The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Disparities in prostate cancer screening, diagnoses, management, and outcomes between Indigenous and non-Indigenous men in a universal health care system.

BACKGROUND: Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought. METHODS: An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals. RESULTS: Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50-70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25-65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2-4.2; p < .01) than non-Indigenous men. CONCLUSIONS: Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.

Clinical analysis of EV-Fingerprint to predict grade group 3 and above prostate cancer and avoid prostate biopsy.

BACKGROUND: There 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. METHODS: This 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. RESULTS: The 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%). CONCLUSIONS: EV-Fingerprint accurately predicted GG ≥3 prostate cancer and would have significantly reduced unnecessary prostate biopsies.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Obesity and Complication Risk From Radical Cystectomy: Identifying a Body Mass Index Threshold.

PURPOSE: There are conflicting reports regarding radical cystectomy complication risk from obesity subcategories, and a BMI threshold below which complication risk is notably reduced is undefined. A BMI threshold may be helpful in prehabilitation to aid patient counseling and inform weight loss strategies to potentially mitigate obesity-associated complication risk. This study aims to identify such a threshold and further investigate the association between BMI subcategories and perioperative complications from radical cystectomy. MATERIALS AND METHODS: Data were extracted from the Canadian Bladder Cancer Information System, a prospective registry across 14 academic centers. Five hundred and eighty-nine patients were analyzed. Perioperative (≤90 days) complications were compared between BMI subcategories. Unconditional multivariable logistic regression and cubic spline analysis were performed to determine the association between BMI and complication risk and identify a BMI threshold. RESULTS: Perioperative complications were reported in 51 (30%), 97 (43%), and 85 (43%) normal, overweight, and obese patients (P = .02). BMI was independently associated with developing any complication (OR 1.04 95% CI 1.01, 1.07). Predicted complication risk began to rise consistently above a BMI threshold of 34 kg/m2. Both overweight (OR 2.00 95% CI 1.26-3.17) and obese (OR 1.98 95% CI 1.24-3.18) patients had increased risk of complications compared to normal BMI patients. CONCLUSIONS: Complication risk from radical cystectomy is independently associated with BMI. Both overweight and obese patients are at increased risk compared to normal BMI patients. A BMI threshold of 34 kg/m2 has been identified, which may inform prehabilitation treatment strategies.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.

Effects of supervised high-intensity interval training on motivational outcomes in men with prostate cancer undergoing active surveillance: results from a randomized controlled trial.

BACKGROUND: Understanding the motivational effects of supervised aerobic high-intensity interval training (HIIT) may help men with prostate cancer undergoing active surveillance initiate and maintain exercise behavior, however, few studies have addressed this question. This report explored exercise motivation in men with prostate cancer undergoing active surveillance participating in a randomized exercise trial. METHODS: The Exercise during Active Surveillance for Prostate Cancer (ERASE) trial randomized 52 men with prostate cancer on active surveillance to the HIIT exercise group or the usual care (UC) group. The exercise program was supervised aerobic HIIT conducted three times per week for 12 weeks. The motivation questions were developed using the Theory of Planned Behavior and included motivational constructs, anticipated and experienced outcomes, and barriers to HIIT during active surveillance. RESULTS: The HIIT group attended 96% of the planned exercise sessions with 100% compliance to the exercise protocol. Motivation outcome data were obtained in 25/26 (96%) participants in the HIIT group and 25/26 (96%) participants in the UC group. At baseline, study participants were generally motivated to perform HIIT. After the intervention, the HIIT group reported that HIIT was even more enjoyable (p < 0.001; d = 1.38), more motivating (p = 0.001; d = 0.89), more controllable (p < 0.001; d = 0.85), and instilled more confidence (p = 0.004; d = 0.66) than they had anticipated. Moreover, compared to UC, HIIT participants reported significantly higher perceived control (p = 0.006; d = 0.68) and a more specific plan (p = 0.032; d = 0.67) for performing HIIT over the next 6 months. No significant differences were found in anticipated versus experienced outcomes. Exercise barriers were minimal, however, the most often reported barriers included pain or soreness (56%), traveling to the fitness center (40%), and being too busy and having limited time (36%). CONCLUSION: Men with prostate cancer on active surveillance were largely motivated and expected significant benefits from a supervised HIIT program. Moreover, the men assigned to the HIIT program experienced few barriers and achieved high adherence, which further improved their motivation. Future research is needed to understand long-term exercise motivation and behavior change in this setting. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03203460 . Registered on June 29, 2017.

