Hormone Therapy For Prostate Cancer Research Articles

PET/CT Imaging of Prostate Cancer. Modern Versions of Radiopharmaceuticals

A review of the literature on the current capabilities of radioisotope imaging of prostate cancer is presented. Various views and experience of using PET/CT for visualization of prostate cancer are considered. Particular attention is paid to the use of various radiopharmaceuticals used in staging, restaging prostate cancer, as well as monitoring the response to treatment. The advantages and disadvantages of most radiotracers used to search for disease recurrence are highlighted, as well as the peculiarities of their use in various clinical situations. The features of the effect of hormonal therapy for prostate cancer on imaging are discussed.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known. We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020. Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03). In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

Factors associated with referral for osteoporosis care in men: a real-life study of a nationwide dataset

Male osteoporosis is associated with an important clinical and economic burden worldwide; nevertheless, undertreatment of men with osteoporosis is common. Understanding the factors associated with referral to bone specialists may help to define future interventions to improve access to osteoporosis care for male patients. We conducted a retrospective analysis of a nationwide cohort (DeFRACalc79 database). DeFRACalc79 is a tool that estimates the fracture risk by considering clinical and densitometric risk factors, including the presence of prior hip or vertebral and non-vertebral or non-hip fractures. We compared the clinical characteristics of male individuals with an age-matched cohort of women. Propensity score generation with a 2:1 female-to-male ratio was performed using a logistic regression model to age-match the cohorts. We analyzed a sample of 4902 men at high risk for osteoporosis. We found that the factors associated with osteoporosis care utilization in men were the presence of comorbidities (OR 1.939, 95% CI 1.799-2.090), adjuvant hormonal therapy for prostate cancer (OR 1.482, 95% CI 1.315-1.670), the presence of vertebral or hip fractures (OR 1.490, 95% CI 1.378-1.611), and glucocorticoid treatment (OR 2.573, 95% CI 2.274-2.832). Men are more commonly referred to the bone specialist with a prevalent fragility fracture and/or diagnosis of secondary osteoporosis as compared with women. Our study suggests that there is a lack of screening for the primary prevention of osteoporosis in men as compared with that in women.

An Overview of Next-Generation Androgen Receptor-Targeted Therapeutics in Development for the Treatment of Prostate Cancer.

Traditional endocrine therapy for prostate cancer (PCa) has been directed at suppression of the androgen receptor (AR) signaling axis since Huggins et al. discovered that diethylstilbestrol (DES; an estrogen) produced chemical castration and PCa tumor regression. Androgen deprivation therapy (ADT) still remains the first-line PCa therapy. Insufficiency of ADT over time leads to castration-resistant PCa (CRPC) in which the AR axis is still active, despite castrate levels of circulating androgens. Despite the approval and use of multiple generations of competitive AR antagonists (antiandrogens), antiandrogen resistance emerges rapidly in CRPC due to several mechanisms, mostly converging in the AR axis. Recent evidence from multiple groups have defined noncompetitive or noncanonical direct binding sites on AR that can be targeted to inhibit the AR axis. This review discusses new developments in the PCa treatment paradigm that includes the next-generation molecules to noncanonical sites, proteolysis targeting chimera (PROTAC), or noncanonical N-terminal domain (NTD)-binding of selective AR degraders (SARDs). A few lead compounds targeting each of these novel noncanonical sites or with SARD activity are discussed. Many of these ligands are still in preclinical development, and a few early clinical leads have emerged, but successful late-stage clinical data are still lacking. The breadth and diversity of targets provide hope that optimized noncanonical inhibitors and/or SARDs will be able to overcome antiandrogen-resistant CRPC.

Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer.

