = 0.96, CI = 0.95-0.98, P < 0.001) were more likely to achieve partial recovery. In a subgroup analysis, men who received extended ADT courses (>12 months) with a GnRH agonist had lower rates of partial T recovery (HR = 0.58, CI = 0.41-0.81, P = 0.001)., Conclusion: T recovery after ADT is variable with roughly one sixth of men remaining castrate. GnRH antagonist use and younger age are associated with higher rates of T recovery after ADT. Longer ADT courses were associated with worse T recovery rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ashley E. Ross, Alicia K. Morgans, Edward Schaeffer reports a relationship with Astellas Pharma Inc that includes: consulting or advisory. Ashley E. Ross, Alicia K. Morgans reports a relationship with AstraZeneca that includes: consulting or advisory. Ashley E. Ross, Alicia K. Morgans reports a relationship with Bayer Corporation that includes: consulting or advisory. Alicia K. Morgans reports a relationship with AAA that includes: consulting or advisory. Ashley E. Ross reports a relationship with Blue Earth Diagnostics that includes: consulting or advisory. Ashley E. Ross reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. Ashley E. Ross reports a relationship with BillionToOne that includes: consulting or advisory. Alicia K. Morgans reports a relationship with Curium that includes: consulting or advisory. Alicia K. Morgans reports a relationship with Exelixis Inc that includes: consulting or advisory. Ashley E. Ross, Alicia K. Morgans reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory. Ashley E. Ross, Alicia K. Morgans reports a relationship with Lantheus Medical Imaging Inc that includes: consulting or advisory. Alicia K. Morgans reports a relationship with Merck that includes: consulting or advisory. Alicia K. Morgans reports a relationship with MacroGenics Inc that includes: consulting or advisory. Ashley E. Ross, Alicia K. Morgans, Edward Schaeffer reports a relationship with Pfizer that includes: consulting or advisory. Ashley E. Ross, Alicia K. Morgans reports a relationship with Sumitomo Pharma America Inc that includes: consulting or advisory. Alicia K. Morgans reports a relationship with Novartis Pharmaceuticals Corporation that includes: consulting or advisory. Alicia K. Morgans reports a relationship with Telix Pharmaceuticals Limited that includes: consulting or advisory. Ashley E. Ross reports a relationship with Veracyte Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: ARASENS was a randomized, double-blind, phase 3 trial comparing darolutamide + docetaxel + androgen deprivation therapy (ADT) with placebo + docetaxel + ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC)., Objective: To use clinical trial data from ARASENS to understand whether the addition of darolutamide to docetaxel + ADT leads to increased hospitalizations and to estimate the budget impact on the US health care system., Methods: We used mixed-effects negative binomial regression to estimate hospitalization and intensive care unit (ICU) admission rates and length of hospital stay (LoHS) counts. Hospitalization rates were estimated per treatment arm for the period during and after administration of docetaxel. Based on these estimates, a budget impact analysis evaluated the hospitalization costs (including ICU admissions) and standalone ICU hospitalization costs for the totality of the US population over a 5-year time horizon. The analysis compared a scenario without darolutamide vs one with darolutamide included in the US payer formulary. Hospitalization estimates were varied in a one-way sensitivity analysis., Results: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalizations across both arms. The addition of darolutamide was associated with a numerical reduction in the rate of hospitalization (per year) due to any reason both during docetaxel treatment (1.01 visits per year [95% CI = 0.82-1.20] vs 1.18 visits per year [95% CI = 0.96-1.41]) and after docetaxel treatment (0.28 visits per year [95% CI = 0.23-0.34] vs 0.33 visits per year [95% CI = 0.27-0.40]). Darolutamide was associated with a marginally longer LoHS per hospitalization compared with placebo (+1.90 days per year) both during and after docetaxel treatment. ICU admissions were low in the ARASENS data; admission rates were assumed to be the same during and after docetaxel treatment. ICU admission rate estimates were equivalent across arms (0.02 visits per year [95% CI = 0.01-0.03]). The budget impact per treated member per month represents a cost-neutral option after Year 5 with a cumulative budget impact of -$9.71., Conclusions: The addition of darolutamide to docetaxel + ADT was associated with a numerically lower rate of hospitalization but marginally longer LoHS compared with docetaxel + ADT alone. Darolutamide represents a cost-neutral alternative per treated member per month compared with docetaxel + ADT with regard to hospitalizations at the end of a 5-year time horizon.

Background: This single-arm prospective study evaluated the feasibility of a novel wrist-worn thermal device that applies cooling to the inside of the wrist for management of bothersome hot flashes in prostate cancer survivors., Methods: 57 individuals were enrolled and instructed to use the thermal device as needed for management of hot flashes for 4 weeks. The primary outcome was thermal device usage (hours and sessions per day). Additional outcomes included the change in Hot Flash Related Daily Interference Scale (HFRDIS, range 0-10) and Patient Reported Outcomes Measurement Information System Sleep Disturbance 4a (PROMIS SD T-score, range 0-100) and Sleep-Related Impairment 8a (PROMIS SRI T-score, range 0-100). Study procedures were conducted remotely from May to Dec 2021 in the US., Results: 44 participants completed the study and 39 had retrievable usage data. The mean ± SD age was 67 ± 6 years and 5 ± 5 years since cancer diagnosis. The baseline mean ± SD HFRDIS score of 4.3 ± 2.0 indicated moderate hot flash interference in this population. During the study, participants used the thermal device (mean ± SD) 3.2 ± 2.5 hours/day and 7.6 ± 3.6 sessions/day. Most (67%) participants reported using the device 7 days and 7 nights each week. Statistically significant improvements from baseline at Week 4 were observed for HFRDIS (mean ± SE change: -1.1 ± 0.3), PROMIS SD (-6.0 ± 1.0), and PROMIS SRI (-5.5 ± 1.2) scores (all p < 0.001). The majority (69%) of participants reported that the thermal device was effective at helping them manage hot flashes. No adverse events were reported., Conclusions: Results support the feasibility of using the thermal device for management of bothersome hot flashes in prostate cancer survivors. Future randomized controlled studies are warranted to evaluate the impact of the thermal device on frequency and severity of hot flashes, sleep quality, fatigue, and overall quality of life., (© 2023. The Author(s).)

Background: Intermittent androgen deprivation therapy (iADT) alleviates some side effects of continuous (c) ADT in patients with prostate cancer (PC), but its relative impact on ADT-associated comorbidities is uncertain. We assessed real-world use of iADT and cADT and associated risk of cardiovascular and endocrine/metabolic events in patients with nonmetastatic (nm) PC., Methods: This retrospective longitudinal cohort study included patients with nmPC initiating systemic ADT with gonadotropin-releasing hormone agonists (goserelin, histrelin, leuprolide, and triptorelin) or antagonists (degarelix) in the US Surveillance, Epidemiology and End Results-Medicare database (2010-2017), who had ≥ 36 months of continuous insurance coverage, unless death occurred, and did not receive chemotherapy or next-generation hormonal therapies during follow-up (through 2019). Risk of major adverse cardiovascular events (MACE [myocardial infarction, stroke, cardiomyopathy/heart failure, pulmonary embolism, ischemic heart disease, all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, and osteoporosis) were examined between cohorts. Inverse probability of treatment-weighted Cox regression models estimated adjusted hazard ratios (HRs) of the outcomes., Results: Of 10,655 eligible patients, 2,095 (19.7%) received iADT and 8,560 (80.3%) cADT. Median follow-up was 43.9 and 48.4 months and median ADT duration (excluding iADT gaps) was 22.0 and 13.5 months for the iADT and cADT cohorts, respectively. Patients receiving cADT had a lower risk of MACE vs. iADT (HR 0.90; 95% confidence interval [CI] 0.83-0.96). No difference in risk of endocrine/metabolic events was observed (HR 0.97; 95% CI 0.92-1.03). Subgroup analysis found that the difference in MACE was maintained in patients with a history of cardiovascular disease (HR 0.90; 95% CI 0.83-0.98) and eliminated in patients without (HR 0.94; 95% CI 0.82-1.08)., Conclusions: Patients with nmPC who received cADT had a lower risk of MACE and similar risk of endocrine/metabolic events vs. those who received iADT. Further research assessing both regimens is needed to inform treatment decisions., Competing Interests: Declaration of competing interest MAP reports a consultancy role for Bayer and Pfizer Inc.; research funding from