Ultrasound Correlates Highly With Cross Sectional Imaging for Small Renal Masses in a Contemporary Cohort.

OBJECTIVE: To determine the correlation between ultrasound (US), cross-sectional imaging, and pathological renal mass sizes. METHODS: Between January 2011 and January 2021, a cohort of patients from 14 academic institutions who had an US and cross-sectional imaging within 8 weeks of each other and within 6 months of surgery were identified. A second cohort of patients with small renal masses (≤4 cm) who had US and cross-sectional imaging within 8 weeks of each other were also examined, regardless of their treatment modality. Correlation coefficients, Bland-Altman plots, and sensitivity tables were generated. RESULTS: A total of 1464 patients were included in the surgical cohort and 1582 patients (1921 imaging pairs) were included in the small renal mass (SRM) cohort. Pearson correlation coefficients between computed tomography (CT)/magnetic resonance imaging (MRI) and pathologic size was 0.93 (P <.0001) and between US and pathological size was 0.90 (P <.0001). The correlation between US and CT/MRI was 0.93 (P <.0001). Bland-Altman plots demonstrated a greater agreement for smaller renal masses. For the SRM cohort when comparing US to CT/MRI, 1441 (75%) SRM measurements were within 0.5 cm and only 149 (7.8%) were greater than 1 cm in difference. Subgroup analysis demonstrated that correlation between US and CT/MRI for SRMs were higher in patients with lower body mass index. CONCLUSION: There is a strong correlation between US and cross-sectional imaging in 75% of patients at baseline imaging. Our study provides support for utilization of US for active surveillance.

A Randomized Trial of the Effects of Exercise on Anxiety, Fear of Cancer Progression and Quality of Life in Prostate Cancer Patients on Active Surveillance.

PURPOSE: We examined the effects of exercise on prostate cancer-specific anxiety, fear of cancer progression, quality of life and psychosocial outcomes in patients with prostate cancer on active surveillance. MATERIALS AND METHODS: The ERASE (Exercise during Active Surveillance for Prostate Cancer) Trial randomized 52 patients with prostate cancer undergoing active surveillance to high-intensity interval training (HIIT, 26 patients) or usual care (UC, 26 patients). The HIIT group performed a 12-week, thrice weekly, supervised, aerobic HIIT program. The UC group did not exercise. Patient-reported outcomes were assessed at baseline and after intervention, including prostate cancer-specific anxiety (Memorial Anxiety Scale for Prostate Cancer), fear of cancer progression (Fear of Cancer Recurrence Inventory), prostate cancer symptoms (Expanded Prostate Cancer Index Composite), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core) and psychological health outcomes (eg fatigue, stress and self-esteem). Analysis of covariance was used to compare between-group differences. RESULTS: Fifty of 52 participants (96%) completed patient-reported outcome assessments at 12 weeks. Adherence to HIIT was 96%. Compared to UC, HIIT significantly improved total prostate cancer-specific anxiety (adjusted between-group mean difference -2.7, 95% confidence interval, range -5.0 to -0.4, p=0.024), as well as the fear of progression subscale (p=0.013), hormonal symptoms (p=0.005), perceived stress (p=0.037), fatigue (p=0.029) and self-esteem (p=0.007). CONCLUSIONS: A 12-week supervised HIIT program may improve prostate cancer-specific anxiety, fear of cancer progression, hormone symptoms, stress, fatigue and self-esteem in men with prostate cancer on active surveillance. Larger trials are needed to confirm the effects of HIIT on patient-reported outcomes in the active surveillance setting.

Outcomes of Cytoreductive Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Real World Data from Canadian Centers.