Gonadotropin-releasing hormone (GnRH) receptor agonists are still the most commonly used androgen deprivation treatment (ADT) drugs for prostate cancer in clinical practice. Currently, the GnRH receptor antagonists used for endocrine therapy for prostate cancer primarily include degarelix and relugolix (TAK-385). The former is administered by subcutaneous injection, while the latter is an oral drug. Compared to GnRH agonists, GnRH antagonists reduce serum testosterone levels more rapidly without an initial testosterone surge or subsequent microsurges. This review focuses on the mechanism of action of GnRH antagonists and agonists, the developmental history of GnRH antagonists, and emerging data from clinical studies of the two antagonists used as endocrine therapy for prostate cancer.

Eighty Years of Targeting Androgen Receptor Activity in Prostate Cancer: The Fight Goes on.

Simple SummaryProstate cancer is the second most common cancer in men world-wide, with nearly 1.3 million new cases each year, and over the next twenty years the incidence and death rate are predicted to nearly double. For decades, this lethal disease has been more or less successfully treated using hormonal therapy, which has the ultimate aim of inhibiting androgen signalling. However, prostate tumours can evade such hormonal therapies in a number of different ways and therapy resistant disease, so-called castration-resistant prostate cancer (CRPC) is the major clinical problem. Somewhat counterintuitively, the androgen receptor remains a key therapy target in CRPC. Here, we explain why this is the case and summarise both new hormone therapy strategies and the recent advances in knowledge of androgen receptor structure and function that underpin them.Prostate cancer (PCa) is the most common cancer in men in the West, other than skin cancer, accounting for over a quarter of cancer diagnoses in US men. In a seminal paper from 1941, Huggins and Hodges demonstrated that prostate tumours and metastatic disease were sensitive to the presence or absence of androgenic hormones. The first hormonal therapy for PCa was thus castration. In the subsequent eighty years, targeting the androgen signalling axis, where possible using drugs rather than surgery, has been a mainstay in the treatment of advanced and metastatic disease. Androgens signal via the androgen receptor, a ligand-activated transcription factor, which is the direct target of many such drugs. In this review we discuss the role of the androgen receptor in PCa and how the combination of structural information and functional screenings is continuing to be used for the discovery of new drug to switch off the receptor or modify its function in cancer cells.

Hormonal Therapy for Prostate Cancer.

Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with nonmetastatic advanced prostate cancer, as well as frankly metastatic disease. Today's standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g., leuprolide), second-generation nonsteroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today's standard of care will require an accounting of an individual's androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.

A review of new hormonal therapies for prostate cancer in black men: is there enough data?

BackgroundProstate cancer among black men is known to have specific molecular characteristics, especially the androgen receptor or enzymes related to the androgen metabolism. These targets are keys to the action of new hormonal therapies. Nevertheless, literature has a lack of data regarding black men. We aimed to gather the available literature data on new hormonal therapies among black populations.MethodsWe conducted a literature review from the PubMed / MEDLINE database until October 2020. All clinical studies of new hormonal therapies and black populations, regardless of methodology, were included.ResultsFour studies provided data on new hormonal therapies in black populations. Three studies reported a PSA decline in black patients treated with Abiraterone, higher in black men than in white men. Overall survival also appears to be higher in black patients treated with Abiraterone only or first.ConclusionFew articles have evaluated the effectiveness and safety of use of these treatments among black populations. The first results seem to show that Abiraterone can provide a benefit in overall survival in black populations. Prospective studies are needed to answer these questions in the future.

ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.

