Optimizing outcomes in men with prostate cancer: the cardiovascular event lowering (CaELo) pathways.

INTRODUCTION: Risk of cardiovascular disease is higher among men with prostate cancer than men without, and prostate cancer treatments (especially those that are hormonally based) are associated with increased cardiovascular risk. MATERIALS AND METHODS: An 11-member panel of urologic, medical, and radiation oncologists (along with a men's health specialist and an endocrinologist/preventive cardiologist) met to discuss current practices and challenges in the management of cardiovascular risk in prostate cancer patients who are taking androgen deprivation therapies (ADT) including LHRH analogues, alone and in combination with androgen-targeted therapies (ATTs). RESULTS: The panel developed an assessment algorithm to categorize patients by risk and deploy a risk-adapted management strategy, in collaboration with other healthcare providers (the patient's healthcare "village"), with the goal of preventing as well as reducing cardiovascular events. The panel also developed a patient questionnaire for cardiovascular risk as well as a checklist to ensure that all aspects of cardiovascular disease risk reduction are completed and monitored. CONCLUSIONS: Prostate cancer patients receiving ADT with or without ATT need to be more zealously assessed for prevention and aggressively managed to reduce cardiovascular events. This can and should include participation from the entire multidisciplinary healthcare team.

A Proposal for the Comprehensive Care of Men on Androgen Deprivation Therapy: Recommendations From the Multidisciplinary Prostate Cancer 360 Working Group.

INTRODUCTION: To promote comprehensive care of patients throughout the androgen deprivation therapy (ADT) prescribing process, the Prostate Cancer 360 (PC360) Working Group developed monitoring and management recommendations intended to mitigate or prevent ADT-associated adverse events. METHODS: The PC360 Working Group included 14 interdisciplinary experts with a dedicated clinical interest in prostate cancer and ADT management. The working group defined challenges associated with ADT adverse event management and then collaboratively developed comprehensive care recommendations intended to be practical for ADT prescribers. RESULTS: The PC360 Working Group developed both overarching recommendations for ADT adverse event management and specific recommendations across 5 domains (cardiometabolic, bone, sexual, psychological, and lifestyle). The working group recommends an interdisciplinary, team-based approach wherein the ADT prescriber retains an oversight role for ADT management while empowering patients and their primary and specialty care providers to manage risk factors. The PC360 recommendations also emphasize the importance of proactive patient education that involves partners or other support providers. Recommended monitoring and assessment tools, risk factor management, and patient counseling points are also included for the 5 identified domains, with an emphasis on lifestyle and behavioral interventions that can improve quality of life and reduce the risk for ADT-associated complications. CONCLUSIONS: Comprehensive care of patients receiving ADT requires early and ongoing coordinated management of a variety of health domains, including cardiometabolic, bone, sexual, psychological health. Patient education and primary care provider involvement should begin prior to ADT initiation and continue throughout treatment to improve patient and partner quality of life.

Cardiovascular Risk in Prostate Cancer Patients Using Luteinizing Hormone-Releasing Hormone Agonists or a Gonadotropin-Releasing Hormone Antagonist.

PURPOSE: Luteinizing hormone-releasing hormone (LHRH) agonists are believed to have higher cardiovascular risk relative to gonadotropin-releasing hormone (GnRH) antagonists. However, previous studies have not consistently demonstrated this. We used real-world clinical practice data to evaluate differences in major adverse cardiovascular events (MACE) risk between LHRH agonists compared to a GnRH antagonist following androgen deprivation therapy (ADT) initiation. MATERIALS AND METHODS: We performed a retrospective analysis of data in the Decision Resources Group (now Clarivate) Real World Evidence repository, which represents >300 million US patients from 1991 to 2020 across all US regions. Patients with prostate cancer who received at least 1 injection of ADT were included. The risks of MACE and all-cause mortality as independent endpoints were evaluated, Kaplan-Meier curves were constructed, and associations between MACE and all available confounding risk factors were evaluated by Cox regression analysis using Statistical Package for the Social Sciences. RESULTS: A total of 45,059 men with prostate cancer treated with ADT were analyzed. Overall, the risks of MACE and all-cause mortality were slightly lower in the first year after ADT initiation compared to subsequent years. MACE risk was higher for the GnRH antagonist compared to LHRH agonists (HR=1.62; 95% CI 1.21-2.18, P = .001). The risk of all-cause mortality was also higher for the GnRH antagonist vs LHRH agonists (HR=1.87; 95% CI 1.39-2.51, P < .001). CONCLUSIONS: The adjusted incidence of MACE was higher for men treated with the GnRH antagonist compared to the LHRH agonists. The demographic and risk factors with the greatest impact on MACE risk were higher age, baseline metastasis, oncology (vs urology) setting, personal MACE history, antagonist (vs agonist), tobacco history, White (vs Black) race, and lower BMI.

Evolving understanding and categorization of prostate cancer: preventing progression to metastatic castration-resistant prostate cancer: RADAR IV.

INTRODUCTION To interpret data and update the traditional categorization of prostate cancer in order to help treating clinicians make more informed decisions. These updates include guidance regarding how to best use next generation imaging (NGI) with the caveat that the new imaging technologies are still a work in progress. MATERIALS AND METHODS: Literature review. RESULTS: Critical goals in prostate cancer management include preventing or delaying emergence of distant metastases and progression to castration-resistant disease. Pathways for progression to metastatic castration-resistant prostate cancer (mCRPC) involve transitional states: nonmetastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and oligometastatic disease. Determination of clinical state depends in part on available imaging modalities. Currently, fluciclovine and gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) are the NGI approaches with the most favorable combination of availability, specificity, and sensitivity. PET imaging can be used to help guide treatment selection in most patients. NGI can help determine patients who are candidates for new treatments, most notably (next-generation androgen antagonists, eg, apalutamide, enzalutamide, darolutamide), that can delay progression to advanced disease. CONCLUSIONS: It is important to achieve a consensus on new and more easily understood terminology to clearly and effectively describe prostate cancer and its progression to health care professionals and patients. It is also important that description of disease states make clear the need to initiate appropriate treatment. This may be particularly important for disease in transition to mCRPC.

The potential role of follicle-stimulating hormone in the cardiovascular, metabolic, skeletal, and cognitive effects associated with androgen deprivation therapy.

PURPOSE: To explore how follicle-stimulating hormone (FSH) may contribute to cardiovascular, metabolic, skeletal, and cognitive events in men treated for prostate cancer, with various forms of androgen deprivation therapy (ADT). MATERIALS AND METHODS: A colloquium of prostate cancer experts was convened in May 2015, to discuss the role of FSH in the development of unwanted effects associated with ADT. Subsequently, a literature review (Medline, PubMed, and relevant congress abstract databases) was performed to further explore and evaluate the collected evidence. RESULTS: It has become evident that, in the setting of ADT, FSH can promote the development of atherosclerotic plaque formation, metabolic syndrome, and insulin resistance. Data also suggest that FSH is an important mediator of bone remodeling, particularly bone resorption, and thereby increases the risk for bone fracture. Additional evidence implicates a role for FSH in bone metastasis as well. The influence of FSH on ADT-induced cognitive deficits awaits further elucidation; however, the possibility that FSH may be involved therein cannot be ruled out. CONCLUSIONS: The widespread molecular and physiological consequences of FSH system activation in normal and pathological conditions are becoming better understood. Progress in this area has been achieved by the development of additional investigative and clinical measures to better evaluate specific adverse effects. More research is needed on FSH function in the development of cancer as well as its association with cardiovascular, metabolic, musculoskeletal, and cognitive effects in ADT.