Merck and Progenics Pharmaceuticals Inc. RE reports honoraria from Chiesi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), and Novo Nordisk; consultancy role for Novo Nordisk; speaker's bureau for Chiesi and Novo Nordisk; research funding from Boehringer Ingelheim. PB, RD, and MSD report being employees of Analysis Group Inc. which received funding from Pfizer Inc. to conduct and report on the study. RG and RD report being employees of Myovant Sciences, Inc., with stock ownership in Myovant Sciences, Inc., at the time of the study. SH and AH report being employees of Pfizer Inc., with stock ownership in Pfizer Inc. AKM reports speaker's bureau for Advanced Accelerator Applications, Astellas Scientific and Medical Affairs, Inc., Astellas Pharma Inc., AstraZeneca, Bayer, Clovis Oncology, Exelixis, Genentech, Janssen, Janssen Oncology, Merck, Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), Sanofi, and Pfizer Inc.; consultancy role or advisory role for  Advanced Accelerator Applications, Astellas Pharma Inc., AstraZeneca, Bayer, Bayer, Blue Earth Diagnostics Ltd, Exelixis, Janssen, Lantheus Medical Imaging, Inc., Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), Myriad Genetics, Merck, Novartis, and Sanofi; research funding from AstraZeneca, Astellas Scientific and Medical Affairs, Inc., Bayer, Dendreon Pharmaceuticals LLC, Genentech, Inc., Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), Sanofi, and Seattle Genetics, Inc./Astellas Pharma Inc.; and travel, accommodations, and expenses from Sanofi., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Novel androgen receptor inhibitors (ARIs; darolutamide, enzalutamide, and apalutamide) are standard-of-care treatments for nonmetastatic castration-resistant prostate cancer (nmCRPC). However, there are sparse data comparing their clinical use and tolerability., Objective: To compare clinical use and outcomes for darolutamide, enzalutamide, and apalutamide in patients with nmCRPC., Design, Setting, and Participants: This retrospective cohort study reviewed electronic medical records from the Precision Point Specialty network of US urology practices. Eligible patients had nmCRPC and no prior novel hormonal therapy and initiated novel ARI treatment between August 1, 2019, and March 31, 2022. Data were analyzed from February 1, 2019, to December 31, 2022., Exposures: Patients were prescribed darolutamide, enzalutamide, or apalutamide as their first novel ARI for nmCRPC., Main Outcomes and Measures: The main outcome was a composite of 2 end points, treatment discontinuation and progression to metastatic CRPC (mCRPC), whichever occurred first. Both end points were also assessed separately., Results: All 870 patients meeting eligibility criteria were included (362 receiving darolutamide [41.6%]; 382, enzalutamide [43.9%]; 126, apalutamide [14.5%]); mean (SD) age was 78.8 (8.7) years. Self-reported race was Black or African American in 187 patients (21.5%), White in 585 (67.2%), and other or unknown in 98 (11.3%). The darolutamide cohort had lower proportions of patients with a composite end point event (134 [37.0%] vs 201 [52.6%] for enzalutamide and 66 [52.4%] for apalutamide), discontinuation (110 [30.4%] for darolutamide vs 156 [40.8%] for enzalutamide and 58 [46.0%] for apalutamide), and progression to mCRPC (64 [17.7%] for darolutamide vs 108 [28.3%] for enzalutamide and 35 [27.8%] for apalutamide) during the study period. After adjusting for baseline covariates, patients receiving darolutamide had a lower risk of a composite end point event compared with enzalutamide (risk reduction, 33.8%; hazard ratio [HR], 0.66 [95% CI, 0.53-0.84]) and apalutamide (risk reduction, 35.1%; HR, 0.65 [95% CI, 0.48-0.88]). Similarly, patients receiving darolutamide had a lower risk of discontinuation compared with enzalutamide (risk reduction, 27.4%; HR, 0.73 [95% CI, 0.56-0.94]) and apalutamide (risk reduction, 39.1%; HR, 0.61 [95% CI, 0.44-0.85]) and a lower risk of progression to mCRPC compared with enzalutamide (risk reduction, 40.6%; HR, 0.59 [95% CI, 0.43-0.82]) and apalutamide (risk reduction, 35.3%; HR, 0.65 [95% CI, 0.42-0.99]). There was no difference between enzalutamide and apalutamide treatment across outcomes., Conclusions and Relevance: In this large cohort study of patients with nmCRPC treated with novel ARIs, results suggest better tolerability for darolutamide compared with enzalutamide and apalutamide, which may be associated with a clinical effectiveness advantage. Comparative clinical studies are needed to guide treatment decisions in the absence of head-to-head clinical trials.

Teverelix drug product (DP) is a parenteral gonadotropin-releasing hormone (GnRH) antagonist that has been successfully tested in phase 2 trials for hormone-sensitive advanced prostate cancer (APC) and benign prostatic hyperplasia (BPH). In previous APC trials, teverelix DP was administered as intramuscular (IM) and subcutaneous (SC) injections, using a loading dose and (in a single trial) a maintenance dose. Our objective was to derive an optimal dosing regimen for phase 3 clinical development, using a pharmacometrics modeling approach. Data from 9 phase 2 studies (229 patients) was utilized to develop a population pharmacokinetic (PK) model that described the concentration profile accommodating both IM and SC routes of administration. A 2-compartment model with sequential first-order absorption (slow and fast) and lag times best described the PK profiles of teverelix following SC and IM administration. An indirect response model with inhibition of production rate was fit to describe testosterone (T) concentrations based on physiological relevance. The final population PK-pharmacodynamic model was used to conduct simulations of various candidate dosing regimens to select the optimal dosing regimen to achieve clinical castration (T < 0.5 ng/mL by day 28) and to sustain clinical castration for 26 weeks. Model simulation showed that a loading dose of 360 mg SC and 180 mg IM with a maintenance dose of 360 mg SC 6-weekly (Q6W) starting at day 28 can achieve a ≥95% castration rate up to 52 weeks. This dose regimen was selected for phase 3 clinical development, which includes cardiovascular safety assessment in comparison to a GnRH agonist., (© 2024, The American College of Clinical Pharmacology.)

Background: Guidelines recommend dual-energy x-ray absorptiometry (DXA) screening to assess fracture risk and benefit from antiresorptive therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT). However, <30% of eligible patients undergo DXA screening. Biomechanical computed tomography (BCT) is a radiomic technique that measures bone mineral density (BMD) and bone strength from computed tomography (CT) scans., Objective: To evaluate the (1) correlations between BCT- and DXA-assessed BMD, and (2) associations between BCT-assessed metrics and subsequent fracture., Design, Setting, and Participants: A multicenter retrospective cohort study was conducted among patients with mHSPC between 2013 and 2020 who received CT abdomen/pelvis or positron emission tomography/CT within 48 wk before ADT initiation and during follow-up (48-96 wk after ADT initiation)., Outcome Measurements and Statistical Analysis: We used univariate logistic regression to assess the associations between BCT measurements and the primary outcomes of subsequent pathologic and nonpathologic fractures., Results and Limitations: Among 91 eligible patients, the median ([interquartile range) age was 67 yr (62-75), 44 (48.4%) were White, and 41 (45.1%) were Black. During the median follow-up of 82 wk, 17 men (18.6%) developed a pathologic and 15 (16.5%) a nonpathologic fracture. BCT- and DXA-assessed femoral-neck BMD T scores were strongly correlated (R 2  = 0.93). On baseline CT, lower BCT-assessed BMD (odds ratio [OR] 1.80, 95% confidence interval or CI [1.10, 3.25], p = 0.03) was associated with an increased risk of a pathologic fracture. Lower femoral strength (OR 1.63, 95% CI [0.99, 2.71], p = 0.06) was marginally associated with an increased risk of a pathologic fracture. Neither BMD (OR 1.52, 95% CI [0.95, 2.63], p = 0.11) nor strength (OR 1.14, 95% CI [0.75, 1.80], p = 0.57) was associated with a nonpathologic fracture. BCT identified nine (9.9%) men eligible for antiresorptive therapy, of whom four (44%) were not treated. Limitations include low fracture numbers resulting in lower power to detect fracture associations., Conclusions: Among men diagnosed with mHSPC, BCT assessments were strongly correlated with DXA, predicted subsequent pathologic fracture, and identified additional men indicated for antiresorptive therapy., Patient Summary: We assess whether biomechanical computer tomography (BCT) from routine computer tomography (CT) scans can identify fracture risk among patients recently diagnosed with metastatic prostate cancer. We find that BCT and dual-energy x-ray absorptiometry-derived bone mineral density are strongly correlated and that BCT accurately identifies the risk for future fracture. BCT may enable broader fracture risk assessment and facilitate timely interventions to reduce fracture risk in metastatic prostate cancer patients., (Published by Elsevier B.V.)

