Clinical Management Of Men Research Articles

Abstract A076: Evaluating cardiometabolic and oncologic risk among Puerto Rican men with prostate cancer

Abstract Background. Cardiovascular and metabolic disorders are significant contributors to mortality among men with prostate cancer. However, no evidence is yet available for the role of cardiometabolic comorbidities in the tumor risk stratification or clinical management of men with prostate cancer. Like African American men, Puerto Rican men have a higher risk of developing and dying from prostate cancer than other racial/ethnic groups in the United States. As cardiovascular and metabolic risk factors are highly prevalent in Puerto Rico, we proposed to investigate coordinated risk evaluation of cardiometabolic and oncologic risk in this population. We hypothesized that a subset of cardiometabolic risk factors consistently correlate with clinically defined aggressive disease. Methods. The Puerto Rico Urology Group (PRUG) is the largest group urology practice in Puerto Rico. It currently consists of eight urologists serving the Western, Southern, Central, and Metropolitan regions of Puerto Rico including the island municipalities of Vieques and Culebra. A cohort (n=401) of patients treated to between 2018 and 2022 by the PRUG have been identified for analysis in this study, of which n=30 have been analyzed to date. Clinical data were extracted from consented patients’ medical records with approval by the Ponce Research Institute Institutional Review Board (IRB approval no. 2210121134). Post-surgical cancer of the prostate risk assessment (CAPRA-S) were used to stratify tumors and cardiovascular and metabolic risk factors were evaluated across tumor risk strata. Results. Of the 14 patients with intermediate or high risk, all had a body mass index over 26 compared to 7/16 patients with low-risk tumors (p=0.0009). Among patients with intermediate/high risk, 12/14 had high blood pressure compared to 8/16 patients with low-risk tumors (p=0.0577, RR=3.0). Hyperlipidemia was present in 5/14 patients with intermediate/high risk and 1/16 patients with low-risk tumors (p=0.0725, RR=2.22). Hypercholesterolemia was detected in 3/14 intermediate/high risk and in 6/16 low risk tumors (p=0.4397, RR=0.63). Other cardiometabolic risk factors including diabetes with complications and smoking status did not differ between cancer risk groups. Discussion. The Puerto Rican population represents the second largest Hispanic/Latino subgroup in the United States and has disproportionately high rates of prostate cancer and cardiometabolic comorbidity. Our preliminary findings indicate that the coordinated evaluation of cancer risk in the context of cardiovascular and metabolic risk factors may provide additional insights for risk stratification for patients with prostate cancer from populations with high prevalence of these chronic diseases. Although the study was limited by sample size, our findings provide insights for ongoing studies to evaluate large, multi-institutional cohorts and identify molecular indicators of cardiometabolic risk predictive of prostate cancer aggressiveness among diverse populations. Citation Format: Carlos J. Diaz Osterman, Nicole Torres Muriel, Shannalee R. Martinez, Noemi Santiago, Brenda L. Rodriguez Ruiz, Geoffrey Rodriguez, Eric Rosa, Ana M. Escalona Cruz, Ralph Krumhansl, Julie Dutil, Kosj Yamoah, Jong Y. Park, William Roman Torreguitart. Evaluating cardiometabolic and oncologic risk among Puerto Rican men with prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A076.

Impact of PSMA-targeted PET/CT in the clinical management of men with advanced prostate cancer.

