Progression In Men Research Articles

Association between lipoprotein particle concentration and size and progression of coronary plaque: the MACS Longitudinal Coronary CT angiography study

Abstract Background People living with HIV have greater risk of cardiovascular diseases (CVD) than people without HIV and tend to have different risk profiles, including higher serum triglycerides and lower LDL cholesterol levels. Nuclear magnetic resonance (NMR) provides a detailed phenotype of lipoproteins. Purpose To examine the associations between lipoprotein particle concentrations and size and progression of coronary artery plaque among people living with and without HIV, and whether these associations differ by HIV serostatus. Methods Men with no clinical CVD in the Multicenter AIDS Cohort Study (MACS) who underwent a coronary CT angiography at baseline (2010-13) and follow-up (2015-17) were included. NMR spectroscopy was completed on fasting serum samples at baseline. Logistic regression models for the change in total coronary plaque volume (in tertiles) were estimated with NMR-derived lipoproteins as predictors. Levels were log-transformed and standardized to make results comparable. Models were adjusted for demographics, statin use and HIV serostatus (model 1) with addition of CVD risk factors (model 2). Interactions by HIV serostatus were also tested. Results A total of 549 men (314 with HIV; 235 without HIV) were included. Mean age was 53 ±7 years; 58% were White, 30% Black, and 12% Hispanic. Coronary plaque was present in 70% and plaque volume progressed in 79% of the cohort. Among men with HIV, 81% had undetectable HIV RNA and 12% had a diagnosis of AIDS at baseline. Men with HIV had significantly higher levels of small LDL-P, and total, medium and large VLDL-P levels compared to men without HIV, and lower levels of total, small and large HDL-P (Table 1). Men with HIV had significantly greater progression of plaque volume (37 mm3) compared to men without HIV (31 mm3, p<0.05). Levels of total and small LDL-P concentrations were directly associated with plaque progression, whereas large HDL-P was inversely associated with plaque progression in the combined sample (Model 2). Associations between total and small LDL-P with plaque progression were stronger in men with HIV than in men without HIV in models 1 and 2 (interaction p<0.01). While associations in fully adjusted models for total VLDL-P and small VLDL-P were significant in men without HIV, there were no significant associations between these particle concentrations with coronary plaque progression among men without HIV (interaction p< 0.01) (Model 2, Table 2). Conclusion Associations between lipid particle concentrations and coronary plaque progression differed between men with and without HIV, with stronger associations seen in men without HIV for total and small LDL-P. Despite having higher VLDL and lower HDL particle concentrations at baseline, these particle concentrations were only associated with plaque progression in men without HIV. Further research is needed to elucidate HIV specific factors for plaque progression to tailor risk reduction strategies.

TCT-798 Echocardiographic Left Ventricular Geometry Patterns and Their Progression in Men vs Women With Moderate Aortic Stenosis

TCT-798 Echocardiographic Left Ventricular Geometry Patterns and Their Progression in Men vs Women With Moderate Aortic Stenosis

Evaluating 4Kscore's role in predicting progression on active surveillance for prostate cancer independently of clinical information and PIRADS score.

4Kscore is used to aid the decision for prostate biopsy, however its role in active surveillance (AS) has not been investigated in a magnetic resonance imaging (MRI)-based protocol. Our objective was to assess the association between 4Kscore and progression in men undergoing AS on a prospective MRI-based protocol. This was a single-institution, single-arm, non-therapeutic, interventional trial of 166 men with biopsy-confirmed prostate cancer enrolled between 2014-2020. Patients were placed on a trial-mandated AS protocol including yearly multiparametric (mp)MRI, prostate biopsy, and 4Kscore followed for 48 months after diagnosis. We analyzed protocol-defined and grade progression at confirmatory and subsequent surveillance biopsies. Out of 166 patients, 83 (50%) men progressed per protocol and of them 41 (24.7% of whole cohort) progressed by grade. At confirmatory biopsy, men with a baseline 4Kscore ≥ 20% had a higher risk of grade progression compared to those with 4Kscore < 20% (OR = 4.04, 95% CI: 1.05-15.59, p = 0.043) after adjusting for National Comprehensive Cancer Network (NCCN) risk and baseline PIRADS score. At surveillance biopsies, most recent 4Kscore ≥ 20% significantly predicted per protocol (OR = 2.61, 95% CI: 1.03-6.63, p = 0.044) and grade progression (OR = 5.13, 95% CI: 1.63-16.11, p = 0.005). For patients on AS, baseline 4Kscore predicted grade progression at confirmatory biopsy, and most recent 4Kscore predicted per-protocol and grade progression at surveillance biopsy.