Current endocrine therapy for prostate cancer (PCa) mainly inhibits androgen/androgen receptor (AR) signaling. However, due to increased intratumoural androgen synthesis and AR variation, PCa progresses to castration-resistant prostate cancer (CRPC), which ultimately becomes resistant to endocrine therapy. A search for new therapeutic perspectives is urgently needed.Methods: By screening lipid metabolism-related gene sets and bioinformatics analysis in prostate cancer database, we identified the key lipid metabolism-related genes in PCa. Bisulfite genomic Sequence Polymerase Chain Reaction (PCR) (BSP) and Methylation-Specific Polymerase Chain Reaction (PCR) (MSP) were preformed to detect the promoter methylation of ACSS3. Gene expression was analyzed by qRT-PCR, Western blotting, IHC and co-IP. The function of ACSS3 in PCa was measured by CCK-8, Transwell assays. LC/MS, Oil Red O assays and TG and cholesterol measurement assays were to detect the levels of TG and cholesterol in cells. Resistance to Enzalutamide in C4-2 ENZR cells was examined in a xenograft tumorigenesis model in vivo.Results: We found that acyl-CoA synthetase short chain family member 3 (ACSS3) was downregulated and predicted a poor prognosis in PCa. Loss of ACSS3 expression was due to gene promoter methylation. Restoration of ACSS3 expression in PCa cells significantly reduced LD deposits, thus promoting apoptosis by increasing endoplasmic reticulum (ER) stress, and decreasing de novo intratumoral androgen synthesis, inhibiting CRPC progression and reversing Enzalutamide resistance. Mechanistic investigations demonstrated that ACSS3 reduced LD deposits by regulating the stability of the LD coat protein perilipin 3 (PLIN3).Conclusions: Our study demonstrated that ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.

Other and All-Cause Mortality among Men Diagnosed with Prostate Cancer in the PLCO Trial

Men with prostate cancer have high cause-specific survival, and most deaths are from other causes. This study aimed to investigate other and all-cause mortality in a large cancer screening cohort. From the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial cohort, we selected men diagnosed with prostate cancer from 1994-2014. We examined other and all-cause survival by prostate cancer risk level, defined as the D'Amico categories for localized disease (low, intermediate and high risk) plus nonlocalized disease. We developed 3 Cox proportional hazards models to assess the relationship between risk level and survival. Model I controlled for age, race, study arm and diagnosis year. Model II additionally controlled for other demographic and medical history factors. Model III additionally controlled for initial treatment. Of 76,672 men in PLCO and 10,859 prostate cancer cases, 9,248 (85.2%) had known prostate cancer risk level (mean±SD age 70.4±6.2 years). Median followup time from diagnosis was 10.8 years (IQR 6.8-15.0). Of 3,318 deaths 81% were from other causes. Compared to the low risk group, other-cause mortality HRs were 1.13 (95% CI 1.04-1.23), 1.35 (95% CI 1.21-1.50) and 1.63 (95% CI 1.35-1.97) for intermediate risk, high risk and advanced disease, respectively, in model II. Model III HRs were similar to model II except for advanced disease, where the HR decreased to 1.35. Other-cause survival was greater in lower vs higher risk disease, even after controlling for lifestyle characteristics and comorbidities. Further research is needed to identify factors contributing to this higher other-cause mortality to help mitigate the risk.

Shared decision making, physicians\u2019 explanations, and treatment satisfaction: a cross-sectional survey of prostate cancer patients

BackgroundHormone therapy is one option for some types of prostate cancer. Shared decision making (SDM) is important in the decision making process, but SDM between prostate cancer patients receiving hormone therapy and physicians is not fully understood. This study tested hypotheses: “Patients’ perception of SDM is associated with treatment satisfaction, mediated by satisfaction with physicians’ explanations and perceived effective decision making” and “The amount of information provided to patients by physicians on diseases and treatment is associated with treatment satisfaction mediated by patients’ perceived SDM and satisfaction with physicians’ explanations.”MethodsThis cross-sectional study was conducted using an online panel via a private research company in Japan. The participants in this study were patients registered with the panel who had received or were currently receiving hormone therapy for prostate cancer and physicians registered with the panel who were treating patients with prostate cancer. Measures used in this study included a nine-item Shared Decision Making Questionnaire, levels of satisfaction with physicians’ explanations and treatment satisfaction, and effective decision making for patients (feeling the choice is informed, value-based, likely to be implemented and expressing satisfaction with the choice), and a Shared Decision Making Questionnaire for Doctors. The hypotheses were examined using path analysis.ResultsIn total, 124 patients and 150 physicians were included in the analyses. In keeping with our hypotheses, perceived SDM significantly correlated with the physicians’ explanations and perceived effective decision making for patients, and satisfaction with physicians’ explanations and perceived effective decision making for patients were both related to treatment satisfaction. Although the amount of information provided to patients was correlated with the perceived SDM, it was indirectly related to their satisfaction with physicians’ explanations.ConclusionsWhen physicians encourage patients to be actively involved in making decisions about treatment through the SDM process while presenting a wide range of information at the start of hormone therapy, patients’ effective decision making and physicians’ explanations may be improved; consequently, the patients’ overall treatment satisfaction may be improved. Physicians who treat patients with prostate cancer may have underestimated the importance of SDM before starting hormone therapy, even greater extent than patients.