e17053 Background: 18F-DCFPyL (piflufolastat F 18) is a PSMA-targeted agent FDA-approved for PET imaging in men with prostate cancer. Given the recent availability for clinical use, we sought to evaluate the impact and potential changes in management after the incorporation of 18F-DCFPyL (PyL) PET/CT at an academic medical center. Methods: We reviewed the first 100 PyL PET/CT scans performed at the Vanderbilt-Ingram Cancer Center for men with prostate adenocarcinoma. Patient demographics, treatment history, and prior imaging results were recorded, along with PyL PET results, most recent PSA, and clinical management plans. Management changes were designated as change in systemic therapy, radiation, or surgery and were determined by two independent reviewers with a third reviewer for any discordant cases. Results: There were 100 men included with PyL PET scans dating from 9/1/21 to 12/31/21. The median age was 69 years, 76% of patients were white and 13% were black. The median Gleason sum at diagnosis was 7 (4+3), 55% of men had prior prostatectomy, and 38% had prior radiation to the prostate/pelvis. The median PSA prior to PyL PET scan was 1.86 (IQR 0.53-9.95 ng/mL), 32% of men had previous ADT exposure, and 15% were on ADT at the time of PyL PET scan. The clinical setting prior to PyL PET scan was initial staging 22%, biochemical recurrence 59%, m1HSPC 14%, m0CRPC 2%, and m1CRPC 3%. There were 16 patients who had a prior 18F-fluciclovine within six months of PyL PET; of these 69% (11/16) had additional disease on PyL PET not previously identified. Activity in lymph nodes was observed in 48%, bone 37%, visceral sites 3%, prostate/prostate bed 46%, and 15% had no PSMA-avid disease. Clinical staging was altered after the PyL PET scan in 55% of patients, with the most common change being from BCR to m1HSPC (40/55). Clinical management was altered in 59% of cases: systemic therapy 38%, radiation planning 46%, and surgical planning 6% (Table). Conclusions: Clinical management was affected in 59% of cases after implementation of PyL PET in this retrospective, single center review. Given the rapid adoption of PSMA-targeted PET imaging agents, further studies are needed to evaluate the clinical impact of subsequent changes to management planning, as well as to develop multidisciplinary consensus statements and protocols to guide management.[Table: see text]

Clinical impact of PSMA PET/CT in primary prostate cancer compared to conventional nodal and distant staging: a retrospective single center study

BackgroundTo evaluate the impact of Gallium-68 [68Ga] labeled prostate specific membrane antigen (PSMA) positron emission tomography (PET)/X-ray computed tomography (CT) compared with conventional imaging on staging and clinical management of men evaluated for primary prostate cancer (PCa).MethodsMen with newly diagnosed biopsy-proven PCa who had been staged with a conventional staging protocol including bone scintigraphy (BS) and additionally underwent [68Ga]PSMA PET/CT, were evaluated retrospectively. Imaging findings from BS, magnetic resonance imaging (MRI) and/or CT were categorized regarding locoregional nodal (N) and distant metastasis (M) status as negative, positive or equivocal before and after addition of the information of PET/CT. Also, the imaging-based level of confidence (LoC) in correct assessment of N and M status was scored. Impact of PET/CT on clinical management was evaluated by the percentage of treatment category changes after PET/CT as determined in the multidisciplinary tumour board.ResultsSixty-four men with intermediate and high-risk PCa were evaluated. With additional information of PET/CT, N status was upstaged in 23%, and downstaged in 9%. M status was upstaged in 13%, and downstaged in 23%. A net increase in LoC of 20% was noted, mainly regarding M status.Treatment category changed from palliative to curative in 9%, and from curative to palliative in 3%. An undecided treatment plan changed to curative in 14%, as well as to palliative in another 9%. In total, a 36% treatment category change was noted.High negative predictive value of PET/CT for M status was indicated by 27 patients that underwent robot-assisted radical prostatectomy and reached postoperative biochemical disease-free status or had a likely other site of disease recurrence.ConclusionsPSMA PET/CT can cause considerable changes in N and M staging, as well as in management compared to conventional staging. Findings of this study support the replacement of BS and CT by PSMA PET/CT in staging primary PCa.

Differences in the clinical management of women and men after detection of a solitary pulmonary nodule in clinical practice.

