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Abstract To test for rates of inpatient palliative care (IPC) in metastatic testicular cancer patients receiving critical care therapy (CCT). Within the Nationwide Inpatient Sample (NIS) database (2008–2019), we tabulated IPC rates in metastatic testicular cancer patients receiving CCT, namely invasive mechanical ventilation (IMV), percutaneous endoscopic gastrostomy tube (PEG), dialysis for acute kidney failure (AKF), total parenteral nutrition (TPN) or tracheostomy. Univariable and multivariable logistic regression models addressing IPC were fitted. Of 420 metastatic testicular cancer patients undergoing CCT, 70 (17%) received IPC. Between 2008 and 2019, the rates of IPC among metastatic testicular cancer patients undergoing CCT increased from 5 to 19%, with the highest rate of 30% in 2018 (EAPC: + 9.5%; 95% CI + 4.7 to + 15.2%; p = 0.005). IPC patients were older (35 vs. 31 years, p = 0.01), more frequently had do not resuscitate (DNR) status (34 vs. 4%, p

ABSTRACT Background This study compared the physical activity level of men with metastatic prostate cancer at baseline of the multicentre INTERVAL‐GAP4 trial to the American Cancer Society guidelines and examined associations with physical fitness. Methods A total of 140 men on androgen deprivation therapy (ADT) were included in this cross‐sectional analysis of baseline data from the INTERVAL‐GAP4 trial. Exclusion criteria included a maximum of 1 h of vigorous aerobic exercise or one structured resistance exercise session per week but no restrictions on habitual physical activity. Moderate‐to‐vigorous physical activity (MVPA) was assessed using a modified Godin–Shephard Leisure‐Time Physical Activity Questionnaire. Physical fitness measurements included peak oxygen consumption (VO2peak), maximal power output (Wmax), 400 m walk time, one‐repetition maximum (1RM) of leg extension, leg press, chest press and seated row, and handgrip strength. Quantile regression was used to analyse associations of MVPA with physical fitness outcomes at the 25th, 50th and 75th percentiles of the physical fitness distributions. Results Total self‐reported MVPA was 60 (IQR: 0, 180) min per week, with 29% meeting the aerobic physical activity guidelines. There was a statistically significant association of higher MVPA with higher relative VO2peak at the 25th (β = 0.53, p = 0.020) and 75th percentiles (β = 0.66, p = 0.001), relative Wmax at the 25th (β = 0.05, p = 0.003), 50th (β = 0.05, p = 0.009) and 75th percentiles (β = 0.07, p = 0.004) and reduced 400 m walk time at the 75th percentile (β = −4.26, p = 0.023), with β corresponding to the change in the dependent variable for each one‐hour increase in weekly MVPA. Conclusion Few men recruited to the INTERVAL‐GAP4 trial were meeting aerobic physical activity guidelines at baseline. Higher MVPA was associated with better aerobic capacity and walking performance but not maximal strength in men with metastatic prostate cancer on ADT. Trial Registration ClinicalTrials.gov: NCT02730338; German Clinical Trials Register: DRKS00010310

Abstract. Objectives. This study aimed to test the association between of type and number of D'Amico high-risk criteria (DHRCs) with cancer-specific mortality (CSM) in high-risk prostate cancer patients treated with radical prostatectomy. Materials and methods. In the Surveillance, Epidemiology, and End Results database (2004–2016), we identified 31,281 radical prostatectomy patients with at least 1 DHRC, namely, prostate-specific antigen (PSA) >20 ng/mL (hrPSA), biopsy Gleason Grade Group (hrGGG) score of 4 and 5, or clinical tumor stage ≥T3 (hrcT). Multivariable Cox regression models and competing risks regression models (adjusting for other cause mortality) tested the association between DHRCs and 5-year CSM. Results. Of 31,281 patients, 14,394 (67%) exclusively harbored hrGGG, 3189 (15%) harbored hrPSA, and 1781 (8.2%) harbored hrcT. Only 2132 patients (6.8%) harbored a combination of the 2 DHRCs, and 138 (0.6%) had all 3 DHRCs. Five-year CSM rates ranged from 0.9% to 3.0% when any individual DHRC was present (hrcT, hrPSA, and hrGGG, in that order), 1.6% to 5.9% when 2 DHRCs were present (hrPSA-hrcT, hrcT-hrGGG, and hrPSA-hrGGG, in that order), and 8.1% when all 3 DHRCs were present. Cox regression models and competing risks regression confirmed the independent predictor status of DHRCs for 5-year CSM that was observed in univariable analyses, with hazard ratios from 1.00 to 2.83 for 1 DHRC, 2.35 to 5.88 for combinations of 2 DHRCs, and 7.13 for all 3 DHRCs. Conclusions. Within individual DHRCs, hrcT and hrPSA exhibited weaker effects than hrGGG did. Moreover, a dose-response effect was identified according to the number of DHRCs. Accordingly, the type and number of DHRCs allow further risk stratification within the high-risk subgroup.

Abstract Background In the global ARASENS study (NCT02799602), darolutamide plus androgen‐deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (177Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of 177Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of 177Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of 177Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies.

Abstract Malignancy grading of prostate cancer (PCa) is fundamental for risk stratification, patient counseling, and treatment decision-making. Deep learning has shown potential to improve the expert consensus for tumor grading, which relies on the Gleason score/grade grouping. However, the core problem of interobserver variability for the Gleason grading system remains unresolved. We developed a novel grading system for PCa and utilized artificial intelligence (AI) and multi-institutional international datasets from 2647 PCa patients treated with radical prostatectomy with a long follow-up of ≥10 years for biochemical recurrence and cancer-specific death. Through survival analyses, we evaluated the novel grading system and showed that AI could develop a tumor grading system with four risk groups independent from and superior to the current five grade groups. Moreover, AI could develop a scoring system that reflects the risk of castration resistant PCa in men who have experienced biochemical recurrence. Thus, AI has the potential to develop an effective grading system for PCa interpretable by human experts.