Abstract 14602: Vascular Calcification is Associated With Major Adverse Cardiovascular Events and Mortality in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Hormone therapy is a front-line therapy for men with prostate cancer and is associated with adverse cardiovascular events. The utility of vascular calcification for cardiovascular risk stratification in men with prostate cancer is unknown. Methods: 211 consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET)/computed tomography (CT) at a single institution for recurrent prostate cancer were retrospectively identified. Clinical and demographic data were obtained from the medical record. Coronary and aortic calcification were qualitatively assessed on non-gated CT scans using standardized scoring systems. The primary outcome was a composite of subsequent major adverse cardiovascular event (MACE; myocardial infarction, stroke, coronary or peripheral revascularization, heart failure hospitalization) or all-cause mortality. Results: Median age was 69 (IQR 64, 75) years and cardiovascular comorbidities were common (70% hypertension, 65% hyperlipidemia, 47% current or former smoking, 20% diabetes mellitus). Over a median of 16.5 months, 8 patients (4%) met the primary outcome. Patients with MACE or death were older and had higher prevalence of traditional cardiovascular comorbidities (risk ratio [RR] 1.3 for hypertension, 1.4 for hyperlipidemia, 1.3 for diabetes mellitus; p&gt;0.05 for all). Coronary and aortic calcification were more common in patients with MACE or death. Severe coronary calcification (RR=6.1, 95% CI 1.6-23.2, p=0.008) and severe thoracic aortic calcification (RR=9.9, 95% CI 2.0-47.6, p=0.004) were associated with significantly increased risk of MACE or death. Conclusions: Coronary and aortic calcification on PET/CT imaging are associated with significantly increased risk of MACE or death in men with recurrent prostate cancer. Vascular calcification may have utility for cardiovascular risk stratification in men receiving hormone therapy for prostate cancer.

Relationship Between Stage-specific Embryonic Antigen-4 and Anti-cancer Effects of Neoadjuvant Hormonal Therapy in Prostate Cancer.

Stage-specific embryonic antigen-4 (SSEA-4) expression is associated with malignant aggressiveness and is useful as a marker for identifying cancer stem cells. Our aim was to assess the relationship between hormonal therapy and SSEA-4 expression in prostate cancer (PC). SSEA-4 expression in paired specimens from PC patients who underwent neoadjuvant hormonal therapy (NHT) and radical prostatectomy (60 pre-NHT specimens and 60 post-NHT specimens) was evaluated using immunohistochemistry. Proliferation index (PI) and apoptotic index (AI) were also evaluated. Post-NHT tissues had significantly elevated SSEA-4 expression whereas anti-tumor effects of NHT were inversely correlated with SSEA-4 expression level. SSEA-4 expression in post-NHT tissues was significantly associated with biochemical recurrence-free survival. SSEA-4 expression in the post-NHT tissues was positively associated with PI and negatively done with AI. SSEA-4 is a potential therapeutic target for limiting the malignant potential in hormone-naïve PC when considering the use of NHT.

