Family History Of Prostate Cancer Research Articles

Guideline-Based, Multi-Gene Panel Germline Genetic Testing for at-Risk Patients with Breast Cancer.

Genetic testing for at-risk patients with breast cancer should be routinely offered. Knowledge generated may influence both treatment decisions and cancer prevention strategies among the patients themselves and their relatives. In this study, we report on the prevalence and patterns of germline mutations, using commercially available next-generation sequencing (NGS)-based multi-gene panels (MGP). Consecutive at-risk breast cancer patients, as determined by international guidelines, were offered germline genetic testing using a 20-gene NGS-based panel at a reference lab. Samples of peripheral blood were obtained for DNA extraction and genetic variants were classified as benign/likely benign (negative), pathogenic/likely pathogenic (positive) or variants of uncertain significance (VUS). A total of 1310 patients, median age (range) 43 (19-82) years, were enrolled. Age ≤45 years (n = 800, 61.1%) was the most common indication for testing. Positive family history of breast, ovarian, pancreatic or prostate cancers, and triple-negative disease were among the common indications. Among the whole group, 184 (14.0%) patients had pathogenic/likely pathogenic variants; only 90 (48.9%) were in BRCA1 or BRCA2, while 94 (51.9%) others had pathogenic variants in other genes; mostly in APC, TP53, CHEK2 and PALB2. Mutation rates were significantly higher among patients with positive family history (p = 0.009); especially if they were 50 years or younger at the time of breast cancer diagnosis (p < 0.001). Patients with triple-negative disease had relatively higher rate (17.5%), and mostly in BRCA1/2 genes (71.4%). Variants of uncertain significance (VUS) were reported in 559 (42.7%) patients; majority (90.7%) were in genes other than BRCA1 or BRCA2. Pathogenic mutations in genes other than BRCA1/2 are relatively common and could have been missed if genetic testing was restricted to BRCA1/2. The significantly high rate of VUS associated with multi-gene panel testing can be disturbing.

Prostate cancers in men under the age of 50: about a series in Togo, Sub-Saharan Africa

BackgroundProstate cancer is a public health problem and increasingly diagnosed in men under 50 years of age. This cancer occurs much more in subjects of advanced age, generally over sixty. The aim of the study was to describe the epidemiological, clinical and histopathological aspects of prostate cancer in men under the age of 50 in Togo.MethodsIt was a retrospective descriptive, cross-sectional study of histologically confirmed cases of prostate cancer in young adults at the Pathological Laboratory of Lomé over a period of 10 years (2011–2020).ResultsIn total, 29 cases of prostate cancer in patients under 50 years of age. The proportion of prostate cancers in men under 50 was 0.7% of all prostate cancers, The average age of the patients was 45 years with extremes of 35 and 49 years. Twelve patients had a family history of prostate cancer, with a statistically significant relationship between the existence of a family history of prostate cancer and the age of onset of the cancer (p-value = 0.03). The dominant clinical information was prostatic hypertrophy (40.37%), followed by acute urine retention (20.69%) and micturition disorders (17.27%). The median Prostate Specific Antigen (PSA) was 188 ng/ml with extremes of 20 ng/ml and 2100 ng/ml. A large proportion of patients had a PSA between 100 and 500 ng/ml. Histologically, they were all prostatic acinar adenocarcinomas. These adenocarcinomas were well differentiated (48%) and moderately differentiated (38%). The predominant histoprognostic grade was ISUP (International Society of Urological Pathology) grade 1 which was noted in 65.52%, followed by grade 2 in 20.69%.ConclusionProstate cancer in men under 50 years of age is relatively rare in Togo, sometimes occurring in the context of a family history of prostate cancer. Hence the importance of raising awareness among the male population, especially with a family history of prostate cancer, to start screening early, around the age of 40.

