Family History Of Prostate Cancer Research Articles

Lethal Prostate Cancer in Mexico: Data from the Can.Prost Mexican Registry and a Project for Early Detection.

Epidemiological data are crucial for adopting primary and secondary prevention strategies and to develop screening protocols against prostate cancer (PCa). Despite the comprehensive characterization of PCa across White and Black men, there is a lack of data from the Mexican population. This manuscript presents data from the Can.Prost registry that captures PCa trends over the past two decades in Mexico City; furthermore, we aimed to compare clinical differences and oncological outcomes before and after the promotion of early detection actions through a campaign against PCa that occurred in 2014. A retrospective observational study on newly diagnosed Mexican PCa patients was carried out at the Instituto Nacional de Cancerología (INCan) in Mexico City. During 2014 and 2015, a project for the early diagnosis of PCa ("OPUS program") was launched in the aforementioned tertiary hospital. Starting at the age of 45 years, all men were invited for a PSA measurement and a specialist urologist consultation. All individuals with clinical or biochemical suspicion of PCa (PSA > 4 ng/mL), in the context of age and prostate volume, underwent ultrasound-guided transrectal prostate biopsy. Then, patients with pathologically confirmed prostate cancer were stratified according to the year of diagnosis: Group A accounted for those diagnosed between 2000 and 2014 and Group B for those patients diagnosed in the timeframe of 2015-2021. Comparisons of PCa characteristics, treatment modalities and oncologic outcomes between Group A and B were performed. Overall, we collected data from 2759 PCa patients from 2000 to 2021. The median PSA at baseline was 32 ng/mL, and 25% had a family history of PCa. Overall, 25.8% were asymptomatic and 46% had a non-metastatic presentation. After the OPUS campaign, PSA at diagnosis was significantly lower across all age groups. The incidence of PCa diagnosis in asymptomatic men was higher (31.4% vs. 19.9%) and a higher proportion of men were diagnosed with organ-confined, palpable disease (46% vs. 28%) (p < 0.001). The rate of patients eligible for active/radical treatment was higher after the OPUS campaign (patients who received surgery increased from 12.78% to 32.41%; patients who underwent radiation increased from 28.38% to 49.61%). The proportion of patients diagnosed with non-clinically significant disease was negligible and remained stable across time. PCa in Mexican patients displays aggressive features at diagnosis, whereas the rate of non-significant disease is negligible. The introduction of early detection strategies may lead to lower symptomatic and metastatic PCa and higher opportunities for radical treatment. This emphasizes the need for public awareness and for adjustment of screening strategies to the peculiarities of the Mexican population.

Perspectives and Misconceptions of an Online Adult Male Cohort Regarding Prostate Cancer Screening.

Congruent with most guideline publishers, the Canadian Urological Association (CUA) recommends shared decision-making (SDM) on PSA screening (PSAS) for prostate cancer (PCa) following a discussion of its benefits and harms. However, there are limited data on how the general male population feels about these topics. A survey was completed by 906 male-identifying participants (age > 18) recruited via Amazon Mechanical Turk (MTurk), which is a crowdsourcing platform providing minimal compensation. Participants answered questions regarding demographics (15), personal/family history (9), PCa/PSA knowledge (41), and opinions regarding PSAS (45). The median age was 38.2 (SD = 12.0), with 22% reporting a family history of PCa and 20% reporting personally undergoing PSAS. Although most participants had heard of PCa (85%) and that they could be screened for it (81%), they generally did not feel knowledgeable about PCa or PSAS guidelines. Most want to talk to their clinician about PCa and PSAS (74%) and are supportive of SDM (48%) or patient-centered decision-making (25%). In general, participants thought PSAS was still worthwhile, even if it led to additional testing or side effects. Similarly, participants thought higher-risk patients should be screened earlier (p < 0.001). A number of misconceptions were evident in the responses. Men approaching the age of PSAS do not feel knowledgeable about PCa or PSAS and want their clinician to discuss these topics with them. The majority believe in PSAS and would like to undergo this screening following SDM. Clinicians also have a role in correcting common misconceptions about PCa.