Association Of Androgen Deprivation Therapy And Coronary Plaque Progression In Men With Prostate Cancer

Association Of Androgen Deprivation Therapy And Coronary Plaque Progression In Men With Prostate Cancer

Diet and Tumor Genetics Conspire to Promote Prostate Cancer Metabolism and Shape the Tumor Microenvironment.

Obesity has been linked to prostate cancer in a stage-dependent manner, having no association with cancer initiation but correlating with disease progression in men with prostate cancer. Given the rising obesity rate and its association to aggressive prostate cancer, there is a growing need to understand the mechanisms underlying this relationship to identify patients at increased risk of lethal disease and inform therapeutic approaches. In this issue of Cancer Research, Boufaied and colleagues describe how diets high in saturated fatty acids promote MYC-driven prostate cancer. Leveraging MYC-expressing genetically engineered and allograft mouse models fed either a control low-fat or high-fat diet (HFD) enriched in saturated fatty acids, the authors found using digital pathology that HFD-fed mice exhibited increased tumor invasion. Metabolomics, transcriptomics, immunoblotting, and positron emission tomography of tumors from these mice demonstrated that a HFD promoted a metabolic shift in the tumors towards glycolysis. These preclinical data were supported by findings from two large clinical cohorts revealing that men diagnosed with prostate cancer and who consumed high levels of saturated fatty acids possessed tumors bearing glycolytic signatures. Deconvolution analyses and immunohistochemistry validation showed that these tumors also displayed increased angiogenesis and infiltration of immunosuppressive macrophages and regulatory T cells, the latter of which was also correlated with high saturated fat intake-associated glycolytic signatures in patient tumors. Together, these findings suggest that diets rich in saturated fatty acids, rather than obesity alone, accelerate MYC-driven prostate cancers through shifting tumor metabolism and shaping the tumor microenvironment. See related article by Boufaied et al., p. 1834.

Plant-Based Diets and Disease Progression in Men With Prostate Cancer.

Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer. To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality. This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023. Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ. The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality. Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7. In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

Repeat Next-Generation Sequencing Testing on Progression in Men With Metastatic Prostate Cancer Can Identify New Actionable Alterations.

There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test. The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB. Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new BRCA2 alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients. Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.

The association between patient and disease characteristics, and the risk of disease progression in patients with prostate cancer on active surveillance.

The objective of this study was to identify and assess patient and disease characteristics associated with an increased risk of disease progression in men with prostate cancer on active surveillance. We studied patients with low-risk (ISUP GG1) or favorable intermediate-risk (ISUP GG2) PCa. All patients had at least one repeat biopsy. Disease progression was the primary outcome of this study, based on pathological upgrading. Univariate and multivariate Cox proportional hazard analyses were used to evaluate the association between covariates and disease progression. In total, 240 men were included, of whom 198 (82.5%) were diagnosed with low-risk PCa and 42 (17.5%) with favorable intermediate-risk PCa. Disease progression was observed in 42.9% (103/240) of men. Index lesion > 10 mm (HR = 2.85; 95% CI 1.74-4.68; p < 0.001), MRI (m)T-stage 2b/2c (HR = 2.52; 95% CI 1.16-5.50; p = 0.02), highest PI-RADS score of 5 (HR 3.05; 95% CI 1.48-6.28; p = 0.002) and a higher PSA level (HR 1.06; 95% CI 1.01-1.11; p = 0.014) at baseline were associated with disease progression on univariate analysis. Multivariate analysis showed no significant baseline predictors of disease progression. In AS patients with low-risk or favorable intermediate-risk PCa, diameter of index lesion, MRI (m)T-stage, height of the PI-RADS score and the PSA level at baseline are significant predictors of disease progression to first repeat biopsy.