Family History of Prostate Cancer and Survival Outcomes in the UK Genetic Prostate Cancer Study

BackgroundA family history (FH) of prostate cancer (PrCa) is associated with an increased likelihood of PrCa diagnosis. Conflicting evidence exists regarding familial PrCa and clinical outcomes among PrCa patients, including all-cause mortality/overall survival (OS), PrCa-specific survival (PCSS), aggressive histology, and stage at diagnosis. ObjectiveTo determine how the number, degree, and age of a PrCa patient’s affected relatives are associated with OS and PCSS of those already diagnosed with PrCa. Design, setting, and participantsThe UK Genetic Prostate Cancer Study is a longitudinal, multi-institutional, observational study collecting baseline and follow-up clinical data since 1992. We examined OS and PCSS in 16340 men by degree and number of relatives with prostate and genetically related cancers (breast, ovarian, and colorectal). Outcome measurements and statistical analysisThe primary outcome was all-cause mortality among PrCa patients. The risk of death with respect to FH was assessed by calculating hazard ratios from Cox proportional hazard regression models, adjusting for relevant factors. Results and limitationsA stronger FH was inversely associated with the risk of all-cause and PrCa-specific mortality. This association was greater in those with an increasing number (p-trend < 0.001) and increasing closeness (p-trend < 0.001) of the diagnosed relatives. Patients with at least one first-degree relative were at a lower risk of all-cause mortality than those with no FH (hazard ratio = 0.82 [95% confidence interval 0.75–0.89]). The population is largely of European ancestry, and this may cause an issue with representation and generalisation. Data are missing on epidemiological risk factors for death such as smoking and on comorbidities. Recall of family members' diagnoses may affect the classification of FH in unconfirmed cases. ConclusionsBased on the investigation of the type and timing of relatives’ cancers, it is likely that reductions in mortality are due almost completely to a greater awareness of the disease. This study provides information for clinicians guiding patients and their relatives based on their familial risk. It shows the importance of screening and awareness programmes, which are likely to improve survival among men with an FH. Patient summaryWe were interested in how a family history of prostate cancer affects survival in prostate cancer patients. We studied 16340 patients, categorised them according to the strength of their family history, and found that the stronger their family history, the better they did in terms of overall survival. We looked at the type and timing of patients’ diagnoses compared with those of their relatives and found that this effect is likely to be explained by awareness, which indicates the importance of screening and awareness programmes.

The Experience of Uncertainty in Individuals With High Risk for Pancreatic Cancer.

Individuals with a strong family history of pancreatic cancer or a known hereditary cancer syndrome that is associated with pancreatic cancer are considered at high risk for developing pancreatic cancer. Living with a high risk for often fatal cancer is accompanied by high levels of uncertainty. Uncertainty is also independently associated with negative health outcomes. By understanding issues, sources, and responses to uncertainty, targeted supportive care strategies can be provided. This study aimed to examine how uncertainty manifests in the experience of being at high risk to develop pancreatic cancer and to describe issues, sources of, and responses to uncertainty. In this secondary qualitative descriptive study, we analyzed 19 interviews with persons living with inherited pancreatic cancer risk. Analysis was guided by a conceptual framework of uncertainty and responses to uncertainty. Participants described multiple personal, practical, and scientific issues of uncertainty, centering on what to expect for their future health. Participants also expressed positive and negative cognitive, emotional, and behavioral responses to uncertainty, including engaging in surveillance. Uncertainty sources were both individual experiences as well as perceptions of healthcare provider uncertainty with managing pancreatic cancer risk. Pancreatic cancer risk includes issues of uncertainty related to personal mortality, defining and managing risk, and experiencing surveillance. Positive and negative responses to this uncertainty could be targeted through interventions. The oncology nurse should assess for sources of and responses to uncertainty in persons at risk for pancreatic cancer and offer psychosocial and educational support.

Investigation of the relationship between endothelial nitric oxide synthase T786C polymorphism and PSA, PSA derivatives, and prostate cancer in the Turkish population.