Real-world genome profiling in Japanese patients with pancreatic ductal adenocarcinoma focusing on HRD implications.

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges due to its high mortality, making it a critical area of research. This retrospective observational study aimed to analyze real-world data from comprehensive genome profiling (CGP) of Japanese patients with PDAC, mainly focusing on differences in gene detection rates among panels and the implications for homologous recombination deficiency (HRD) status. This study enrolled 2568 patients with PDAC who had undergone CGP between June 2019 and December 2021 using data from the nationwide Center for Cancer Genomics and Advanced Therapeutics database. Two types of CGP assays (tissue and liquid biopsies) were compared and a higher detection rate of genetic abnormalities in tissue specimens was revealed. HRD-related gene alterations were detected in 23% of patients, with BRCA1/2 mutations accounting for 0.9% and 2.9% of patients, respectively. Treatment outcome analysis indicated that patients with BRCA1/2 mutations had a longer time to treatment discontinuation with FOLFIRINOX than gemcitabine plus nab-paclitaxel as first-line therapy (9.3 vs. 5.6 months, p = 0.028). However, no significant differences were observed in the treatment response among the other HRD-related genes. Logistic regression analysis identified younger age and family history of breast, prostate, and ovarian cancers as predictive factors for HRD-related gene alterations. Despite the lack of progression-free survival data and the inability to discriminate between germline and somatic mutations, this study provides valuable insights into the clinical implications of CGP in Japanese patients with PDAC. Further research is warranted to optimize panel selection and elucidate the efficacy of platinum-based therapies depending on the HRD status.

Abstract C123: Exploring the cancer phenotype of a potential CDKN2A founder variant, c.146T&amp;gt;C (p.Ile49Thr), in Hispanic/Latinos of predominately Mexican ancestry

Abstract BACKGROUND: CDKN2A germline pathogenic/likely pathogenic variants (PVs) cause familial atypical multiple mole melanoma syndrome, which increases melanoma (MEL) and pancreatic cancer (PC) risk. The interpretation of genetic test results can be complicated by discordant variant classifications. CDKN2A c.146T&amp;gt;C (ClinVar ID:127523) is such a variant and is classified as likely pathogenic at some laboratories and as uncertain at others. Furthermore, the variant frequency in Hispanic/Latinos (H/Ls) is higher than typically expected for a PV in CDKN2A and some functional studies support that it is a PV. METHODS: Genetic counseling databases at various institutions were queried for demographic, personal and family cancer history data for individuals with known PVs in CDKN2A, with c.146T&amp;gt;C, and c.–2G&amp;gt;A (ClinVar ID:141245), a benign CDKN2A variant (BV) seen in H/Ls to serve as a comparator. The association between personal and/or family history of PC and/or MEL and demographic/clinical characteristics was tested using Fischer exact test, Chi-square test, and post-hoc test with ANOVA. Odds ratios were calculated with multinomial logistic regression. RESULTS: Overall, 219 individuals were identified; 109 with c.146T&amp;gt;C, 60 with other CDKN2A PVs, and 50 with the BV; 82% were female, 76% H/L, and 70% had a personal cancer history – 18% (n=27) had MEL and 10% (n=16) had PC. By variant group, 99% (c.146T&amp;gt;C) and 96% (BV) were H/L; 85% and 84% of Mexican ancestry, respectively. MEL was reported in 38% (n=22) of other PVs, 5% (n=5) of c.146T&amp;gt;C, and not at all in the BV group. Those with c.146T&amp;gt;C were 92% less likely to have MEL than other CDKN2A PVs (p&amp;lt;0.001), with no difference in mean age at diagnosis, 32y vs. 40y, respectively (p=0.71). Seven (12%) of other PVs had PC compared to 6% (n=7) of c.146T&amp;gt;C and 4% (n=2) of the BV. While this difference was not significant (p=0.27), the mean age at diagnosis in c.146T&amp;gt;C was significantly younger than other PVs (32y vs. 71y; p=0.02). When including family history, those with c.146T&amp;gt;C were 80% less likely to have a personal AND family history of MEL than other PVs (p&amp;lt;0.001), but the odds of having both a personal AND family history of PC was not significantly different (p=0.52). CONCLUSION: In the largest CDKN2A c.146T&amp;gt;C study (n=109) to date, MEL was significantly less frequent in individuals with this variant compared to other PVs CDKN2A. A similar, non-significant, trend was seen for PC. Notably, individuals with c.146T&amp;gt;C who developed PC presented at a significantly younger age than individuals with other CDKN2A PVs. The presence of c.146T&amp;gt;C in H/Ls of mostly Mexican ancestry suggests it may be a founder variant. While more research is needed to further refine cancer penetrance and associations, the conservative approach is to manage c.146T&amp;gt;C as per CDKN2A PV guidelines. Given the frequency of this variant in genomic databases, clarifying clinical impact is vital for risk- appropriate management and to reduce existing cancer disparities faced by many H/Ls. Citation Format: Daisy Hernandez, Ashlie Browning, Amber Gemmell, Karlena Lara-Otero, Mariana Niell-Swiller, Kathyrn A. Mraz, Amie Blanco, Yvonne Cardona, Emmeline Chang, Jacob Comeaux, Julie O. Culver, James M. Ford, Natalia Gutierrez, Daniella Kamara, Beth Y. Karlan, Ming Li, Jacqueline Mersch, Qi Nie, Maria L. Wei, Charité N. Ricker. Exploring the cancer phenotype of a potential CDKN2A founder variant, c.146T&amp;gt;C (p.Ile49Thr), in Hispanic/Latinos of predominately Mexican ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C123.