BACKGROUND: Treatment options for metastatic renal cell carcinoma (mRCC) include cytoreductive nephrectomy (CN) and systemic therapy (ST). Results from the CARMENA and SURTIME trials suggest that CN before ST may not be the optimal treatment strategy for mRCC. OBJECTIVE: To use real-world data to evaluate and compare outcomes for patients with mRCC who underwent CN before, after, or without ST to those patients who only received ST. DESIGN, SETTING, AND PARTICIPANTS: The Canadian Kidney Cancer information system (CKCis) database was used to identify patients diagnosed with mRCC between January 2011 and April 2020. Only patients with synchronous disease, treated within 12 mo from their initial RCC diagnosis, with International Metastatic Renal Cell Carcinoma Database Consortium intermediate/high risk, and confirmed RCC histology were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were classified into four groups according to the initial treatment received for mRCC. Inverse probability of treatment weighting using propensity scores was used to balance the treatment groups. Cox proportional hazards models were used to assess the impact of CN after adjusting for potential confounding variables in the weighted cohorts. RESULTS AND LIMITATIONS: A total of 788 patients were included in the study cohort. Of these 383 patients underwent CN before ST, 73 underwent CN after ST, 80 underwent CN only, and 252 patients received ST only. The median patient age was 63 yr and 73% of the cohort were men. In weighted analysis, the groups undergoing CN before ST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52-0.82) and CN after ST (HR 0.41, 95% CI 0.28-0.60) both had better survival compared to the ST only group. No survival benefit was observed for CN only compared to ST only, or for CN before ST compared to CN after ST. CONCLUSIONS: We evaluated the association between different sequences of treatment with CN and survival in patients with mRCC using CKCis real world data. The results demonstrate that the selected patients who undergo CN, whether performed before or after ST, have an associated improvement in survival. PATIENT SUMMARY: Two of the treatment options for metastatic kidney cancer are surgery and systemic therapy (chemotherapy or immunotherapy). We used data from the Canadian Kidney Cancer information system to determine whether there are differences in survival according to the sequencing of these treatments. Patients who had both surgery and systemic therapy, regardless of which treatment was first, had better survival than patients who only received systemic therapy.

Associations between body mass index and bladder cancer survival: Is the obesity paradox short-lived?

INTRODUCTION: We investigated the associations of pre-surgical body mass index (BMI) with bladder cancer outcomes in patients treated with radical cystectomy. METHODS: We retrospectively analyzed data from 488 bladder cancer patients treated with radical cystectomy between 1994 and 2007 and followed up until 2016. Cox regression with step function (time-segment analysis) was conducted for overall survival because the proportional hazard assumption was violated. RESULTS: Of 488 bladder cancer patients, 155 (31.8%) were normal weight, 186 (38.1%) were overweight, and 147 (30.1%) were obese. During the median followup of 59.5 months, 363 (74.4%) patients died, including 197 (40.4%) from bladder cancer. In adjusted Cox regression analyses, BMI was not significantly associated with bladder cancer-specific survival for overweight (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.10, p=0.16) or obese (HR 0.76, 95% CI 0.52-1.09, p=0.13) patients. In the Cox regression with step function for overall survival, the time interaction was significant overall (p=0.020) and specifically for over-weight patients (p=0.006). In the time-segment model, the HR for overweight during the first 63 months was 0.66 (95% CI 0.49-0.90, p=0.008), whereas it was 1.41 (95% CI 0.89-2.23, p=0.14) after 63 months. Although not statistically significant, a similar pattern was observed for obese patients. CONCLUSIONS: Our findings suggest that overweight and obese bladder cancer patients had better outcomes within the first five years after radical cystectomy; however, there were no differences in longer-term survival. These data suggest that the obesity paradox in bladder cancer patients treated with radical cystectomy may be short-lived.

How I Do It: Technical report on surgically-initiated rectus sheath catheter using catheter-over-needle assembly.

Development of chronic postsurgical pain following major abdominal or pelvic surgeries is increasingly recognized. Multimodal analgesia including regional anesthesia such as rectus sheath block is growing in popularity. While the literature mainly describes ultrasound-guided rectus sheath blocks, there are many advantages to surgically-initiated rectus sheath catheter performed at the end of surgery. In this technical description, we describe the rationale and technique of surgical insertion of rectus sheath catheters following major urologic surgery with midline incision which is routinely performed by urologists at our institution. Furthermore, we would like to highlight the type of catheter used during rectus sheath catheter insertion, namely the catheter-over-needle assembly. It is simple to insert while minimizes complications such as local anesthetic leakage at the insertion site causing dressing disruption and premature catheter dislodgement, as the catheter-over-needle assembly fits snugly with the skin after insertion.