Risk of developing hypertension after hormone therapy for prostate cancer: a nationwide propensity score-matched longitudinal cohort study

BackgroundAndrogen deprivation therapy (ADT) is essential in the treatment of advanced and metastatic prostate cancer. As the correlation between hormone therapy and hypertension remains unclear and prostate cancer is less prevalent in the Asian population, the clinician should focus on not only anticancer therapy but also the side effects of the intervention and quality of life of these patients.ObjectiveThis study aimed to investigate the risk of subsequent hypertension in patients undergoing androgen deprivation therapy for prostate cancer.SettingData of 10,843 patients with prostate cancer were retrospectively collected from the Longitudinal Health Insurance Database of Taiwan. The institutional review board of Kaohsiung Medical University Hospital approved our study.MethodIn propensity score matching, 3001 patients with prostate cancer aged ≥ 40 years who underwent androgen deprivation therapy were included in the study cohort (androgen deprivation therapy-ever), and 3001 patients with cancer who did not undergo androgen deprivation therapy were included in the control group (androgen deprivation therapy-never), after adjusting for age and other comorbidities.Main outcome measureThe event of new-onset hypertension between the study cohort and control cohort.ResultsDuring the average 5-year follow-up period, the incidence rates of new-onset hypertension were 22.6 and 33.0 per 1000 person-years in the androgen deprivation therapy-never and androgen deprivation therapy-ever cohorts, respectively. The androgen deprivation therapy-ever cohort was found to be 1.78 times more likely to develop new-onset hypertension than was the control group (95% confidence interval [CI], 1.61-1.96; P < 0.001). Moreover, the subgroup of combined androgen blockade had almost doubled the risk of subsequent hypertension (adjusted hazard ratio, 1.93; 95% CI 1.71-2.18; P < 0.001).ConclusionsOur study suggests that men with prostate cancer who underwent androgen deprivation therapy are at risk of developing hypertension in the future.

PROACTA: a survey on the actual attitude of the Italian radiation oncologists in the management and prescription of hormonal therapy in prostate cancer patients.

To investigate the actual attitude of Radiation Oncologists in the prescription of hormonal therapy in prostate cancer (PC) with or without Radiation Therapy (RT). In 2019, a survey named Prescription of Radiation Oncologists ACtual Attitude including 18 items was sent to all Italian Radiation Oncologists of the Italian Association of Radiotherapy and Clinical Oncology. The first 4 items were about the Radiation Oncology Centers characteristics and years of practice of the respondents. The remaining 14 items concerned the setting in which hormone therapy was prescribed in PC patients (radical, postprostatectomy/oligometastatic state), the kind of drug, the choice modality (Multidisciplinary Group/autonomy decision) and other factors. A total of 127 questionnaires were returned, mainly by Northern Italy Radiation Oncology Centres (44.9%), and by experienced Radiation Oncologists (78%), who declared to prescribe independently hormone therapy in 85.8% of cases. The Androgen deprivation therapy (ADT) prescription in castration naive PC was made independently by 56.7% of respondents and associated with radical RT, postoperative or salvage RT according to various risk factors. In castration-sensitive oligorecurrent PC, the majority (51.2%) administered ADT only if local ablative treatment was not feasible, while in metastatic castration resistant disease novel hormone therapy use was established in almost half of cases within multidisciplinary board. Radiation Oncologists could prescribe these drugs independently in 64% of cases. Our survey established the prescription attitude of ADT and new hormonal agents (abiraterone, enzalutamide, apalutamide) by Italian Radiation Oncologists and highlighted the importance of expertise in global PC management.

Genitourinary cancer management during a severe pandemic: Utility of rapid communication tools and evidence-based guidelines.