Background: Guidelines recommend VENUSS and GRANT models for the prediction of cancer control outcomes after nephrectomy for nonmetastatic papillary renal cell carcinoma (pRCC). Objective: To test the ability of VENUSS and GRANT models to predict 5-yr cancer-specific survival in a North American population. Design, setting, and participants: For this retrospective study, we identified 4184 patients with unilateral surgically treated nonmetastatic pRCC in the Surveillance, Epidemiology, and End Results database (2004–2019). Outcome measurements and statistical analysis: The original VENUSS and GRANT risk categories were applied to predict 5-yr cancer-specific survival. A cross-validation method was used to test the accuracy and calibration of the models and to conduct decision curve analyses for the study cohort. Results and limitations: The VENUSS and GRANT categories represented independent predictors of cancer-specific mortality. On cross-validation, the accuracy of the VENUSS and GRANT risk categories was 0.73 and 0.65, respectively. Both models showed good calibration and performed better than random predictions in decision curve analysis. Limitations include the retrospective nature of the study and the absence of a central pathological review. Conclusion: VENUSS risk categories fulfilled prognostic model criteria for predicting cancer-specific survival 5 yr after surgery in North American patients with nonmetastatic pRCC as recommended by guidelines. Conversely, GRANT risk categories did not. Thus, VENUSS risk categories represent an important tool for counseling, follow-up planning, and patient selection for appropriate adjuvant trials in pRCC. Patient summary: We tested the ability of two validated methods (VENUSS and GRANT) to predict death due to papillary kidney cancer in a North American population. The VENUSS risk categories showed good performance in predicting 5-year cancer-specific survival.

There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.

Abstract. Background. The National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic lymph node dissection (PLND) in NCCN high- and intermediate-risk prostate cancer patients. We tested for PLND nonadherence (no-PLND) rates within the Surveillance Epidemiology and End Results (2010–2015). Materials and methods. We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria (n = 23,495). Nonadherence rates to PLND were tabulated and further stratified according to NCCN risk subgroups, race/ethnicity, geographic distribution, and year of diagnosis. Results. Overall, the no-PLND rate was 26%; it was 41%, 25%, and 11% in the NCCN intermediate favorable, intermediate unfavorable, and high-risk prostate cancer patients, respectively (p < 0.001). Over time, the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup. Georgia exhibited the highest no-PLND rate (49%), whereas New Jersey exhibited the lowest (15%). Finally, no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup, where Asians exhibited the lowest no-PLND rate (20%) versus African Americans (27%) versus Whites (26%) versus Hispanic-Latinos (25%). Conclusions. The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order. Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination. In all the NCCN risk subgroups, the no-PLND rates decreased over time.

Background: Survival data regarding cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) patients according to the type and extent of tumor-associated vascular thrombus are scarce. Objective: To test for survival differences in mRCC patients treated with CN according to the type and extent of tumor-associated vascular thrombus. Design, setting, and participants: Within Surveillance, Epidemiology, and End Results Research Plus (2004–2017), we identified CN mRCC patients with renal vein (pT3a-TT) versus infradiaphragmatic inferior vena cava (IVC; pT3b) versus supradiaphragmatic IVC tumor thrombus/IVC invasion (pT3c). Outcome measurements and statistical analysis: Overall survival (OS) was addressed in Kaplan-Meier and Cox regression analyses, in addition to 3-mo landmark analyses. Results and limitations: Of 2170 mRCC patients, 1880 (87%), 204 (9%), and 86 (4%) harbored pT3a-TT, pT3b, and pT3c, respectively. The respective median OS periods were 21, 23, and 12 mo (p

Abstract Objectives To describe patterns of practice of PSA testing and imaging for Ontario men receiving continuous ADT for the treatment of non‐metastatic castration‐resistant prostate cancer (nmCRPC). Patients and Methods This was a retrospective, longitudinal, population‐based study of administrative health data from 2008 to 2019. Men 65 years and older receiving continuous androgen deprivation therapy (ADT) with documented CRPC were included. An administrative proxy definition was applied to capture patients with nmCRPC and excluded those with metastatic disease. Patients were indexed upon progression to CRPC and were followed until death or end of study period to assess frequency of monitoring with PSA tests and conventional imaging. A 2‐year look‐back window was used to assess patterns of care leading up to CRPC as well as baseline covariates. Results At a median follow‐up of 40.1 months, 944 patients with nmCRPC were identified. Their median time from initiation of continuous ADT to CRPC was 26.0 months. 60.7% of patients had their PSA measured twice or fewer in the year prior to index, and 70.7% patients did not receive any imaging in the year following progression to CRPC. Throughout the study period, 921/944 (97.6%) patients with CRPC progressed to high‐risk (HR‐CRPC) with PSA doubling time ≤ 10 months, of which more than half received fewer than three PSA tests in the year prior to developing HR‐CRPC, and 30.9% received no imaging in the subsequent year. Conclusion PSA testing and imaging studies are underutilized in a real‐world setting for the management of nmCRPC, including those at high risk of developing metastatic disease. Infrequent monitoring impedes proper risk stratification, disease staging and detection of treatment failure and/or metastases, thereby delaying the necessary treatment intensification with life‐prolonging therapies. Adherence to guideline recommendations and the importance of timely staging should be reinforced to optimize patient outcomes.

Summary: Background: Radium-223, a targeted alpha therapy, is approved to treat bone-dominant metastatic castration-resistant prostate cancer (mCRPC), based on significantly prolonged overall survival versus placebo and a favourable safety profile in the phase 3 ALSYMPCA study. ALSYMPCA was conducted when few other treatment options were available, and prospectively collected data are limited on the use of radium-223 in the current mCRPC treatment landscape. We sought to understand long-term safety and treatment patterns in men who received radium-223 in real-world clinical practice. Methods: REASSURE (NCT02141438) is a global, prospective, observational study of radium-223 in men with mCRPC. Primary outcomes are adverse events (AEs), including treatment-emergent serious AEs (SAEs) and drug-related AEs during and ≤30 days after radium-223 completion, grade 3/4 haematological toxicities ≤6 months after last radium-223 dose, drug-related SAEs after radium-223 therapy completion, and second primary malignancies. Findings: Data collection commenced on Aug 20, 2014, and the data cutoff date for this prespecified interim analysis was Mar 20, 2019 (median follow-up 11.5 months [interquartile range 6.0–18.6]), 1465 patients were evaluable. For second primary malignancies, 1470 patients were evaluable, 21 (1%) of whom had a total of 23 events. During radium-223 therapy, 311 (21%) of 1465 patients had treatment-emergent SAEs, and 510 (35%) had drug-related AEs. In the 6 months after completion of radium-223 therapy, 214 (15%) patients had grade 3/4 haematological toxicities. Eighty patients (5%) had post-treatment drug-related SAEs. Median overall survival was 15.6 months (95% confidence interval 14.6–16.5) from radium-223 initiation. Patient-reported pain scores declined or stabilised. Seventy (5%) patients had fractures. Interpretation: REASSURE offers insight into radium-223 use in global real-world clinical practice with currently available therapies. At this interim analysis, with a median follow-up of almost 1 year, 1% of patients had second primary malignancies, and safety and overall survival findings were consistent with clinical trial experience. Final analysis of REASSURE is due in 2024. Funding: Bayer HealthCare.

