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"Chesnut, Gregory"
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Biomarkers of Aggressive Prostate Cancer at Diagnosis
by
York, Monica E.
,
Boehm, Brock E.
,
Kohaar, Indu
in
Antigens
,
Biomarkers
,
Biomarkers, Tumor - metabolism
2023
In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25–30%) representing an aggressive subtype (Gleason score 7–10) that is prone to metastatic progression. This fact, coupled with the criticism surrounding the role of prostate specific antigen in prostate cancer screening, demonstrates the current need for a biomarker(s) that can identify clinically significant CaP and avoid unnecessary biopsy procedures and psychological implications of being diagnosed with low-risk prostate cancer. Although several diagnostic biomarkers are available to clinicians, very few comparative trials have been performed to assess the clinical effectiveness of these biomarkers. It is of note, however, that a majority of these clinical trials have been over-represented by men of Caucasian origin, despite the fact that African American men have a 1.7 times higher incidence and 2.1 times higher rate of mortality from prostate cancer. Biomarkers for CaP diagnosis based on the tissue of origin include urine-based gene expression assays (PCA3, Select MDx, ExoDx Prostate IntelliScore, Mi-Prostate Score, PCA3-PCGEM1 gene panel), blood-based protein biomarkers (4K, PHI), and tissue-based DNA biomarker (Confirm MDx). Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.
Journal Article
Five-year survival of patients with late-stage prostate cancer: comparison of the Military Health System and the U.S. general population
2023
BackgroundWhile the 5-year survival rate for local and regional prostate cancer is nearly 100%, it decreases dramatically for advanced tumours. Accessibility to health care is an important factor for cancer prognosis. The U.S. Military Health System (MHS) provides universal health care to its beneficiaries, reducing financial barriers to medical care. However, whether the universal care translates into improved survival among patients with advanced prostate cancer in the MHS is unknown. In this study, we compared the MHS and the U.S. general population in survival of patients with advanced prostate cancer (stages III and IV).MethodsThe MHS patients (N = 5379) were identified from the Department of Defense’s (DoD) Automated Central Tumor Registry (ACTUR). Patients in the U.S. general population (N = 21,516) were identified from the Surveillance, Epidemiology, and End Results (SEER) programme. The two populations were matched on age, race, and diagnosis year.ResultsThe ACTUR patients exhibited longer 5-year survival than the matched SEER patients (HR = 0.74, 95% CI = 0.67–0.83), after adjustment for the potential confounders. The improved survival was observed for ages 50 years or older, both White patients and Black patients, all tumour stages and grades. This was also demonstrated despite the receipt of surgery or radiation treatment.ConclusionsMHS beneficiaries with advanced prostate cancer had longer survival than their counterparts in the U.S. general population.
Journal Article
Music As Medicine: The Impact of Music On Pain Reported After Surgery
2025
The impact of music on subjective reporting of pain and anxiety has been increasingly described in medical literature. Multimodal methods of alleviating postoperative pain and anxiety, including the use of live or recorded music in perioperative settings, have been shown to improve patient-reported pain levels and, in some studies, to result in decreased opioid usage. The overprescription of opioids after surgery can contribute to long-term abuse or trafficking of medications, and the use of non-opioid medications, alternative methods of pain relief, and environmental/auditory stimuli offer new mechanisms to promote safe opioid prescribing while improving both pain control and patient wellbeing. Soothing music has been shown to potentially lower heart rate, blood pressure, and breathing rate. As pain is a subjective sensation that has complex neural pathways, it is important to evaluate auditory inputs and their impact on these pathways and the subjective pain response.
Journal Article
Ancestry-Specific DNA Damage Repair Gene Mutations and Prostate Cancer
2025
This review is intended to reflect the currently available literature on both clinically significant germline mutations in DNA damage repair (DDR) genes as well as the importance of ancestral diversity in the pathogenesis of prostate cancer (PCa). The second most prevalent cancer worldwide in men is PCa, causing significant morbidity and mortality in its advanced stage. Emerging data highlight the substantial role of germline mutations of DDR genes in PCa pathogenesis, especially in progression to aggressive forms of the disease. Germline genetic testing is recognized as a necessary tool for efficient, individualized patient care. NCCR guidelines recommend inquiring about the family history of PCa and known germline variants and, if indicated, proceeding with germline multigene testing followed by post-test genetic counseling. Depending on the germline mutations in HR repair genes or in MMR genes, specific treatment options may provide clinical benefit. We will discuss specific germline mutations that are involved in PCa progression and prognosis in racially diverse populations.
Journal Article
Understanding Racial Disparities in Prostate Cancer: A Multifaceted Approach
by
Cobbs, Charles
,
Shafi, Ayesha A.