To explore differences in the clinical management of men and women in the 5years after detecting a solitary pulmonary nodule (SPN) by chest radiograph or CT in routine clinical practice. We followed up 545 men and 347 women with an SPN detected by chest radiograph or CT in a retrospective cohort of 25,422 individuals undergoing routine thoracic imaging in 2010-2011. We compared the frequency of each management strategy (no further test, immediate intervention or follow up) according to sex by means of chi-squared. We estimated the relative risk of women versus men of having been followed up instead of an immediate intervention using multivariate logistic regression. We compared by sex the time between detection of the nodule and lung cancer diagnosis, the time between diagnosis and death by means of Mann-Whitney U test and the cumulative effective dose of radiation in each management strategy by means of t test. Women were more likely than men to have follow-up rather than immediate intervention (aRR = 1.8, CI 1.3-2.7, p = 0.002), particularly in those who underwent CT (aRR = 4.2, CI 1.9-9.3, p < 0.001). The median time between SPN detection and lung cancer diagnosis was higher in women (4.2months, interquartile range (IQR) 5.1) than in men (1.5months, IQR 16.2). The mean cumulative effective dose was 21.3mSv, 19.4mSv in men and 23.9mv in women (p = 0.023). Our results could reflect decisions based on a greater suspicion of lung cancer in men. The incidental detection of SPNs is increasing, and it is necessary to establish clear strategies aimed to reduce variability in their management according to patient's sex. • After incidental finding of SPN, women were less likely to receive an immediate intervention. • Accumulative radiation was higher in women than in men. • Our results could reflect decisions based on a greater suspicion of lung cancer in men.

Abstract P4-07-05: Matched germline and tumor profiling in male breast cancer for the discovery of molecular subtypes with clinical relevance

Abstract Background: Breast cancer (BC) in men is a rare disease, but morbidity and mortality in male BC (MBC) patients is a serious concern. Because of its rarity, to date, clinical management of men with BC has been informed almost entirely by female BC research. However, BC in men and women may behave differently. Inherited mutations in homologous recombination (HR) genes, mainly BRCA1,BRCA2 and PALB2, play a major role in MBC predisposition. MBCs associated with mutations in HR gene are likely to represent a subgroup of tumors with a peculiar tumor phenotype. Here, we performed a transcriptome analysis of MBCs characterized for germline mutations in HR genes in order to provide insight into underlying HR pathways and characterize distinct molecular subtypes of MBC with possible clinical relevance. Materials and methods: MBC cases were selected to include cases with and without germline mutations in HR genes. Tumor samples with pathology and outcome data were selected within the Italian multicenter study on MBC that comprises 750 MBCs with information on germline mutations in 50 cancer-related genes. To enrich the series of MBC cases with germline mutations in HR genes, tumor samples from kConFab were also included. Overall, 63 tumor samples, including 26 cases with germline mutations in HR genes (BRCA2, BRCA1, PALB2, RAD50 and RAD51D) and 37 without germline mutations, were analyzed. Whole transcriptome data were obtained by RNA-sequencing using Illumina technology. A bioinformatic pipeline including FastQC tool for quality control, STAR for alignment, RSeQC-FPKM for counting reads, DESeq2 package for differential expression and DAVID for enrichment, was used. Tumor immunophenotype was evaluated using CIBERSORT, which accurately determines the fraction of 22 immune cell types. Statistical analyses were performed using Fisher exact test, t-test and log-rank test as appropriate. Results: A total of 724 differentially expressed genes, of which 355 up-regulated and 369 down-regulated, emerged between MBC cases with and without germline mutations in HR genes. Pathway-based analyses revealed different transcriptome profiles for genes involved in key biological processes, including translational initiation, cell cycle, DNA damage and repair. A higher fraction of activated CD4 memory T cells was observed in tumors with germline mutations in HR genes compared to those without mutations (p=0.04). Unsupervised clustering approach, based on the 2000 most variable transcripts among tumors, revealed two distinct subgroups with different biologic features and clinical outcome. In particular, tumors in subgroup 1 showed higher expression of genes involved in cell proliferation, were enriched for cases with germline mutations in HR genes (p=0.03), had lymph node involvement (p=0.04) and displayed a trend toward worse overall survival (p=0.09), when compared to tumors in subgroup 2. Conclusions: Integration of matched germline and tumor profiling seem to be a valuable approach for the identification of biologically and clinically relevant subtypes of MBC. Germline mutations in HR genes could impact on MBC transcriptome, defining molecular subgroups with peculiar biological features. Overall, these results may help to improve the clinical managements of MBC patients. Study supported by AIRC (IG 21389) to L.O. Citation Format: Veronica Zelli, Valentina Silvestri, Virginia Valentini, Agostino Bucalo, Piera Rizzolo, Ines Zanna, Laura Cortesi, Daniele Calistri, Maria Grazia Tibiletti, Giuseppe Giannini, Stephen B Fox, Domenico Palli, Laura Ottini. Matched germline and tumor profiling in male breast cancer for the discovery of molecular subtypes with clinical relevance [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-05.