Prognostic significance of extent of venous tumor thrombus in patients with non-metastatic renal cell carcinoma: Results from a Canadian multi-institutional collaborative.

PURPOSE: The prognostic significance of level of venous tumor thrombus (VTT) extension in patients with non-metastatic renal cell carcinoma (RCC) has been controversial. The aim of this study was to examine the prognostic significance of VTT extent in patients who underwent surgery for non-metastatic RCC. MATERIALS AND METHODS: The Canadian Kidney Cancer information system database was used to identify patients who underwent surgery for non-metastatic RCC and VTT from January 2011 to December 2019. Association between VTT level and recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) was examined. Univariable and multivariable analyses were performed to estimate predictors of survival. RESULTS: Out of 6,340 patients during the study period, 228 patients (3.6%) had VTT. VTT was level 0 in 84 (37%), level I to II in 112 (49%), and level III to IV in 33 (14%) patients as per the Mayo Clinic classification. Median age was 65.4 years (interquartile range [IQR] 57.6-72.2) and 169 (74.1%) were male. After a median follow-up of 21.2 months, VTT level did not significantly impact the RFS, CSS, or OS. For VTT level 0, I to II, and III to IV, there was no significant difference in estimated 5-year RFS (31%, 23%, and 30.5%; P > 0.05), CSS (70%, 69%, and 55%; P > 0.05) and OS (64%, 66%, and 50%; P > 0.05). Adjusting for known prognostic factors, thrombus level was not associated with risk of recurrence or death. CONCLUSION: In a large, multi-institutional cohort of patients undergoing surgery for non-metastatic RCC with tumor thrombus, thrombus extent was not independently associated with recurrence or death.

Bladder cancer and exeRcise trAining during intraVesical thErapy-the BRAVE trial: a study protocol for a prospective, single-centre, phase II randomised controlled trial.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of newly diagnosed bladder cancers. The treatment for NMIBC involves surgical removal of the tumour followed by 6 weekly instillations of immunotherapy or chemotherapy directly into the bladder (ie, intravesical therapy). NMIBC has a high rate of recurrence (31%-78%) and progression (15%). Moreover, bladder cancer and its treatment may affect patient functioning and quality of life. Exercise is a safe and effective intervention for many patient with cancer groups, however, no studies have examined exercise during intravesical therapy for NMIBC. The primary objective of the Bladder cancer and exeRcise trAining during intraVesical thErapy (BRAVE) trial is to examine the safety and feasibility of an exercise intervention in patients with bladder cancer undergoing intravesical therapy. The secondary objectives are to investigate the preliminary efficacy of exercise on health-related fitness and patient-reported outcomes; examine the social cognitive predictors of exercise adherence; and explore the potential effects of exercise on tumour recurrence and progression. METHODS AND ANALYSIS: BRAVE is a phase II randomised controlled trial that aims to include 66 patients with NMIBC scheduled to receive intravesical therapy. Participants will be randomly assigned to the exercise intervention or usual care. The intervention consists of three supervised, high-intensity interval training sessions per week for 12 weeks. Feasibility will be evaluated by eligibility, recruitment, adherence and attrition rates. Preliminary efficacy will focus on changes in cardiorespiratory fitness and patient-reported outcomes from baseline (prior to intravesical therapy) to pre-cystoscopy (3 months). Cancer outcomes will be tracked at 3 months, and 1-year follow-up by cystoscopy. Analysis of covariance will compare between-group differences at post-intervention (pre-cystoscopy) for all health-related fitness and patient-reported outcomes. ETHICS AND DISSEMINATION: The study was approved by the Health Research Ethics Board of Alberta-Cancer Committee (#20-0184). Dissemination will include publication and presentations at scientific conferences and public channels. TRIAL REGISTRATION NUMBER: NCT04593862; Pre-results.

Evaluation of the Implementation of Multiple Enhanced Recovery After Surgery Pathways Across a Provincial Health Care System in Alberta, Canada.