The clinical rationale for treatment of castration-sensitive prostate cancer (CSPC) with novel hormonal therapy (NHT) or androgen receptor pathway inhibitor is reviewed. A PubMed search was conducted to identify relevant publications on NHTs for CSPC treatment. Level 1 clinical evidence demonstrated that intensification of androgen deprivation therapy (ADT) with NHT prolongs life and improves or maintains quality of life in patients with metastatic CSPC (mCSPC). Despite these results, real-world evidence demonstrated that 47%-88% of patients with mCSPC are treated with single agent ADT. Possible explanations for the underutilization of NHTs include patient characteristics, misperceptions about the overall survival benefit, lack of physician and patient awareness of the magnitude of clinical trial results, physician bias, safety concerns, misconceptions about the magnitude of prostate-specific antigen response needed for patient improvement, and barriers to NHT access. For patients with biochemical recurrence and no evidence of metastatic disease, limited clinical data exist with no consensus on an effective treatment strategy. Therefore, treatment strategies are developed using patient risk stratification according to clinicopathological characteristics, genomics, and next-generation imaging. Patients with high-risk biochemical recurrence may benefit from the early initiation of NHT based on outcomes from the phase III EMBARK trial. Lifestyle management is also an important aspect of treatment for CSPC, helping to mitigate the side effects of hormonal treatment and ensuring patients can maintain treatment while optimizing quality of life. In conclusion, to improve outcomes in patients with mCSPC, it is important to implement solutions addressing the barriers to underutilization of treatment intensification., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stephen J. Freedland – consultant to Astellas Pharma, AstraZeneca, Bayer, Exact Sciences, Johnson & Johnson Innovative Medicine (formerly Janssen Biotech), Merck, Sumitomo Pharma America, Inc. (formerly Myovant Sciences), Pfizer, and Sanofi. Daniel J. George – reported receiving grants from Acerta Pharmaceuticals; other from American Association for Cancer Research; grants and personal fees from Astellas Pharma; personal fees from AstraZeneca; personal fees from Axess Oncology; grants, personal fees, and nonfinancial support from Bayer H/C Pharmaceuticals; grants and personal fees from Bristol Myers Squibb; grants from Calithera; grants from Capio Biosciences; grants from EMD Serono; grants, personal fees, and nonfinancial support from Exelixis, Inc.; personal fees from Flatiron; personal fees from Ipsen; grants and personal fees from Johnson & Johnson Innovative Medicine (formerly Janssen Biotech); personal fees from Merck, Sharp & Dohme; personal fees from Michael J Hennessey Associates; personal fees from Millennium Medical Publishing; personal fees from Modra Pharmaceuticals B.V.; personal fees from Sumitomo Pharma America, Inc. (formerly Myovant Sciences); personal fees from NCI Genitourinary; personal fees from Nektar Therapeutics; grants and personal fees from Novartis; personal fees from Physician Education Resource; grants and personal fees from Pfizer Inc.; grants, personal fees, and nonfinancial support from Sanofi; personal fees from UroGPO; personal fees and nonfinancial support from UroToday; personal fees from Vizuri Health Sciences; and personal fees from Platform Q, outside the submitted work. Alicia K. Morgans – reports honoraria from Genentech, Johnson & Johnson Innovative Medicine (formerly Janssen), Sanofi, AstraZeneca, Astellas Scientific and Medical Affairs Inc., Astellas Pharma, Johnson & Johnson Innovative Medicine (formerly Janssen), Bayer, Clovis Oncology, Sumitomo Pharma America, Inc. (formerly Myovant Sciences), Advanced Accelerator Applications, Exelixis, Pfizer, and Merck; consulting or advisory roles with AstraZeneca, Sanofi, Bayer, Astellas Pharma, Johnson & Johnson Innovative Medicine (formerly Janssen), Advanced Accelerator Applications, Sumitomo Pharma America, Inc. (formerly Myovant Sciences), Blue Earth Diagnostics, Exelixis, Novartis, Myriad Genetics, Lantheus Medical Imaging, and Merck; research funding from Bayer, Seattle Genetics/Astellas, Genentech, AstraZeneca, Astellas Scientific and Medical Affairs Inc., Dendreon, Sanofi, and Sumitomo Pharma America, Inc. (formerly Myovant Sciences); and travel, accommodation, and expenses from Sanofi. Cora N. Sternberg – Served as a consultant for Janssen-Cilag, Astellas Pharma, Sanofi–Genzyme, Novartis, Bayer, Pfizer Inc., Merck, Merck Sharp & Dohme, AstraZeneca, Gilead (formerly Immunomedics), Johnson & Johnson Innovative Medicine (formerly Janssen), Eli Lilly, Foundation Medicine, UroToday, and Medscape; and has received prior institutional funding from Johnson & Johnson Innovative Medicine (formerly Cougar Biotechnology and Janssen), Pfizer (formerly Medivation), Clovis Oncology, and Roche-Genentech., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Prostate cancer survivors may benefit from a supportive social environment. We investigated associations of social integration and long-term physical and psychosocial quality of life among prostate cancer survivors who were participants in the Health Professionals Follow-up Study., Methods: We included 1,428 individuals diagnosed with non-metastatic prostate cancer between 2008 and 2016. Social integration was measured by the Berkman-Syme Social Network Index (SNI) and marital status. We fit generalized linear mixed effect models for associations of SNI and marital status with patient reported outcome measures on physical and psychosocial quality of life captured between 2008 and 2020, adjusting for age, race, employment status, body mass index, comorbidities, smoking history, and clinical factors., Results: Among those with baseline SNI (N = 1,362), 46.4% were socially integrated, 20.3% were moderately integrated, 27.4% were moderately isolated, and 5.9% were socially isolated. Among those reporting baseline marital status (N = 1,428), 89.5% were married. Socially integrated survivors (vs. socially isolated) reported fewer depressive signs and better psychosocial wellbeing. Physical quality of life did not differ by social integration. Married survivors (vs. not married) reported fewer urinary symptoms, but there were no differences in bowel, sexual, or vitality/hormonal symptoms., Conclusions: Among prostate cancer survivors, being socially integrated was associated with fewer depressive signs and better psychosocial wellbeing, and married prostate cancer survivors had fewer urinary symptoms., Implications for Cancer Survivors: This study highlighted aspects of long-term physical and psychosocial quality of life that are more favorable among prostate cancer survivors with a supportive social environment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Enzalutamide is an oral androgen receptor signaling inhibitor utilized in the treatment of men with prostate cancer. It is a moderate inducer of the cytochrome P450 (CYP) enzymes CYP2C9 and CYP2C19, and a strong inducer of CYP3A4. It was also shown to be a mild inhibitor of the efflux transporter P-glycoprotein in patients with prostate cancer. Enzalutamide is primarily metabolized by CYP3A4 and CYP2C8. The risk of enzalutamide drug interactions arises primarily when it is coadministered with other drugs that interact with these CYPs, including CYP3A4. In this review, we begin by providing an overview of enzalutamide including its dosing, use in special populations, pharmacokinetics, changes to its prescribing information, and potential for interaction with coadministered drugs. Enzalutamide interactions with drugs from a wide range of medication classes commonly prescribed to patients with prostate cancer are described, including oral androgen deprivation therapy, agents used to treat a range of cardiovascular diseases, antidiabetic drugs, antidepressants, anti-seizure medications, common urology medications, analgesics, proton pump inhibitors, immunosuppressants, and antigout drugs. Enzalutamide interactions with common vitamins and supplements are also briefly discussed. This review provides a resource for healthcare practitioners and patients that will help provide a basis for the understanding and management of enzalutamide drug-drug interactions to inform decision making, improve patient safety, and optimize drug efficacy., (© 2024. Pfizer Inc.)

Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([ 177 Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [ 177 Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies. Further, the drug development pipeline is deep with variations of PSMA-targeting radionuclides, including higher energy alpha particles conjugated to PSMA-honing vectors. It is safe to assume that an increasing number of patients will be exposed to PSMA-targeted radiopharmaceuticals during the course of their cancer treatment. In this setting, it is important to better understand and mitigate the most commonly encountered toxicities. One particularly vexing side effect is xerostomia. In this review, we discuss the scope of the problem, inventories to better characterize and monitor this troublesome side effect, and approaches to preserve salivary function and effectively palliate symptoms. This article aims to serve as a useful reference for prescribers of PSMA-targeted radiopharmaceuticals, while also commenting on areas of missing data and opportunities for future research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC), information regarding health related quality of life (HR-QoL) is sparse. We aimed at summarizing current evidence on the impact of ARSIs on HR-QoL., Methods: We performed a systematic review of the published literature on PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane libraries between January 2011 and April 2022. We included only phase III randomized controlled trials (RCT), which were selected according to the PRISMA guidelines. We aimed at evaluating differences in HR-QoL, assessed by validated patient reported outcomes instruments. We analyzed global scores and sub-domains such as sexual functioning, urinary symptoms, bowel symptoms, pain/fatigue, emotional and social/family wellbeing. We reported data descriptively., Results: Six RCTs were included: two used enzalutamide with ADT as intervention arms (ARCHES, ENZAMET); one used apalutamide with ADT (TITAN); two abiraterone acetate and prednisone (AAP) with ADT (STAMPEDE, LATITUDE); and one darolutamide with ADT (ARASENS). Enzalutamide or AAP with ADT increase overall HR-QoL in comparison with ADT alone, ADT with first generation nonsteroideal anti-androgens or ADT with docetaxel, whereas apalutamide and darolutamide with ADT maintain HR-QoL similarly to ADT alone or ADT with docetaxel, respectively. Time to first deterioration of pain was longer with combination therapy with enzalutamide, AAP or darolutamide, but not with apalutamide. No worsening of emotional wellbeing was reported from the addition of ARSIs to ADT than ADT alone., Conclusions: The addition of ARSIs to ADT in mHSPC tends to increase overall HR-QoL and prolong time to first deterioration of pain/fatigue compared with ADT alone, ADT with first generation nonsteroideal anti-androgens, and ADT with docetaxel. ARSIs show a complex interaction with remaining HR-QoL domains. We advocate a standardization of HR-QoL measurement and reporting to allow further comparisons., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Plant-based diets have many health benefits, including a lower risk of fatal prostate cancer, and greater environmental sustainability. However, less is known regarding the impact of plant-based diets on quality of life among individuals diagnosed with prostate cancer. The authors' objective was to examine the relationship between plant-based diet indices postdiagnosis with quality of life., Methods: This prospective cohort study included 3505 participants in the Health Professionals Follow-Up Study (1986-2016) with nonmetastatic prostate cancer. Food-frequency questionnaires were used to calculate overall and healthful plant-based diet indices. Quality-of-life scores were calculated using the Expanded Prostate Cancer Index Composite. Generalized estimating equations were used to examine associations over time between plant-based diet indices and quality-of-life domains (sexual functioning, urinary irritation/obstruction, urinary incontinence, bowel functioning, hormonal/vitality), adjusted for demographics, oncologic history, body mass index, caloric intake, health-related behaviors, and comorbidities., Results: The median age at prostate cancer diagnosis was 68 years; 48% of patients underwent radical prostatectomy, and 35% received radiation as primary therapy. The median time from diagnosis/treatment to first the quality-of-life questionnaire was 7.0 years. A higher plant-based diet index was associated with better scores for sexual function, urinary irritation/obstruction, urinary incontinence, and hormonal/vitality. Consuming more healthful plant-based foods was also associated with better sexual and bowel function, as well as urinary incontinence and hormonal/vitality scores in the age-adjusted analysis, but not in the multivariable analysis., Conclusions: This prospective study provides supportive evidence that greater consumption of healthful plant-based foods is associated with modestly higher scores in quality-of-life domains among patients with prostate cancer., (© 2024 American Cancer Society.)

