Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice

Genetic Testing Among Patients with High-Risk Breast, Ovarian, Pancreatic, and Prostate Cancers

Mainstream germline genetic testing for patients with epithelial ovarian cancer leads to higher testing rates and a reduction in genetics-related healthcare costs from a healthcare payer perspective.

Health professionals not specialized in genetics are expected to take an increasing role in genetic services delivery. This article aims to identify legal and ethical challenges related to a collaborative oncogenetics service model, where non-genetic health professionals provide genetic services to patients. Through a scoping literature review, we identified issues to the provision of hereditary breast and ovarian cancer, or other hereditary adult cancers, genetic testing under this model. Concerns that arose in the literature were informed consent, lack of adherence to best practice guidelines, lack of education of non-genetic health professionals on the provision of genetic services, psychological impacts of genetic testing, continuity of care, the complexity of genetic test results, confidentiality, risks of medical mismanagement, and the associated medical responsibility liabilities. Despite these challenges, there is a growing consensus towards the feasibility of cancer genetic testing being undertaken by non-genetic healthcare professionals in a collaborative oncogenetics service model. 

Integrating hereditary breast and ovarian cancer genetic counselling and testing into mainstream clinical practice: Legal and ethical challenges.

Muscle invasive bladder cancer (MIBC) is a common malignancy amongst elderly. Increasing life expectancy, prevalence of smoking, lifelong exposure to environmental pollutants and immunosenescence contribute to growing number of cases. Traditionally, radical cystectomy (RC) with pelvic lymph node dissection (PLND) constituted the mainstay of treatment for MIBC, but despite proven feasibility in elderly population, it has been associated with significant burden of morbidity, mortality, and complications.We aimed to re-evaluate the safety and efficacy of RC amongst the elderly patients with MIBC.This single-center, retrospective, observational comparative study was conducted among 568 patients who underwent RC due to MIBC between 2003 and 2021. We evaluated the influence of chronological age (<70 vs ≥70 years) on clinical, demographic, and pathological variables related to MIBC and RC.Elderly patients had similar clinical and pathological features of disease compared to their younger counterparts; nonetheless, they more often received simplified urinary diversion, ie ureterostomy (60.25% vs 39.33%, p<0.001) and had no PLND (15.76% vs 8.5%, p=0.01) during RC. Furthermore, more elderly patients were treated for secondary MIBCs and fewer had history of smoking. Severe complication and 90-day mortality rates were comparable between groups; however, the elderly had significantly higher all-cause mortality at one year post RC (46.67% vs 33.25%, p=0.003). On multivariate analysis, one-year mortality risk was independently associated with elderly age (HR=2.119, 95% CI: 1.227-3.660, p=0.007), rural residency (HR=1.760, 95% CI: 1.043-2.968, p=0.034), extravesical extension of tumor (HR=2.109, 95% CI: 1.155-3.850, p=0.015), lymph node metastasis (HR=2.268, 95% CI: 1.290-3.987, p=0.004) and omission of PLND (HR=6.064, 95% CI: 2.926-12.568, p<0.001).Radical cystectomy in elderly patients is associated with significant one-year mortality. Our study emphasizes the unmet need for considerate planning of treatment for MIBC in potentially vulnerable groups of elderly patients. Efforts are needed to reliably identify those unlikely to benefit from surgery and facilitate patient-centered choice of alternative therapies. 

Increased One-Year Mortality Among Elderly Patients After Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Retrospective, Observational Comparative Study

Simple Summary Germline genetic testing for patients with cancer can have important implications for treatment, preventive options, and for family members. In a mainstream genetic testing pathway, pre-test counseling is performed by non-genetic healthcare professionals, thereby making genetic testing more accessible to all patients who might benefit from it. These mainstream genetic testing pathways are being implemented in different hospitals around the world, and for different cancer types. It is important to evaluate how a mainstream genetic testing pathway can be made sustainable and if quality of genetic care is maintained. We show in this systematic review that it is feasible to incorporate a mainstream genetic testing pathway into routine cancer care while maintaining quality of care. A training procedure for non-genetic healthcare professionals and a close collaboration between genetics and other clinical departments are highly recommended to ensure sustainability. Abstract Background: Non-genetic healthcare professionals can provide pre-test counseling and order germline genetic tests themselves, which is called mainstream genetic testing. In this systematic review, we determined whether mainstream genetic testing was feasible in daily practice while maintaining quality of genetic care. Methods: PubMed, Embase, CINAHL, and PsychINFO were searched for articles describing mainstream genetic testing initiatives in cancer care. Results: Seventeen articles, reporting on 15 studies, met the inclusion criteria. Non-genetic healthcare professionals concluded that mainstream genetic testing was possible within the timeframe of a routine consultation. In 14 studies, non-genetic healthcare professionals completed some form of training about genetics. When referral was coordinated by a genetics team, the majority of patients carrying a pathogenic variant were seen for post-test counseling by genetic healthcare professionals. The number of days between cancer diagnosis and test result disclosure was always lower in the mainstream genetic testing pathway than in the standard genetic testing pathway (e.g., pre-test counseling at genetics department). Conclusions: Mainstream genetic testing seems feasible in daily practice with no insurmountable barriers. A structured pathway with a training procedure is desirable, as well as a close collaboration between genetics and other clinical departments.

