PSA, an outdated biomarker for prostate cancer: In search of a more specific biomarker, citrate takes the spotlight.

The prevailing biomarker employed for prostate cancer (PCa) screening and diagnosis is the prostate-specific antigen (PSA). Despite excellent sensitivity, PSA lacks specificity, leading to false positives, unnecessary biopsies and overdiagnosis. Consequently, PSA is increasingly less used by clinicians, thus underscoring the imperative for the identification of new biomarkers. An emerging biomarker in this context is citrate, a molecule secreted by the normal prostate, which has been shown to be inversely correlated with PCa. Here, we discuss about PSA and its usage for PCa diagnosis, its lack of specificity, and the various conditions that can affect its levels. We then provide our vision about what we think would be a valuable addition to our PCa diagnosis toolkit, citrate. We describe the unique citrate metabolic program in the prostate and how this profile is reprogrammed during carcinogenesis. Finally, we summarize the evidence that supports the usage of citrate as a biomarker for PCa diagnosis, as it can be measured in various patient samples and be analyzed by several methods. The unique relationship between citrate and PCa, combined with the stability of citrate levels in other prostate-related conditions and the simplicity of its detection, further accentuates its potential as a biomarker.

Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities.

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

Mapping inter-professional collaboration in oncogenetics: Results from a scoping review.

Inter-professional collaboration could improve timely access and quality of oncogenetic services. Here, we present the results of a scoping review conducted to systematically identify collaborative models available, unpack the nature and extent of collaboration proposed, synthesize evidence on their implementation and evaluation, and identify areas where additional research is needed. A comprehensive search was conducted in four journal indexing databases on June 13th, 2022, and complemented with searches of the grey literature and citations. Screening was conducted by two independent reviewers. Eligible documents included those describing either the theory of change, planning, implementation and/or evaluation of collaborative oncogenetic models. 165 publications were identified, describing 136 unique interventions/studies on oncogenetic models with somewhat overlapping collaborative features. Collaboration appears to be mostly inter-professional in nature, often taking place during risk assessment and pre-testing genetic counseling. Yet, most publications provide very limited information on their collaborative features, and only a few studies have set out to formally evaluate them. Better quality research is needed to comprehensively examine and make conclusions regarding the value of collaboration in this oncogenetics. We propose a definition, logic model, and typology of collaborative oncogenetic models to strengthen future planning, implementation, and evaluation in this field.

Disruptions in Cancer Care Due to the COVID-19 Pandemic and Fear of Cancer Recurrence in Women with Breast Cancer: A Mixed-Methods Study.

OBJECTIVE: This study investigated if fear of cancer recurrence (FCR) levels and the proportion of women having a clinical level of FCR differed by whether women had or had not experienced disruptions in their cancer tests and treatments due to the pandemic. METHODS: We conducted a mixed-methods study between November 2020 and March 2021 among women diagnosed with breast cancer in the previous five years at the time of their entry in the study. Women completed a questionnaire online assessing disruptions in breast cancer tests and treatments due to the pandemic and the severity subscale of the Fear of Cancer Recurrence Inventory. Semi-structured interviews were also conducted with a subsample of 24 participants and were thematically analyzed. RESULTS: The proportion of patients with a clinical level of FCR was significantly higher among those who experienced the postponement or cancellation of diagnostic and disease progression tests (e.g., blood tests, X-rays, or magnetic resonance imaging; adjusted PR = 1.27 95% CI = 1.13-1.43). Qualitative findings suggest that FCR was exacerbated by the pandemic context. In particular, perceived or actual barriers to care access due to the pandemic were identified as significant FCR-enhancing factors. CONCLUSIONS: These results highlight the need to keep diagnostic and progression tests as timely as possible to prevent increases in FCR levels and offer counselling about FCR when postponing or cancellation are inevitable.

A Systematic Review and Critical Assessment of Breast Cancer Risk Prediction Tools Incorporating a Polygenic Risk Score for the General Population.

Single nucleotide polymorphisms (SNPs) in the form of a polygenic risk score (PRS) have emerged as a promising factor that could improve the predictive performance of breast cancer (BC) risk prediction tools. This study aims to appraise and critically assess the current evidence on these tools. Studies were identified using Medline, EMBASE and the Cochrane Library up to November 2022 and were included if they described the development and/ or validation of a BC risk prediction model using a PRS for women of the general population and if they reported a measure of predictive performance. We identified 37 articles, of which 29 combined genetic and non-genetic risk factors using seven different risk prediction tools. Most models (55.0%) were developed on populations from European ancestry and performed better than those developed on populations from other ancestry groups. Regardless of the number of SNPs in each PRS, models combining a PRS with genetic and non-genetic risk factors generally had better discriminatory accuracy (AUC from 0.52 to 0.77) than those using a PRS alone (AUC from 0.48 to 0.68). The overall risk of bias was considered low in most studies. BC risk prediction tools combining a PRS with genetic and non-genetic risk factors provided better discriminative accuracy than either used alone. Further studies are needed to cross-compare their clinical utility and readiness for implementation in public health practices.