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and develops from biochemically recurrent PC treated with androgen deprivation therapy (ADT) following definitive therapy for localized PC, or from metastatic castration-sensitive PC (mCSPC). In the mCSPC setting, treatment intensification of ADT plus androgen receptor (AR)-signaling inhibitors (ARSIs), with or without chemotherapy, improves outcomes vs ADT alone. Despite multiple phase 3 trials demonstrating a survival benefit of treatment intensification in PC, there remains high use of ADT monotherapy in real-world clinical practice. Prior studies indicate that co-inhibition of AR and poly(ADP-ribose) polymerase (PARP) may result in enhanced benefit in treating tumors regardless of alterations in DNA damage response genes involved either directly or indirectly in homologous recombination repair (HRR). Three recent phase 3 studies evaluated the combination of a PARP inhibitor (PARPi) with an ARSI as first-line treatment for mCRPC: TALAPRO-2, talazoparib plus enzalutamide; PROpel, olaparib plus abiraterone acetate and prednisone (AAP); and MAGNITUDE, niraparib plus AAP. Results from these studies have led to the recent approval in the United States of talazoparib plus enzalutamide for the treatment of mCRPC with any HRR alteration, and of both olaparib and niraparib indicated in combination with AAP for the treatment of mCRPC with BRCA alterations., Summary: Here, we review the newly approved PARPi plus ARSI treatments within the context of the mCRPC treatment landscape, provide an overview of practical considerations for the combinations in clinical practice, highlight the importance of HRR testing, and discuss the benefits of treatment intensification for patients with mCRPC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.R.M. reports a consulting or advisory board role for AstraZeneca, AVEO Pharmaceuticals, Bayer, Blue Earth Diagnostics, Bristol Myers Squibb, Calithera, Caris, Dendreon, Eisai, Eli Lilly, Exelixis, Janssen, Merck, MOMA, Myovant, Novartis, Pfizer, Sanofi, Seagen, Sorrento Therapeutics, Telix, and Tempus; and research funding (to her institution) from AstraZeneca, Artera, Bayer, Bristol Myers Squibb, Exelixis, Oncternal, and Tempus. A.K.M. reports a consulting role for Antev, Astellas, AstraZeneca, Bayer, Exelixis, Janssen, Lantheus, Merck, Myovant, Novartis, Pfizer, Sanofi, and Telix; and research funding from Bayer, Lantheus, Myovant, Pfizer, and Sanofi. N.D.S. reports a consulting or advisory role for AbbVie, Alessa Therapeutics, AIkido, Amgen, Arquer, Asieris, Astellas Pharma, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, CG Oncology, Clarity Pharmaceuticals, Clovis Oncology, Dendreon, Exact Imaging, Exact Sciences, FerGene, Ferring, FIZE Medical, Foundation Medicine, GenesisCare, Genentech, Guardant Health, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, Mdxhealth, Merck, Minomic, Myovant Sciences, Myriad Genetics, Nymox, Pacific Edge Biotechnology, Pfizer, Photocure, PlatformQ, Profound, Promaxo, Propella Therapeutics, Protara, Sanofi, Sesen Bio, Speciality Networks, Telix Pharmaceuticals, Tolmar, UroGen Pharma, Vaxiion, and Vessi; providing expert testimony for Ferring; and leadership or other fiduciary role in other board, society, committee, or advocacy group with Photocure. C.D. reports participation on advisory boards for Astellas Pharma, Bayer, Janssen, and Pfizer; and research funding from AstraZeneca, Bayer, Dendreon, Hengrui Pharmaceuticals, Janssen, Laekna Therapeutics, Myovant Sciences, and Pfizer. G.D. is an employee of Pfizer and may hold Pfizer stock/stock options. N.A. has received an honorarium for consultancy before May 2021 from Astellas Pharma, AstraZeneca, AVEO, Bayer, Bristol Myers Squibb, Calithera Biosciences, Eisai, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead Sciences, Immunomedics, Janssen, Lilly, and MEI Pharma; and research funding (to his institution) from Arvinas, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera Biosciences, Celldex, Clovis Oncology, CRISPR Therapeutics, Eisai, EMD Serono, Exelixis, Genentech, Gilead Sciences, GlaxoSmithKline, Immunomedics, Janssen, Lava, Lilly, Merck, Nektar, Neoleukin, Novartis, ORIC Pharmaceuticals, Pfizer, Rexahn, Roche, Sanofi, Seagen, Takeda, and TRACON., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chemohormonal therapy with androgen deprivation therapy and docetaxel (ADT + D) improves overall survival (OS) and quality of life (QOL) at 12 mo versus androgen deprivation therapy (ADT) alone in men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the prognostic role of QOL is unknown in this population., Objective: To study the relationship between QOL, disease characteristics, and OS in men with mHSPC., Design, Setting, and Participants: In this exploratory post hoc analysis, 790 patients with mHSPC completed the QOL instruments Functional Assessment of Cancer Therapy-Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Brief Pain Inventory (BPI)., Outcome Measurements and Statistical Analysis: Log-rank test and Cox proportional hazard models tested the association between QOL and OS by clinical and disease characteristics., Results and Limitations: Baseline higher FACT-P trended toward improved survival after accounting for clinical variables (hazard ratio [HR] 0.80 [0.62, 1.04], p = 0.09), while higher 3-mo FACT-P was independently associated with better survival (HR 0.76 [0.58, 1.0], p = 0.05). Patients with the poorest QOL (bottom quartile) at baseline and 3 mo had longer survival if they received ADT + D rather than ADT alone (median OS 45.2 vs 34.4 mo, HR 0.75 [0.53, 1.05], p = 0.09, and 48.3 vs 29.3 mo, HR 0.69 [0.48, 0.99], p = 0.05 respectively). In contrast, patients with the best QOL (top quartile) at baseline and 3 mo had comparable survival irrespective of whether or not docetaxel was added (median OS 72.1 vs 51.7 mo, HR 0.92 [0.63, 1.36], p = 0.69, and 69.9 vs 68.9 mo, HR 1.11 [0.73, 1.67], p = 0.63, respectively). Survival was linked with baseline FACIT-F (HR 0.76 [0.57, 1.0], p = 0.05), but not BPI (HR 0.98 [0.75, 1.28], p = 0.90)., Conclusions: Three-month QOL had a stronger independent association with survival. The most symptomatic patients had longer survival with the addition of docetaxel; conversely, the least symptomatic patients did not appear to benefit. Consideration of QOL may enhance decision-making and patient selection when choosing chemohormonal treatment in mHSPC., Patient Summary: Quality of life independently forecasted the survival of men with metastatic hormone-sensitive prostate cancer in the CHAARTED study. Close tracking of quality of life could help patients and clinicians make decisions about the appropriate treatment in this setting., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC., Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy., Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC., Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC., Competing Interests: CONFLICTS OF INTEREST The authors declare the following competing interests: Alan H. Bryce has received compensation for a consulting or advisory role from Merck, Janssen, Astellas, AstraZeneca, Pfizer, Myovant, and Lantheus; and grant funding from Janssen. Andrew J. Armstrong has received compensation for a consulting or advisory role from Astellas, Epic Sciences, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Clovis, Exact Sciences, Myovant, Exelixis, GoodRx, and Novartis; and his institution has received research funding from Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen, and Novartis. AI has received compensation for a consulting or advisory role from Alpha9Tx, Clarity Pharmaceuticals, Novartis, Progenics, Radionetics, RayzeBio, and Telix; and research/grant funding from GE Healthcare and Novartis. Ana M. Aparicio has received compensation for a consulting or advisory role from Pfizer, Janssen, and Bristol Myers Squibb. Alicia K. Morgans has received compensation for a consulting or advisory role from Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Myovant, Myriad Genetics, Lantheus, Novartis, Merck, Pfizer, Telix, and Sanofi; and research funding from Bayer, Astellas, Myovant, Pfzer, Sanofi, and Janssen. Brian F. Chapin has received compensation for a consulting or advisory role from Blue Earth Diagnostics, Astellas, Pfizer, and Janssen; and is a clinical trial investigator for Regeneron and Blue Earth Therapeutics. Daniel P. Petrylak has received compensation for a consulting or advisory role from Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Ipsen, Janssen, Merck & Company Inc, Mirati, Monopteros, Pfizer, Pharmacyclics, Regeneron, Roche, Sanofi Aventis Pharmaceuticals, Seattle Genetics, and Urogen; has received grant support from Ada Cap (Advanced Accelerator Applications), Agensys Inc, Arvinas, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo Company Limited, Eisai, Eli Lilly, Endocyte, Ferring, Genentech, Gilead Sciences, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi Aventis, and Seattle Genetics; and has owned stock in Bellicum and Tyme. Daniel E. Spratt has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Boston Scientific, Elekta, Janssen, Novartis, Pfizer, and Varian. Emmanuel S. Antonarakis has received compensation for a consulting or advisory role from Sanofi, Dendreon, Janssen Biotech, ESSA, Merck, AstraZeneca, Clovis Oncology, Lilly, Bayer, Amgen, Astellas Pharma, Blue Earth Diagnostics, Bristol Myers Squibb/Celgene, Constellation Pharmaceuticals, Curium Pharma, Exact Sciences, Foundation Medicine, GlaxoSmithKline, InVitae, Ismar Health Care, Medivation, Tempus, Orion, and Alkido Pharma; he has received research funding from Celgene and Clovis Oncology; his institution has received research funding from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, Constellation Pharmaceuticals, Celgene, and Clovis Oncology; and he is co-inventor of a biomarker technology that has been licensed to Qiagen. E. David Crawford has received compensation for a consulting or advisory role from Janssen, Bayer, MDx, Tolmar, Pfizer, and Astellas; has received research/grant funding from the NIH and University of Colorado Cancer Center; and has received compensation for a leadership position from Carden Jennings. Eric Small has received compensation for a consulting or advisory role from Janssen, Fortis, and Deciphera; received honoraria from Janssen and Johnson & Johnson; and owns stock/stock options in Fortis, Harpoon, and Teon. Evan Y. Yu has received compensation for a consulting or advisory role from Aadi Bioscience, Advanced Accelerator Applications, Bayer, Janssen, Merck, and Oncternal; and his institution has received research funding from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen, Surface, Taiho, and Tyra. Felix Y. Feng has received compensation for a consulting or advisory role from Astellas, Bayer, Blue Earth Diagnostics, Janssen, Myovant, Novartis, Roivant, Sanofi, Tempus, Artera, BMS (Tumor Microenvironment Group), ClearNote, and Serimmune, Himisha Beltran has received compensation for a consulting or advisory role from Janssen, Merck, Pfizer, Foundation Medicine, Blue Earth Diagnostics, Amgen, Bayer, Oncorus, LOXO, Daicchi Sankyo, Sanofi, Curie Therapeutics, Fusion Pharma, Astra Zeneca, and Novartis; and her institution has received research funding from Janssen, Bristol Myers Squibb, Circle Pharma, Daicchi Sankyo, and Novartis. Jeremie Calais has received compensation for a consulting, advisory, or blinded image reading role from Advanced Accelerator Applications, Amgen, Astellas, Bayer, Blue Earth Diagnostics Inc., Curium Pharma, DS Pharma, GE Healthcare, Isoray, IBA RadioPharma, Janssen Pharmaceuticals, Monrol, Lightpointmedical, Lantheus, Novartis, Pfizer, POINT biopharma, Progenics, Radiomedix, Sanofi, Siemens-Varian, SOFIE, and Telix Pharmaceuticals; and grant funding from the Prostate Cancer Foundation. John W. Davis has received research funding from Janssen. Katie S. Murray has received compensation for a consulting or advisory role from Curium and Urogen Pharma. Michael S. Cookson has received compensation for a consulting or advisory role from LynxDx, Natera, Bayer, Consulting JW, Remedica Medical Education & Publishing, Pfizer, Lantheus, Nonagen Bioscience Corp, MJH LifeSciences, Pacific Edge Diagnostics USA Ltd, Janssen, Prokarium, BioPharm Communications, Myovant, Merck, Clinical Education Alliance, TesoRx Pharma; and has received research support from Ferring Pharmaceuticald and MDXHealth. Maha H. Hussain has received compensation for a consulting or advisory role from GSK, Novartis, and Bayer; honoraria for educational event or lecture from Merck, Mubarak Mahdi Almansour (Chairman, International Genitourinary Cancer Conference), MJH, and Academic CME; her institution has received research/grant funding from AstraZeneca and Arvinas. Michael Morris has received compensation for a consulting or advisory role from AstraZeneca, Lantheus, Daiichi, Convergent Therapeutics, Pfizer, ITM Isotope Technologies, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, and Z-Alpha; he is an uncompensated advisor to Bayer and Novartis; his institution has received research funding from Bayer, Corcept, Roche, Janssen, Celgene, Novartis, and Astellas. Matthew B. Rettig has received compensation for a consulting or advisory role from Myovant, INmune Bio, Bayer, and Johnson & Johnson; is a member of the Speakers’ Bureau for Johnson & Johnson and Bayer; and has received grants/research support from Merck, Lantheus, Progenics, Clovis, ORIC, Pfizer, Novartis, Amgen. Neeraj Agarwal has received compensation for a consulting or advisory role from Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; his institution has received research funding from Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Neal Shore has received compensation for a consulting or advisory role from AbbVie, Alessa Therapeutics, Akido, Amgen, Arquer, Asieris, Astellas, Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis, Cold Genesys, Dendreon, Exact Images, Exact Sciences, FerGene, FIZE Medical, GConcology, GenesisCare, Genetech, Guardant, Ferring, Foundation Medicine, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Photocure, Pfizer, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar, Urogen, Vaxiion, and Vessi; received payment for expert testimony from Ferring; and is on the board of Photocure. Oliver Sartor has received compensation for a consulting or advisory role from Advanced Accelerator Applications, Amgen, ART BioScience, Astellas Pharma, AstraZeneca, Bayer, Clarity Pharmaceuticals, EMD Serono, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, MacroGenics, Novartis, Pfizer, Point Biopharma, Ratio, Sanofi, Telix Pharmaceuticals, and TeneoBio; he has stock or other ownership interested with AbbVie, Cardinal Health, Clarity Pharmaceuticals, Convergent, Eli Lilly, Fusion Pharmaceuticals, Point Biopharma, Ratio, Telix, and United Health Group; he has patents for Saposin C and receptors as targets for treatment of benign and malignant disorders (U.S. patent awarded January 23, 2007; patent no. 7,166,691); he has provided expert testimony for Sanofi; he has received reimbursement for travel, accommodations, or expenses from AstraZeneca, Bayer, Lantheus, and Sanofi; and his institution has received research/grant funding from Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, InVitae, Janssen, Lantheus, Merck, and Sanofi. Phillip J. Koo has received compensation for a consulting or advisory role from Lantheus, Blue Earth Diagnostics, Merck, Janssen, Pfizer, Astellas, AstraZeneca, Bayer, Novartis, Sanofi, Telix, and Curium. Scott E. Eggener has received compensation for a consulting or advisory role Candel Therapeutics, A3P Biomedical, Cellvax, MetasTx, Optum-Health, and Janssen. Sandy Srinivas has received compensation for a consulting or advisory role from Novartis and Janssen. Scott T. Tagawa has received compensation for a consulting or advisory role from Sanofi, Medivation, Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, Abbvie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Clarity, Genomic Health, POINT Biopharma, Blue Earth, AIkido Pharma, Telix Pharma, Convergent Therapeutics, EMD Serono, Myovant, Merck, Daiichi Sankyo, TransThera, and Regeneron; he is an unpaid consultant for Atlab Pharma, Phosplatin Therapeutics, Amgen, and Ambrx; he and his institution hold patents for biomarkers for sacituzumab govitecan therapy (Immunomedics/Gilead); and his institution has received research funding from Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, Abbvie, Karyopharm, Endocyte, Clovis, Seattle Genetics, Novartis, Gilead, POINT Biopharma, Ambrx, Clarity. Thomas P. Boike has received compensation for a consulting or advisory role from Lantheus, Myovant, Novartis, Pfizer, Janssen, Astellas, Blue Earth, AstraZeneca, Palette Life Sciences, and Boston Scientific. Tanya Dorff has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Janssen, and Sanofi. Tian Zhang has received compensation for a consulting or advisory role from Merck, Exelixis, Sanofi-Aventis, Janssen, Astra Zeneca, Pfizer, Amgen, BMS, Dendreon, SeaGen, Eisai, Aveo, Bayer, and Eli Lilly; honoraria from MJH Associates, Vaniam, Aptitude Health, PlatformQ, IntegrityCE, PeerView, and WJ Weiser; and her institution has received research funding from Novartis, Merck, Janssen, Astra Zeneca, Pfizer, Tempus, and Eli Lilly. Wendy Poage is an employee of Servier Pharmaceuticals; and she has ownership interests in 3D biopsy.