Abstract A031: Methylomic Biomarkers Associated with Prostate Cancer in Black Men

Abstract Introduction: The prostate cancer (PCa) disparity remains the highest cancer disparity in the US, with Black men facing an estimated 78% higher incidence and 230% higher mortality than White men. However, current understanding of risk factors for PCa such as socioeconomic status (SES), diet, and genetics cannot fully explain these disparities. Our objective is to examine DNA methylation (DNAm) markers in a cohort of Black men and assess their associations with PCa status. Methods: We randomly selected 100 Black men for DNAm profiling (50 cases diagnosed with clinically significant (Gleason Grade 3+) prostate cancer and 50 age-matched controls) from two larger cohorts. The cohorts recruited 400 Black men who were newly diagnosed with sporadic PCa as well as 400 controls matched on age and race. All men were 40-79 at recruitment and were enrolled from urology clinics at five Chicago-area medical institutions. All PCa cases underwent a transrectal prostate biopsy for abnormal prostate-specific antigen (PSA) or digital rectal exam and had a histologically confirmed prostate cancer and were not previously diagnosed with PCa. All men in the control group had been recruited from community prostate cancer screening events or were referred to participating urology clinics and had a negative prostate biopsy for a PSA &amp;lt;10ng/ml and were not diagnosed with PCa for 2 years of follow-up. Men with prior PCa diagnosis or conditions known to affect PSA levels were excluded. After enrollment and informed consent, all men provided demographic and lifestyle data via three questionnaires, followed by venipuncture for DNA collection. These specimens were obtained using buffy coat extraction after red blood cell lysis, centrifugation, and pipetting off the overlying plasma and buffy coat for freezing followed by Illumina EPIC arrays for DNAm assays. We examined DNAm markers in gene promoter regions associated with PCa using logistic regression and adjusted for multiple testing using Bonferroni correction. All models controlled for age, BMI, smoking status, first degree family history of PCa, blood cell types, and technical control variables. Results: We found 2,180 CpG sites in gene promoter regions associated with any PCa in this population. The top ten strongest associations identified in our models include loci on genes that have already been associated with prostate cancer progression (MAFG, FAM65B, OSM, PRKAG2), risk (SLC11A1, LAT), and metastasis (S1PR4) as well as immune system functioning (RAP1GAP2). Conclusions: Our initial findings suggest that DNAm markers may be useful predictors of clinically significant PCa status among Black men. Additional research is currently ongoing to expand the sample size of the DNAm profiling and to explore links between these loci and social determinants of health, as well as associations with more advanced (i.e., higher Gleason Grade) PCa. Citation Format: Brian T. Joyce, Yishu Qu, Jun Wang, Kai Zhang, Zequn Sun, Lifang Hou, Adam B. Murphy. Methylomic Biomarkers Associated with Prostate Cancer in Black Men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A031.