Abstract Background Positron emission tomography targeting the prostate specific membrane antigen (PSMA PET/CT) has demonstrated unparalleled performance as a staging examination for prostate cancer resulting in substantial changes in management. However, the impact of altered management on patient outcomes is largely unknown. This study aims to assess the impact of intensified radiotherapy or surgery guided by PSMA PET/CT in patients at risk of advanced prostate cancer. Methods This pan-Canadian phase III randomized controlled trial will enroll 776 men with either untreated high risk prostate cancer (CAPRA score 6–10 or stage cN1) or biochemically recurrent prostate cancer post radical prostatectomy (PSA > 0.1 ng/mL). Patients will be randomized 1:1 to either receive conventional imaging or conventional plus PSMA PET imaging, with intensification of radiotherapy or surgery to newly identified disease sites. The primary endpoint is failure free survival at 5 years. Secondary endpoints include rates of adverse events, time to next-line therapy, as well as impact on health-related quality of life and cost effectiveness as measured by incremental cost per Quality Adjusted Life Years gained. Discussion This study will help create level 1 evidence needed to demonstrate whether or not intensification of radiotherapy or surgery based on PSMA PET findings improves outcomes of patients at risk of advanced prostate cancer in a manner that is cost-effective. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04557501 on September 21, 2020.

Pre-activation of autophagy mediates resistance to olaparib by decreasing nuclear SQSTM1/p62, which increases homologous recombination-mediated repair through filamin A expression and BRCA1/Rad51 recruitment.

Background: Up- and/or downgrading rates in single intermediate-risk positive biopsy core are unknown. Methods: We identified single intermediate-risk (Gleason grade group (GGG) 2/GGG3) positive biopsy core prostate cancer patients (≤ cT2c and PSA ≤ 20 ng/mL) within the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). Subsequently, separate uni- and multivariable logistic regression models tested for independent predictors of up- and downgrading. Results: Of 1,328 assessable patients with single core positive intermediate-risk prostate cancer at biopsy, 972 (73%) harbored GGG2 versus 356 (27%) harbored GGG3. Median PSA (5.5 vs 5.7; p = 0.3), median age (62 vs 63 years; p = 0.07) and cT1-stage (77 vs 75%; p = 0.3) did not differ between GGG2 and GGG3 patients. Of individuals with single GGG2 positive biopsy core, 191 (20%) showed downgrading to GGG1 versus 35 (4%) upgrading to GGG4 or GGG5 at RP. Of individuals with single GGG3 positive biopsy core, 36 (10%) showed downgrading to GGG1 versus 42 (12%) significant upgrading to GGG4 or GGG5 at RP. In multivariable logistic regression models, elevated PSA (10–20 ng/mL) was an independent predictor of upgrading to GGG4/GGG5 in single GGG3 positive biopsy core patients (OR:2.89; 95%-CI: 1.31–6.11; p = 0.007). Conclusion: In single GGG2 positive biopsy core patients, downgrading was four times more often recorded compared to upgrading. Conversely, in single GGG3 positive biopsy core patients, up- and downgrading rates were comparable and should be expected in one out of ten patients.

BackgroundWe tested whether a model identifying prostate cancer (PCa) patients at risk of pT3-4/pN1 can be developed for use during COVID19 pandemic, in order to guarantee appropriate treatment to patients harboring advanced disease patients without compromising sustainability of care delivery.MethodsWithin the Surveillance, Epidemiology and End Results database 2010-2016, we identified 27,529 patients with localized PCa and treated with radical prostatectomy. A multivariable logistic regression model predicting presence of pT3-4/pN1 disease was fitted within a development cohort (n=13,977, 50.8%). Subsequently, external validation (n=13,552, 49.2%) and head-to-head comparison with NCCN risk group stratification was performed.ResultsIn model development, age, PSA, biopsy Gleason Grade Group (GGG) and percentage of positive biopsy cores were independent predictors of pT3-4/pN1 stage. In external validation, prediction of pT3-4/pN1 with novel nomogram was 74% accurate versus 68% for NCCN risk group stratification. Nomogram achieved better calibration and showed net-benefit over NCCN risk group stratification in decision curve analyses. The use of nomogram cut-off of 49% resulted in pT3-4/pN1 rate of 65%, instead of the average 35%.ConclusionThe newly developed, externally validated nomogram predicts presence of pT3-4/pN1 better than NCCN risk group stratification and allows to focus radical prostatectomy treatment on individuals at highest risk of pT3-4/pN1.

Mehra et al. investigate the role of CdGAP in early biochemical recurrence and bone metastasis in prostate cancer. The authors find that knocking down CdGAP leads to reduced cell motility, invasion and proliferation in PC-3 and 22Rv1 cells while orthotopic injection of CdGAP-depleted PC-3 cells reduces distant metastatic burden.