Background: Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature., Materials and Methods: The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators., Results: This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non- BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies., Conclusions: The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state., Competing Interests: CONFLICTS OF INTEREST The authors declare the following competing interests: Alan H. Bryce has received compensation for a consulting or advisory role from Merck, Janssen, Astellas, AstraZeneca, Pfizer, Myovant, and Lantheus; and grant funding from Janssen. Andrew J. Armstrong has received compensation for a consulting or advisory role from Astellas, Epic Sciences, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Clovis, Exact Sciences, Myovant, Exelixis, GoodRx, and Novartis; and his institution has received research funding from Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen, and Novartis. Andrei Iagaru has received compensation for a consulting or advisory role from Alpha9Tx, Clarity Pharmaceuticals, Novartis, Progenics, Radionetics, RayzeBio, and Telix; and research/grant funding from GE Healthcare and Novartis. Ana M. Aparicio has received compensation for a consulting or advisory role from Pfizer, Janssen, and Bristol Myers Squibb. Alicia K. Morgans has received compensation for a consulting or advisory role from Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Myovant, Myriad Genetics, Lantheus, Novartis, Merck, Pfizer, Telix, and Sanofi; and research funding from Bayer, Astellas, Myovant, Pfzer, Sanofi, and Janssen. Brian F. Chapin has received compensation for a consulting or advisory role from Blue Earth Diagnostics, Astellas, Pfizer, and Janssen; and is a clinical trial investigator for Regeneron and Blue Earth Therapeutics. Daniel P. Petrylak has received compensation for a consulting or advisory role from Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Ipsen, Janssen, Merck & Company Inc, Mirati, Monopteros, Pfizer, Pharmacyclics, Regeneron, Roche, Sanofi Aventis Pharmaceuticals, Seattle Genetics, and Urogen; has received grant support from Ada Cap (Advanced Accelerator Applications), Agensys Inc, Arvinas, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo Company Limited, Eisai, Eli Lilly, Endocyte, Ferring, Genentech, Gilead Sciences, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi Aventis, and Seattle Genetics; and has owned stock in Bellicum and Tyme. Daniel E. Spratt has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Boston Scientific, Elekta, Janssen, Novartis, Pfizer, and Varian. Emmanuel S. Antonarakis has received compensation for a consulting or advisory role from Sanofi, Dendreon, Janssen Biotech, ESSA, Merck, AstraZeneca, Clovis Oncology, Lilly, Bayer, Amgen, Astellas Pharma, Blue Earth Diagnostics, Bristol Myers Squibb/Celgene, Constellation Pharmaceuticals, Curium Pharma, Exact Sciences, Foundation Medicine, GlaxoSmithKline, InVitae, Ismar Health Care, Medivation, Tempus, Orion, and Alkido Pharma; he has received research funding from Celgene and Clovis Oncology; his institution has received research funding from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, Constellation Pharmaceuticals, Celgene, and Clovis Oncology; and he is co-inventor of a biomarker technology that has been licensed to Qiagen. E. David Crawford has received compensation for a consulting or advisory role from Janssen, Bayer, MDx, Tolmar, Pfizer, and Astellas; has received research/grant funding from the NIH and University of Colorado Cancer Center; and has received compensation for a leadership position from Carden Jennings. Eric Small has received compensation for a consulting or advisory role from Janssen, Fortis, and Deciphera; received honoraria from Janssen and Johnson & Johnson; and owns stock/stock options in Fortis, Harpoon, and Teon. Evan Y. Yu has received compensation for a consulting or advisory role from Aadi Bioscience, Advanced Accelerator Applications, Bayer, Janssen, Merck, and Oncternal; and his institution has received research funding from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen, Surface, Taiho, and Tyra. Felix Y. Feng has received compensation for a consulting or advisory role from Astellas, Bayer, Blue Earth Diagnostics, Janssen, Myovant, Novartis, Roivant, Sanofi, Tempus, Artera, BMS (Tumor Microenvironment Group), ClearNote, and Serimmune, Himisha Beltran has received compensation for a consulting or advisory role from Janssen, Merck, Pfizer, Foundation Medicine, Blue Earth Diagnostics, Amgen, Bayer, Oncorus, LOXO, Daicchi Sankyo, Sanofi, Curie Therapeutics, Fusion Pharma, Astra Zeneca, and Novartis; and her institution has received research funding from Janssen, Bristol Myers Squibb, Circle Pharma, Daicchi Sankyo, and Novartis. Jeremie Calais has received compensation for a consulting, advisory, or blinded image reading role from Advanced Accelerator Applications, Amgen, Astellas, Bayer, Blue Earth Diagnostics Inc, Curium Pharma, DS Pharma, GE Healthcare, Isoray, IBA RadioPharma, Janssen Pharmaceuticals, Monrol, Lightpointmedical, Lantheus, Novartis, Pfizer, POINT biopharma, Progenics, Radiomedix, Sanofi, Siemens-Varian, SOFIE, and Telix Pharmaceuticals; and grant funding from the Prostate Cancer Foundation. John W. Davis has received research funding from Janssen. Katie S. Murray has received compensation for a consulting or advisory role from Curium and Urogen Pharma. Michael S. Cookson has received compensation for a consulting or advisory role from LynxDx, Natera, Bayer, Consulting JW, Remedica Medical Education & Publishing, Pfizer, Lantheus, Nonagen Bioscience Corp, MJH LifeSciences, Pacific Edge Diagnostics USA Ltd, Janssen, Prokarium, BioPharm Communications, Myovant, Merck, Clinical Education Alliance, TesoRx Pharma; and has received research support from Ferring Pharmaceuticald and MDXHealth. Maha H. Hussain has received compensation for a consulting or advisory role from GSK, Novartis, and Bayer; honoraria for educational event or lecture from Merck, Mubarak Mahdi Almansour (Chairman, International Genitourinary Cancer Conference), MJH, and Academic CME; her institution has received research/grant funding from AstraZeneca and Arvinas. Michael Morris has received compensation for a consulting or advisory role from AstraZeneca, Lantheus, Daiichi, Convergent Therapeutics, Pfizer, ITM Isotope Technologies, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, and Z-Alpha; he is an uncompensated advisor to Bayer and Novartis; his institution has received research funding from Bayer, Corcept, Roche, Janssen, Celgene, Novartis, and Astellas. Matthew B. Rettig has received compensation for a consulting or advisory role from Myovant, INmune Bio, Bayer, and Johnson & Johnson; is a member of the Speakers’ Bureau for Johnson & Johnson and Bayer; and has received grants/research support from Merck, Lantheus, Progenics, Clovis, ORIC, Pfizer, Novartis, Amgen. Neeraj Agarwal has received compensation for a consulting or advisory role from Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; his institution has received research funding from Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Neal Shore has received compensation for a consulting or advisory role from AbbVie, Alessa Therapeutics, Akido, Amgen, Arquer, Asieris, Astellas, Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis, Cold Genesys, Dendreon, Exact Images, Exact Sciences, FerGene, FIZE Medical, GConcology, GenesisCare, Genetech, Guardant, Ferring, Foundation Medicine, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Photocure, Pfizer, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar, Urogen, Vaxiion, and Vessi; received payment for expert testimony from Ferring; and is on the board of Photocure. Oliver Sartor has received compensation for a consulting or advisory role from Advanced Accelerator Applications, Amgen, ART BioScience, Astellas Pharma, AstraZeneca, Bayer, Clarity Pharmaceuticals, EMD Serono, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, MacroGenics, Novartis, Pfizer, Point Biopharma, Ratio, Sanofi, Telix Pharmaceuticals, and TeneoBio; he has stock or other ownership interested with AbbVie, Cardinal Health, Clarity Pharmaceuticals, Convergent, Eli Lilly, Fusion Pharmaceuticals, Point Biopharma, Ratio, Telix, and United Health Group; he has patents for Saposin C and receptors as targets for treatment of benign and malignant disorders (U.S. patent awarded January 23, 2007; patent no. 7,166,691); he has provided expert testimony for Sanofi; he has received reimbursement for travel, accommodations, or expenses from AstraZeneca, Bayer, Lantheus, and Sanofi; and his institution has received research/grant funding from Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, InVitae, Janssen, Lantheus, Merck, and Sanofi. Phillip J. Koo has received compensation for a consulting or advisory role from Lantheus, Blue Earth Diagnostics, Merck, Janssen, Pfizer, Astellas, AstraZeneca, Bayer, Novartis, Sanofi, Telix, and Curium. Scott E. Eggener has received compensation for a consulting or advisory role Candel Therapeutics, A3P Biomedical, Cellvax, MetasTx, OptumHealth, and Janssen. Sandy Srinivas has received compensation for a consulting or advisory role from Novartis and Janssen. Scott T. Tagawa has received compensation for a consulting or advisory role from Sanofi, Medivation, Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, Abbvie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Clarity, Genomic Health, POINT Biopharma, Blue Earth, AIkido Pharma, Telix Pharma, Convergent Therapeutics, EMD Serono, Myovant, Merck, Daiichi Sankyo, TransThera, and Regeneron; he is an unpaid consultant for Atlab Pharma, Phosplatin Therapeutics, Amgen, and Ambrx; he and his institution hold patents for biomarkers for sacituzumab govitecan therapy (Immunomedics/Gilead); and his institution has received research funding from Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, Abbvie, Karyopharm, Endocyte, Clovis, Seattle Genetics, Novartis, Gilead, POINT Biopharma, Ambrx, Clarity. Thomas P. Boike has received compensation for a consulting or advisory role from Lantheus, Myovant, Novartis, Pfizer, Janssen, Astellas, Blue Earth, AstraZeneca, Palette Life Sciences, and Boston Scientific. Tanya Dorff has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Janssen, and Sanofi. Tian Zhang has received compensation for a consulting or advisory role from Merck, Exelixis, Sanofi-Aventis, Janssen, Astra Zeneca, Pfizer, Amgen, BMS, Dendreon, SeaGen, Eisai, Aveo, Bayer, and Eli Lilly; honoraria from MJH Associates, Vaniam, Aptitude Health, PlatformQ, IntegrityCE, PeerView, and WJ Weiser; and her institution has received research funding from Novartis, Merck, Janssen, Astra Zeneca, Pfizer, Tempus, and Eli Lilly. Wendy Poage is an employee of Servier Pharmaceuticals; and she has ownership interests in 3D biopsy.