Prevalence and spectrum of germline pathogenic variants in cancer susceptibility genes among mexican patients with exocrine pancreatic cancer

BackgroundAlthough universal germline genetic testing is recommended for patients with exocrine pancreatic cancer (PC), access to genetic testing remains limited in low- and middle-income countries. This study aims to narrow the gap in our understanding of the spectrum of germline pathogenic and likely pathogenic variants (PVs) in cancer susceptibility genes in the Mexican population. MethodsThe landscape of PVs in cancer susceptibility genes was identified by next-generation sequencing multigene panel assays among patients with PC who were enrolled in the Clinical Cancer Genomics Community Research Network prospective registry in Mexico City. ResultsFrom August 2019 to April 2023, 137 patients underwent genetic testing. The median age at diagnosis was 60 years (range 36–85), 58.4 % were women, and 38.7 % were metastatic at diagnosis. The frequency of germline PVs was 16 % (n = 22): ATM 36.4 % (n = 8), CDKN2A/p16INK4A 27.3 % (n = 6), BRCA2 9.1 % (n = 2), PALB2 9.1 % (n = 2), CHEK2 9.1 % (n = 2), TP53 4.5 % (n = 1), and NF1 4.5 % (n = 1). Additionally, 2 carriers of monoallelic germline variants in MUTYH were identified. No significant differences were observed between carriers and non-carriers in terms of family history of pancreatic cancer. ConclusionsWe identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.

Machine learning to predict completion of treatment for pancreatic cancer.

Chemotherapy enhances survival rates for pancreatic cancer (PC) patients postsurgery, yet less than 60% complete adjuvant therapy, with a smaller fraction undergoing neoadjuvant treatment. Our study aimed to predict which patients would complete pre- or postoperative chemotherapy through machine learning (ML). Patients with resectable PC identified in our institutional pancreas database were grouped into two categories: those who completed all intended treatments (i.e., surgery plus either neoadjuvant or adjuvant chemotherapy), and those who did not. We applied logistic regression with lasso penalization and an extreme gradient boosting model for prediction, and further examined it through bootstrapping for sensitivity. Among 208 patients, the median age was 69, with 49.5% female and 62% white participants. Most had an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. The PC predominantly affected the pancreatic head. Neoadjuvant and adjuvant chemotherapies were received by 26% and 47.1%, respectively, but only 49% completed all treatments. Incomplete therapy was correlated with older age and lower ECOG status. Negative prognostic factors included worsening diabetes, age, congestive heart failure, high body mass index, family history of PC, initial bilirubin levels, and tumor location in the pancreatic head. The models also flagged other factors, such as jaundice and specific cancer markers, impacting treatment completion. The predictive accuracy (area under the receiver operating characteristic curve) was 0.67 for both models, with performance expected to improve with larger datasets. Our findings underscore the potential of ML to forecast PC treatment completion, highlighting the importance of specific preoperative factors. Increasing data volumes may enhance predictive accuracy, offering valuable insights for personalized patient strategies.

How a population-based cohort of men estimate lifetime risk of prostate cancer in a survey before entering a prostate cancer screening trial in Sweden?

ObjectivesInvestigating men’s perceived lifetime risk of prostate cancer.DesignSurvey-based study to men invited for prostate-specific antigen (PSA) screening in the GÖTEBORG-2 trial between September 2015 and June 2020.Setting38 775 men in...

Targeted Prostate Health Checks, a novel system to identify men with prostate cancer-A pilot study.