Canadian Healthcare Professionals' Views and Attitudes toward Risk-Stratified Breast Cancer Screening.

Given the controversy over the effectiveness of age-based breast cancer (BC) screening, offering risk-stratified screening to women may be a way to improve patient outcomes with detection of earlier-stage disease. While this approach seems promising, its integration requires the buy-in of many stakeholders. In this cross-sectional study, we surveyed Canadian healthcare professionals about their views and attitudes toward a risk-stratified BC screening approach. An anonymous online questionnaire was disseminated through Canadian healthcare professional associations between November 2020 and May 2021. Information collected included attitudes toward BC screening recommendations based on individual risk, comfort and perceived readiness related to the possible implementation of this approach. Close to 90% of the 593 respondents agreed with increased frequency and earlier initiation of BC screening for women at high risk. However, only 9% agreed with the idea of not offering BC screening to women at very low risk. Respondents indicated that primary care physicians and nurse practitioners should play a leading role in the risk-stratified BC screening approach. This survey identifies health services and policy enhancements that would be needed to support future implementation of a risk-stratified BC screening approach in healthcare systems in Canada and other countries.

Regulating cancer risk prediction: legal considerations and stakeholder perspectives on the Canadian context.

Risk prediction models hold great promise to reduce the impact of cancer in society through advanced warning of risk and improved preventative modalities. These models are evolving and becoming more complex, increasingly integrating genetic screening data and polygenic risk scores as well as calculating risk for multiple types of a disease. However, unclear regulatory compliance requirements applicable to these models raise significant legal uncertainty and new questions about the regulation of medical devices. This paper aims to address these novel regulatory questions by presenting an initial assessment of the legal status likely applicable to risk prediction models in Canada, using the CanRisk tool for breast and ovarian cancer as an exemplar. Legal analysis is supplemented with qualitative perspectives from expert stakeholders regarding the accessibility and compliance challenges of the Canadian regulatory framework. While the paper focuses on the Canadian context, it also refers to European and U.S. regulations in this domain to contrast them. Legal analysis and stakeholder perspectives highlight the need to clarify and update the Canadian regulatory framework for Software as a Medical Device as it applies to risk prediction models. Findings demonstrate how normative guidance perceived as convoluted, contradictory or overly burdensome can discourage innovation, compliance, and ultimately, implementation. This contribution aims to initiate discussion about a more optimal legal framework for risk prediction models as they continue to evolve and are increasingly integrated into landscape for public health.

Risk-Stratified Breast Cancer Screening Incorporating a Polygenic Risk Score: A Survey of UK General Practitioners' Knowledge and Attitudes.

A polygenic risk score (PRS) quantifies the aggregated effects of common genetic variants in an individual. A 'personalised breast cancer risk assessment' combines PRS with other genetic and nongenetic risk factors to offer risk-stratified screening and interventions. Large-scale studies are evaluating the clinical utility and feasibility of implementing risk-stratified screening; however, General Practitioners' (GPs) views remain largely unknown. This study aimed to explore GPs': (i) knowledge of risk-stratified screening; (ii) attitudes towards risk-stratified screening; and (iii) preferences for continuing professional development. A cross-sectional online survey of UK GPs was conducted between July-August 2022. The survey was distributed by the Royal College of General Practitioners and via other mailing lists and social media. In total, 109 GPs completed the survey; 49% were not familiar with the concept of PRS. Regarding risk-stratified screening pathways, 75% agreed with earlier and more frequent screening for women at high risk, 43% neither agreed nor disagreed with later and less screening for women at lower-than-average risk, and 55% disagreed with completely removing screening for women at much lower risk. In total, 81% felt positive about the potential impact of risk-stratified screening towards patients and 62% felt positive about the potential impact on their practice. GPs selected training of healthcare professionals as the priority for future risk-stratified screening implementation, preferring online formats for learning. The results suggest limited knowledge of PRS and risk-stratified screening amongst GPs. Training-preferably using online learning formats-was identified as the top priority for future implementation. GPs felt positive about the potential impact of risk-stratified screening; however, there was hesitance and disagreement towards a low-risk screening pathway.

Adherence to CONSORT Guidelines and Reporting of the Determinants of External Validity in Clinical Oncology Randomized Controlled Trials: A Review of Trials Published in Four Major Journals between 2013 and 2015.