Background: Androgen deprivation therapy (ADT) for prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonists can be improved. Objective: To assess safety, the frequency and severity of hot flushes (HFs), bone health, and antitumor effects of high-dose estetrol (HDE4) when combined with ADT. Design, setting and participants: A phase II, double-blind, randomized, placebo-controlled study was conducted in advanced prostate cancer patients requiring ADT (the PCombi study). Intervention: Patients receiving LHRH agonist treatment were randomized 2:1 to 40 mg HDE4 (n = 41) or placebo (n = 21) cotreatment for 24 wk. Outcome measurements and statistical analysis: Coprimary endpoints were frequency/severity of HFs and levels of total and free testosterone (T). Secondary endpoints included assessments of bone metabolism (osteocalcin and type I collagen telopeptide [CTX1]), prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH). Efficacy analysis was based on the selected per-protocol (PP) population. Results and limitations: Of 62 patients included in the study, 57 were suitable for a PP analysis (37 HDE4; 20 placebo). No E4-related serious cardiovascular adverse events occurred at 24 wk. Weekly HFs were reported by 13.5% of patients with HDE4 and 60.0% with placebo (p

BackgroundTo test the effect of race/ethnicity on cancer-specific mortality (CSM) after salvage radical prostatectomy (SRP).Material and methodsWe relied on the Surveillance, Epidemiology and End Results database (SEER, 2004–2016) to identify SRP patients of all race/ethnicity background. Univariate and multivariate Cox regression models addressed CSM according to race/ethnicity.ResultsOf 426 assessable SRP patients, Caucasians accounted for 299 (69.9%) vs. 68 (15.9%) African-Americans vs. 39 (9.1%) Hispanics vs. 20 (4.7%) Asians. At diagnosis, African-Americans (64 years) were younger than Caucasians (66 years), but not younger than Hispanics (66 years) and Asians (67 years). PSA at diagnosis was significantly higher in African-Americans (13.2 ng/ml), Hispanics (13.0 ng/ml), and Asians (12.2 ng/ml) than in Caucasians (7.8 ng/ml, p = 0.01). Moreover, the distribution of African-Americans (10.3%–36.6%) and Hispanics (0%–15.8%) varied according to SEER region. The 10-year CSM was 46.5% in African-Americans vs. 22.4% in Caucasians vs. 15.4% in Hispanics vs. 15.0% in Asians. After multivariate adjustment (for age, clinical T stage, lymph node dissection status), African-American race/ethnicity was an independent predictor of higher CSM (HR: 2.2, p < 0.01), but not Hispanic or Asian race/ethnicity. The independent effect of African-American race/ethnicity did not persist after further adjustment for PSA.ConclusionAfrican-Americans treated with SRP are at higher risk of CSM than other racial/ethnic groups and also exhibited the highest baseline PSA. The independent effect of African-American race/ethnicity on higher CSM no longer applies after PSA adjustment since higher PSA represents a distinguishing feature in African-American patients.

Background CheckMate 9KD (NCT03338790) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib.Methods CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0–1. Cohort A1 included patients with postchemotherapy mCRPC (1–2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 mg every 4 weeks plus rucaparib 600 mg two times per day (nivolumab dosing ≤2 years). Coprimary endpoints were objective response rate (ORR) per Prostate Cancer Clinical Trials Working Group 3 and prostate-specific antigen response rate (PSA50-RR; ≥50% PSA reduction) in all-treated patients and patients with homologous recombination deficiency (HRD)-positive tumors, determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety.Results Outcomes (95% CI) among all-treated, HRD-positive, and BRCA1/2-positive populations for cohort A1 were confirmed ORR: 10.3% (3.9–21.2) (n=58), 17.2% (5.8–35.8) (n=29), and 33.3% (7.5–70.1) (n=9); confirmed PSA50-RR: 11.9% (5.9–20.8) (n=84), 18.2% (8.2–32.7) (n=44), and 41.7% (15.2–72.3) (n=12); median rPFS: 4.9 (3.7–5.7) (n=88), 5.8 (3.7–8.4) (n=45), and 5.6 (2.8–15.7) (n=12) months; and median OS: 13.9 (10.4–15.8) (n=88), 15.4 (11.4–18.2) (n=45), and 15.2 (3.0–not estimable) (n=12) months. For cohort A2 they were confirmed ORR: 15.4% (5.9–30.5) (n=39), 25.0% (8.7–49.1) (n=20), and 33.3% (7.5–70.1) (n=9); confirmed PSA50-RR: 27.3% (17.0–39.6) (n=66), 41.9 (24.5–60.9) (n=31), and 84.6% (54.6–98.1) (n=13); median rPFS: 8.1 (5.6–10.9) (n=71), 10.9 (6.7–12.0) (n=34), and 10.9 (5.6–12.0) (n=15) months; and median OS: 20.2 (14.1–22.8) (n=71), 22.7 (14.1–not estimable) (n=34), and 20.2 (11.1–not estimable) (n=15) months. In cohorts A1 and A2, respectively, the most common any-grade and grade 3–4 treatment-related adverse events (TRAEs) were nausea (40.9% and 40.8%) and anemia (20.5% and 14.1%). Discontinuation rates due to TRAEs were 27.3% and 23.9%, respectively.Conclusions Nivolumab plus rucaparib is active in patients with HRD-positive postchemotherapy or chemotherapy-naïve mCRPC, particularly those harboring BRCA1/2 mutations. Safety was as expected, with no new signals identified. Whether the addition of nivolumab incrementally improves outcomes versus rucaparib alone cannot be determined from this trial.Trial registration number NCT03338790.