The objective of this study is to report the pilot phase of the Targeted Prostate Health Check programme that aims to identify men in the Surrey and Sussex region who have prostate cancer and who failed to be detected during the Covid era. Men aged 50 to 70, or 45 to 70 if Black or with a family history of prostate cancer, were identified from participating general practitioner (GP) records. Short message service (SMS) texts invited men to visit www.talkprostate.co.uk for information on prostate cancer and give consent to prostate-specific antigen (PSA) checks coordinated by a third-party virtual healthcare provider. Elevated age-related PSA levels, or levels below age-related thresholds but at 3ng/mL or more, triggered referral to a rapid access urology clinic. GPs were informed of the results. From 1842 text messages inviting 1549 people, 544 men consented to a PSA check. From 500 phlebotomy appointments, 485 (30% of invited men) took the PSA test of whom 68 (14%) were referred with an elevated PSA. After clinical review with multiparametric magnetic resonance imaging (mp-MRI), 22 patients underwent transperineal biopsies, and prostate cancer was detected in 18 men of whom 17 (95%) had clinically significant cancer. Our Targeted Prostate Cancer Health Check system identifies men at risk without burdening primary care. Awareness on prostate cancer risk was raised in 1549 invited men, half of whom were further educated via the registration website. One third of invited men were checked in whom clinically significant prostate cancer was found in 3.5%.

Prevalence of CDKN2A, CDK4, POT1, BAP1, MITF, ATM, and TERT Pathogenic Variants in a Single-Center Retrospective Series of Patients With Melanoma and Personal or Family History Suggestive of Genetic Predisposition.

Approximately 20%-45% of familial melanoma (FM) cases are associated with genetic predisposition. This single-center retrospective study aimed to assess the frequency of pathogenic variants (PV) in the main melanoma-predisposing genes in patients with cutaneous melanoma and investigate the clinical predictors of genetic predisposition. Patients included were those diagnosed with cutaneous melanoma at the Dermatology Unit of the University Hospital of Verona, Italy, from 2000 to 2022, presenting at least one of the followings: multiple melanomas (≥ 3); personal/family history of pancreatic cancer (PC) (up to 2nd-degree relatives); ≥ 2 1st-degree relatives with melanoma; ≥ 1 1st-degree relatives with early-onset (<45 years) melanoma and tested for CDKN2A, CDK4, POT1, BAP1, MITF, ATM, and TERT. During the study period, 35 out of 1320 patients (2.7%) underwent genetic testing. Four patients (11.4%) harbored a PV in a melanoma-predisposing gene, three in CDKN2A (8.6%), and one in MITF (2.9%). Variants currently classified as being of unknown clinical significance (VUS) were detected in CDKN2A (N = 1), MITF (N = 1), and ATM (N = 2). Family history of PC and ≥5 melanomas, personal history of ≥50 nevi, and ≥4 melanomas were significantly associated with PV in tested genes (P < 0.05). The prevalence of PV in predisposing genes in FM was lower than previously reported in Italian registries. Possible reasons include deleterious variants in untested intermediate/low-penetrance genes or yet-to-be-discovered high-penetrance genes and environmental risk factors. A family history of PC, a high number of nevi and melanomas predict a monogenic predisposition to melanoma.

Does the type of the previous biopsy affect the fusion prostate biopsy results?

BackgroundIt has been more than a decade since fusion prostate biopsy (FPB) has been used in the diagnosis of prostate cancer (PCa). Therefore, patients with a previous history of negative FPB and ongoing suspicion of PCa are beginning to emerge. This study investigated whether the first biopsy type (standard or fusion) should be effective in deciding on a second biopsy. MethodsMale patients aged 40–75, with a serum prostate-specific antigen (PSA) value of less than 10 ng/mL and a negative biopsy history within the last 24 months, who underwent FPB in our clinic due to persistent PSA elevation and/or suspicious multiparametric prostate magnetic resonance imaging (MpMRI) findings were included to the study. Patients were divided into groups according to the type of first biopsy (Group 1; those whose first biopsy was FPB, Group 2; those whose first biopsy was standard prostate biopsy). Some demographic and clinical data of the groups, as well as PCa detection rates, were compared. A p value of less than 0.05 was considered statistically significant. ResultsA total of 275 patients (Group 1: 84, Group 2: 191) were included in this study. The groups were similar in terms of age, PSA values before the first biopsy, PSA values before the second biopsy, family history of PCa, and prostate volume. PCa was detected at a higher rate in Group 2 than Group 1 (23% vs 15.5%, p = 0.044). ConcluisonThe data obtained from this study indicate that the type of initial biopsy should be taken into account when deciding on FPB in secondary patients with a previous negative biopsy history.