The Impact of Physical Activity on the Outcomes of Active Surveillance in Prostate Cancer Patients: A Scoping Review

Introduction: Active surveillance has emerged as a valid therapeutic option in patients with low-risk prostate cancer, allowing for the deferral of definitive treatment until the time of possible disease progression. Although it is known that physical activity plays a protective role in the onset and progression of this tumor, its impact on patients with low-risk disease who are managed with active surveillance remains unclear. Our scoping review aims to summarize the existing evidence on this subject. Evidence Acquisition: On 9 April 2023, a systematic search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: (“prostate cancer” OR “prostate tumor”) AND (“active surveillance”) AND (“physical activity” OR “physical exercise” OR “physical intensive activity” OR “intensive exercise”) AND (“lifestyle”). Out of the 506 identified articles, 9 were used for the present scoping review, and their results were reported according to the PRISMA-ScR statement. Evidence Synthesis: We discovered a lack of uniformity in the assessment of PA and its stratification by intensity. There was no consensus regarding what constitutes cancer progression in patients choosing expectant management. In terms of the impact of PA on AS outcomes, conflicting results were reported: some authors found no correlation, while others (six of total studies included) revealed that active men experience smaller increases in PSA levels compared to their sedentary counterparts. Additionally, higher levels of exercise were associated with a significantly reduced risk of PCa reclassification. Conclusion: Due to the heterogeneity of the methodologies used in the available studies and the conflicting results reported, it is not possible to draw definitive conclusions concerning the role physical activity may play in the risk of prostate cancer progression in men managed with active surveillance.

Association of PSMA PET-derived Parameters and Outcomes of Patients Treated for Oligorecurrent Prostate Cancer.

Background Prostate-specific membrane antigen (PSMA) PET is useful in the early detection of oligorecurrent prostate cancer (PCa), but whether PSMA PET parameters can be used to identify patients who would benefit from metastasis-directed therapy (MDT) with radiation or surgery remains uncertain. Purpose To assess the association of PSMA PET parameters with outcomes of patients with oligorecurrent PCa after MDT. Materials and Methods In this retrospective analysis of a single-center phase II trial that enrolled patients with biochemical recurrence of PCa after maximal local therapy and with no evidence of disease at conventional imaging, patients underwent PSMA PET (between May 2017 and November 2021), and unveiled recurrences were treated with MDT. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) and PSMA tumor volume derived using thresholds of 2.5 (SUVmean2.5) and 41% (SUVmean41%), respectively, were recorded for sites of recurrence on PSMA PET scans, and a molecular imaging PSMA score was assigned. These parameters were also corrected for smooth filter and partial volume effects, and the PSMA score was reassigned. Cox proportional hazards models were used to evaluate the relationship between PSMA PET parameters and outcomes. Results A total of 74 men (mean age, 68.3 years ± 6.6 [SD]) with biochemical recurrence of PCa were included. PSMA PET revealed 145 lesions in the entire cohort, of which 125 (86%) were metastatic lymph nodes. Application of the correction factor changed the PSMA score in 88 of 145 lesions (61%). Mean SUVmax, SUVmean2.5, and SUVmean41% were associated with lower risk of biochemical progression (hazard ratio [HR] range, 0.77-0.95; 95% CI: 0.61, 1.00; P = .03 to P = .04). For corrected parameters, mean SUVmax, mean SUVmean2.5, mean SUVmean41%, mean PSMA score, maximum SUVmean2.5, maximum SUVmean41%, and maximum PSMA score were associated with a lower risk of biochemical progression (HR, 0.61-0.98; 95% CI: 0.39, 1.00; P = .01 to P = .04). Conclusion Measured and corrected PSMA PET parameters were associated with biochemical progression in men with oligorecurrent PCa treated with MDT. Clinical trial registration no. NCT03160794 © RSNA, 2023 See also the editorial by Civelek in this issue.