The FALCON trial: Impact of 18F-fluciclovine PET/CT on clinical management choices for men with biochemically recurrent prostate cancer.

165 Background: Detection of the extent of local recurrence and of metastases in biochemical recurrence (BCR) of prostate cancer facilitates selection of appropriate treatment. The FALCON trial (NCT02578940) assessed the impact of 18F-fluciclovine PET/CT on the clinical management of men with BCR of prostate cancer following initial radical therapy. Methods: Men being considered for curative-intent salvage therapy following first BCR were recruited at 6 UK sites. Management plans were documented prior to and following 18F-fluciclovine PET/CT imaging. Post-scan changes to treatment modality such as salvage radiotherapy [RT] to systemic therapy were classed as ‘major’, while changes within a modality (e.g. modified RT fields) were classed as ‘other’. A pre-planned interim analysis of the first 85 patients was conducted; recruitment was to be stopped for efficacy if the number of treatment changes was &gt; 45 (52.9%; 97.5% CI: 40.3–62.3%), or for futility if ≤ 8 (9.4%, 97.5% CI: 3.6–18.9%). Results: The 85 enrolled patients were a mean 4.8 y post-initial diagnosis, with a median age of 67 y and median PSA of 0.63ng/mL. Twelve (14.1%) had a Gleason score ≤ 6, 60 (70.6%) had a score of 7 and 13 (15.3%) had a score ≥ 8. Most (56; 65.9%) had previously undergone radical prostatectomy (RP), with 27 having received RT (± other therapy). The majority of those imaged (52; 61.2%) had a change in management (CIM) post-scan (Table). Recruitment was subsequently stopped as the pre-specified condition defining overwhelming efficacy was met. Conclusions: This prospective trial shows 18F-fluciclovine PET/CT has substantial impact on clinical decisions for men with a first BCR of prostate cancer after curative-intent primary therapy. Clinical trial information: NCT02578940. [Table: see text]

Prostate cancer: Novel xenografts in mice--a new wave of preclinical models.

Robust preclinical models of prostate cancer are required as clinical management of men with this disease evolves, and increasing genomic understanding makes currently available cell lines less relevant. A novel orthotopic xenograft mouse model is state of the art for preclinical models of prostate cancer.

Does Treatment Change with Gender in Acute Coronary Syndrome?

Abstract Coronary artery disease (CAD) is the leading cause of death in women, with higher mortality and morbidity compared to men. We sought to evaluate whether an inequality in the primary medical treatment of acute myocardial infarction (AMI) exists in a sample population in a tertiary care hospital setting. There were no statistically significant differences in use of beta receptor blockers, aspirin, cholesterol lowering agent or cclopidogrel in both genders. However, women were slightly more likely to receive angiotensin converting enzyme inhibitor. There is an extensive literature suggesting gender bias in the management of patients with AMI, with women being treated less intensively than men. Our research highlights the fact that there were no statistically significant differences in the AMI medical management. Clinical management of men and women with AMI is similar and should follow the standard of care recommended by the related guidelines.