A case-cohort study of per- and polyfluoroalkyl substance concentrations and incident prostate cancer in the cancer prevention Study-II LifeLink cohort study

IntroductionPer- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics. MethodsWe conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998–2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline–June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption). ResultsProstate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88–1.59)] and PFOS [HR (95% CI): 1.18 (0.89–1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02–2.31) and PFOS 1.62 (1.08–2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage. ConclusionsOur findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation.

Evaluation of a Rapid PSA Test for Prostate Cancer Screening

Abstract Background Prostate-specific antigen (PSA) is a protein produced by normal prostate cells. This enzyme participates in the dissolution of the seminal fluid coagulum and plays an important role in fertility. The highest amounts of PSA are found in the seminal fluid; some PSA escapes the prostate and can be found in the serum. Aim of the Work to detemine accuracy, sensitivity, specificity of one-step PSA test (Fortel Test®) “FDA approved” for screening for prostate cancer in comparison to a conventional quantitative assay. Patients and Methods This Prospective cohort clinical study was conducted at tertiary care hospital at Urology Department, Outpatient clinic, Faculty of Medicine, Ain Shams University from January 2022 till June 2022 and performed on a total of 150 patients who were above 50 years old or above 40 years old with family history of prostate cancer. Results Our study results revealed that Fortel PSA test had high Sensitivity (97.2%), specificity (96.2%), positive predictive value (95.9%) and negative predictive value (97.4%) in accuracy of screening of prostatic cancer. Conclusion The Fortel PSA test is a simple, feasible, and reproducible tool for PC screening. The lower cost, ease of handling, and rapid procedure could make this test useful in the general practitioner or urologist office setting as well as for mass primary PC screening.

Current Practices in Genetic Testing for Prostate Cancer: The Indian Scenario.

Despite genetic testing being recommended by international guidelines for the selection of targeted therapy for prostate cancer (PCa), limited data are available on genetic testing for PCa in India. The objective is to understand the current genetic testing practice pattern for PCa in India. A panel of 9 experts developed and validated a premeeting online questionnaire comprising 12 objective questions. The questionnaire was circulated from February 2022 to May 2022 among medical oncologists and uro-oncologists across pan-India, followed by response collection over 3 months. Descriptive statistics were used to summarize results and concluding statements were formulated on current genetic testing practice patterns for PCa. A total of 103 responses were received. Genetic testing was advised by 35.9% of the participants in <5% of patients with PCa. Patients with a family history of PCa (88.3%) were most commonly referred for genetic testing. Nearly half (50.2%) of the participants routinely tested for homologous recombination repair (HRR) genes; 52% used blood and tissue as the most preferred specimen for performing genetic testing and 44.7% followed the testing sequence of tumor tissue followed by blood. Major barriers to genetic testing were affordability and scarcity of genetic counselors, while a major change could be brought by making it cost-effective and improving access to medication. We observed a lower prescription frequency of genetic testing for the HRR gene across pan-India. Improving the quality and access to genetic testing and the availability of cost-effective-targeted therapies will aid in delivering personalized care to patients with metastatic PCa.

Healthy lifestyle and prostate cancer risk in the Million Veteran Program.

This study aims to assess the impact of healthy lifestyle on prostate cancer (PCa) risk in a diverse population. Data for 281,923 men from the Million Veteran Program (MVP), a nationwide, health system-based cohort study, were analyzed. Self-reported information at enrollment included smoking status, exercise, diet, family history of PCa, and race/ethnicity. Body mass index (BMI) was obtained from clinical records. Genetic risk was assessed via a validated polygenic score. Cox proportional hazards models were used to assess associations with PCa outcomes. After accounting for ancestry, family history, and genetic risk, smoking was associated with an increased risk of metastatic PCa (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.64-2.02; p<10-16) and fatal PCa (HR, 2.73; 95% CI, 2.36-3.25; p<10-16). Exercise was associated with a reduced risk of fatal PCa (HR, 0.86; 95% CI, 0.76-0.98; p=.03). Higher BMI was associated with a slightly reduced risk of fatal PCa, and diet score was not independently associated with any end point. Association with exercise was strongest among those who had nonmetastatic PCa at MVP enrollment. Absolute reductions in the risk of fatal PCa via lifestyle factors were greatest among men of African ancestry (1.7% for nonsmokers vs. 6.1% for smokers) or high genetic risk (1.4% for nonsmokers vs. 4.3% for smokers). Healthy lifestyle is minimally related to the overall risk of developing PCa but is associated with a substantially reduced risk of dying from PCa. In multivariable analyses, both exercise and not smoking remain independently associated with reduced metastatic and fatal PCa.