Objective: We performed a population-based analysis focusing on primary extranodal lymphoma of either testis, kidney, bladder or prostate (PGUL). Methods: We identified all cases of localized testis, renal, bladder and prostate primary lymphomas (PL) versus primary testis, kidney, bladder and prostate cancers within the Surveillance, Epidemiology, and End Results database (1998–2015). Estimated annual proportion change methodology (EAPC), multivariable logistic regression models, cumulative incidence plots and multivariable competing risks regression models were used. Results: The rates of testis-PL, renal-PL, bladder-PL and prostate-PL were 3.04%, 0.22%, 0.18% and 0.01%, respectively. Patients with PGUL were older and more frequently Caucasian. Annual rates significantly decreased for renal-PL (EAPC: −5.6%; p=0.004) and prostate-PL (EAPC: −3.6%; p=0.03). In multivariable logistic regression models, older ager independently predicted testis-PL (odds ratio [OR]: 16.4; p

In this brief correspondence, we evaluate the potential impact of pivoting from face-to-face supervised to unsupervised home-based exercise programmes to contextualise the coronavirus disease 2019 (COVID-19) pandemic in prostate cancer patients. A meta-analysis was undertaken in fatigue, quality of life, and lean and fat mass outcomes in the four studies included. Our analysis indicates that unsupervised home-based exercise maintains patient-reported outcomes, except for fat mass. In summary, changing to unsupervised exercise is unlikely to provide further benefits on patient-reported and body composition outcomes, but may help maintain initial gains during physical distancing restrictions. Patient summary: We discuss the potential impacts of transitioning from face-to-face supervised to unsupervised home-based exercise programmes in prostate cancer patients during the coronavirus disease 2019 (COVID-19) pandemic. Our analysis suggests that patients are likely to maintain patient-reported and body composition benefits from current nonsupervised programmes; however, evolution of exercise delivery to prostate cancer patients is required to continue health and fitness improvement in this group.

Skeletal-related events (SREs) are complications of bone metastases and carry a significant patient and economic burden. Denosumab is a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor approved for SRE prevention in patients with multiple myeloma and patients with bone metastases from solid tumors. In phase 3 trials, denosumab showed superiority to the bisphosphonate zoledronate in reducing the risk of first on-study SRE by 17% (median time to first on-study SRE delayed by 8.2 months) and the risk of first and subsequent on-study SREs by 18% across multiple solid tumor types, including some patients with multiple myeloma. Denosumab also improved pain outcomes and reduced the need for strong opioids. Additionally, a phase 3 trial showed denosumab was noninferior to zoledronate in delaying time to first SRE in patients with newly diagnosed multiple myeloma. Denosumab has a convenient 120 mg every 4 weeks recommended dosing schedule with subcutaneous administration. Rare but serious toxicities associated with denosumab include osteonecrosis of the jaw, hypocalcemia, and atypical femoral fracture events, with multiple vertebral fractures reported following treatment discontinuation. After a decade of real-world clinical experience with denosumab, we are still learning about the optimal use and dosing for denosumab. Despite the emergence of novel and effective antitumor therapies, there remains a strong rationale for the clinical utility of antiresorptive therapy for SRE prevention. Ongoing studies aim to optimize clinical management of patients using denosumab for SRE prevention while maintaining safety and efficacy.

BackgroundCancer is a leading cause of disease burden worldwide and the first cause of mortality in Canada with 30.2% of deaths attributable to cancer. Given aging of the population and the improvement of prevention and treatment protocols, the number of cancer survivors is steadily increasing. These individuals have unique physical and mental health needs some of which can be addressed by integrating physical activity promotion into ongoing and long-term care. Despite the benefits of being active, delivery of PA programs for cancer patients in both clinical and community settings remains challenging. This knowledge-to-action protocol-called Kiné-Onco-aims to develop a practice guideline for the delivery, implementation, and scaling-up of cancer-specific physical activity promotion programs and services in clinical and community settings located in Québec, Canada.MethodThe Kiné-Onco project involves knowledge synthesis of scientific and grey literature to establish the benefits and added value of physical activity for cancer patients and survivors, describes current practices in delivering physical activity programs, analyses quantitative data from electronic health records (EHR) of patients participating in a novel hospital-based physical activity program, collects and analyses qualitative data from patients and healthcare providers interviews about lived experience, facilitators, and barriers to physical activity promotion, outlines deliberative workshops among multidisciplinary team members to develop implementation guidelines for physical activity promotion, and summarizes a variety of knowledge transfer and exchange activities to disseminate the practice guidelines.DiscussionThis paper describes the protocol for a knowledge-to-action project aimed at producing and sharing actionable evidence. Our aim is that physical activity promotion programs and services be scaled up in such a way as to successfully integrate physical activity promotion throughout cancer treatment and survivorship in order to improve the physical and mental health of the growing population of individuals having received a cancer diagnosis.

Although salvage prostate bed radiotherapy is highly effective in biochemically-relapsing prostate cancer patients following prostatectomy, relapses remain frequent and improvements are needed. Randomized phase 3 trials have shown the benefit of adding androgen-depriving therapy to irradiation, but not all patients benefit from this combination. Preclinical studies have shown that novel agents targeting the androgen receptor, DNA repair, PI3K/AKT/mTOR pathways, or the hypoxic microenvironment may help increase the response to prostate bed irradiation while minimizing potential side effects. This perspective review focuses on the most relevant molecules that may have an impact when combined with salvage radiotherapy, and underlines the strategies that need to be developed to increase the efficacy of salvage post-prostatectomy radiotherapy in prostate cancer patients.

Background and Objectives: The impact of pure histological subtypes in testicular non-seminoma germ cell tumors on survival, specifically regarding pure embryonal carcinoma, is not well established. Therefore, this study aimed to test for differences between pure embryonal carcinoma and mixed germ cell tumor patients within stages I, II and III in a large population-based database. Materials and Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004–2019) to identify testicular pure embryonal carcinoma vs. mixed germ cell tumor patients. Cumulative incidence plots depicted cancer-specific mortality that represented the main endpoint of interest. Multivariable competing risks regression models tested for differences between pure embryonal carcinoma and mixed germ cell tumor patients in analyses addressing cancer-specific mortality and adjusted for other-cause mortality. Results: Of 11,223 patients, 2473 (22%) had pure embryonal carcinoma. Pure embryonal carcinoma patients exhibited lower cancer-specific mortality relative to their mixed germ cell tumor counterparts for both stage III (13.9 vs. 19.4%; p < 0.01) and stage II (0.5 vs. 3.4%, p < 0.01), but not in stage I (0.9 vs. 1.6%, p = 0.1). In multivariable competing risks regression models, pure embryonal carcinoma exhibited more favorable cancer-specific mortality than mixed germ cell tumor in stage III (hazard ratio 0.71, p = 0.01) and stage II (hazard ratio 0.11, p < 0.01). Conclusions: Pure embryonal carcinoma exhibits a more favorable cancer-specific mortality profile relative to mixed germ cell tumor in stage II and III testicular cancers. Consequently, the presence of mixed germ cell tumor elements may be interpreted as a risk factor for cancer-specific survival.