IGF-1 axis changes with ADT and docetaxel in metastatic prostate cancer.

Androgen deprivation therapy (ADT) forms the cornerstone of treatment in locally advanced and metastatic prostate cancer (PCa). Since the growth hormone-insulin-like growth factor (GH-IGF-1) axis has been implicated in prostate tumorigenesis, we aimed to evaluate the association between IGF-1 and its binding proteins on outcomes in men with metastatic PCa treated with ADT, with or without docetaxel (D). We analyzed serum samples for IGF-1 and its family proteins from baseline, 6 months post-randomization, and at the time of progression in men enrolled to receive ADT +/- D in the phase 3 CHAARTED trial. The key outcomes were time to the development of castrate-resistant prostate cancer and overall survival (OS). About 560 patients had samples available for analysis. At 6 months, significant increases in IGF-BP1 (mean Δ+27.4%, P = 0.033), IGF-BP3 (mean Δ+10.3%, P < 0.001), and IGF-BP4 (mean Δ+31.1%, P < 0.001) were seen in the ADT + D group, while the ADT group showed an increase in IGF-BP3 (mean Δ+5.5%, P = 0.015). A higher IGF-1:IGF-BP1 ratio at baseline and after 6 months was associated with improved OS in both the ADT (baseline: hazard ratio (HR) = 0.77, P = 0.026; 6 months: HR = 0.83, P = 0.036) and ADT + D groups (baseline: HR = 0.78, P = 0.04; 6 months: HR = 0.81, P = 0.018). Patients with a log10IGF-1:IGF-BP1 ratio >1.3 at baseline had improved OS when meta-analyzed with data from a prior cohort (HR = 0.71). A higher baseline and 6-month IGF-1:IGF-BP1 ratio was associated with better OS. Further exploration of the IGF-1 axis will be important to assess its role as a predictive biomarker and to target this axis in therapeutic trials.

Finishing the “unfinished revolution”?: College‐educated mothers' resistance to intensive mothering

AbstractIntensive mothering, a classed and gendered practice optimally performed by stay‐at‐home mothers, is a dominant parenting ideology, particularly in developed societies with wide disparities in wealth. Ironically, in these societies, women tend to be well educated and have good employment prospects that are expected to free them from domestic obligations. Facing competing expectations shaped by the institutions of work and the family, how do college‐educated mothers consider ending or limiting their participation in the workforce or holding jobs while resolving the moral dilemma of being both a worker and a mother? We compared 33 college‐educated Hong Kong mothers engaged in different professions and constructed typologies that describe how intersecting ideologies of mothering and work shape work‐family arrangements. We paid special attention to mothers with strong commitment to their work, but with different ideologies about mothering. Some espouse the ideology of intensive mothering. Their belief in gender essentialism proved exhausting for them, both at work and at home. While away from home, these mothers supervised domestic helpers from their workplaces. Other women value their professions as emblematic of their identity as the perfect mother—an integrated form of mothering, thus feeling no guilt for delegating childcare responsibilities. We argue that given the entrenched gender inequality in workplaces and men's slow progress in doing their share of domestic work, the emergence of integrated mothering both rhetorically and in practice reflects women's striving to bring the “unfinished revolution” closer to the finish line.

MBOAT7 rs641738 (C>T) is associated with NAFLD progression in men and decreased ASCVD risk in elder Chinese population.