,
Chesnut, Gregory T.
in
access to healthcare
,
Biomarkers
,
Biomedical research
2025
Prostate cancer (PCa) remains a significant public health challenge in the United States, disproportionately affecting African American (AA) men, who face higher incidence rates, more aggressive disease, and elevated mortality compared to Caucasian American (CA) men. This review explores the multifactorial underpinnings of these disparities, integrating genomic, socioeconomic, environmental, and systemic contributors. Genomic analyses reveal that AA men harbor distinct molecular alterations, including higher frequencies of FOXA1, BRAF, and CHD1 mutations, as well as DNA damage repair defects, highlighting the critical need for population‐specific precision medicine. Immune‐oncologic pathways and stromal interactions within the tumor microenvironment further underscore biological differences driving aggressive disease phenotypes. Concurrently, adverse social determinants—including limited access to care, lower PSA screening rates, delayed treatment, medical mistrust, and underrepresentation in clinical trials—contribute to poorer outcomes. Despite these challenges, evidence from equal‐access healthcare systems indicates that when provided equitable treatment, AA men can achieve outcomes comparable to or better than their CA counterparts. This review emphasizes actionable strategies to reduce disparities, including increasing AA representation in clinical trials, enhancing culturally competent patient‐provider communication, improving access to early detection and high‐quality care, and expanding community‐based outreach initiatives. A holistic, interdisciplinary approach is essential to dismantle systemic barriers and achieve health equity in prostate cancer outcomes. Prostate cancer disproportionately affects African American men. Genomic studies reveal distinct mutational burdens in AA men, highlighting the need for race‐specific therapies. However, limited representation in research hinders progress. Addressing disparities requires diverse clinical trials, improved access to care, and tackling socioeconomic inequities.
Journal Article
Ten-Year Trends in Digital Rectal Exam Results and Prostate Cancer Detection: Insights from the PLCO Trial
2025
Digital Rectal Examination (DRE) remains an important preventive measure in primary care settings, but a single screening may produce false positives. We sought to explore the trend of abnormal DRE (suspicious and non-suspicious) findings in men with and without prostate cancer.
We utilized data on 34,756 men (1,713 Black and 33,043 White) from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Serial DRE measurements were collected over a 10-year follow-up prior to prostate cancer diagnosis. DRE results were categorized as: normal, abnormal non-suspicious, and suspicious DRE. Generalized estimating equation (GEE) model was used to evaluate the trend in suspicious DRE findings over time.
After adjusting for potential confounders, the interaction term of time to diagnosis and prostate cancer status was statistically significant indicating a 23.0% increase in the odds of suspicious DRE (OR=1.230, 95% CI: 1.193-1.268) and a 5.2% increase in the odds of non-suspicious DRE (OR=1.052, 95% CI: 1.033-1.072) per year closer to diagnosis. The positive predictive value of abnormal suspicious DRE was 4.74% at 10 years prior to diagnosis, 36.82% at 5 years prior to diagnosis, 60.63% at 2 years prior to diagnosis, and 90.48% at diagnosis. Older age and benign prostatic hyperplasia (BPH) were more likely to have increased suspicious DRE findings.
Our results suggest that incorporating serial DRE findings into screening strategies may reduce false positives and improve early detection of clinically significant prostate cancer. This study demonstrates a rising probability of abnormal DRE findings in men with prostate cancer, whereas no temporal change was observed in men without prostate cancer.
Journal Article
General Obesity and Prostate Cancer in Relation to Abdominal Obesity and Ethnic Groups: A US Population-Based Cross-Sectional Study
2024
Research suggests inconsistent evidence regarding the association between general obesity and prostate cancer among men in the United States. This study aimed to examine whether the association between general obesity and prostate cancer is influenced by abdominal obesity and ethnic groups.
The study utilized data from the National Health and Nutrition Examination Survey (NHANES). The analysis was restricted to non-Hispanic men (10,683 White and 6,020 Black). Obesity was defined as body mass index (BMI) ≥30 and abdominal obesity as waist circumference (WC) ≥102 cm.
No significant difference was identified in the overall prevalence of prostate cancer between obese and non-obese (2.14% vs 2.25%, P = 0.678). When both obesity measures were combined, the general and abdominal obesity category was associated with a significant increase in the odds of prostate cancer in Black men [odds ratio (OR) = 1.49, 95% confidence interval (CI) (1.09, 2.04)], but not in White men [OR = 1.29, 95% CI (0.91, 1.82)]. In both Black [OR = 2.46, 95% CI (1.48, 4.06)] and White men [OR = 1.60, 95% CI (1.16, 2.21)], abdominal obesity was associated with significant increase in the odds of prostate cancer.
The association between general obesity and prevalence of prostate cancer depends on abdominal obesity and ethnic groups. Our study utilized a nationally representative survey and emphasized the potential of combined effect of general and abdominal obesity as a modifiable factor to decrease racial disparity in prostate cancer screening and poor outcomes.
Journal Article
Hematological Toxicities with PARP Inhibitors in Prostate Cancer: A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials
by
Bowling, Gartrell C.