IntroductionRandomized clinical trials demonstrated improved overall survival in chemotherapy exposed metastatic prostate cancer patients. However, real-world data validating this effect with large scale epidemiological data sets are scarce and might not agree with trials. We tested this hypothesis.Materials and MethodsWe identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results (SEER) database (2014-2015). Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed patients vs chemotherapy-naïve patients. All analyses were repeated in propensity-score matched cohorts. Additionally, landmark analyses were applied to account for potential immortal time bias.ResultsOverall, 4295 de novo metastatic prostate cancer patients were identified. Of those, 905 (21.1%) patients received chemotherapy vs 3390 (78.9%) did not. Median overall survival was not reached at 30 months follow-up. Chemotherapy-exposed patients exhibited significantly better overall survival (61.6 vs 54.3%, multivariable HR:0.82, CI: 0.72-0.96, p=0.01) at 30 months compared to their chemotherapy-naïve counterparts. These findings were confirmed in propensity score matched analyses (multivariable HR: 0.77, CI:0.66-0.90, p

BackgroundThis study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa).Material and MethodsWithin the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004–2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer vs. secondary PCa diagnoses.ResultsWe identified 24,848 secondary PCa patients (skin, n = 3,871; rectal, n = 798; colon, n = 3,665; lymphoma, n = 2,583; leukemia, n = 1,102; pancreatic, n = 118; stomach, n = 361; esophagus, n = 219; liver, n = 160; lung, n = 1,328) vs. 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa.ConclusionPatients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.

Abstract Background Intraductal carcinoma of the prostate (IDC-P) is an independent biomarker of recurrence and survival with particular treatment response, yet no study has tested its response to radiotherapy. The aim of our project was to test the impact of adjuvant radiotherapy (ART) in patients with localized to locally advanced prostate cancer (PC) and IDC-P. Materials and methods We performed a retrospective study of men with pT2-T3 PC treated by radical prostatectomy (RP) with or without ART, from two centres (1993–2015). Exclusion criteria were the use of another type of treatment prior to biochemical recurrence (BCR), and detectable prostate- specific antigen (PSA) following RP or ART. Primary outcome was BCR (2 consecutive PSA ≥ 0.2 ng/ml). Patients were grouped by treatment (RPonly/RP + ART), IDC-P status, and presence of high-risk features (HRF: Grade Groups 4–5, positive margins, pT3 stage). Results We reviewed 293 RP specimens (median follow-up 99 months, 69 BCR). Forty-eight patients (16.4%) were treated by RP + ART. Multivariate Cox regression for BCR indicated that IDC-P had the strongest impact (hazard ratio [HR] = 2.39, 95% confidence interval [CI]:1.44–3.97), while ART reduced the risk of BCR (HR = 0.38, 95%CI: 0.17–0.85). Other HRF were all significant except for pT3b stage. IDC-P[+] patients who did not receive ART had the worst BCR-free survival (log-rank P = 0.023). Furthermore, IDC-P had the same impact on BCR-free survival as ≥1 HRF (log-rank P = 0.955). Conclusion Men with IDC-P who did not receive ART had the highest BCR rates, and IDC-P had the same impact as ≥1 HRF, which are often used as ART indications. Once validated, ART should be considered in patients with IDC-P.

Androgen deprivation therapy (ADT) is the foundation of treatment for patients with locally advanced, recurrent and metastatic prostate cancer, most commonly using luteinizing releasing hormone (LHRH) agonists. More recently, a new approach to ADT has emerged with the development of gonadotropin-releasing hormone (GnRH) antagonists, which aim to overcome some of the potential adverse physiologic effects of LHRH agonists. This article focuses on the newest GnRH antagonist, relugolix – a once-daily treatment and the only oral GnRH antagonist that has now been approved for the treatment of advanced prostate cancer. In phase II and III studies, relugolix achieved rapid and sustained castration without the testosterone surge associated with LHRH agonists, thus avoiding the potential clinical consequences of tumor flare and the necessity for concomitant anti-androgen therapy. Relugolix also achieved rapid testosterone recovery, which may potentially reduce ADT-related adverse events and offer opportunities for combination and intermittent therapy strategies. Cardiovascular safety is a particular concern in men with prostate cancer and ADT further increases cardiovascular risk: indeed, LHRH agonists are required to have a drug label warning about an increased risk of cardiovascular disease. Data from the phase III HERO study demonstrate an improved cardiac safety profile for the GnRH antagonist relugolix compared with the LHRH agonist leuprolide, including a significantly reduced risk for a major adverse cardiovascular event. Taken together, the data indicate that relugolix may mitigate some of the cardiovascular concerns surrounding ADT and has the potential to become a new standard of care for men with prostate cancer. In summary, relugolix represents a novel and recently available prostate cancer management strategy, incorporating the mechanistic advantages of GnRH antagonists and the potential benefits of oral administration.

BackgroundTo test the effect of variant histology relative to urothelial histology on stage at presentation, cancer specific mortality (CSM), and overall mortality (OM) after chemotherapy use, in urethral cancer.Materials and MethodsWithin the Surveillance, Epidemiology and End Results (2004–2016) database, we identified 1,907 primary variant histology urethral cancer patients. Kaplan-Meier plots, Cox regression analyses, cumulative incidence-plots, multivariable competing-risks regression models and propensity score matching for patient and tumor characteristics were used.ResultsOf 1,907 eligible urethral cancer patients, urothelial histology affected 1,009 (52.9%) vs. squamous cell carcinoma (SCC) 455 (23.6%) vs. adenocarcinoma 278 (14.6%) vs. other histology 165 (8.7%) patients. Urothelial histological patients exhibited lower stages at presentation than SCC, adenocarcinoma or other histology patients. In urothelial histology patients, five-year CSM was 23.5% vs. 34.4% in SCC [Hazard Ratio (HR) 1.57] vs. 40.7% in adenocarcinoma (HR 1.69) vs. 43.4% in other histology (HR 1.99, p < 0.001). After matching in multivariate competing-risks regression models, variant histology exhibited 1.35-fold higher CSM than urothelial. Finally, in metastatic urethral cancer, lower OM was recorded after chemotherapy in general, including metastatic adenocarcinoma and other variant histology subtypes, except metastatic SCC.ConclusionAdenocarcinoma, SCC and other histology subtypes affect fewer patients than urothelial histology. Presence of variant histology results in higher CSM. Finally, chemotherapy for metastatic urethral cancer improves survival in adenocarcinoma and other variant histology subtypes, but not in SCC.