The MBOAT7 rs641738 (C>T) variant has demonstrated an association with non-alcoholic fatty liver disease (NAFLD) in both adult and pediatric patients, while few studies have been conducted in elderly populations. Hence, a case-control study was undertaken to assess their correlation in elderly residents in a Beijing community. A total of 1,287 participants were included. Medical history, abdominal ultrasound, and laboratory tests were recorded. Liver fat content and fibrosis stage were detected by Fibroscan. Genotyping of genomic DNA was performed using the 96.96 genotyping integrated fluidics circuit. Of the recruited subjects, 638 subjects (56.60%) had NAFLD, and 398 subjects (35.28%) had atherosclerotic cardiovascular disease (ASCVD). T allele carriage was associated with higher ALT (p=0.005) and significant fibrosis in male NAFLD patients (p=0.005) compared to CC genotype. TT genotype was associated with reduced risk of metabolic syndrome (OR=0.589, 95%CI: 0.114-0.683, p=0.005) and type 2 diabetes (OR=0.804, 95%CI: 0.277-0.296, p=0.048) in NAFLD population when compared to the CC genotype. In addition, TT genotype was also associated with reduced risk of ASCVD (OR=0.570, 95%CI:0.340-0.953, p=0.032) and less obesity (OR=0.545, 95%CI: 0.346-0.856, p=0.008) in the whole population. MBOAT7 rs641738 (C>T) variant was associated with fibrosis in male NAFLD patients. The variant also reduced risk of metabolic traits and type 2 diabetes in NAFLD and ASCVD risk in Chinese elders.

Abstract #1405106: The Associations of Total Testosterone with Nonalcoholic Fatty Liver Disease Inflammatory and Fibrotic Progression in Men with Type 2 Diabetes: A Cross-Sectional Study

Men with type 2 diabetes mellitus (T2DM) are predisposed to hypogonadism. Testosterone has an impact on metabolic disorders and it may play different roles in the progression of nonalcoholic fatty liver disease (NAFLD). We aim to investigate whether total testosterone is associated with NAFLD progression in men with T2DM. It is a cross-sectional study. A total of 1782 male participants with T2DM were enrolled from seven communities in Shanghai. Probable nonalcoholic steatohepatitis (NASH) was defined by the concurrence of NAFLD and metabolic syndrome (MetS). NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Multinomial logistic regression and ordinal logistic regression was used to measure the association of total testosterone (independent variable) and the progression category of NAFLD (dependent variable). In male, TT quartiles were negatively associated with probable NASH (Q1 vs. Q4 OR 2.07 95%CI, 1.31-3.28, P for trend=0.001) and inflammatory progression of NAFLD with OR of 1 SD increment of ln (TT) 0.81 (95% CI 0.72-0.92, P for trend<0.001), but positively with fibrotic progression (Q1 vs. Q4 OR 0.45, 95% CI 0.29-0.72, P for trend=0.001) with OR of 1 SD increment of ln(TT) 1.24 (95% CI 1.07-1.45). According to stratified analyses, for inflammatory progression, the interactions of age strata, duration of diabetes strata and dyslipidemia status with 1 SD increment of ln (TT) were significant (P for interaction 0.007,0.003 and 0.012 respectively); as for fibrotic progression, we found no interactoins (all P for interaction ≥0.05). In this population-based study including 1782 male patients with T2DM, we found that TT of male patients was negatively associated with probable NASH and NAFLD inflammatory progression but positively with fibrotic progression. Our results indicate that in male patients with T2DM, testosterone may play significant but opposite roles in inflammatory and fibrotic progression of NAFLD. Hence, understanding androgen hormone changes during T2DM and differentiating the stages of NAFLD may help clinicians personalize treatment strategy for male NAFLD patients with T2DM.

Blood microRNA-7 as a Progression Biomarker in men with Parkinson's disease (S37.006)