Our primary objective was to determine the proportion of trials that report the number of patients assessed for eligibility before randomization. We performed the systematic retrieval and analysis of all phase II, III, and IV RCTs published between 2013 and 2015 in four high-impact-factor journals in the field of clinical oncology. Among 456 RCTs reviewed, 236 trials (51.8%) reported the number of patients assessed for eligibility. Among the 236 trials that reported the entire enrollment process, the reasons for patient exclusion could be found in 184 trials (78%). A flow diagram was presented in 452 trials (99.1%), and 98 trials (21.5%) included a discussion on generalizability. Reporting the parameters of external validity in medical oncology RCTs is challenging. Improving adherence to the 2010 CONSORT guidelines concerning the enrollment process could help clinicians and health policymakers establish to whom trial results apply.

Scope of coverage of medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine: A curriculum analysis.

We appraised the scope of medical genetics and genomics concepts covered in the pre-clerkship programs of Canadian faculties of medicine through an analysis of course objectives. All course objectives linked to medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine were compiled. From this, the fraction of objectives dedicated to medical genetics and genomics was calculated. Course objectives were also categorized according to a curriculum and a competency classification. Of the 17 Canadian faculties of medicine, the complete set of course syllabi (5 faculties) or the listing of learning objectives (4 faculties) were obtained and reviewed. The fraction of learning objectives dedicated to medical genetics and genomics varied between 0.65% and 5.05%. From the objectives classification, "foundational knowledge" was most frequently covered (64% of the compiled objectives), while topics such as: "ethics and professionalism," "communicate genetics information," and "obtain specialist help" were covered by less than 5%. Coverage of medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine appears to be low. Genetics and genomics are playing a rapidly expanding role in healthcare and clinical practice and educational programs should consider this new reality.

Examining interprofessional collaboration in oncogenetic service delivery models for hereditary cancers: a scoping review protocol.

INTRODUCTION: In a context of limited genetic specialists, collaborative models have been proposed to ensure timely access to high quality oncogenetic services for individuals with inherited cancer susceptibility. Yet, extensive variability in the terminology used and lack of a clear understanding of how interprofessional collaboration is operationalised and evaluated currently constrains the development of a robust evidence base on the value of different approaches used to optimise access to these services. To fill in this knowledge gap, this scoping review aims to systematically unpack the nature and extent of collaboration proposed by these interventions, and synthesise the evidence available on their implementation, effectiveness and economic impact. METHODS AND ANALYSIS: Following the Joanna Briggs Institute guidelines for scoping reviews, a comprehensive literature search will be conducted to identify peer-reviewed and grey literature on collaborative models used for adult patients with, or at increased risk of, hereditary breast, ovarian, colorectal and prostate cancers. An initial search was developed for Medline, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane and Web of Science on 13 June 2022 and will be complemented by searches in Google and relevant websites. Documents describing either the theory of change, planning, implementation and/or evaluation of these interventions will be considered for inclusion. Results will be summarised descriptively and used to compare relevant model characteristics and synthesise evidence available on their implementation, effectiveness and economic impact. This process is expected to guide the development of a definition and typology of collaborative models in oncogenetics that could help strengthen the knowledge base on these interventions. Moreover, because we will be mapping the existing evidence on collaborative models in oncogenetics, the proposed review will help us identify areas where additional research might be needed. ETHICS AND DISSEMINATION: This research does not require ethics approval. Results from this review will be disseminated through peer-reviewed articles and conferences.

Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals.

PURPOSE: Health care professionals are expected to take on an active role in the implementation of risk-based cancer prevention strategies. This study aimed to explore health care professionals' (1) self-reported familiarity with the concept of polygenic risk score (PRS), (2) perceived level of knowledge regarding risk-stratified breast cancer (BC) screening, and (3) preferences for continuing professional development. METHODS: A cross-sectional survey was conducted using a bilingual-English/French-online questionnaire disseminated by health care professional associations across Canada between November 2020 and May 2021. RESULTS: A total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%). Online courses and webinar conferences were the preferred continuing professional development modalities. CONCLUSION: The study indicates that health care professionals are currently not familiar with the concept of PRS or a risk-stratified approach for BC screening. Online information and training seem to be an essential knowledge transfer modality.

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

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.

Personalized Approaches for the Prevention and Treatment of Breast Cancer.

Breast cancer (BC) remains a major public health issue worldwide [...].

Issues associated with a hereditary risk of cancer: Knowledge, attitudes and practices of nurses in oncology settings.