Importance: Engaging multidisciplinary care teams in surgical practice is important for the improvement of surgical outcomes. Objective: To evaluate the association of multiple Enhanced Recovery After Surgery (ERAS) pathways with ERAS guideline adherence and outcomes. Design, Setting, and Participants: This quality improvement study compared a pre-ERAS cohort (2013-2017) with a post-ERAS cohort (2014-2018). All patients were from Alberta Health Services in Alberta, Canada, and had available ERAS and up to 1-year postsurgery administrative data. Data collected included age, sex, body mass index, tobacco and alcohol use, diabetes, comorbidity index, and surgical characteristics. Data analysis was performed from May 7, 2020, to February 1, 2021. Interventions: Implementation of 5 ERAS pathways (colorectal, liver, pancreas, gynecologic oncology, and radical cystectomy) across 9 sites. Main Outcomes and Measures: Adherence to ERAS guidelines was measured by the percentage of patients whose care met the common ERAS pathway care element criteria. Surgical procedures were grouped by complexity; complications were classified by severity. Outcome measures for the pre-post-ERAS cohorts included length of stay (LOS), readmission, complications, and mortality. Results: A total of 7757 patients participated in the study, including 984 in the pre-ERAS cohort (median [interquartile range] age, 62 [53-71] years; 526 [53.5%] female) and 6773 in the post-ERAS cohort (median [interquartile range] age, 62 [53-71] years; 3470 [51.2%] male). In the total cohort, care-element adherence improved from 52% to 76% (P < .001), no significant differences were found in serious complications (from 6.2% to 4.9%; P = .08) or 30-day mortality (from 0.71% to 0.93%; P = .50), 1-year mortality decreased from 7.1% to 4.6% (P < .001), mean (SD) LOS decreased from 9.4 (7.0) to 7.8 (5.0) days (P < .001), and 30-day readmission rates were unchanged (from 13.4% to 11.7%; P = .12). After adjustment for patient characteristics, the LOS mean difference decreased 0.71 days (95% CI, -1.13 to -0.29 days; P < .001), with no significant differences in adjusted 30-day readmission (-3.5%; 95% CI, -22.7% to 20.4%; P = .75), serious complications (1.3%; 95% CI, -26.2% to 39.0%; P = .94), or mortality (30-day mortality: 42% [95% CI, -35.4% to 212.3%]; P = .38; 1-year mortality: 8% [95% CI, -20.5% to 46.8%]; P = .62). The adjusted 1-year readmission rate was -15.6% (95% CI, -27.7% to -1.5%; P = .03) in favor of ERAS, and readmission LOS was shorter by 1.7 days (95% CI, -3.3 to -0.1 days; P = .04). Conclusions and Relevance: The results of this quality improvement study suggest that implementation of ERAS across multiple pathways may improve health care practitioner adherence to ERAS guidelines, LOS, and readmission rates at a system level.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Effects of Exercise on Cardiorespiratory Fitness and Biochemical Progression in Men With Localized Prostate Cancer Under Active Surveillance: The ERASE Randomized Clinical Trial.