Purpose of Review: Cardiovascular disease (CVD) is the leading cause of non-cancer mortality in men with prostate cancer. This review summarizes the existing and emerging literature examining the cardiometabolic effects of androgen deprivation therapy (ADT) in prostate cancer., Recent Findings: The evidence behind the metabolic effects of ADT is derived from older studies and has not been validated in modern cohorts. Most of the newer studies focus on the risk of cardiovascular disease (CVD) with ADT. Recently published studies like the HERO and PRONOUNCE trials have once again sparked debate about the effects of different types and durations of ADT on cardiovascular outcomes. The link between ADT and CVD is inherently complex with a majority of the evidence collected from population-based or non-randomized trials without enriching for high-risk populations. Ongoing clinical trials may provide more informative data to guide the cardiovascular care of prostate cancer survivors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recently approved treatments and updates to genetic testing recommendations for prostate cancer have created a need for correlated analyses of patient outcomes data via germline genetic mutation status. Genetic registries address these gaps by identifying candidates for recently approved targeted treatments, expanding clinical trial data examining specific gene mutations, and understanding effects of targeted treatments in the real-world setting., Methods: The PROMISE Registry is a 20-year (5-year recruitment, 15-year follow-up), US-wide, prospective genetic registry for prostate cancer patients. Five thousand patients will be screened through an online at-home germline testing to identify and enroll 500 patients with germline mutations, including: pathogenic or likely pathogenic variants and variants of uncertain significance in genes of interest. Patients will be followed for 15 years and clinical data with real time patient reported outcomes will be collected. Eligible patients will enter long-term follow-up (6-month PRO surveys and medical record retrieval). As a virtual study with patient self-enrollment, the PROMISE Registry may fill gaps in genetics services in underserved areas and for patients within sufficient insurance coverage., Results: The PROMISE Registry opened in May 2021. 2114 patients have enrolled to date across 48 US states and 23 recruiting sites. 202 patients have met criteria for long-term follow-up. PROMISE is on target with the study's goal of 5000 patients screened and 500 patients eligible for long-term follow-up by 2026., Conclusions: The PROMISE Registry is a novel, prospective, germline registry that will collect long-term patient outcomes data to address current gaps in understanding resulting from recently FDA-approved treatments and updates to genetic testing recommendations for prostate cancer. Through inclusion of a broad nationwide sample, including underserved patients and those unaffiliated with major academic centers, the PROMISE Registry aims to provide access to germline genetic testing and to collect data to understand disease characteristics and treatment responses across the disease spectrum for prostate cancer with rare germline genetic variants., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear., Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer., Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022., Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease., Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function., Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy., Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

To assess the clinical impact of delayed testosterone recovery (TR) following the discontinuation of medical androgen deprivation therapy (ADT), a retrospective, longitudinal analysis was conducted in adult males with prostate cancer using the Optum® de-identified Electronic Health Record data set and Optum® Enriched Oncology Data (2010-2021). Of 3875 patients who initiated and discontinued ADT, 1553 received one or more testosterone-level tests within the 12 mo following discontinuation and were included in this study. These 1553 patients were categorized into two cohorts: 25% as TR (testosterone levels >280 ng/dl at any test within 12 mo following ADT discontinuation) and 75% as non-TR. At baseline, non-TR patients were older, had lower testosterone levels, and were more likely to have diabetes, hyperlipidemia, and hypertension, but less likely to have sexual dysfunction. After adjustment for baseline characteristics, the TR cohort had a lower risk of new-onset diabetes (hazard ratio [HR] 0.47; 95% confidence interval [CI] 0.27-0.79), trended toward a lower risk of new-onset depression (HR 0.58; 95% CI 0.33-1.02), and had a higher likelihood of seeking treatment for sexual dysfunction (HR 1.33; 95% CI 0.99-1.78) versus the non-TR cohort. These findings support monitoring testosterone levels after ADT discontinuation to manage potential long-term comorbidities in patients with prostate cancer., Patient Summary: This real-world analysis of males with prostate cancer who were treated with medical androgen deprivation therapy (ADT) found that most patients did not have their testosterone level checked in the 12 mo after stopping ADT. Of those who did, 75% did not achieve normal testosterone levels (>280 ng/dl), and these patients were more likely to experience new-onset diabetes than those who achieved normal testosterone levels. These results suggest that to ensure effective clinical decision-making, physicians should check patients' testosterone levels after stopping ADT., (© 2023 Published by Elsevier B.V. on behalf of European Association of Urology.)

Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44-4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales., Significance: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: Effective treatment of locally advanced or metastatic urothelial carcinoma (mUC) remains an unmet need. Antibody-drug conjugates (ADC) providing targeted drug delivery have shown antitumor activity in this setting. AGS15E is an investigational ADC that delivers the cytotoxic drug monomethyl auristatin E to cells expressing SLITRK6, a UC-associated antigen., Patients and Methods: This was a multicenter, single-arm, phase I dose-escalation and expansion trial of AGS15E in patients with mUC (NCT01963052). During dose escalation, AGS15E was administered intravenously at six levels (0.10, 0.25, 0.50, 0.75, 1.00, 1.25 mg/kg), employing a continual reassessment method to determine dose-limiting toxicities (DLT) and the recommended phase II dose (RP2D) for the dose-expansion cohort. The primary objective was to evaluate the safety and pharmacokinetics of AGS15E in patients with and without prior chemotherapy and with prior checkpoint inhibitor (CPI) therapy. Best overall response was also examined., Results: Ninety-three patients were recruited, including 33 patients previously treated with CPI. The most common treatment-emergent adverse events were fatigue (54.8%), nausea (37.6%), and decreased appetite (35.5%). Peripheral neuropathy and ocular toxicities occurred at doses of ≥0.75 mg/kg. AGS15E increased in a dose-proportional manner after single- and multiple-dose administration; accumulation was low. Five DLT occurred from 0.50 to 1.25 mg/kg. The RP2D was assessed at 1.00 mg/kg; the objective response rate (ORR) was 35.7% at this dose level. The ORR in the total population and CPI-exposed subgroup were 18.3% and 27.3%, respectively., Conclusions: DLT with AGS15E were observed at 0.75, 1.00, and 1.25 mg/kg, with an RP2D of 1.00 mg/kg being determined., (©2023 The Authors; Published by the American Association for Cancer Research.)

Patients with cancer have the unique ability of being able to offer valuable insights into how cancer therapeutics may impact the overall patient experience and improve clinical outcomes. Patient engagement could therefore contribute to tailoring treatment strategies and research design according to patient needs. This study evaluated patient engagement in prostate cancer research by identifying patient input in the prostate cancer literature. We performed a keyword cluster analysis of articles from multiple databases and congresses in which patients provided input on disease management or were involved in study design, manuscript authorship or presentation of results (patient voice). In total, 112 studies were included. Patients were involved in the design of 11 studies and were credited as authors in four studies. This review suggests a lack of meaningful patient involvement in prostate cancer research and publications.