Prostate cancer is a slowly progressing cancer. However, it has remained a major medical problem for affected men. Risk factors of prostate cancer include age, race, and prostate cancer family history. Prostate cancer may occur at different frequencies between ethnic populations and countries. Currently, studies on genetic risk factors in prostate cancer aetiology have been increasing. Due to the importance of changes in endothelial nitric oxide synthase in carcinogenesis, we aimed to reveal whether eNOS T786C polymorphism is associated with prostate cancer. Archival samples included in this study were whole blood samples taken from patients who were grouped according to prostate biopsy pathology results (BPH, n: 42; PCa, n: 48) and from healthy participants (controls, n:27). DNA was isolated from these whole blood samples and real-time polymerase chain reaction analysis was performed for endothelial nitric oxide synthase T786C polymorphism with LightCycler 480 II. Measured free and total prostate-specific antigen serum levels were evaluated retrospectively. There was a statistical difference between patient-healthy control and control-healthy control groups regarding genotype distributions for eNOS T786C hism. Controls were more likely to have TC and CC genotypes and C alleles than the other two groups. Compared to other groups, the percentage of the eNOS786C allele in the control group was found to be higher. As a result of these data, it can be thought that carrying the allele may be protective against the disease.

A NEW MUTATION IN THE PALB2 GENE ASSOCIATED WITH HEREDITARY BREAST CANCER IN A YOUNG PATIENT BELONGING TO THE YAKUT ETHNIC GROUP

Breast cancer is the most common cancer worldwide. The oncosuppressor gene PALB2, along with such genes as BRCA1 and BRCA2, is involved in the repair of damaged DNA. The incidence of germline mutations in the PALB2 gene in breast cancer and in familial cases of pancreatic cancer is approximately 1–2% and 3–4%, respectively. A clinical case of a 39-year-old woman belonging to the Yakut ethnic group, diagnosed with breast cancer and with a family history of pancreatic cancer, is presented hereby.

Germline mutations in prostate cancer: a systematic review of the evidence for personalized medicine.

The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate of genetic predisposition compared with other cancers in men, with an estimated rate of cancers ascribable to hereditary factors of 5-15%. A systematic search (PubMed, Web of Science, and ClinicalTrials.gov) of English literature from 2000 to 2022, using the keywords "prostate cancer", "germline mutations", "family history", and "inheritance" was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The search identified 980 publications. Of these, 200 papers were removed before screening (duplicates, non-English literature, and publication year before 2000) and 245 records were excluded after title/abstract screening. Finally, 50 articles were included in the final analysis. We analyze the latest evidence on the genetic basis of PCa predisposition and clinical implications for more personalized screening protocols and therapeutic management of this high-prevalent cancer. Emerging data show that germline mutations in homologous recombination genes (BRCA1/2, ATM, CHECK2), in mismatch repair genes (MLH1, MLH2, MSH6), and other additional genes are associated with the development and aggressiveness of PCa. Germline testing and genetic counseling have increasingly important implications in cancer screening and therapeutic decisions making for patients affected by PCa. Patients with localized PCa and some gene mutations are more likely to develop aggressive cancer, so active treatment may be preferable to active surveillance for these patients. Moreover, in patients with metastatic PCa, these gene alterations may be useful biomarkers for predicting response to specific therapy such as PARP inhibitors, recently approved for the treatment of metastatic castration-resistant PCa. The evidence supports recent guidelines and recommendations considering germline genetic testing for patients with a positive family history of PCa or men with high risk or metastatic disease.

An Extremely Rare Variant of Pancreatic Ductal Adenocarcinoma Masquerading as Chronic Pancreatitis