Objectives: To determine the usefulness of social media for rapid communication with experts to discuss strategies for prioritization and safety of deferred treatment for urologic malignancies during COVID‐19 pandemic, and to determine whether the discourse and recommendations made through discussions on social media (Twitter) were consistent with the current peer‐reviewed literature regarding the safety of delayed treatment. Methods: We reviewed and compiled the responses to our questions on Twitter regarding the management and safety of deferred treatment in the setting of COVID‐19 related constraints on non‐urgent care. We chronicled the guidance published on this subject by various health authorities and professional organizations. Further, we analyzed peerreviewed literature on the safety of deferred treatment (surgery or systemic therapy) to make made evidence‐based recommendations. Results: Due to the rapidly changing information about epidemiology and infectious characteristics of COVID‐19, the health authorities and professional societies guidance required frequent revisions which by design take days or weeks to produce. Several active discussions on Twitter provided real‐time updates on the changing landscape of the restrictions being placed on non‐urgent care. For separate discussion threads on prostate cancer and bladder cancer, dozens of specialists with expertise in treating urologic cancers could be engaged in providing their expert opinions as well as share evidence to support their recommendations. Our analysis of published studies addressing the safety and extent to which delayed cancer care does not compromise oncological outcome revealed that most prostate cancer care and certain aspects of the bladder and kidney cancer care can be safely deferred for 2‐6 months. Urothelial bladder cancer and advanced kidney cancer require a higher priority for timely surgical care. We did not find evidence to support the idea of using nonsurgical therapies, such as hormone therapy for prostate cancer or chemotherapy for bladder cancer for safer deferment of previously planned surgery. We noted that the comments and recommendations made by the participants in the Twitter discussions were generally consistent with our evidence‐based recommendations for safely postponing cancer care for certain types of urologic cancers. Conclusion: The use of social media platforms, such as Twitter, where the comments and recommendations are subject to review and critique by other specialists is not only feasible but quite useful in addressing the situations requiring urgent resolution, often supported by published evidence. In circumstances such as natural disasters, this may be a preferable approach than the traditional expert panels due to its ability to harness the collective intellect to available experts to provide responses and solutions in real‐time. These real‐time communications via Twitter provided sound guidance which was readily available to the public and participants, and was generally in concordance with the peerreviewed data on safety of deferred treatment.

Integrated immunohistochemical and molecular analysis improves diagnosis of high-grade carcinoma in the urinary bladder of patients with prior radiation therapy for prostate cancer.

Prostatic adenocarcinoma and urothelial carcinoma typically demonstrate distinct morphologic and immunohistochemical features. However, high-grade prostate and urothelial carcinomas sometimes show significant morphologic and immunohistochemical overlap, which can result in misdiagnosis and mistreatment. This diagnostic dilemma is particularly acute in patients previously treated with radiation and/or hormone therapy for prostate cancer, who later present with high-grade carcinoma in the urinary bladder. To address the diagnostic utility of integrated immunohistochemical and molecular analysis in this setting, we evaluated 25 high-grade carcinomas of the bladder for which morphologic features were deemed indeterminate. Our analysis included immunohistochemistry for urothelial markers (GATA3, p63, uroplakin II), prostate markers (NKX3.1, prostate specific antigen, P501S), androgen receptor (AR) and ERG, along with molecular characterization using capture-based next generation DNA sequencing. Immunohistochemical findings were concordant with the final integrated diagnosis in 21 (84%) cases. However, in three (12%) cases, immunohistochemistry supported a diagnosis of urothelial carcinoma, but molecular analysis identified the correct diagnosis of prostate cancer based on the presence of a TMPRSS2-ERG fusion. One case remained unclassifiable even after this integrated analysis. Notably, in 1 of 21 cases, the presence of a TERT promoter mutation and the absence of a TMPRSS2-ERG fusion would typically favor a diagnosis of urothelial carcinoma, but the aggregate immunohistochemical and molecular findings instead supported a diagnosis of microsatellite unstable prostatic adenocarcinoma with deep deletion of MSH2 and MSH6. Our findings highlight the importance of considering prostatic origin in high-grade carcinoma of the urinary bladder of patients with a history of treated prostate cancer, even when the immunohistochemical findings favor urothelial carcinoma. In a subset of cases, an approach that integrates immunophenotypic and molecular data may help correctly assign site of origin and prevent misdiagnosis that can result from overreliance on any individual immunohistochemical or molecular result.