Natural language processing pipeline to extract prostate cancer-related information from clinical notes.

To develop an automated pipeline for extracting prostate cancer-related information from clinical notes. This retrospective study included 23,225 patients who underwent prostate MRI between 2017 and 2022. Cancer risk factors (family history of cancer and digital rectal exam findings), pre-MRI prostate pathology, and treatment history of prostate cancer were extracted from free-text clinical notes in English as binary or multi-class classification tasks. Any sentence containing pre-defined keywords was extracted from clinical notes within one year before the MRI. After manually creating sentence-level datasets with ground truth, Bidirectional Encoder Representations from Transformers (BERT)-based sentence-level models were fine-tuned using the extracted sentence as input and the category as output. The patient-level output was determined by compilation of multiple sentence-level outputs using tree-based models. Sentence-level classification performance was evaluated using the area under the receiver operating characteristic curve (AUC) on 15% of the sentence-level dataset (sentence-level test set). The patient-level classification performance was evaluated on the patient-level test set created by radiologists by reviewing the clinical notes of 603 patients. Accuracy and sensitivity were compared between the pipeline and radiologists. Sentence-level AUCs were ≥ 0.94. The pipeline showed higher patient-level sensitivity for extracting cancer risk factors (e.g., family history of prostate cancer, 96.5% vs. 77.9%, p < 0.001), but lower accuracy in classifying pre-MRI prostate pathology (92.5% vs. 95.9%, p = 0.002) and treatment history of prostate cancer (95.5% vs. 97.7%, p = 0.03) than radiologists, respectively. The proposed pipeline showed promising performance, especially for extracting cancer risk factors from patient's clinical notes. The natural language processing pipeline showed a higher sensitivity for extracting prostate cancer risk factors than radiologists and may help efficiently gather relevant text information when interpreting prostate MRI. When interpreting prostate MRI, it is necessary to extract prostate cancer-related information from clinical notes. This pipeline extracted the presence of prostate cancer risk factors with higher sensitivity than radiologists. Natural language processing may help radiologists efficiently gather relevant prostate cancer-related text information.

Predictors of time to diagnosis and treatment: A retrospective cohort study of patients with clinically localized prostate cancer in Nigeria.

e23123 Background: Equitable access to the management of early-stage prostate cancer is important for optimal outcome in the diagnostic and curative treatment pathway of patients. This study aimed to identify the predictors of time to treatment and time to diagnosis in these patients. Methods: This was a cohort study of 110 patients with clinically localized prostate cancer (T1-T3a, N0, M0) in three government-funded tertiary hospitals in Nigeria. Retrospective data on sociodemographic status, co-morbid conditions, clinical, pathological and radiological quality metrics, date of first presentation for cancer-related complaint in the tertiary hospital, date of diagnosis of prostate cancer, and the date of commencement of first cancer-directed treatment were collected. Primary endpoint was the time from diagnosis to treatment and the secondary endpoint was the time from presentation to diagnosis. Predictors were determined by Cox proportional hazards using Stata software, version 18.0 with a p-value of less than 0.05 considered significant. Results: Twelve percent (n = 13) of the patients had a family history of prostate cancer. Fifty-four percent (n = 59) had other co-morbid conditions. Nearly one-third, 29% (n = 32) had retired from their primary occupation and 10% (n = 11) were covered by health insurance. The overall median time to diagnosis was 30 (interquartile range (IQR) 10 - 48) days. The median time to treatment commencement was 32 (IQR 19 - 82) days for ADT; 57 (IQR 50 - 63) days for active surveillance; 45 (IQR 21 - 78) days for radical radiotherapy; and 100 (IQR 0 - 127) days for radical prostatectomy. Diagnostic PSA documentation independently predicted delayed time to diagnosis (adjusted HR = 0.22 with 95% CI [0.05,0.97]) while those with guideline concordant imaging investigations independently predicted longer time to treatment (adjusted HR = 0.63 with 95% CI [0.40,0.99]). Conclusions: The documentation of PSA level and use of guideline concordant imaging investigations were significantly associated with delayed time to care. Studies on interventions to reduce barriers associated with these factors is warranted to strengthen equitable access to care in this setting.