IMPORTANCE: Men with prostate cancer who are undergoing active surveillance are at an increased risk of cardiovascular death and disease progression. Exercise has been shown to improve cardiorespiratory fitness, physical functioning, body composition, fatigue, and quality of life during and after treatment; however, to date only 1 exercise study has been conducted in this clinical setting. OBJECTIVE: To examine the effects of exercise on cardiorespiratory fitness and biochemical progression in men with prostate cancer who were undergoing active surveillance. DESIGN, SETTING, AND PARTICIPANTS: The Exercise During Active Surveillance for Prostate Cancer (ERASE) trial was a single-center, 2-group, phase 2 randomized clinical trial conducted at the University of Alberta, Edmonton, Canada. Eligible patients were recruited from July 24, 2018, to February 5, 2020. Participants were adult men who were diagnosed with localized very low risk to favorable intermediate risk prostate cancer and undergoing active surveillance. They were randomized to either the high-intensity interval training (HIIT) group or usual care group. All statistical analyses were based on the intention-to-treat principle. INTERVENTIONS: The HIIT group was asked to complete 12 weeks of thrice-weekly, supervised aerobic sessions on a treadmill at 85% to 95% of peak oxygen consumption (V̇o2). The usual care group maintained their normal exercise levels. MAIN OUTCOMES AND MEASURES: The primary outcome was peak V̇o2, which was assessed as the highest value of oxygen uptake during a graded exercise test using a modified Bruce protocol. Secondary and exploratory outcomes were indicators of biochemical progression of prostate cancer, including prostate-specific antigen (PSA) level and PSA kinetics, and growth of prostate cancer cell line LNCaP. RESULTS: A total of 52 male patients, with a mean (SD) age of 63.4 (7.1) years, were randomized to either the HIIT (n = 26) or usual care (n = 26) groups. Overall, 46 of 52 participants (88%) completed the postintervention peak V̇o2 assessment, and 49 of 52 participants (94%) provided blood samples. Adherence to HIIT was 96%. The primary outcome of peak V̇o2 increased by 0.9 mL/kg/min in the HIIT group and decreased by 0.5 mL/kg/min in the usual care group (adjusted between-group mean difference (1.6 mL/kg/min; 95% CI, 0.3-2.9; P = .01). Compared with the usual care group, the HIIT group experienced decreased PSA level (-1.1 µg/L; 95% CI, -2.1 to 0.0; P = .04), PSA velocity (-1.3 µg /L/y; 95% CI, -2.5 to -0.1; P = .04), and LNCaP cell growth (-0.13 optical density unit; 95% CI, -0.25 to -0.02; P = .02). No statistically significant differences were found in PSA doubling time or testosterone. CONCLUSIONS AND RELEVANCE: The ERASE trial demonstrated that HIIT increased cardiorespiratory fitness levels and decreased PSA levels, PSA velocity, and prostate cancer cell growth in men with localized prostate cancer who were under active surveillance. Larger trials are warranted to determine whether such improvement translates to better longer-term clinical outcomes in this setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03203460.

The increasing use of renal tumor biopsy amongst Canadian urologists: When is biopsy most utilized?

INTRODUCTION: The role of renal tumor biopsy (RTB) in the management of small renal masses (SRMs) is progressively being recognized as a tool to decrease overtreatment. While an increasing number of studies assessing its role in diagnostics are becoming available, RTB remains variably used amongst urologists. Many patient-, tumor-, and institution-related factors may influence urologists on whether to perform a RTB to help guide management. OBJECTIVE: We aimed at identifying factors associated with the use of RTB for localized SRMs within a number of centers contributing data to the Canadian Kidney Cancer information system. MATERIAL AND METHODS: We identified 3,838 patients diagnosed with a localized SRM (≤4 cm) between January 2011 and December 2018. Patients were stratified based on whether a RTB was performed prior to the primary therapeutic intervention. Factors associated with use of RTB were assessed using univariable and multivariable logistic regression models. RESULTS: A total of 993 patients (25.9%) underwent an RTB. There was an overall increase in RTB use over time (P < 0.001), with patients diagnosed between 2015 and 2018 undergoing more RTB than patients diagnosed between 2011 and 2014 (29.8% vs. 22.2%, respectively; P < 0.001). Patients managed in centers with the highest patient-volume had RTB more frequently than patients managed in low-volume centers. On multivariable analysis, increasing year of diagnosis was significantly associated with more RTB use. Patients treated with surgery underwent RTB statistically less often than patients undergoing thermal ablation (P < 0.001) or managed with active surveillance (P < 0.001). Larger SRMs were associated with more RTB use in patients on active surveillance (P = 0.009), but with less RTB in patients undergoing surgery (P = 0.045). CONCLUSION: This large multicenter cohort study reveals an increasing adoption and overall use of RTB amongst Canadian urologists. Patients managed in high-volume centers and those undergoing non-surgical management were associated with greater use of RTB. Tumor size was also associated with RTB use. This study highlights the influence that physician perceptions and clinical factors may have in the decision to use RTB prior to initiating a therapeutic approach.

Adrenalectomy During Radical Nephrectomy- Incidence and Oncologic Outcomes From the Canadian Kidney Cancer Information System (CKCis) -A Modern Era, Nationwide, Multicenter Cohort.

OBJECTIVE: To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low. METHODS: All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis. RESULTS: During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P <.0001), higher T stage (71.1% vs 43.4% pT3/4; P <.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P <.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48). CONCLUSION: Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.