Abstract Introduction/Objective Primary Pancreatic signet-ring cell carcinoma (PPSRCC) is an extremely rare histologic variant with sparse literature. Herein, we describe a case of PPSRCC in a 75-year-old female with positive family history of pancreatic cancer (47y/o brother). The diagnosis was delayed secondary to diagnostic challenges on initial fine-needle aspiration (FNA). Methods/Case Report Diagnosing PPSRCC on FNA can be extremely difficult. Primary, and metastatic neoplasms to the pancreas may exhibit cytomorphological similarities to signet-ring cells, posing diagnostic challenges. Further, sampling of abundant background inflammatory cells during a biopsy can result in incorrect diagnosis of pancreatitis. Given the strong clinical suspicion based on imaging findings, a second FNA was performed which showed few atypical cells suspicious for carcinoma. Subsequently, the patient underwent neoadjuvant chemotherapy and Whipple resection. The tumor morphology is characterized by infiltrating cells with large mucin vacuoles and peripheric nucleus comprising &amp;gt; 50% of the mass lesion with perineural invasion, in a background of chronic inflammation and pancreatic intraepithelial neoplasia, grade III. A diagnosis of PPSRCC was rendered. Notably, lymph nodes (LN) showed no evidence of metastasis. Results (if a Case Study enter NA) NA. Conclusion Based on limited literature, PPSRCC is considered an aggressive malignancy with low survival rate, because of a high rate of metastasis. However, our case was rather unique given the lack of LN metastasis and the neodjuvant treatment strategy. As of February 2022, &amp;lt;10 cases have been reported with ill-defined characteristics and treatment guidelines.

Prostate Cancer Screening Practice and Associated Factors Among Men in Public Health Facilities of Hossana Town, Ethiopia.

Prostate cancer is a disease of the prostate gland. It is a recognized tumour in men and is common worldwide. It is the second most frequent cancer and the fifth leading cause of death in males worldwide. Worldwide, prostate cancer screening continues to be a highly contested topic with a variety of differences in recommendations for screening uptake. However, for men considered to be at risk, screening continues to be the most effective method for lowering death through early identification of prostate cancer. To determine prostate cancer screening practice and associated factors among adult men in public health facilities of Hossana Town, Ethiopia. Facility-based cross-sectional design was used. All adult men, whose age >40 years attending public health facilities found in Hossana town were included in this study. From each public health facility, representative numbers of participants who fulfilled inclusion criteria were included in the study. A total of 422 sample sizes of adult men were used. A consecutive sampling technique was used to select study participants in each health facility. An interviewer-administered questionnaire was employed to collect data. Both descriptive and advanced analyses were performed using SPSS software version 26.0. In bivariable analysis, variables with a p-value <0.25 were considered for multivariable analysis. Finally, odds ratio with 95% CI and p-value <0.05 were used to declare factors as significantly associated with the outcome variable. About 7.2% (30) of the participants were screened for prostate cancer in this study. Ever heard about prostate cancer [AOR=26 (7.06-96.90)], family history of prostate cancer [AOR=15.5(5.18-46.77)] and awareness of anyone who has undergone prostate cancer screening [AOR= 6.8(1.95-23.64)] were identified independent predictors for prostate screening practice. In this study, prostate cancer screening practice is low. Ever heard about prostate cancer, family history of prostate cancer and awareness of anyone who has undergone prostate cancer screening were independent predictors of prostate cancer screening practice. Intervention measures aiming to increase awareness about prostate cancer and prostate cancer screening should be done.

122. Prostate cancer and other clinical features by polygenic risk score

Prostate cancer is the second most common cancer in American men and the second leading cause of cancer death in the USA. Genome-wide association studies (GWAS) have identified more than 170 single nucleotide polymorphisms (SNPs) associated with prostate cancer, which can be combined to make a Polygenic Risk Score (PRS) and give an individual their risk to develop prostate cancer. To our knowledge, studies have not been done to determine if there is a relationship between PRS and features of prostate cancer in men ascertained in a clinical setting. Thus, this study aims to investigate risk factors associated with prostate cancer including: age of diagnosis, ISUP Grade Group, metastatic status, histology, and family history of prostate cancer, to determine how they correlate with PRS amongst men who do not have a germline pathogenic variant in a known prostate cancer related gene. A quantitative retrospective chart review of 175 men diagnosed with prostate cancer, who received genetic counseling services at the Ohio State University's Genitourinary Cancer Genetics Clinic, and a PRS through Ambry Genetics was generated. Men diagnosed over 60 years of age were more likely to have a low PRS (57%) than a high PRS (32%) (p-value of 0.009). This supports the hypothesis that men diagnosed with prostate cancer at younger ages will have higher PRS and vice versa. We did not find a significant relationship between PRS and ISUP GG, metastatic status, histology, or family history in a first or second-degree relative.