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The Feasibility of Implementing Mainstream Germline Genetic Testing in Routine Cancer Care—A Systematic Review

Background Despite treatment with radical cystectomy, patients with muscle invasive bladder cancer (MIBC) have a poor survival. It has been reported that survival is worse in NMIBC patients who progressed to MIBC in comparison to patients with de novo MIBC. The objective of this study was to compare survival of progressive versus de novo MIBC. Secondary objective was to explain this difference in survival by clinicopathological factors. Methods 431 patients with MIBC who underwent radical cystectomy between 1998 and 2016 in the Radboudumc, Nijmegen, were retrospectively analyzed. 313 patients were identified with de novo MIBC and 118 with progressive MIBC. Results 5- and 10-year overall survival (OS) of patients with progressive MIBC was 37% and 20%, respectively. Patients with de novo MIBC had significantly better survival, with a 5- and 10-year OS of 49% and 39%, respectively. Patients with progressive MIBC were more frequently diagnosed with concomitant carcinoma in situ and positive surgical margins in bladder, ureters or urethra. In multivariable analysis that adjusted for these factors, progressive MIBC was associated with a hazard ratio of 1.40 (0.99 – 1.98). Kaplan-Meier survival curves show a detrimental effect of progressive MIBC in patients with pT2 versus pT3–4 tumors and in patients with negative versus positive surgical margins. In multivariable analysis, this effect modification disappeared. Conclusions Progressive MIBC is associated with poorer survival than de novo MIBC. Because most patients with progressive MIBC had a history of high risk NMIBC, considering radical cystectomy is most important in the highest risk NMIBC.

Survival after radical cystectomy: Progressive versus De novo muscle invasive bladder cancer.

Multicentric validation of diagnostic tests based on BC-116 and BC-106 urine peptide biomarkers for bladder cancer in two prospective cohorts of patients

In international guidelines, germline genetic testing is recommended for patients with metastatic prostate cancer. Before undergoing germline genetic testing, these patients should receive pre-test counseling. In the standard genetic care pathway, pre-test counseling is provided by a healthcare professional of a genetics department. Because the number of patients with metastatic prostate cancer is large, the capacity in the genetics departments might be insufficient. Therefore, we aim to implement so-called mainstream genetic testing in the Netherlands for patients with metastatic prostate cancer. In a mainstream genetic testing pathway, non-genetic healthcare professionals discuss and order germline genetic testing. In our DISCOVER study, we will assess the experiences among patients and non-genetic healthcare professionals with this new pathway.A multicenter prospective observational cohort study will be conducted in 15 hospitals, in different regions of the Netherlands. We developed an online training module on genetics in prostate cancer and the counseling of patients. After completion of this module, non-genetic healthcare professionals will provide pre-test counseling and order germline genetic testing in metastatic prostate cancer patients. Both non-genetic healthcare professionals and patients receive three questionnaires. We will determine the experience with mainstream genetic testing, based on satisfaction and acceptability. Patients with a pathogenic germline variant will also be interviewed. We will determine the efficacy of the mainstreaming pathway, based on time investment for non-genetic healthcare professionals and the prevalence of pathogenic germline variants.This study is intended to be one of the largest studies on mainstream genetic testing in prostate cancer. The results of this study can improve the mainstream genetic testing pathway in patients with prostate cancer.The study is registered in the WHO's International Clinical Trials Registry Platform (ICTRP) under number NL9617. 

/pdf/mainstream-germline-genetic-testing-in-men-with-metastatic-2ibrx15o.pdf

Mainstream germline genetic testing in men with metastatic prostate cancer: design and protocol for a multicenter observational study

Multicentric validation of nomograms based on urine peptide biomarkers for bladder cancer diagnostics and monitoring in two prospective cohorts of patients

Michiel Vlaming

Papers

The Feasibility of Implementing Mainstream Germline Genetic Testing in Routine Cancer Care—A Systematic Review

Survival after radical cystectomy: Progressive versus De novo muscle invasive bladder cancer.

Multicentric validation of diagnostic tests based on BC-116 and BC-106 urine peptide biomarkers for bladder cancer in two prospective cohorts of patients

Mainstream germline genetic testing in men with metastatic prostate cancer: design and protocol for a multicenter observational study

Multicentric validation of nomograms based on urine peptide biomarkers for bladder cancer diagnostics and monitoring in two prospective cohorts of patients