Active surveillance (AS) has gained acceptance as a primary management approach for patients diagnosed with low-risk prostate cancer (PC). In this qualitative study, we compared perspectives between patients and health care professionals (HCP) to identify what may contribute to patient–provider discordance, influence patient decision-making, and interfere with the uptake of AS. We performed a systematic comparison of perspectives about AS reported from focus groups with men eligible for AS (7 groups, N = 52) and HCP (5 groups, N = 48) who engaged in conversations about AS with patient. We used conventional content analysis to scrutinize separately focus group transcripts and reached a consensus on similar or divergent viewpoints between them. Patients and clinicians agreed that AS was appropriate for low grade PC and understood the low-risk nature of the disease. They shared the perspective that disease status was a critical factor to pursue or discontinue AS. However, men expressed a greater emphasis on quality of life in their decisions related to AS. Patients and clinicians differed in their perspectives on the clarity, availability, and volume of information needed and offered; clinicians acknowledged variations between HCP when presenting AS, while patients were often compelled to seek additional information beyond what was provided by physicians and experienced difficulty in finding or interpreting information applicable to their situation. A greater understanding of discordant perspectives about AS between patients and HCP can help improve patient engagement and education, inform development of knowledge-based tools or aids for decision-making, and identify areas that require standardization across the clinical practice.

BACKGROUND:Prostate cancer (PC) is the most frequently diagnosed cancer in North American men. Pathologists are in critical need of accurate biomarkers to characterize PC, particularly to confirm the presence of intraductal carcinoma of the prostate (IDC-P), an aggressive histopathological variant for which therapeutic options are now available. Our aim was to identify IDC-P with Raman micro-spectroscopy (RμS) and machine learning technology following a protocol suitable for routine clinical histopathology laboratories. METHODS AND FINDINGS:We used RμS to differentiate IDC-P from PC, as well as PC and IDC-P from benign tissue on formalin-fixed paraffin-embedded first-line radical prostatectomy specimens (embedded in tissue microarrays [TMAs]) from 483 patients treated in 3 Canadian institutions between 1993 and 2013. The main measures were the presence or absence of IDC-P and of PC, regardless of the clinical outcomes. The median age at radical prostatectomy was 62 years. Most of the specimens from the first cohort (Centre hospitalier de l'Université de Montréal) were of Gleason score 3 + 3 = 6 (51%) while most of the specimens from the 2 other cohorts (University Health Network and Centre hospitalier universitaire de Québec-Université Laval) were of Gleason score 3 + 4 = 7 (51% and 52%, respectively). Most of the 483 patients were pT2 stage (44%-69%), and pT3a (22%-49%) was more frequent than pT3b (9%-12%). To investigate the prostate tissue of each patient, 2 consecutive sections of each TMA block were cut. The first section was transferred onto a glass slide to perform immunohistochemistry with H&E counterstaining for cell identification. The second section was placed on an aluminum slide, dewaxed, and then used to acquire an average of 7 Raman spectra per specimen (between 4 and 24 Raman spectra, 4 acquisitions/TMA core). Raman spectra of each cell type were then analyzed to retrieve tissue-specific molecular information and to generate classification models using machine learning technology. Models were trained and cross-validated using data from 1 institution. Accuracy, sensitivity, and specificity were 87% ± 5%, 86% ± 6%, and 89% ± 8%, respectively, to differentiate PC from benign tissue, and 95% ± 2%, 96% ± 4%, and 94% ± 2%, respectively, to differentiate IDC-P from PC. The trained models were then tested on Raman spectra from 2 independent institutions, reaching accuracies, sensitivities, and specificities of 84% and 86%, 84% and 87%, and 81% and 82%, respectively, to diagnose PC, and of 85% and 91%, 85% and 88%, and 86% and 93%, respectively, for the identification of IDC-P. IDC-P could further be differentiated from high-grade prostatic intraepithelial neoplasia (HGPIN), a pre-malignant intraductal proliferation that can be mistaken as IDC-P, with accuracies, sensitivities, and specificities > 95% in both training and testing cohorts. As we used stringent criteria to diagnose IDC-P, the main limitation of our study is the exclusion of borderline, difficult-to-classify lesions from our datasets. CONCLUSIONS:In this study, we developed classification models for the analysis of RμS data to differentiate IDC-P, PC, and benign tissue, including HGPIN. RμS could be a next-generation histopathological technique used to reinforce the identification of high-risk PC patients and lead to more precise diagnosis of IDC-P.

Failure to suppress testosterone below 0.7 nM in castrated prostate cancer patients is associated with poor clinical outcomes. Testosterone levels in castrated patients are therefore routinely measured. Although mass spectrometry is the gold standard used to measure testosterone, most hospitals use an immunoassay method. In this study, we sought to evaluate the accuracy of an immunoassay method to measure castrate testosterone levels, with mass spectrometry as the reference standard. We retrospectively evaluated a cohort of 435 serum samples retrieved from castrated prostate cancer patients from April to September 2017. No follow-up of clinical outcomes was performed. Serum testosterone levels were measured in the same sample using liquid chromatography coupled with tandem mass spectrometry and electrochemiluminescent immunoassay methods. The mean testosterone levels were significantly higher with immunoassay than with mass spectrometry (0.672 ± 0.359 vs 0.461 ± 0.541 nM; P < 0.0001). Half of the samples with testosterone ≥0.7 nM assessed by immunoassay were measured 0.7 nM was significantly higher with immunoassay (22.1%) than with mass spectrometry (13.1%; P < 0.0001). Quantitative measurement of serum testosterone levels >0.7 nM by immunoassay can result in an inaccurately identified castration status. Suboptimal testosterone levels in castrated patients should be confirmed by either mass spectrometry or an immunoassay method validated at low testosterone levels and interpreted with caution before any changes are made to treatment management.