<h3>Objective:</h3> To investigate the use of microRNA-7-5p (miR-7-5p) as a potential biomarker for Parkinson9s disease (PD) progression. <h3>Background:</h3> Animal models have shown that MiR-7-5p regulates alpha-synuclein (α-syn) translation, transcription and autophagy, in addition to NLRP3 inflammasome activity. Furthermore, MiR-7-5p is diminished in the substantia nigra and the peripheral blood of PD patients. <h3>Design/Methods:</h3> Data was obtained at two longitudinal points (Baseline and 36 months) from 315 (208 male/107 female) drug-naïve PD patients and 160 (108 male /52 female) age- and sex-matched healthy controls (HC) from the Parkinson9s Progression Marker Initiative (PPMI). Whole blood miR-7-5p was longitudinally correlated with a) clinical assessment tools (MDS-UPDRS motor and total scores), b) markers of inflammation (NLRP3 mRNA, IL-1β mRNA, and NfL), and c) α-syn expression (α-syn mRNA, CSF α-syn). Analyses were done using rmcorr in R. <h3>Results:</h3> MiR-7-5p levels decreased by 17% in PD patients over 36 months. Longitudinal, Ln miR-7-5p had a strong negative correlation with MDS-UPDRS-motor and total scores in men with PD and with NfL for all PD subjects. There was no correlation between miR-7-5p and CSF α-syn protein in either group. <h3>Conclusions:</h3> Our data demonstrate the importance of gender differences in biomarker discovery and suggest a robust association between lower levels of miR-7-5p and markers of clinical progression in men with PD. These findings support the use of miR-7-5p as a progression biomarker, which could lead to a quantifiable tool for disease-modifying therapies. <b>Disclosure:</b> Dr. Schiess has nothing to disclose. Dr. Suescun has nothing to disclose. Dr. Block has nothing to disclose. Dr. Tharp has nothing to disclose. The institution of Prof. Ellmore has received research support from NIMH. The institution of Dr. Shahnawaz has received research support from American Parkinson Disease Association. The institution of Dr. Shahnawaz has received research support from NIH. The institution of Dr. Shahnawaz has received research support from Texas Alzheimer’s Research &amp; Care Consortium . Dr. Shahnawaz has received intellectual property interests from a discovery or technology relating to health care. Dr. Adams has stock in Medtronic.

Abstract 5261: Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression

Abstract Prostate cancer is the most common cancer in men. Commensurate with risk, current approaches to localized prostate cancer include prostatectomy, prostate radiation with or without radiation therapy or active surveillance. Recent data suggest that systemic anti-androgen therapy with enzalutamide reduced the risk of prostate cancer progression in men on active surveillance but was associated with considerable side effects. We developed a novel polymer-based drug delivery method to provide sustained localized drug administration of anti-androgens selectively to the prostate. In vitro and in vivo mouse and canine studies show that this drug eluting implant delivers sustained high prostate to plasma therapeutic anti-androgen levels for an anticipated range of 2 years while preventing accumulation of anti-androgens in the liver, lungs, heart and brain. We performed a proof of concept study in a canine prostate model implanting an 15mm x 1mm bicalutamide eluting implant into each lobe of the prostate. Bicalutamide levels in the prostate measured near the implant at 6 months were 3250 ± 1622 ng/g, n = 3 compared to 3809 ± 638 ng/g, n = 3 to those achieved at steady-state oral administration. Plasma and other off target levels were over 1000-fold lower in the implant cohort compared to oral administration: Plasma: 5.9 ± 0.2 ng/ml, liver: 11.3 ±4.3 ng/g, and brain: 5.4 ±0.8 ng/g versus plasma: 18170 ± 3820 ng/ml, liver: 35407 ±8510 ng/g, and brain: 8870 ±1797 ng/g. The implants were well tolerated without local toxicity and imaged easily with ultrasound. The design characteristics of the implant facilitates minimally invasive surgical implantation under standard image guidance and withstands the concomitant use of prostate radiation. This novel technology warrants future clinical exploration of prostate specific anti-androgen therapy for (neo)adjuvant therapy or in active surveillance. Tissue Bicalutamide oral (2m)(ng/g) Bicalutamide implant (6m)(ng/g) Plasma 18,170 (3820) 5.9 (0.2) Prostate 3,809 (638) 3,250 (1622) Liver 35,407 (8510) 11.3 (4.3) Cerebrum 8,870 (1797) 5.4 (0.8) Cerebellum 8,737 (1550) 6.2 (1.3) Spleen 7,727 (1288) 4.2 (0.9) Lung 27,013 (2896) 11.3 (4.3) Heart 11,737 (3491) 10.0 (1.9) Kidneys 17,413 (6581) 8.5 (2.0) Citation Format: Pujan Desai, Maithili Rairkar, Nela Pawlowska, Scott Thomas, Pamela N. Munster. Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5261.