,
Swargaloganathan, Piragash
,
Madan, Ravi A.
in
Adverse events
,
Androgens
,
Anemia
2023
Background: Poly ADP-ribose polymerase inhibitors (PARPis) are an important class of therapeutics for metastatic castration-resistant prostate cancer (mCRPC). Unlike hormone-based treatments for mCRPC, PARPis are not without drug-related hematological adverse events. Objective: To review the evidence on hematological toxicities, including anemia, thrombocytopenia, and neutropenia from PARPis in prostate cancer. Study Methodology: A systematic review and meta-analysis using the PRISMA guidelines was performed for phase II and III randomized controlled trials (RCTs) of PARPis in prostate cancer. PubMed, Embase, and Ovid All EBM reviews—Cochrane were queried from inception to 9 June 2023. The Mantel–Haenszel method was used to report risk ratios (RR) and 95% confidence intervals (CI) for all-grade and high-grade anemia, thrombocytopenia, and neutropenia toxicities. Results: The systematic review retrieved eight phase II and III RCTs; specifically, eight were included in the anemia, five in the all-grade thrombocytopenia and neutropenia, and four in the high-grade thrombocytopenia and neutropenia outcomes. Compared to a placebo and/or other non-PARPi treatments, PARPi use was associated with an increased risk of all-grade anemia (RR, 3.37; 95% CI, 2.37–4.79; p < 0.00001), thrombocytopenia (RR, 4.54; 95% CI, 1.97–10.44; p = 0.0004), and neutropenia (RR, 3.11; 95% CI, 1.60–6.03; p = 0.0008). High-grade anemia (RR, 6.94; 95% CI, 4.06–11.86; p < 0.00001) and thrombocytopenia (RR, 5.52; 95% CI, 2.80–10.88; p < 0.00001) were also associated with an increased risk, while high-grade neutropenia (RR, 3.63; 95% CI, 0.77–17.23; p = 0.10) showed no significant association. Subgroup stratification analyses showed differences in various all-grade and high-grade toxicities. Conclusion: PARPis were associated with an increased risk of hematological AEs. Future studies with more pooled RCTs will enhance this understanding and continue to inform patient–physician shared decision-making. Future studies may also have a role in improving the current management strategies for these AEs.
Journal Article
Germline Mutations and Ancestry in Prostate Cancer
by
Isensee, Kathryn A
,
Kohaar, Indu
,
Bataba, Eudoxie
in
Clinical medicine
,
DNA damage
,
DNA repair
2024
Purpose of ReviewProstate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European and Asian ancestry. Germline mutations and, in particular, mutations in DNA damage repair genes (DDRGs) have been implicated in the pathogenesis of prostate cancer. This review intends to discuss the implication of ancestry on prostate cancer, specifically in regard to lack of diversity in genomic and genetic databases and the ability of providers to properly counsel patients on the significance of cancer genetic results.Recent FindingsAncestral differences in prostate cancer-associated DDRG germline mutations are increasingly recognized. Guidelines for treatment by the National Comprehensive Cancer Network® (NCCN®) support germline testing in certain patients, and a myriad of genetic testing panels for DDRG mutations are now available in clinical practice. However, the consensus among providers on what genes and mutations to include in the genetic tests has evolved from experience from men of European ancestry (EA). Gaps in ancestry-informed clinical practice exist in genetic risk assessment, implementation of screening, counseling, guiding recommendations, treatment, and clinical trial enrollment.SummaryThe lack of diversity in tumor genomic and genetic databases may hinder ancestry-specific disease-predisposing alterations from being discovered and targeted in prostate cancer and, therefore, impede the ability of providers to accurately counsel patients on the significance of cancer genetic test results.
Journal Article
The effect of race on treatment patterns and subsequent health-related quality of life outcomes in men undergoing treatment for localized prostate cancer
by
Posielski, Natasza M
,
Jiang, Jiji
,
Elsamanoudi, Sally
in
African Americans
,
Bowel disease
,
Cancer surgery
2023
IntroductionRacial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT).MethodsMen diagnosed with PCa from 2007–2017 in the Center for Prostate Disease Research Database were identified. HRQoL was evaluated using Expanded PCa Index Composite and SF-36 Health Survey.ResultsIn 1006 men with localized PCa, 223 (22.2%) were AA (mean follow up 5.2 yrs). AA men with low-risk disease were less likely to undergo AS (28.5 vs. 38.8%) and more likely to undergo XRT (22.3 vs. 10.6%) than non-AA men, p < 0.001. In intermediate-risk disease, AA received more XRT (43.0 vs. 26.9%) and less RP (50.5 vs 66.8%), p = 0.016. In all men, RP resulted in worse urinary function and sexual HRQoL compared to AS and XRT. Bowel HRQoL did not vary by treatment in AA men, however, in non-AA men, XRT resulted in worse bowel scores than AS and RP. HRQoL was then compared for each treatment modality. AA men had worse sexual bother (p = 0.024) after RP than non-AA men, No racial differences were found in urinary, bowel, hormonal, or SF-36 scores for men undergoing AS, RP or XRT.ConclusionAA men are less often treated with AS for low-risk disease and are more likely to undergo XRT. AA men experience worse sexual bother after RP, however, the effect of XRT on bowel symptoms is worse in non-AA men.
Journal Article