Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study

Margel, David; Benjaminov, Ofer; Ozalvo, Rachel; Grievink, Liat Shavit; Kedar, Inbal; Yerushalmi, Rinat; Ben‐Aharon, Irit; Neiman, Victoria; Yossepowitch, Ofer; Kedar, Daniel; Levy, Zohar; Shohat, Mordechai; Brenner, Baruch; Baniel, Jack; Rosenbaum, Eli

doi:10.1186/1471-2407-14-528

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…This is further supported by the IMPACT trial findings of an average age of onset among BRCA2 mut men of 58.5 versus 65 years in non‐carriers. Limited by a small sample size, a second prospective study, among BRCA2 mut male carriers aged 40–70 in Israel, is being conducted to assess screening methods and will offer more data regarding average age of onset . Ideally, these prospective studies may also assess optimal PSA dynamics and thresholds for diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Implications of High Rates of Metastatic Prostate Cancer inBRCA2Mutation Carriers

et al. 2016

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BACKGROUND Patients with germline BRCA2 gene mutations (BRCA2mut) have more aggressive prostate cancer. Analysis of all reported germline BRCA2mut prostate cancer cases allows better understanding of the clinicopathologic features and survival outcomes of these men. METHODS A systematic review was performed with the MEDLINE database to capture articles evaluating clinicopathologic characteristics of men with BRCA2mut associated prostate cancer. Inclusion criteria were at least five subjects, confirmation of BRCA2mut status, and data for at least 2 clinical parameters of disease. Meta-analysis was performed on outcomes data. Chi-squared tests were used to compare disease features among men undergoing formal versus ad hoc screening, as well as an age of diagnosis less than versus greater than 65 years. Rates of metastatic disease among BRCA2mut cases were compared to rates among non-carrier control subjects and the general population using the SEER database. RESULTS Twelve out of 289 studies met our inclusion criteria, representing 261 BRCA2mut men. Among carriers, the median age at diagnosis was 62 years and median PSA was 15 ng/dl with 95% of men having a PSA>3. Over 40% of BRCA2mut patients had T3/T4 disease and over 25% were metastatic at presentation. Survival was worse in BRCA2mut men with prostate cancer when compared to non-BRCA2mut subjects. BRCA2mut carriers had significantly higher rates of metastatic disease (18%) versus non-carrier controls (8%) and the SEER population (4%). CONCLUSIONS BRCA2mut carriers are more likely to have poor risk of prostate cancer at presentation and exhibit worse oncologic outcomes relative to non-carriers, including a fourfold increase in metastatic disease. Younger men and those undergoing formal screening present with less advanced disease which supports a need for earlier identification and screening protocols. Additionally, this population may benefit from alternative therapeutic paradigms.

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Section: Discussionmentioning

confidence: 99%

Implications of High Rates of Metastatic Prostate Cancer inBRCA2Mutation Carriers

et al. 2016

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“…The study design and methods were previously reported. 12 The protocol was approved by the Rabin Medical Center Ethics Committee in Israel. Written informed consent was obtained for all participants.…”

Section: Methodsmentioning

confidence: 99%

Imaging-based prostate cancer screening among BRCA mutation carriers—results from the first round of screening

et al. 2020

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Background: Male-carriers of BRCA1/2 gene mutations have an increased risk of prostate cancer (PCa) with a more aggressive phenotype. Current screening-guidelines suggest the use of prostate-specific antigen (PSA) only among BRCA2 carriers. Female carriers have extensive guidelines that include imaging. Our objective was to test the prevalence of PCa among BRCA carriers and examine screening strategies, using PSA and multiparametric magnetic resonance imaging (mpMRI). Patients and methods: We recruited men aged 40e70 years with BRCA1/2 germline mutations and no prior history of prostate biopsy. All men underwent an initial round of screening which included PSA, and prostate mpMRI. PSA was considered elevated using an age-stratified threshold of !1 ng/ml for 40e50 years of age, !2 ng/ml for 50e60 years of age, and 2.5 ng/ml for 60e70 years of age. Men with elevated PSA and/or suspicious lesion on mpMRI were offered a prostate biopsy. PSA levels, MRI findings, PCa incidence, and tumor characteristics were evaluated. Decision curve analysis was used to compare screening strategies. Results: We recruited 188 men (108 BRCA1, 80 BRCA2), mean age 54 years (9.8). One hundred and ten (57%) had either elevated age-stratified PSA (75; 40%), a suspicious MRI lesion (67; 36%), or both (32; 17%). Of these, 92 (85%) agreed to perform a prostate biopsy. Sixteen (8.5%) were diagnosed with PCa; 44% of the tumors were classified as intermediateor high-risk disease. mpMRI-based screening missed only one of the cancers (6%), while age-stratified PSA would have missed five (31%). Decision curve analysis showed that mpMRI screening, regardless of PSA, had the highest net benefit for PCa diagnosis, especially among men younger than 55 years of age. We found no difference in the risk of PCa between BRCA1 and BRCA2 (8.3% versus 8.7%, P ¼ 0.91). Ninety percent had a Jewish founder mutation, thus the results cannot be generalized to all ethnic groups. Conclusions: PCa is prevalent among BRCA carriers. Age may affect screening strategy for PCa in this population. Young carriers could benefit from initial MRI screening. BRCA carriers aged older than 55 years should use PSA and be referred to mpMRI if elevated. Trial registration: ClinicalTrial.gov ID: NCT02053805.

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“…A number of PARPi agents are being pursued and hold promise for personalized treatment for patients with GL or somatic BRCA mutations. Therefore, genetic testing for known founder mutations is currently recommended for high‐risk populations . Subsequently, family members of patients with identified GL mutations are offered to undergo genetic screening.…”

Section: Discussionmentioning

confidence: 99%

Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study

et al. 2017

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BRCA-associated CCA is uncommon but a very important subtype of hepatic malignancies, due to its rising prevalence. Better clinical characterization of this subtype might allow application of targeted therapy for CCA patients with germline or somatic mutations in genes, especially due to previously reported success of such therapies in other BRCA-associated malignancies. Thus this study, first of its kind, provides a basis for future multi-centered analyses in larger cohorts, as well as clinical trials. Additionally, this study emphasizes the importance of both germline and somatic genotyping for all CCA patients.

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Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study

Cited by 5 publications

References 31 publications

Implications of High Rates of Metastatic Prostate Cancer inBRCA2Mutation Carriers

Implications of High Rates of Metastatic Prostate Cancer inBRCA2Mutation Carriers

Imaging-based prostate cancer screening among BRCA mutation carriers—results from the first round of screening

Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study

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