MP38-18 INCORPORATING THE PRECISE RECOMMENDATIONS TO EVALUATE PROGRESSION IN MEN ON ACTIVE SURVEILLANCE FOR LOW-GRADE PROSTATE CANCER: WHICH PATIENTS WITH LOW PRECISE SCORE NEED A CONFIRMATORY BIOPSY?

You have accessJournal of UrologyCME1 Apr 2023MP38-18 INCORPORATING THE PRECISE RECOMMENDATIONS TO EVALUATE PROGRESSION IN MEN ON ACTIVE SURVEILLANCE FOR LOW-GRADE PROSTATE CANCER: WHICH PATIENTS WITH LOW PRECISE SCORE NEED A CONFIRMATORY BIOPSY? Riccardo Leni, Giorgio Gandaglia, Armando Stabile, Vito Cucchiara, Elio Mazzone, Giuseppe Rosiello, Daniele Robesti, Antony Pellegrino, Mattia Longoni, Pietro Scilipoti, Emanuele Zaffuto, Francesco De Cobelli, Brembilla Giorgio, Francesco Giganti, Francesco Montorsi, and Alberto Briganti Riccardo LeniRiccardo Leni More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Armando StabileArmando Stabile More articles by this author , Vito CucchiaraVito Cucchiara More articles by this author , Elio MazzoneElio Mazzone More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Daniele RobestiDaniele Robesti More articles by this author , Antony PellegrinoAntony Pellegrino More articles by this author , Mattia LongoniMattia Longoni More articles by this author , Pietro ScilipotiPietro Scilipoti More articles by this author , Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Francesco De CobelliFrancesco De Cobelli More articles by this author , Brembilla GiorgioBrembilla Giorgio More articles by this author , Francesco GigantiFrancesco Giganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003276.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The PRECISE score evaluates MRI characteristics for prostate cancer (PCa) patients with serial scans during active surveillance (AS). Although patients with reassuring characteristics at follow-up MRI (PRECISE 1-3) might have low risk of reclassification, a subgroup of these men should receive a re-biopsy. METHODS: We identified 207 PCa patients on AS (2016-2022) with at least two consecutive MRIs assessed with the PRECISE recommendations. Follow-up biopsies were performed at clinical or radiological progression. One radiologist reviewed the images and retrospectively assigned the PRECISE score. Reclassification was defined as an increase in biopsy grade group from baseline biopsy. Kaplan-Meier analyses assessed reclassification-free survival (RFS). Cox regression tested the prognostic impact of the first PRECISE score. Multivariable Cox regression tested predictors of reclassification among men with reassuring characteristics (PRECISE 1-3). RESULTS: Overall, 144 men had visible lesions (PI-RADS 3-5) at baseline scan. At a median follow-up of 43 months, 21 patients had MRI regression (PRECISE 1-2), 54 were stable without lesions (PRECISE 3), 98 were stable with lesions (PRECISE 3), and 34 had progression (PRECISE 4-5). The 5-year RFS for PRECISE 1-2, non-visible 3, visible 3, and 4-5 was 85%, 73%, 57%, and 52% (Figure 1a). A PRECISE score of 4-5 was an independent predictor of reclassification (HR 4.62, p=0.01). At two years from the second MRI, RFS was 91% for PI-RADS 1-3 and PSAD <0.15 ng/cc/cc, and 55% for either PI-RADS 4-5 or PSAD ≥0.15 ng/cc/cc (p<0.001, Figure 1b). At multivariable analyses suspicious findings at the second scan (PI-RADS 4-5, HR 3.47, p=0.001), and PSAD ≥0.15 ng/cc/cc (HR 2.17, p=0.03) were independently associated with reclassification among men with PRECISE 1-3 score. CONCLUSIONS: Up to 50% of men with PRECISE 1-3 MRIs and PSAD ≥0.15 ng/cc/cc or PI-RADS 4-5 lesions at first MRI experience reclassification at 2-year. Despite stable MRI, these patients should undergo a re-biopsy. In patients with signs of progression, or persistence of visible lesions, a more stringent follow-up is warranted. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e531 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Riccardo Leni More articles by this author Giorgio Gandaglia More articles by this author Armando Stabile More articles by this author Vito Cucchiara More articles by this author Elio Mazzone More articles by this author Giuseppe Rosiello More articles by this author Daniele Robesti More articles by this author Antony Pellegrino More articles by this author Mattia Longoni More articles by this author Pietro Scilipoti More articles by this author Emanuele Zaffuto More articles by this author Francesco De Cobelli More articles by this author Brembilla Giorgio More articles by this author Francesco Giganti More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...