ODP050 Oncocytic Adrenocortical Carcinoma Presenting with Hematuria

Abstract Introduction Adrenocortical carcinoma (ACC) is rare and aggressive endocrine tumor. It is commonly noticed due to symptoms of hormone excess, mass-effect, or incidentalomas. Different histological variants are noted, which include: oncocytic, myxoid, sarcomatoid, and the conventional subtype. The oncocytic variant is usually seen on the left side, and usually presents with symptoms of mass-effect. Only around 17% were noted to be functional. We present an interesting case of ACC (oncocytic type) which presented with hematuria. Case Presentation 70-year-old female with a history of morbid obesity, hypertension, anxiety, GERD, tubular adenoma, hyperlipidemia, and lumbar radiculopathy came in to see her primary care for hematuria and back pain. She has a long-standing history of back pain, for which she has had an EMG, which showed mild axonal polyneuropathy and bilateral L5 radiculopathy. Apart from hematuria, she denies any other urinary complaints. Additionally, she denied any fever, chills, nausea, abdominal pain, sweating, tremor, headache, palpitations, easy bruising, fractures, muscle weakness, hirsutism, or changes in her weight. She has a family history of pancreatic cancer and is currently retired, and denies alcohol, tobacco, or recreational drug use. A KUB X-ray was ordered which showed calcification in the left upper quadrant, concerning for a splenic artery aneurysm; this led to a CTA abdomen, which showed a large 7.2 cm heterogenous enhancing solid left adrenal mass, concerning for primary adrenal carcinoma, which was new compared to imaging 2 years ago. Also seen was a 0.7 cm enhancing right hepatic lobe lesion, along with a 1.5 cm splenic artery aneurysm. Following this, an abdomen MRI with contrast showed a 7×7×7 cm solid heterogeneously enhancing left upper quadrant mass beside the left adrenal gland and pancreas. Subsequently, a CT guided needle biopsy was done, which revealed scant adrenal tissue. PET scan showed a hypermetabolic mass, arising from the left adrenal, consistent with adrenal carcinoma. At this point, an endocrinology referral was placed, and other lab work including 24-hour urine free cortisol, DHEA-S, 24-hour urine metanephrine, and aldosterone/renin ratio was done. DHEA-S level was elevated at 264 mcg/dl (12-133). She was then transferred to a tertiary care facility, where she underwent a left adrenalectomy, para-aortic lymphadenectomy, nephrectomy, splenectomy, and distal pancreatectomy. Pathology confirmed adrenal cortical carcinoma (oncocytic type), with negative margins, Ki-67 labelling index of 25%, and no lymphovascular invasion, pT2pNO. She was then discharged home with visiting nurses. Conclusion Oncocytic ACC is an infrequent tumor, which presents with symptoms of mass effect, and definitive diagnosis requires histopathological assessment. The Lin–Weiss–Bisceglia (LWB) system and Helsinki score help establish malignant potential. Fortunately, it has a decreased tendency to metastasize and a better prognosis than other ACC subtypes. Further studies to understand oncocytic ACC are needed. Presentation: No date and time listed

Patient-Factors Influencing the 2-Year Trajectory of Mental and Physical Health in Prostate Cancer Patients.

This study aimed to examine the physical and mental Quality of Life (QoL) trajectories in prostate cancer (PCa) patients participating in the Pros-IT CNR study. QoL was assessed using the Physical (PCS) and Mental Component Score (MCS) of Short-Form Health Survey upon diagnosis and two years later. Growth mixture models were applied on 1158 patients and 3 trajectories over time were identified for MCS: 75% of patients had constantly high scores, 13% had permanently low scores and 12% starting with low scores had a recovery; the predictors that differentiated the trajectories were age, comorbidities, a family history of PCa, and the bowel, urinary and sexual functional scores at diagnosis. In the physical domain, 2 trajectories were defined: 85% of patients had constantly high scores, while 15% started with low scores and had a further slight decrease. Two years after diagnosis, the psychological and physical status was moderately compromised in more than 10% of PCa patients. For mental health, the trajectory analysis suggested that following the compromised patients at diagnosis until treatment could allow identification of those more vulnerable, for which a level 2 intervention with support from a non-oncology team supervised by a clinical psychologist could be of help.