Abstract Background Radium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking. Methods This was a prospective, single-arm phase 3b study. Patients with metastatic CRPC (malignant lymphadenopathy not exceeding 6 cm was allowed, visceral disease was excluded) received radium-223, 55 kBq/kg intravenously, every 4 weeks for up to 6 cycles. Co-primary endpoints were safety and overall survival. Post hoc analyses were performed according to baseline asymptomatic or symptomatic disease status. Asymptomatic status was defined as no pain and no opioid use at baseline. Results Seven hundred eight patients received ≥1 radium-223 injection: 548 (77%) were symptomatic to various degrees, and 135 (19%) were asymptomatic. Asymptomatic patients had more favorable baseline disease characteristics than symptomatic. A lower proportion of asymptomatic versus symptomatic patients had received prior abiraterone (25% vs 35%) and prior docetaxel (52% vs 62%). A higher proportion of asymptomatic (71%) versus symptomatic (55%) patients completed radium-223 treatment. Overall survival (hazard ratio [HR] 0.486), time to disease progression (HR 0.722) and time to first symptomatic skeletal event (HR 0.328) were better in asymptomatic than symptomatic patients. Alkaline phosphatase (ALP) response rates were similar (46% vs 47%), and ALP normalization (44% vs 25%) and prostate-specific antigen response rates (21% vs 13%) were higher in asymptomatic than symptomatic patients. A lower proportion of asymptomatic patients reported treatment-emergent adverse events (TEAEs, 61% vs 79%), grade 3–4 TEAEs (29% vs 40%) and drug-related TEAEs (28% vs 44%). There were two treatment-related deaths, both in patients with baseline symptomatic disease. Conclusions Using radium-223 earlier in the disease course, when patients are asymptomatic or minimally symptomatic, may enable patients to complete treatment and optimize treatment outcome compared to symptomatic patients, and therefore may allow sequencing with other life-prolonging therapies. Trial registration The study was registered with ClinicalTrials.gov, number NCT01618370 on June 13, 2012 and the European Union Clinical Trials Register, EudraCT number 2012–000075-16 on April 4, 2012.

Abstract Background Refinement of parameters defining prostate cancer (PC) prognosis are urgently needed to identify patients with indolent versus aggressive disease. The Canadian Prostate Cancer Biomaker Network (CPCBN) consists of researchers from four Canadian provinces to create a validation cohort to address issues dealing with PC diagnosis and management. Methods A total of 1512 radical prostatectomy (RP) specimens from five different biorepositories affiliated with teaching hospitals were selected to constitute the cohort. Tumoral and adjacent benign tissues were arrayed on tissue microarrays (TMAs). A patient clinical database was developed and includes data on diagnosis, treatment and clinical outcome. Results Mean age at diagnosis of patients in the cohort was 61 years. Of these patients, 31% had a low grade (≤6) Gleason score (GS), 55% had GS 7 (40% of 3 + 4 and 15% of 4 + 3) and 14% had high GS (≥8) PC. The median follow-up of the cohort was 113 months. A total of 34% had a biochemical relapse, 4% developed bone metastasis and 3% of patients died from PC while 9% died of other causes. Pathological review of the TMAs confirmed the presence of tumor and benign tissue cores for > 94% of patients. Immunohistochemistry and FISH analyses, performed on a small set of specimens, showed high quality results and no biorepository-specific bias. Conclusions The CPCBN RP cohort is representative of real world PC disease observed in the Canadian population. The frequency of biochemical relapse and bone metastasis as events allows for a precise assessment of the prognostic value of biomarkers. This resource is available, in a step-wise manner, for researchers who intend to validate prognostic biomarkers in PC. Combining multiple biomarkers with clinical and pathologic parameters that are predictive of outcome will aid in clinical decision-making for patients treated for PC.

Abstract Background Over the last decade, active surveillance has proven to be a safe approach for patients with low-risk prostate cancer. Although active surveillance presents several advantages for both patients and the health care system, all eligible patients do not adopt this approach. Our goal was to evaluate the factors that influence physicians to recommend active surveillance and the barriers that impact adherence to this approach. Methods Focus groups (n = 5) were held with physicians who provided care for men with low-risk prostate cancer and had engaged in conversations with men and their families about active surveillance. The experience of health care professionals (HCPs) was captured to understand their decisions in proposing active surveillance and to reveal the barriers and facilitators that affect the adherence to this approach. A content analysis was performed on the verbatim transcripts from the sessions. Results Although physicians agreed that active surveillance is a suitable approach for low-risk prostate cancer patients, they were concerned about the rapidly evolving and non-standardized guidelines for patient follow-up. They pointed out the need for additional tools to appropriately identify proper patients for whom active surveillance is the best option. Urologists and radiation-oncologists were keen to collaborate with each other, but the role of general practitioner remained controversial once patients were referred to a specialist. Conclusions Integration of more reliable tools and/or markers in addition to more specific guidelines for patient follow-up would increase the confidence of both patients and physicians in the choice of active surveillance.

Abstract Background In prostate cancer, men diagnosed with low risk disease may be monitored through an active surveillance. This research explored the perspectives of men with prostate cancer regarding their decision-making process for active surveillance to identify factors that influence their decision and assist health professionals in having conversations about this option. Methods Focus group interviews (n = 7) were held in several Canadian cities with men (N = 52) diagnosed with prostate cancer and eligible for active surveillance. The men’s viewpoints were captured regarding their understanding of active surveillance, the factors that influenced their decision, and their experience with the approach. A content and theme analysis was performed on the verbatim transcripts from the sessions. Results Patients described their concerns of living with their disease without intervention, but were reassured by the close monitoring under AS while avoiding harmful side effects associated with treatments. Conversations with their doctor and how AS was described were cited as key influences in their decision, in addition to availability of information on treatment options, distrust in the health system, personality, experiences and opinions of others, and personal perspectives on quality of life. Conclusions Men require a thorough explanation on AS as a safe and valid option, as well as guidance towards supportive resources in their decision-making.