Addition of abiraterone to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Model to estimate long-term survival, quality-adjusted survival, and cost-effectiveness.

204 Background: Results from randomised trials show adding abiraterone acetate plus prednisolone (AAP) to standard of care (SOC) improves disease-free and overall survival in men with prostate cancer (PC) starting long-term hormone therapy for first time. Formal assessment is required of whether funding AAP here shows appropriate use of resources. This cost-effectiveness decision model tests if giving AAP to these patients is cost-effective using costs from English National Health Service, the largest nation where STAMPEDE recruited. Methods: Health outcomes and costs were modelled using patient data from AAP comparison of STAMPEDE (recruitment 2011-14). This included 1917 men with high-risk, locally advanced metastatic or recurrent PC starting 1st-line hormone therapy. SOC was hormone therapy for ≥2 years with radiotherapy in pre-selected patients. If allocated to research group, AAP (AA 1000mg/day, P 5mg/day) was added to SOC. The model makes lifetime predictions of survival, costs and quality-adjusted lifeyears (QALYs), with costs and QALYs discounted at 3.5% annually. Sensitivity analyses were performed. Results: The model predicted AAP would extend survival (discounted quality-adjusted survival) by 2.68y (1.46 QALYs) for metastatic patients and 0.30y (0.29 QALYs) for non-metastatic. The cost of AAP means it is not currently cost-effective in this setting, including with Patient Access Scheme costs for AAP and enzalutamide and similar reductions for cabazitaxel and Ra. If AAP’s price reduces after patent expiry as expected (90% reduction on BNF cost), it would be cost-effective in both patient groups, with incremental cost-effectiveness ratios below £10,000 (US$12,665) per QALY. AAP could also dominate in non-metastatic patients (i.e. lower costs and higher QALYs than SOC alone). Conclusions: AAP could be cost-effective for patients with non-metastatic and metastatic disease with expected future pricing and may be cost-saving in the former. Policymakers should encourage license submissions and generic price reductions to facilitate use of AAP given cost-saving potential in addition to improving survival. Clinical trial information: NCT00268476.

Family history in primary hormone therapy for prostate cancer: Analysis from a community-based multi-institutional Japan-wide database.

To determine the association between hormone therapy and outcomes in a cohort of prostate cancer patients with a family history of prostate cancer. Data of patients with prostate cancer who had received hormone therapy were extracted from a nationwide community-based database established by the Japan Study Group for Prostate Cancer. Family history of prostate cancer was available for 13346 of these patients, who thus comprised the study cohort. Prognostic variables, including progression-free survival, cancer-specific survival and overall survival, were compared between men with familial and men with sporadic prostate cancer. A positive family history was identified in 220 patients (1.6%). Patients with a positive family history were younger than those without; however, other clinicopathological characteristics and prognoses were comparable. In subgroup analysis, family history was identified as a possible favorable prognostic factor for overall survival among patients with a prostate-specific antigen level at diagnosis <100ng/mL and those with low or intermediate Japan Cancer of the Prostate Risk Assessment. Our findings show that familial prostate cancer has an early-onset feature or is diagnosed earlier than sporadic prostate cancer. However, the prognosis of individuals with familial prostate cancer undergoing hormone therapy is comparable to those with sporadic prostate cancer.

Editorial Comment to Family history in primary hormone therapy for prostate cancer: Analysis from a community-based multi-institutional Japan-wide database.

Editorial Comment to Family history in primary hormone therapy for prostate cancer: Analysis from a community-based multi-institutional Japan-wide database.