Effets négatifs sur la sexualité des traitements médicamenteux des symptômes du bas appareil urinaire liés a l’hypertrophie bénigne de la prostate

The aim of this review is to discuss the negative effects on sexual function of medications for lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS-BPH). An international non-systematic literature review was performed. It included randomized trials of seven drugs of interest and the summaries of the characteristics of these products. This work did not aim comparison between the drugs. Only maximal reported frequencies are presented in this abstract. With prolonged-release alfuzosin, they were 2.8% vs. 1.3% for erectile dysfunction, compared to placebo and 1% vs. 0% for ejaculatory dysfunction. With doxazosin, the incidence was 5.8% vs. 3.3% for erectile dysfunction, 3.6% vs. 1.9% for reduced libido and 0.4% vs. 1.4% for ejaculatory disorders. The incidence of ejaculatory disorders with tamsulosin, was 11% vs. <1% with the placebo and with silodosin, it was 28.1% vs. 1.1%. With finasteride, at 12 months, the highest frequency was 9% vs. 5% for erectile dysfunction, 4.4% vs. 1.5% for ejaculatory disorders and 6.4% vs. 3.4% for reduced libido. At 24 months, for dutatsteride, frequencies were 7.3% vs. 4.0% for erectile dysfunction, 2.2% vs. 0.8% for ejaculatory disorders and 4.2% vs. 2.1% for reduced libido. For tadalafil, a phosphodiesterase-5 inhibitor, and tolerodine, an anticholinergic drug, no negative effect on ejaculation or libido has been reported. For plant extracts, no sexual adverse effects (AEs) were reported among the most common AEs. The medications for LUTS-BPH may alter erection, ejaculation or libido. A greater knowledge of the adverse effects of each of these drugs could guide physicians in the clinical management of men with BPH-LUTS.

Clinical management of infertile men with nonobstructive azoospermia.

The clinical management of men with nonobstructive azoospermia (NOA) seeking fertility has been a challenge for andrologists, urologists, and reproductive medicine specialists alike. This review presents a personal perspective on the clinical management of NOA, including the lessons learned over 15 years dealing with this male infertility condition. A five-consecutive-step algorithm is proposed to manage such patients. First, a differential diagnosis of azoospermia is made to confirm/establish that NOA is due to spermatogenic failure. Second, genetic testing is carried out not only to detect the males in whom NOA is caused by microdeletions of the long arm of the Y chromosome, but also to counsel the affected patients about their chances of having success in sperm retrieval. Third, it is determined whether any intervention prior to a surgical retrieval attempt may be used to increase sperm production. Fourth, the most effective and efficient retrieval method is selected to search for testicular sperm. Lastly, state-of-art laboratory techniques are applied in the handling of retrieved gametes and cultivating the embryos resulting from sperm injections. A coordinated multidisciplinary effort is key to offer the best possible chance of achieving a biological offspring to males with NOA.

Gender differences in presentation, management, and in-hospital outcomes for patients with AMI in a lower-middle income country: evidence from Egypt.

BackgroundMany studies in high-income countries have investigated gender differences in the care and outcomes of patients hospitalized with acute myocardial infarction (AMI). However, little evidence exists on gender differences among patients with AMI in lower-middle-income countries, where the proportion deaths stemming from cardiovascular disease is projected to increase dramatically. This study examines gender differences in patients in the lower-middle-income country of Egypt to determine if female patients with AMI have a different presentation, management, or outcome compared with men.Methods and FindingsUsing registry data collected over 18 months from 5 Egyptian hospitals, we considered 1204 patients (253 females, 951 males) with a confirmed diagnosis of AMI. We examined gender differences in initial presentation, clinical management, and in-hospital outcomes using t-tests and χ2 tests. Additionally, we explored gender differences in in-hospital death using multivariate logistic regression to adjust for age and other differences in initial presentation.We found that women were older than men, had higher BMI, and were more likely to have hypertension, diabetes mellitus, dyslipidemia, heart failure, and atrial fibrillation. Women were less likely to receive aspirin upon admission (p<0.01) or aspirin or statins at discharge (p = 0.001 and p<0.05, respectively), although the magnitude of these differences was small. While unadjusted in-hospital mortality was significantly higher for women (OR: 2.10; 95% CI: 1.54 to 2.87), this difference did not persist in the fully adjusted model (OR: 1.18; 95% CI: 0.55 to 2.55).ConclusionsWe found that female patients had a different profile than men at the time of presentation. Clinical management of men and women with AMI was similar, though there are small but significant differences in some areas. These gender differences did not translate into differences in in-hospital outcome, but highlight differences in quality of care and represent important opportunities for improvement.