Diet Quality and Pancreatic Cancer Incidence in the Multiethnic Cohort.

Data on diet quality and pancreatic cancer are limited. We examined the relationship between diet quality, assessed by the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED) score, the Dietary Approaches to Stop Hypertension (DASH) score and the energy-adjusted Dietary Inflammatory Index (E-DII), and pancreatic cancer incidence in the Multiethnic Cohort Study. Diet quality scores were calculated from a validated food frequency questionnaire administered at baseline. Cox models were used to calculate HR and 95% confidence intervals (CI) adjusted for age, sex, race/ethnicity, education, diabetes, family history of pancreatic cancer, physical activity, smoking variables, total energy intake, body mass index (BMI), and alcohol consumption. Stratified analyses by sex, race/ethnicity, smoking status, and BMI were conducted. Over an average follow-up of 19.3 years, 1,779 incident pancreatic cancer cases were identified among 177,313 participants (average age of 60.2 years at baseline, 1993-1996). Overall, we did not observe associations between the dietary pattern scores and pancreatic cancer (aMED: 0.98; 95% CI, 0.83-1.16; HEI-2015: 1.03; 95% CI, 0.88-1.21; AHEI-2010: 1.03; 95% CI, 0.88-1.20; DASH: 0.92; 95% CI, 0.79-1.08; E-DII: 1.05; 95% CI, 0.89-1.23). An inverse association was observed with DASH for ever smokers (HR, 0.75; 0.61-0.93), but not for nonsmokers (HR, 1.05; 0.83-1.32). The DASH diet showed an inverse association with pancreatic cancer among ever smokers, but does not show a protective association overall. Modifiable measures are needed to reduce pancreatic cancer burden in these high-risk populations; our study adds to the discussion of the benefit of dietary changes.

Diabetes, metabolic syndrome and prostate cancer risk: Results from the EPICAP case-control study

BackgroundDiabetes may be associated with decreased prostate cancer (PCa) risk. However, previous studies have not always accounted for time since diabetes diagnosis or antidiabetic drug use. Futhermore, the role of metabolic syndrome (MetS) in PCa risk is still debated. We investigated the role of diabetes and MetS in PCa risk based on data from the Epidemiological study of PCa (EPICAP). MethodsEPICAP is a population-based case-control study that included 819 incident PCa cases in 2012–2013 and 879 controls frequency matched by age. MetS was characterized according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Logistic regression models adjusted for age, family history of PCa and ethnicity, were used to assess odds ratios (ORs) and their 95%conficence intervals (CIs) for the associations between diabetes, MetS and PCa risk. ResultsWhereas we did not observed an association between diabetes and PCa, a decreased risk of PCa has been highlighted with an increasing treated diabetes duration (p-trend=0.008). No association has been observed between MetS, the number of MetS criteria and the risk of PCa. However, we suggested that NSAIDs use could modify the association between MetS and PCa risk. ConclusionOur results suggest an inverse association between the duration of diabetes and PCa risk. The role of metabolic factors, such as MetS and its components, in PCa risk remains unclear and requires further investigations.

Initial outcomes and insights from a novel high-risk prostate cancer screening clinic.

