Germline testing and genetic counselling in prostate cancer

Russo, Jessica; Giri, Veda N.

doi:10.1038/s41585-022-00580-7

Cited by 32 publications

(20 citation statements)

References 74 publications

(202 reference statements)

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“…However, the decision to biopsy based on urinary markers or a PSAD of >0.10 ng/mL/mL in the context of negative mpMRI increased the detection of ISUP grade >1 cancers. In this study, the youngest patient (who did not carry a BRCA mutation) was diagnosed at the age of 45 years suggesting, along with previous reports [28,29] and in line with guidelines [13,35], that screening should begin at 40 years in this population of men at high genetic risk of PCa. The delays between two screenings require further investigations.…”

Section: Discussionsupporting

confidence: 85%

Clinical performance of magnetic resonance imaging and biomarkers for prostate cancer diagnosis in men at high genetic risk

et al. 2023

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Objectives To evaluate different scenarios for the management of early diagnosis of cancer (PCa) in men at high genetic risk, using recently developed blood and urinary molecular biomarkers in combination with clinical information alongside multiparametric magnetic resonance imaging (mpMRI). Patients and Methods A total of 322 patients with a high genetic risk (familial or personal history of cancers or a predisposing germline variant) were included in this study. The primary outcome was the detection rates of PCa (positive biopsy) or clinically significant PCa (biopsy with International Society of Urological Pathology [ISUP] grade >1). Clinical parameters included age, body mass index, ancestry, and germline mutational status, mpMRI, prostate‐specific antigen density (PSAD), Prostate Health Index and urinary markers (Prostate Cancer Associated 3, SelectMdx™ and T2:ERG score) were assessed. Sensitivity (Se) and specificity (Sp) for each marker at their recommended cut‐off for clinical practice were calculated. Comparison between diagnoses accuracy of each procedure and scenario was computed using mutual information based and direct effect contribution using a supervised Bayesian network approach. Results A mpMRI Prostate Imaging‐Reporting and Data System (PI‐RADS) score ≥3 showed higher Se than mpMRI PI‐RADS score ≥4 for detection of PCa (82% vs 61%) and for the detection of ISUP grade >1 lesions (96% vs 80%). mpMRI PI‐RADS score ≥3 performed better than a PSA level of ≥3 ng/mL (Se 96%, Sp 53% vs Se 91%, Sp 8%) for detection of clinically significant PCa. In case of negative mpMRI results, the supervised Bayesian network approach showed that urinary markers (with the same accuracy for all) and PSAD of ≥0.10 ng/mL/mL were the most useful indicators of decision to biopsy. Conclusions We found that screening men at high genetic risk of PCa must be based on mpMRI without pre‐screening based on a PSA level of >3 ng/mL, to avoid missing too many ISUP grade >1 tumours and to significantly reduce the number of unnecessary biopsies. However, urinary markers or a PSAD of ≥0.10 ng/mL/mL when mpMRI was negative increased the detection of ISUP grade >1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from the age of 40 years.

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Section: Discussionsupporting

confidence: 85%

Clinical performance of magnetic resonance imaging and biomarkers for prostate cancer diagnosis in men at high genetic risk

et al. 2023

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“…The optimal delivery model of PCa genetics care remains unclear. 7,17 Historically, germline testing has been conducted after pretest counseling by GCs. Recently, novel approaches involving oncology staff, with or without GC involvement, that is, hybrid or mainstream models, respectively, have been advocated to increase accessibility and speed.…”

Section: Introductionmentioning

confidence: 99%

“…Some variants carry an increased risk for cancer and noncancer conditions that may prompt screening, risk-modifying interventions, or cascade testing in relatives. 7,8 Certain variants also carry treatment implications, for example, DNA damage repair gene alterations may confer sensitivity to poly (ADP-ribose) polymerase inhibitors and other therapies. [9][10][11][12][13] Consequently, germline testing is recommended in men with metastatic, regional, or high-or very high-risk localized PCa; personal history of breast cancer; known family history of familial cancer risk mutation; or suspicious family history.…”

Section: Corresponding Author Introductionmentioning

confidence: 99%

Implementation of a Telehealth Genetic Testing Station to Deliver Germline Testing for Men With Prostate Cancer