Limited Evidence of Shared Decision Making for Prostate Cancer Screening in Audio-Recorded Primary Care Visits Among Black Men and their Healthcare Providers

Prostate-specific antigen (PSA)-based prostate cancer screening is a preference-sensitive decision for which experts recommend a shared decision making (SDM) approach. This study aimed to examine PSA screening SDM in primary care. Methods included qualitative analysis of audio-recorded patient-provider interactions supplemented by quantitative description. Participants included 5 clinic providers and 13 patients who were: (1) 40–69 years old, (2) Black, (3) male, and (4) attending clinic for routine primary care. Main measures were SDM element themes and “observing patient involvement in decision making” (OPTION) scoring. Some discussions addressed advantages, disadvantages, and/or scientific uncertainty of screening, however, few patients received all SDM elements. Nearly all providers recommended screening, however, only 3 patients were directly asked about screening preferences. Few patients were asked about prostate cancer knowledge (2), urological symptoms (3), or family history (6). Most providers discussed disadvantages (80%) and advantages (80%) of PSA screening. Average OPTION score was 25/100 (range 0–67) per provider. Our study found limited SDM during PSA screening consultations. The counseling that did take place utilized components of SDM but inconsistently and incompletely. We must improve SDM for PSA screening for diverse patient populations to promote health equity. This study highlights the need to improve SDM for PSA screening.

Analysis of BRCA1 germline variants (exons 5, 11 and 20) in breast cancer families from Libya

ABSTRACT Breast cancer (BC) is a leading cause of cancer deaths in Libyan women. BRCA1 variants differ globally due to the diversity of genetic makeup and populations history. Their distribution, prevalence, and significance in Libyans remain largely unexplored. This study investigated the characteristics and distribution of BRCA1 variants in exons 5, 11, and 20 in Libyan families with BC. Thirty-six BC patients at ≤ 45 years, between 46–50 years and with a family history of breast, ovarian, pancreatic or prostate cancer in close relatives, or with triple-negative BC, were selected from 33 unrelated families during 2018–2020 at the National Cancer Institute, Sabratha, Libya. From these 33 families, 20 women (18 BC patients and two unaffected) were screened for BRCA1 exons 5, 11 and 20 using Sanger sequencing. All families completed an epidemiology and family history questionnaire. Twenty-seven variants (26 in exon 11 and 1 in exon 20, minor allele frequency of < 0.01) were detected in 10 of 18 unrelated families (55.6%.) Among the 27 variants, 26 (96%) were heterozygous. A frameshift pathogenic variant, c.2643del, and one novel variant c.1366A>G were identified. Furthermore, seven variants with unknown clinical significance were detected: c.1158T>A, c.1346C>G, c.1174C>G, c.3630 G>T, c.3599A>T, and c.3400 G>C in exon 11, and c.5244T>A in exon 20. Six variants with conflicting pathogenicity interpretations, c. 3460T>A, c. 3572 G>A, c. 3700 G>C, c. 1246C>G, c. 1344C>G, and c. 1054 G>A, were also identified. Twelve benign/likely benign variants were identified. Rare BRCA1 variants that have not been reported in North Africa were found in Libyan patients. These findings provide preliminary insights into the BRCA1 variants that could contribute to hereditary BC risk in Libyans. Further functional, computational, and population analyses are essential to determine their significance and potential impact on BC risk, which could ultimately lead to more personalized management strategies.

The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study.

GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. We analyzed TriNetX's deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval. Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe. The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect.