Prostate Cancer Canada

The current prostate cancer (PCa) screen test, prostate-specific antigen (PSA), has a high sensitivity for PCa but low specificity for high-risk, clinically significant PCa (csPCa), resulting in overdiagnosis and overtreatment of non-csPCa. Early identification of csPCa while avoiding unnecessary biopsies in men with non-csPCa is challenging. We built an optimized machine learning platform (ClarityDX) and showed its utility in generating models predicting csPCa. Integrating the ClarityDX platform with blood-based biomarkers for clinically significant PCa and clinical biomarker data from a 3448-patient cohort, we developed a test to stratify patients’ risk of csPCa; called ClarityDX Prostate. When predicting high risk cancer in the validation cohort, ClarityDX Prostate showed 95% sensitivity, 35% specificity, 54% positive predictive value, and 91% negative predictive value, at a ≥ 25% threshold. Using ClarityDX Prostate at this threshold could avoid up to 35% of unnecessary prostate biopsies. ClarityDX Prostate showed higher accuracy for predicting the risk of csPCa than PSA alone and the tested model-based risk calculators. Using this test as a reflex test in men with elevated PSA levels may help patients and their healthcare providers decide if a prostate biopsy is necessary.

BackgroundThere is an unmet clinical need for minimally invasive diagnostic tests to improve the detection of grade group (GG) ≥3 prostate cancer relative to prostate antigen‐specific risk calculators. We determined the accuracy of the blood‐based extracellular vesicle (EV) biomarker assay (EV Fingerprint test) at the point of a prostate biopsy decision to predict GG ≥3 from GG ≤2 and avoid unnecessary biopsies.MethodsThis study analyzed 415 men referred to urology clinics and scheduled for a prostate biopsy, were recruited to the APCaRI 01 prospective cohort study. The EV machine learning analysis platform was used to generate predictive EV models from microflow data. Logistic regression was then used to analyze the combined EV models and patient clinical data and generate the patients' risk score for GG ≥3 prostate cancer.ResultsThe EV‐Fingerprint test was evaluated using the area under the curve (AUC) in discrimination of GG ≥3 from GG ≤2 and benign disease on initial biopsy. EV‐Fingerprint identified GG ≥3 cancer patients with high accuracy (0.81 AUC) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cutoff, 95% of men with GG ≥3 would have been recommended a biopsy while avoiding 144 unnecessary biopsies (35%) and missing four GG ≥3 cancers (5%). Conversely, a 5% cutoff would have avoided 31 unnecessary biopsies (7%), missing no GG ≥3 cancers (0%).ConclusionsEV‐Fingerprint accurately predicted GG ≥3 prostate cancer and would have significantly reduced unnecessary prostate biopsies.

Prostate cancer (PCa) is one of the most commonly diagnosed types of malignancy and is the second leading cause of cancer-related death in men in developed countries. Cyclin dependent kinase 2 associate protein 1(CDK2AP1) is an epigenetic and cell cycle regulator gene which has been downregulated in several malignancies, but its involvement in PCa has not yet been investigated in a clinical setting. We assessed the prognostic value of CDK2AP1 expression in a cohort of men diagnosed with PCa (n = 275) treated non-surgically by transurethral resection of the prostate (TURP) and studied the relationship between CDK2AP1 expression to various PCa molecular subtypes (ERG, PTEN, p53 and AR) and evaluated the association with clinical outcome. Further, we used bioinformatic tools to analyze the available TCGA PRAD transcriptomic data to explore the underlying mechanism. Our data confirmed increased expression of CDK2AP1 with higher Gleason Grade Group (GG) and metastatic PCa (p <0.0001). High CDK2AP1 expression was associated with worse overall survival (OS) (HR: 1.62, CI: 1.19-2.21, p = 0.002) and cause-specific survival (CSS) (HR: 2.012, CI 1.29-3.13, p = 0.002) using univariate analysis. When compared to each sub-molecular type. High CDK2AP1/PTEN-loss, abnormal AR or p53 expression showed even worse association to poorer OS and CCS and remained significant when adjusted for GG. Our data indicates that CDK2AP1 directly binds to p53 using the Co-Immunoprecipitation (Co-IP) technique, which was validated using molecular docking tools. This suggests that these two proteins have a significant association through several binding features and correlates with our observed clinical data. In conclusion, our results indicated that the CDK2AP1 overexpression is associate with worse OS and CSS when combined with certain PCa molecular subtypes; interaction between p53 stands out as the most prominent candidate which directly interacts with CDK2AP1.

This study aimed to highlight the biopsychosocial recommendations provided to prostate cancer survivors and their partners during sexual rehabilitation. Retrospective analysis of a prospectively maintained patient database was conducted for visits between 2013 and 2019. The sexual health rehabilitation action plan (SHRAP) is a standardized 29-item list of biopsychosocial recommendations. The frequency of biopsychosocial recommendations provided to patients via their SHRAPs was assessed. Among 913 patients, across 2671 appointments, nearly 74% of patients underwent radical prostatectomy. Other treatments included combination therapy (surgery, radiation, and/or androgen deprivation therapy (ADT)) (13%), radiation (external beam radiation or brachytherapy) (5%), and active surveillance (2%). Each patient had a median of 2 (SD 2.06) appointments and received a mean of 10.0 (SD 3.9) recommendations at each visit. Educational recommendations (penile rehabilitation, orgasmic guidelines, and climacturia management) were provided in 84% of visits followed by psychosexual recommendations (pleasure-focused, dedicated time, simmering, sexual aids, and sensate focus) in 71% of all appointments. The top recommendations (total n, frequency of recommendation) were penile rehabilitation (2253, 84%), pleasure-focus (1887, 71%), phosphodiesterase inhibitors (1655, 62%), clinical counselor (1603, 60%), vacuum erectile device (1418, 53%) and intracavernosal injections (1383, 52%). Biopsychosocial programs are evolving to be a key part of prostate cancer survivorship. This study's insight suggests that prostate cancer survivors require education around their sexual consequences and psychosexual counseling alongside proven biomedical strategies for erectile dysfunction. Cancer survivorship programs should integrate educational and psychosocial strategies alongside biological strategies for prostate cancer survivors and their partners.

243 Background: Androgen deprivation therapy (ADT) is commonly prescribed for advanced prostate cancer (PCa) patients, but ADT has many side effects that can impair patients’ quality of life. In various Canadian cities, we are running an educational program to help PCa patients and their partners deal with the side effects of ADT, and maintain a strong relationship with each other while on ADT. Methods: Patients, who are about to start or have been on ADT, and their partners are invited to attend an educational program. Each patient is given a copy of the book Androgen Deprivation Therapy: An essential guide for men with prostate cancer and their partners (Wassersug et al., 2014) and attends a 1.5 hour educational class, where they learn strategies for managing ADT side effects and how to effectively make healthier lifestyle changes using goal-setting exercises. At the end of the class, participants are given the option to attend a monthly follow-up session. To evaluate the effectiveness of the program, participants are asked to complete questionnaire package before attending the class and again 2-3 months later. Results: As of August 2015, 179 patients and 113 partners have attended the ADT Educational Program at Victoria, Vancouver, and Calgary. About 40% of patients returned for the follow-up session. 62 attendees participated in the research evaluation portion of the program. Uniquely designed for this study, the questionnaire package assesses ADT side effect frequency, bother associated with side effects, use of management strategies, and self-efficacy regarding side effect management. An assessment of physical activity and relationship adjustment, and feedback about the class are also included. Conclusions: Patients and partners appreciate being informed about ADT side effects managements and how to make healthier lifestyle changes while on ADT. It remains to be seen how effective the program is in limiting the bother from ADT side effects and helping couples maintain a strong dyadic relationship in the fact of the challenges brought on by ADT. Good enrollment in the in-person program in the 3 cities has propelled the development of the program in Halifax and Toronto starting in fall 2015, and an online version to be available in early 2016.

BackgroundMen with localized prostate cancer often have unrealistic expectations. Practitioners are poor judges of men’s preferences, contributing to preference misdiagnosis and unwarranted practice variation. Patient decision aids (PtDAs) can support men with decisions about localized prostate cancer. This is a comparative case study of two strategies for implementing PtDAs in clinical pathways for men with localized prostate cancer, evaluating (a) PtDA use; (b) impact on men, practitioners, and health system outcomes; and (c) factors influencing sustained use.Methods/designGuided by the Knowledge to Action Framework, this comparative case study will be conducted using administrative data, interviews, and surveys. Cases will be bound by geographic location (one hospital in Ontario; province of Saskatchewan) and time. Eligible participants will be all men newly diagnosed with localized prostate cancer, with outcomes assessed using administrative data and interviews. Nurses, urologists, radiation oncologists, and managers will be surveyed and a smaller sample interviewed. Cases will be established for each setting with findings compared across cases. Changes in the proportions of men given the PtDA over 2 years will be determined from administrative data. Factors associated with receiving the PtDA will be explored using multivariable logistic regression analysis. To assess the impact of the PtDA, outcomes will be described using mean and standard deviation (men’s decisional conflict) and frequency and proportions (practitioners consulted, uptake of treatment). To estimate the effect of the PtDA on these outcomes, adjusted mean differences and odds ratios will be calculated using exploratory multivariable general linear regression and binary or multinomial logistic regression. Factors influencing sustained PtDA use will be assessed using descriptive analysis of survey findings and thematic analysis of interview transcripts.DiscussionDetermining how to embed PtDAs effectively within clinical pathways for men with localized prostate cancer is essential. PtDAs have the potential to strengthen men’s active role in making prostate cancer decisions, enhance uptake of shared decision-making by practitioners, and reduce practice variation. Our team of researchers and knowledge users will use findings to improve current PtDA use and consider scaling-up implementation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13012-016-0451-1) contains supplementary material, which is available to authorized users.

Background. The prognostic significance of ERG expression in prostate cancer (PCA) has generated mixed results. We sought to investigate the prognostic significance of ERG expression in a localized cohort of men with PCA. Material and Methods. We investigated ERG protein expression in a cohort of 198 men with localized PCA. ERG expression was correlated with patients' clinical outcome and several pathological parameters, including Gleason score (GS), pathological stage, surgical margin, and extra-capsular extension. Results. ERG expression was detected in 86/198 (43.4%) patients exclusively in neoplastic epithelium. Overall, ERG mean expression intensity was 1.01 ± 1.27 versus 0.37 ± 0.83 in acinar PCA compared to foamy type PCA (P < 0.001). In HGPIN, ERG intensity levels were comparable to those in foamy type PCA (0.13 ± 0.56) but significantly lower than those in acinar PCA (P < 0.001). ERG expression was significantly associated with extra-prostatic extension and higher pathological stage and showed a trend toward seminal vesicle invasion. Herein, ERG expression was documented in 50/131 (38.1%) patients with pT2 versus 30/55 (54.5%) patients with pT3 (P = 0.04). ERG association with higher pathological stage was more pronounced in patients with GS > 7. Grouping patients into those with GS ≤ 7 versus >7, there was no significant association between ERG expression and GS. Similarly, no association was present in relation to either surgical margins or postsurgical serum PSA levels. Conclusion. We report significant association between ERG protein levels and extra-prostatic extension and higher pathological stage. ERG expression is not associated with adverse clinical outcome and is of limited prognostic value in localized PCA.

Background: Consumers with chronic conditions account for approximately 70% of all healthcare spending. The Chronic Care Model is a healthcare paradigm whose purpose is the achievement of improved patient outcomes by facilitating the delivery of patient-centered, evidence-based care. We conducted a review of the literature to examine the role patient accessible electronic health records (PAEHR) may play in implementing and supporting the Chronic Care Model. Methods: A review of the literature was conducted using multiple databases (1950-2012). Publications included in the review were restricted to those using experimental or quasi-experimental methodology, English language and peer review. Results: Published results indicated that PAEHR facilitated improvements in health literacy and patient-provider communication, and that personalization of content was viewed favourably. Research on the use of PAEHR by some disease groups suggest improvements in clinical outcomes. Conclusions: The literature reviewed indicated that the patient experience for individuals with chronic illnesses could be enhanced through access to PAEHR. Improved satisfaction was noted for individuals with access to PAEHR with personalized content (e.g lab results etc). Use of PAEHR also improved patient-provider communication and increased personal knowledge and comprehension concerning individual condition and state of health. PAEHR for individuals living with chronic illnesses are an effective management technique that can help patients better manage the challenges of living with a chronic illness. These results indicate PAEHR have the potential to be a key component for actualizing the theoretical constructs of the Chronic Care Model by providing a platform for increased patient-provider collaboration.