Kwon

Gordon

Tong

et al. 2023

JCO Oncology Practice

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PURPOSE: Germline testing for men with prostate cancer (PCa) poses numerous implementation barriers. Alternative models of care delivery are emerging, but implementation outcomes are understudied. We evaluated implementation outcomes of a hybrid oncologist– and genetic counselor–delivered model called the genetic testing station (GTS) created to streamline testing and increase access. METHODS: A prospective, single-institution, cohort study of men with PCa referred to the GTS from October 14, 2019, to October 14, 2021, was conducted. Using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, we described patients referred to GTS (Reach), the association of GTS with germline testing completion rates within 60 days of a new oncology appointment in a pre- versus post-GTS multivariable logistic regression (Effectiveness), Adoption, Implementation, and Maintenance. Because GTS transitioned from an on-site to remote service during the COVID-19 pandemic, we also compared outcomes for embedded versus remote GTS. RESULTS: Overall, 713 patients were referred to and eligible for GTS, and 592 (83%) patients completed germline testing. Seventy-six (13%) patients had ≥ 1 pathogenic variant. Post-GTS was independently associated with higher odds of completing testing within 60 days than pre-GTS (odds ratio, 8.97; 95% CI, 2.71 to 29.75; P < .001). Black race was independently associated with lower odds of testing completion compared with White race (odds ratio, 0.35; 95% CI, 0.13 to 0.96; P = .042). There was no difference in test completion rates or patient-reported decisional conflict for embedded versus remote GTS. GTS has been adopted by 31 oncology providers across four clinics, and implementation fidelity was high with low patient loss to follow-up, but staffing costs are a sustainability concern. CONCLUSION: GTS is a feasible, effective model for high-volume germline testing in men with PCa, both in person and using telehealth. GTS does not eliminate racial disparities in germline testing access.

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“…Nowadays, with the advancement of gene sequencing technology, somatic gene mutation analysis is more and more widely used in clinical practice ( 5 ). Different mutation status can be used to identify different molecular subtypes and thus predict prognosis and guide treatment.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer

et al. 2022

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BackgroundAlthough TP53 and SPOP are frequently mutated in metastatic prostate cancer (PCa), their prognostic value is ambiguous, and large sample studies are lacking, especially when they co-occur with other genetic alterations.MethodsGenomic data and patients’ clinical characteristics in PCa were downloaded from the cBioPortal database. We extensively analyzed other gene alterations in different mutation status of TP53 and SPOP. We further subdivided TP53 and SPOP mutation into subgroups based on different mutation status, and then evaluated the prognostic value. Two classification systems for TP53 survival analysis were used.ResultsA total of 2,172 patients with PCa were analyzed in our study, of which 1,799 were metastatic PCa patients. The mutual exclusivity analysis showed that TP53 and SPOP mutation has a strong mutual exclusion (p<0.001). In multivariable analysis, truncating TP53 mutations (HR=1.773, 95%CI:1.403-2.239, p<0.001) and other TP53 mutations(HR=1.555, 95%CI:1.267-1.908, p<0.001) were independent negative prognostic markers in metastatic PCa, whereas SPOP mutations(HR=0.592, 95%CI:0.427-0.819, p<0.001) were an independent prognostic factor for better prognosis. Mutations in TP53 were significantly associated with wild-type status for SPOP and CDK12, structural variants/fusions for TMPRSS2 and ERG, AR amplification and PTEN deletion (p<0.001). And truncating TP53 mutations have higher AR amplification rates than other TP53 mutations (p=0.022). Consistently, truncating TP53 mutations had a worse prognosis than other TP53 mutations (p<0.05). Then Kaplan-Meier survival curve showed that Co-occurring TP53 mutations in AR amplification or PTEN deletion tumors significantly reduced survival (p<0.05). Furthermore, those with SPOP-mutant tumors with co-occurring TP53 truncating mutations had shorter overall survival than those with SPOP-mutant tumors with wild-type or other TP53 mutations.ConclusionsThis study found that TP53 and SPOP mutations were mutually exclusive and both were independent prognostic markers for metastatic PCa. Genomic alteration and survival analysis revealed that TP53 and SPOP mutations represented distinct molecular subtypes. Our data suggest that molecular stratification on the basis of TP53 and SPOP mutation status should be implemented for metastatic PCa to optimize and modify clinical decision-making.

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Germline testing and genetic counselling in prostate cancer

Cited by 32 publications

References 74 publications

Clinical performance of magnetic resonance imaging and biomarkers for prostate cancer diagnosis in men at high genetic risk

Clinical performance of magnetic resonance imaging and biomarkers for prostate cancer diagnosis in men at high genetic risk

Implementation of a Telehealth Genetic Testing Station to Deliver Germline Testing for Men With Prostate Cancer

Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer

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