Ejaculatory dysfunction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

To assess, using the psychometrically validated Male Sexual Health Questionnaire (MSHQ), the prevalence of ejaculatory dysfunction (EjD) and bother due to EjD in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH), and to assess predictors of EjD in this population. In all, 5999 sexually active men with LUTS completed the International Prostate Symptom Score (IPSS) which rates LUTS severity, and the MSHQ long-form, which evaluates seven EjD symptoms and bother due to EjD. Concomitant intake of medical treatments for BPH and previous BPH-related surgery were collected. The impact of treatments on EjD was compared to a control group (i.e. no previous BPH-related surgery and no medical treatment for BPH). The relationship between EjD, bother due to EjD and selected clinical characteristics was analysed using multiple regression analysis. EjD was highly prevalent and bothersome in men with LUTS, with decreased force of ejaculation (77.9%) and decreased amount of semen (74.4%) being the most commonly reported symptoms. LUTS severity was the strongest predictor of EjD and bother due to EjD. EjD was considered a problem by 35.6%, 51.6% and 64.1% of men with mild, moderate and severe LUTS, respectively (P < 0.001). EjD (except pain/discomfort on ejaculation) and bother due to EjD were also strongly related to age. Men with previous BPH-related surgery and men treated with a 5α-reductase inhibitor plus an α(1)-blocker or tamsulosin alone showed the highest rates of dry ejaculation (67.4%, 57.2% and 52.3%, respectively) compared to controls (31.6%, P < 0.001). Conversely, in men treated with alfuzosin, most EjD symptoms were significantly lower than in controls. Bother due to EjD was also significantly lower with alfuzosin than in controls (34.4% vs 53.1%, P < 0.001) while there was no significant difference for other treatments. EjD is highly prevalent and bothersome in sexually active men with LUTS, and is strongly related to LUTS severity and age. Treatment options for BPH do not have the same effect on EjD. EjD should be considered in the initial evaluation and clinical management of men with LUTS.

Sperm Retrieval and Outcome of Treatment in Non-Obstructive Azoospermia

ICSI using sperm retrieved from the testis is a routine fertility treatment for patients with obstructive azoospermia (OA). However, sperm retrieval in cases of non obstructive azoospermia (NOA) is difficult and variable outcomes have been reported. In this study, we aim to examine rates of sperm retrieval and outcome of treatment according to NOA subgroup. The findings may assist in the clinical management of men with NOA seeking treatment for infertility.

Men's attitudes toward prostate cancer and seeking prostate-specific antigen testing.

Although the Australian Cancer Society recommends against performing PSA tests to screen for prostate cancer, many Australian men currently undergo such screening. This study investigated attitudinal variables that may predict prostate cancer screening behaviors in this context. A questionnaire was administered by mail in a two-phase procedure, first to a sample of 1,461 men (46% response), then to 919 men from the initial sample. Prostate cancer screening behaviors of men > 40 years old were examined. The questionnaire assessed worry about prostate cancer, perceived vulnerability to prostate cancer, belief in the efficacy of PSA testing for detection, having received a PSA test for detection, and the presence of urologic symptoms at the time of testing. Men who had had PSA testing with urologic symptoms at the time of the test were more worried about prostate cancer and perceived themselves as more vulnerable to prostate cancer compared with both asymptomatic tested and untested men. Men who had undergone PSA testing believed the test to be more effective in the detection of prostate cancer than did men who had not. Urologic symptoms act as a risk cue for men to prostate cancer. Asymptomatic men should be considered separately from symptomatic men in the investigation of psychological variables predictive of seeking screening for prostate cancer. These findings are discussed in terms of both the focus and design of interventions to alter prostate cancer screening behavior and their implications for the clinical management of men with urologic symptoms.