Biochemical recurrence (BCR) occurs in 20-50% of patients with prostate cancer (PCa) undergoing primary definitive treatment. Patients with high-risk BCR have an increased risk of metastatic progression and subsequent PCa-specific mortality, and thus could benefit from treatment intensification. Given the increasing complexity of diagnostic and therapeutic modalities, multidisciplinary care (MDC) can play a crucial role in the individualized management of this patient population. This review explores the role for MDC when evaluating the clinical evidence for the evolving definition of high-risk BCR and the emerging therapeutic strategies, especially with novel hormone therapies (NHTs), for patients with either high-risk BCR or oligometastatic PCa. Clinical studies have used different characteristics to define high-risk BCR and there is no consensus regarding the definition of high-risk BCR nor for management strategies. Next-generation imaging and multigene panels offer potential enhanced patient identification and precision-based decision-making, respectively. Treatment intensification with NHTs, either alone or combined with radiotherapy or metastasis-directed therapy, has been promising in clinical trials in patients with high-risk BCR or oligometastases. As novel risk-stratification and treatment options as well as evidence-based literature evolve, it is important to involve a multidisciplinary team to identify patients with high-risk features at an earlier stage, and make informed decisions on the treatments that could optimize their care and long-term outcomes. Nevertheless, MDC data are scarce in the BCR or oligometastatic setting. Efforts to integrate MDC into the standard management of this patient population are needed, and will likely improve outcomes across this heterogeneous PCa patient population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jason A. Efstathiou reports consulting roles for Blue Earth Diagnostics, Boston Scientific, AstraZeneca, and Genentech; honoraria from IBA; advisory boards for Merck, Roviant Pharma, Myovant Sciences, Janssen, Bayer Healthcare, Progenics Pharmaceuticals, Pfizer, Inc., Genentech, Gilead, Blue Earth Diagnostics, and Lantheus Medical Imaging. Alicia K. Morgans reports grant support from Bayer, Sanofi, Myovant Sciences, Pfizer, Inc., Astellas Scientific and Medical Affairs Inc., and Dendreon Pharmaceuticals; honoraria from AstraZeneca, Advanced Accelerator Applications, Novartis, and Pfizer, Inc.; consulting or advisory roles for AstraZeneca, Sanofi, Bayer, Astellas Pharma, Janssen, Advanced Accelerator Applications, Myovant Sciences, Blue Earth Diagnostics, Exelixis, Novartis, Myriad Genetics, Lantheus Medical Imaging, Merck, and Gilead. Christopher S. Bland reports being an employee and shareholder of Pfizer, Inc. Neal D. Shore reports grant support from AbbVie, Amgen, Astellas Pharma, Bayer, Dendreon Pharmaceuticals, Ferring Pharmaceuticals, Janssen Oncology, Pfizer, Inc., Sanofi–Genzyme, and Tolmar Pharmaceuticals; consulting or advocacy roles for AbbVie, Akido, Alessa Therapeutics, Amgen, Arquer, Asieris, Astellas Pharma, Inc., Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis, Cold Genesys, Dendreon Pharmaceuticals, Exact Images, Exact Sciences, FerGene, Ferring Pharmaceuticals, Foundation Medicine, FIZE Medical, GConcology, GenesisCare, Genetech, Guardant, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Pfizer, Inc., Photocure, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar Pharmaceuticals, Urogen, Vaxiion, and Vessi., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, demonstrated testosterone suppression to castrate levels in men with advanced prostate cancer (PCa) in the HERO study. Since advanced PCa and its treatments can impact patients' daily life, it is imperative to understand the impact of systemic therapy on patient health-related quality of life (HRQOL)., Objective: To report the HRQOL for patients on relugolix compared with those on leuprolide in on-treatment and testosterone recovery periods of the HERO study., Design, Setting, and Participants: A phase 3 randomized controlled study was conducted in 934 patients with advanced PCa., Intervention: Patients underwent 2:1 randomization and received relugolix 120 mg orally once daily or leuprolide 3-mo injections for 48 wk. Testosterone recovery was evaluated in a patient subset., Outcome Measurements and Statistical Analysis: HRQOL evaluations were based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) and the Prostate Cancer Module (EORTC QLQ-PR25) during treatment and testosterone recovery phases. In a post hoc analysis, predictors of HRQOL deterioration were evaluated., Results and Limitations: No statistically significant differences between the two groups were found in changes from baseline to the end of treatment in either the EORTC QLQ-C30 or the EORTC QLQ-PR25 instrument. During the testosterone recovery phase, hormonal treatment-related symptoms scores were lower for relugolix than for leuprolide, suggesting a lower burden of hormone-related symptoms associated with a treatment that has more rapid testosterone recovery after treatment cessation. Limitations include low patient numbers in the testosterone recovery group., Conclusions: Oral relugolix is a therapeutic option with similar patient-reported HRQOL to leuprolide, providing an oral option for androgen deprivation therapy associated with a more rapid testosterone reduction., Patient Summary: In men with advanced prostate cancer, relugolix had similar health-related quality of life to leuprolide., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Little is known about the rates of catastrophic health care expenditures among survivors of prostate and bladder cancer or the factors that place patients at highest risk for undue cost., Materials and Methods: The Medical Expenditure Panel Survey was utilized to identify prostate and bladder cancer survivors from 2011 to 2019. Rates of catastrophic health care expenditures (out-of-pocket health care spending >10% household income) were compared between cancer survivors and adults without cancer. A multivariable regression model was used to identify risk factors for catastrophic expenditures., Results: Among 2620 urologic cancer survivors, representative of 3,251,500 (95% CI 3,062,305-3,449,547) patients annually after application of survey weights, there were no significant differences in catastrophic expenditures among respondents with prostate cancer compared to adults without cancer. Respondents with bladder cancer had significantly greater rates of catastrophic expenditures (12.75%, 95% CI 9.36%-17.14% vs. 8.33%, 95% CI 7.66%-9.05%, P = .027). Significant predictors of catastrophic expenditures in bladder cancer survivors included older age, comorbidities, lower income, retirement, poor health status, and private insurance. Though White respondents with bladder cancer had no significantly increased risk of catastrophic expenditures, among Black respondents the risk of catastrophic expenditures increased from 5.14% (95% CI 3.95-6.33) without bladder cancer to 19.49% (95% CI 0.84-38.14) with bladder cancer (OR 6.41, 95% CI 1.28-32.01, P = .024)., Conclusions: Though limited by small sample size, these data suggest that bladder cancer survivorship is associated with catastrophic health care expenditures, particularly among Black cancer survivors. These findings should be taken as hypothesis-generating and warrant further investigation with larger sample sizes and, ideally, prospective investigation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC) have broadened, and treatment decisions can have a long-lasting impact on patients' quality of life. Data on patient preferences can improve therapeutic decision-making by helping physicians suggest treatments that align with patients' values and needs., Objective: This study aims to quantify patient preferences for attributes of chemohormonal therapies among patients with mHSPC in the USA, Canada, and the UK., Methods: A discrete-choice experiment survey instrument was developed and administered to patients with high- and very-high-risk localized prostate cancer and mHSPC. Patients chose between baseline androgen-deprivation therapy (ADT) alone and experimentally designed, hypothetical treatment alternatives representing chemohormonal therapies. Choices were analyzed using logit models to derive the relative importance of attributes for each country and to evaluate differences and similarities among patients across countries., Results: A total of 550 respondents completed the survey (USA, 200; Canada, 200; UK, 150); the mean age of respondents was 64.3 years. Treatment choices revealed that patients were most concerned with treatment efficacy. However, treatment-related convenience factors, such as route of drug administration and frequency of monitoring visits, were as important as some treatment-related side effects, such as skin rash, nausea, and fatigue. Patient preferences across countries were similar, although patients in Canada appeared to be more affected by concomitant steroid use., Conclusion: Patients with mHSPC believe the use of ADT alone is insufficient when more effective treatments are available. Efficacy is the most significant driver of patient choices. Treatment-related convenience factors can be as important as safety concerns for patients., (© 2023. The Author(s).)

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that imposes a major burden on patients and healthcare systems. Three structured literature reviews (treatment guidelines, treatment landscape, and human/clinical/patient burden) and one systematic literature review (economic burden) were conducted to better understand the disease burden and unmet needs for patients with late-stage mCRPC, for whom optimal treatment options are unclear., Methods: Embase ® , MEDLINE ® , MEDLINE ® In-Process, the CENTRAL database (structured and systematic reviews), and the Centre for Reviews and Dissemination database (systematic review only) were searched for English-language records from 2009 to 2021 to identify mCRPC treatment guidelines and studies related to the treatment landscape and the humanistic/economic burden of mCRPC in adult men (aged ≥18 years) of any ethnicity., Results: In total, six records were included for the treatment patterns review, 14 records for humanistic burden, nine records for economic burden, three records (two studies) for efficacy, and eight records for safety. Real-world treatment patterns were broadly aligned with treatment guidelines and provided no optimal treatment sequencing beyond second line other than palliative care. Current post-docetaxel treatments in mCRPC are associated with adverse events that cause relatively high rates of treatment discontinuation or disruption. The humanistic and economic burdens associated with mCRPC are high., Conclusion: The findings highlight a lack of treatment options with novel mechanisms of action and more tolerable safety profiles that satisfy a risk-to-benefit ratio aligned with patient needs and preferences for patients with late-stage mCRPC. Treatment approaches that improve survival and health-related quality of life are needed, ideally while simultaneously reducing costs and healthcare resource utilization., Competing Interests: Author SC reports honoraria from Clovis and Novartis; funding from Sanofi; acting as a speaker for AstraZeneca, Pfizer, and Janssen; and a consultant role with Clovis, Astellas Pharma, Bayer, Pfizer, Janssen, BeiGene, Remedy Bio, Telix, and Novartis. Author DL has received fees from Advanced Accelerator Applications (AAA) and Boston Scientific for consultancy work. Authors RG and OM are employees of Advanced Accelerator Applications (AAA), A Novartis Company. Author GK was an employee of Parexel International at the time of the original and updated literature reviews. Author AM reports honoraria, consulting/advisory, research funding, and/or travel/accommodations from Genentech, Janssen, Sanofi, AstraZeneca, Astellas Scientific and Medical Affairs Inc, Astellas Pharma, Janssen Oncology, Bayer, Clovis Oncology, Myovant Sciences, Advanced Accelerator Applications (AAA), Exelixis, Pfizer, Merck, Telix Pharmaceuticals, Blue Earth Diagnostics, Novartis, Myriad Genetics, Lantheus Medical Imaging, Seattle Genetics/Astellas, and Dendreon., (Copyright © 2023 Leaning, Kaur, Morgans, Ghouse, Mirante and Chowdhury.)