Guidelines for germline testing in patients with prostate cancer (PCa) are identifying family members who require additional surveillance given pathogenic variants (PVs) that confer increased PCa risk. We established an interdisciplinary clinic for cancer surveillance in high-risk individuals aimed to implement screening recommendations. This study aimed to characterize the clinical features of this cohort. The Prostate Cancer Risk Clinic (PCRC) was established for unaffected individuals with germline PVs or a strong PCa family history. PCa screening, urine labs, and questionnaires were included in the visit. Individuals with BRCA1/2 PVs underwent clinical breast exam as well. Data from the initial visit were abstracted from the medical record and questionnaires for analysis. Thirty-five individuals with increased PCa risk were followed by the PCRC with a median age of 47 years of age. Twenty individuals (57%) had a family history of PCa, and 34 (97%) had a germline PV associated with an increased risk for developing PCa. Four individuals underwent biopsy due to care in the PCRC, with one PCa identified in an individual with TP53 PV. Median patient response scores indicated mild symptoms of an enlarged prostate (AUASS), normal erectile function (SHIM), and relatively low anxiety about developing PCa (MAX-PC). However, there were notable "outlier" scores on each questionnaire. Individuals with prostates and BRCA1/2 PVs, among other germline PVs, can benefit from a comprehensive interdisciplinary approach to high-risk management. PCa was identified in an individual with a non-BRCA PV, emphasizing the importance and need for high-risk screening guidelines across all genes with increased risk for PCa. "Outlier" patient response scores demonstrate that some participants experienced worse symptoms or anxiety than was indicated by median scores alone.

Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial.

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high risk (>3ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening.

FAMILY MATTERS: CHEST PAIN AS THE INITIAL PRESENTATION OF EARLY-ONSET METASTATIC PROSTATE CANCER

FAMILY MATTERS: CHEST PAIN AS THE INITIAL PRESENTATION OF EARLY-ONSET METASTATIC PROSTATE CANCER

S3114 Painless Jaundice With a Significantly Elevated CA 19-9: It Is Not Always Pancreaticobiliary Cancer

Introduction: Carbohydrate antigen 19-9 (CA 19-9) is often very high in pancreaticobiliary cancers but can be substantially elevated in benign diseases too. We present a case of painless jaundice with a significantly elevated CA 19-9 from vanishing bile duct syndrome (VBDS). Case Description/Methods: 65-year-old white male with history of obesity, hypertension, hyperlipidemia, prior cholecystectomy and no family history of pancreatic cancer presented with two weeks of painless jaundice and 10 pounds unintentional weight loss. Physical exam noted scleral icterus and jaundice with a T.Bili of 23 mg/dL (Table 1). CT scan showed intrahepatic bile duct dilation and a 10 mm common bile duct without a discrete mass. CA 19-9 was elevated to 1,480 U/mL, concerning for malignancy. ERCP found a low-grade main bile duct stricture which was stented. Bile duct brushings and fine needle aspiration of the pancreas were negative for malignancy. Biliary dilation was resolved on follow-up MRCP but his bilirubin remained high. Infectious and autoimmune workup was unremarkable. Repeat cholangiography and brushings confirmed no obstruction or malignancy (Fig. 1a). An infiltrative versus drug induced liver injury was suspected. EUS-guided liver biopsies revealed cholestasis with dilated bile canaliculi, hepatocytes with ballooning degeneration and a paucity of bile ductules. Cytokeratin-7 immunostaining demonstrated >50% ductopenia, confirming VBDS (Fig. 1b and c). Follow up at hepatology clinic determined triamterene-HCTZ, atorvastatin or omeprazole stopped during hospitalization to be the likely culprit. His CA 19-9, LFTs and symptoms improved over the following weeks (Table 1). Discussion: VBDS is an acquired cholestatic liver disease that may mimic the presentation of pancreatic cancer. CA 19-9 can be substantially elevated through T-cell mediated destruction of small bile ducts causing impaired excretion, inflammatory production, and decreased clearance. Severity of liver damage depends on the duration of injury and degree of bile duct loss at the time of diagnosis. Prompt diagnosis is important to prevent cirrhotic progression, improve outcomes, and avoid unnecessary treatments. Recognizing its association with an elevated CA 19-9 may help with this, but is scarcely reported in the literature. CA 19-9 is not typically checked in cases of VBDS but is likely commonly elevated. Providers should be aware of this association when faced with a patient with painless jaundice and a significantly elevated CA 19-9 but no obvious malignancy. Table 1. - LFT Trends During the Course of Presentation Normal Range Hospital Admission * 2 weeks 3 weeks ** 4 weeks *** 7 weeks 13 weeks Total bilirubin 0.2-1.3 mg/dL 23 22.7 22 19.7 4.7 1.3 Direct bilirubin 0.0-0.2 mg/dL >13 n/a 14.9 14.6 4.2 0.6 AST 0-45 U/L 107 134 172 200 121 27 ALT 0-50 U/L 190 130 163 182 120 35 ALP 40-150 U/L 267 179 187 168 132 109 CA 19-9 0-35 U/mL 1480 n/a n/a 85 49 n/a AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CA19-9, carbohydrate antigen 19-9; n/a, not available. * ANA, anti-AMA, anti-SMA, anti-mitochondrial, anti-TTG, anti-LKM 1/2 IgG, and EBV IgG antibodies were negative. Serum IgA, A1AT, ceruloplasmin, TSH, iron levels, hepatitis panel, serum protein electrophoresis and acetaminophen levels were normal. Acetaminophen, multivitamin, iron, triamterene- HCTZ, omeprazole and atorvastatin were stopped on discharge. ** Three weeks post hospitalization. Repeat EUS/ERCP showed biliary decompression. VBDS diagnosed on liver biopsies. *** Seen in liver clinic. Started ursodiol 2000mg daily. Figure 1.: (A) ERCP with cholangiogram showing a low-grade distal biliary stricture without significant upstream dilation. (B) Liver biopsy with H&E stain, 500 μm magnification showing small portal tracts with no bile ducts (red circle); note marked cholestasis (arrows) in dilated canaliculi and lack of ductular reaction. Also visible at this magnification is the ballooning degeneration of hepatocytes. (C) Liver biopsy with cytokeratin 7 immunostain, 500 μm magnification. Small portal tracts with no terminal/small bile ducts. Early signs of ductular reaction seen by hepatocytes taking up CK7 stain (arrows).