MP11-06 THE PROGNOSTIC ROLE OF 68Ga-PSMA PET/CT AND THE IMPACT OF METASTASIS-DIRECTED THERAPY ON CANCER PROGRESSION IN MEN WITH BIOCHEMICAL RECURRENCE FROM PROSTATE CANCER. RESULTS FROM A LARGE, SINGLE INSTITUTION SERIES

MP11-06 THE PROGNOSTIC ROLE OF 68Ga-PSMA PET/CT AND THE IMPACT OF METASTASIS-DIRECTED THERAPY ON CANCER PROGRESSION IN MEN WITH BIOCHEMICAL RECURRENCE FROM PROSTATE CANCER. RESULTS FROM A LARGE, SINGLE INSTITUTION SERIES

Associations between plant-based diets and risk of disease progression in men with prostate cancer.

392 Background: Plant-based diets have been linked to multiple health benefits. For prostate cancer (PC), individual plant foods (e.g., tomatoes with lycopene) appear to reduce PC incidence and mortality. However, less is known about plant-based dietary patterns and PC survivorship. Methods: We examined 2038 men diagnosed with T1-T3a PC who were enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) and had completed a food frequency questionnaire (FFQ) a median of 31.5 months post-diagnosis. “Overall” and “healthy plant-based” dietary indices (PDI and hPDI, respectively,) were calculated from the FFQ. Multivariable Cox proportional hazards models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between plant-based diets and risk of PC progression (recurrence, secondary treatment, bone metastases, or PC death) as the primary outcome, and PC recurrence as a secondary outcome. We also examined whether age, stage, grade, and walking pace modified associations. Results: We observed 204 progression events (169 due to biochemical recurrence) over a median follow up of 7.4 years after the FFQ. Men in the highest quintile of PDI had a 52% lower risk of progression (HR 0.48, 95% CI 0.36-0.65, p-trend&lt;0.001) and a 53% lower risk of recurrence (HR 0.47, 95% CI 0.32-0.68, p-trend&lt;0.001) compared to men in the lowest quintile. Although the hPDI was not associated with PC progression or recurrence overall (p-trend &gt;0.05), men in the higher quintiles had statistically significant reductions in risk of recurrence. Among men &gt;65 years, greater consumption of a healthful plant-based diet was associated with lower risk of PC recurrence (HR 0.41, 95% CI 0.24-0.7, p-trend=0.03). In addition, among those with a brisk/fast walking pace (&gt;3 h/wk), men in the highest PDI quintile had a 56% (HR 0.33, 95% CI 0.26, 0.73) lower risk of PC progression, and a 59% (HR 0.41, 95% CI 0.25, 0.68) decrease in risk of PC recurrence. Grade and stage did not modify associations between either index and PC progression or recurrence. Conclusions: This study indicates that plant-based dietary patterns are associated with lower risk of PC progression and recurrence, particularly among older men and those who reported a higher intensity walking pace. PC survivors may be recommended diet and exercise counseling to improve clinical outcomes after PC diagnosis.

The prognostic role of 68Ga-PSMA PET/CT and the impact of metastasis-directed therapy on cancer progression in men with biochemical recurrence from prostate cancer. Results from a large, single Institution series

The prognostic role of 68Ga-PSMA PET/CT and the impact of metastasis-directed therapy on cancer progression in men with biochemical recurrence from prostate cancer. Results from a large, single Institution series