Documenting a patient's family history of cancer is useful in assessing their predisposition to some types of hereditary cancers. A group of nurses working with cancer patients were surveyed, by way of a questionnaire, to determine their level of knowledge about oncogenetics, describe various issues related to their capacity to identify, refer and support individuals with a hereditary risk of cancer, and explore their interest in continuing education on this topic. The findings show limited knowledge and a low sense of competence among the participating nurses, as well as a lack of access to university and continuing education programs in this field. Training focused on competency development would enhance their capacity to carry out an initial assessment of individuals who are potentially at risk for cancer and refer them to specialized resources.

Cross-Cultural Adaptation and Validation of a French Version of the Genetic Counseling Satisfaction Scale (GCSS) as an Outcome Measure of Genetic Counseling for Hereditary Breast and Ovarian Cancer.

(1) Background: The Genetic Counseling Satisfaction Scale (GCSS) is a widely used tool to evaluate patient satisfaction. To our knowledge, a validated French-language version of this tool is not yet available. This article reports on the cross-cultural adaptation and validation of a French version of the Genetic Counseling Satisfaction Scale (GCSS) to evaluate genetic counseling services for patient consultation in hereditary breast and ovarian cancer (HBOC). (2) Methods: The scale was culturally adapted following guidelines from Beaton et al. (2000). Cognitive interviews were conducted to ensure items were understood according to the intended meaning. The internal consistency, floor and ceiling effects, and testing of group differences were assessed using a sample of 172 patients who attended a pretest group genetic counseling session. (3) Results: Participants understood all items according to the intended meaning. The internal consistency was high for the total scale (0.90) and for the corrected item-to-total correlations (varying between 0.62 and 0.78). No floor or ceiling effects were observed. Group difference analyses generally followed expectations. (4) Conclusion: This process generated a French version of the GCSS that is clearly understood by patients, and has psychometric properties adequately in line those reported for its original English version.

Identifying Clinicopathological Factors Associated with Oncotype DX® 21-Gene Recurrence Score: A Real-World Retrospective Cohort Study of Breast Cancer Patients in Quebec City, Canada.

Gene expression profiling tests such as the Oncotype DX (ODX) 21-gene recurrence score (RS) assay is increasingly used in clinical practice to predict the risk of recurrence and support treatment planning for early-stage breast cancer (BC). However, this test has some disadvantages such as a high cost and a long turnaround time to get results, which may lead to disparities in access. We aim to identify clinicopathological factors associated with ODX RS in women with early-stage BC. We conducted a retrospective cohort study of women identified in the medical database of the Deschênes-Fabia Breast Disease Center of Quebec City University, Canada. Our sample consists of 425 women diagnosed with early-stage BC who have obtained an ODX RS between January 2011 and April 2015. The ODX RS has been categorized into three levels as originally defined: low (0-17), intermediate (18-30), and high (>30). The mean RS was 17.8 (SD = 9.2). Univariate analyses and multinomial logistic regressions were performed to identify factors associated with intermediate and high RS compared with low RS. A total of 237 (55.8%) patients had low RS, 148 (34.8%) had intermediate RS, and 40 (9.4%) had high RS. Women with progesterone receptor (PR)-negative (ORs ranging from 3.51 to 10.34) and histologic grade II (ORs ranging from 3.16 to 23.04) tumors were consistently more likely to have intermediate or high RS than low RS. Similar patterns of associations were observed when the RS was categorised using redefined thresholds from (i.e., from the TAILORx study or dichotomized). This study provides evidence suggesting that histologic grade and PR status are predictive factors for intermediate or high RS in women with early-stage BC. If these results are confirmed in future studies, considering these clinicopathological factors could spare women the need to get such a test before the beginning of a possible adjuvant therapy. This option could be considered in settings where the cost of testing is an issue.

Should Age-Dependent Absolute Risk Thresholds Be Used for Risk Stratification in Risk-Stratified Breast Cancer Screening?

In risk-stratified cancer screening, multiple risk factors are incorporated into the risk assessment. An individual's estimated absolute cancer risk is linked to risk categories with tailored screening recommendations for each risk category. Absolute risk, expressed as either remaining lifetime risk or shorter-term (five- or ten-year) risk, is estimated from the age at assessment. These risk estimates vary by age; however, some clinical guidelines (e.g., enhanced breast cancer surveillance guidelines) and ongoing personalised breast screening trials, stratify women based on absolute risk thresholds that do not vary by age. We examine an alternative approach in which the risk thresholds used for risk stratification vary by age and consider the implications of using age-independent risk thresholds on risk stratification. We demonstrate that using an age-independent remaining lifetime risk threshold approach could identify high-risk younger women but would miss high-risk older women, whereas an age-independent 5-year or 10-year absolute risk threshold could miss high-risk younger women and classify lower-risk older women as high risk. With risk misclassification, women with an equivalent risk level would be offered a different screening plan. To mitigate these problems, age-dependent absolute risk thresholds should be used to inform risk stratification.