Family History of Prostate and Breast Cancer Integrated with a Polygenic Risk Score Identifies Men at Highest Risk of Dying from Prostate Cancer before Age 75 Years.

Family history of prostate cancer is one of the few universally accepted risk factors for prostate cancer. How much an assessment of inherited polygenic risk for prostate cancer adds to lifetime risk stratification beyond family history is unknown. We followed 10,120 men in the Health Professionals Follow-up Study with existing genotype data for risk of prostate cancer and prostate cancer-specific death. We assessed to what extent family history of prostate or breast cancer, combined with a validated polygenic risk score (PRS) including 269 prostate cancer risk variants, identifies men at risk of prostate cancer and prostate cancer death across the age span. During 20 years of follow-up, 1,915 prostate cancer and 166 fatal prostate cancer events were observed. Men in the top PRS quartile with a family history of prostate or breast cancer had the highest rate of both prostate cancer and prostate cancer-specific death. Compared with men at lowest genetic risk (bottom PRS quartile and no family history), the HR was 6.95 [95% confidence interval (CI), 5.57-8.66] for prostate cancer and 4.84 (95% CI, 2.59-9.03) for prostate cancer death. Men in the two upper PRS quartiles (50%-100%) or with a family history of prostate or breast cancer (61.8% of the population) accounted for 97.5% of prostate cancer deaths by age 75 years. Our study shows that prostate cancer risk stratification on the basis of family history and inherited polygenic risk can identify men at highest risk of dying from prostate cancer before age 75 years.

Prospective evaluation of the role of imaging techniques and TMPRSS2:ERG mutation for the diagnosis of clinically significant prostate cancer.

ObjectivesTo test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa).Materials and methodsThis is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with >=1 suspicious lesion (PI-RADS>2) at mpMRI or PR-IMUS >2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone.ResultsThe cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83.ConclusionsT2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role.