An in-depth analysis on the effects of body composition in patients receiving neoadjuvant chemotherapy for urothelial cell carcinoma.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is the standard of care for patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC); however, NAC can be associated with significant side effects and morbidity in some patients. NAC may contribute to sarcopenia, obesity, and the combination of the two. Our study examined the effects of NAC on body composition and the association between body composition and adverse events. METHODS: We created a retrospective database of patients with non-metastatic MIBC receiving NAC prior to RC. The change in skeletal muscle index (SMI) and fat mass index (FMI) was calculated using computed tomography (CT) scans done within three months prior to NAC and after the first two cycles. The association between body composition (sarcopenia, obesity, and sarcopenic obesity) and preoperative adverse events was investigated using a multivariable logistic regression. Changes in body composition were calculated using a paired Student's t-test. RESULTS: A total of 70 patients were included in our study. There was a mean decrease in SMI of 2.2±3.2 cm2/m2. Adiposity and FMI were unchanged by NAC. Sarcopenic obesity was found to be associated with adverse events among patients receiving NAC in the multivariable analysis. There was a total of 637 preoperative complications with grades 1-2 and 33 complications with grades 3-5. CONCLUSIONS: Based on our retrospective cohort study, NAC did not affect obesity and FMI, but there was a significant decrease in SMI. Sarcopenic obesity was associated with increased severity of NAC adverse events. As such, the presence of this factor may help predict tolerance of NAC.

Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

The impact of robotic surgery access on the management of patients with clinical stage I kidney tumors.

INTRODUCTION: Robotic surgery is used in the treatment of kidney tumors. We aimed to determine if robotic access was associated with initial choice of management for patients with a clinical stage I kidney mass. METHODS: Patients with a clinical stage I kidney mass were identified from the Canadian Kidney Cancer information system (CKCis) cohort. Sites were classified by year and access to robotic surgery. Associations between robotic access and initial management were determined using logistic regression. Univariable and multivariable analyses were performed, adjusting for tumor size and stage, and presented as relative risks (RR ) or adjusted RR (aRR) and 95% confidence intervals (CI). RESULTS: Overall, 4160 patients were included. Among patients treated with surgery, the proportion of partial nephrectomy compared to radical nephrectomy was significantly higher in robotic sites (77.3% for robotic sites vs. 65.9% for non-robotic sites; RR 1.17, 95% CI 1.12-1.23, p<0.0001; aRR 1.12, 95% CI 1.08-1.17, p<0.0001). Patients receiving partial nephrectomy at sites with robotic access were more likely to receive a minimally invasive approach compared to patients at non-robotic sites (61.4% vs. 50.9%, RR 1.21, 95% CI 1.12-1.30; aRR 1.16, 95% CI 1.08-1.25, p<0.0001). The proportion of patients managed by active surveillance was not significantly different between robotic (405, 16.9%) and non-robotic (258, 14.7%) sites (RR 1.15, 95% CI 0.99-1.32; aRR 0.97, 95% CI 0.84-1.12). CONCLUSIONS: Access to robotic kidney surgery was associated with increased use of partial nephrectomy and minimally invasive partial nephrectomy. Use of active surveillance was similar at robotic and non-robotic institutions. Limitations of this study include lack of data on perioperative complications and cancer recurrence.

A comparison of the sarcopenic effect of androgen receptor-axis-targeted agents vs. androgen deprivation alone in patients with metastatic prostate cancer.

INTRODUCTION: Androgen deprivation therapy (ADT) with androgen receptor axis-targeted (ARAT) therapy is the standard of care provided to patients with metastatic prostate cancer. While effective, it results in sequelae, such as loss of skeletal muscle mass. In this study, we compared the sarcopenic effects of abiraterone and enzalutamide, two ARATs used to treat metastatic prostate cancer. METHODS: Our cohort was comprised of 55 patients diagnosed with metastatic hormonenaive prostate cancer from 2014-2019. Patients were divided into three treatment groups: gonadotropin-releasing hormone (GnRH ) agonist alone; GnRH agonist combined with abiraterone acetate; and GnRH agonist combined with enzalutamide. We then compared axial computed tomographic (CT) scans at the L3 level before and after the initiation of hormone therapy for each patient. A skeletal muscle index (SMI) was calculated for each patient, and alongside clinical data, was compared between the three groups. One-way analysis of variance (ANOVA) and Fisher's exact test were used to compare means and proportions, respectively. RESULTS: Baseline clinical characteristics were not significantly different between the three groups. The percent SMI change and number of newly sarcopenic patients were not found to be significantly different between the groups. The only variable that was significantly different across the three groups was time between CT scans. CONCLUSIONS: Although we found no significant difference in the sarcopenic effects of GnRH alone, GnRH with abiraterone, or GnRH with enzalutamide in our cohort of 55 hormone-naive metastatic prostate cancer patients, overall decreases in muscle mass were observed for all three groups. This highlights the importance of muscle-retaining strategies for patients undergoing ADT for metastatic prostate cancer, regardless of therapeutic regimen.

Genetic testing practices among specialist physicians who treat prostate cancer A Canadian, cross-sectional survey.

INTRODUCTION: In patients with prostate cancer (PCa), the identification of an alteration in genes associated with homologous recombination repair (HRR) has implications for prognostication, optimization of therapy, and familial risk mitigation. The aim of this study was to assess the genomic testing landscape of PCa in Canada and to recommend an approach to offering germline and tumor testing for HRR-associated genes. METHODS: The Canadian Genitourinary Research Consortium (GURC) administered a cross-sectional survey to a largely academic, multidisciplinary group of investigators across 22 GURC sites between January and June 2022. RESULTS: Thirty-eight investigators from all 22 sites responded to the survey. Germline genetic testing was initiated by 34%, while 45% required a referral to a genetic specialist. Most investigators (82%) reported that both germline and tumor testing were needed, with 92% currently offering germline and 72% offering tissue testing to patients with advanced PCa. The most cited reasons for not offering testing were an access gap (50%), uncertainties around who to test and which genes to test, (33%) and interpreting results (17%). A majority reported that patients with advanced PCa (74-80%) should be tested, with few investigators testing patients with localized disease except when there is a family history of PCa (45-55%). CONCLUSIONS: Canadian physicians with academic subspecialist backgrounds in genitourinary malignancies recognize the benefits of both germline and somatic testing in PCa; however, there are challenges in accessing testing across practices and specialties. An algorithm to reduce uncertainty for providers when ordering genetic testing for patients with PCa is proposed.

Examining the impact of postoperative opioid use on length of hospital stay following radical cystectomy.

INTRODUCTION: Radical cystectomy (RC) is associated with high rates of morbidity, prolonged hospital stay, and increased opioid use for postoperative pain management; however, the relationship between postoperative opioid use and length of stay (LOS ) remains uncharacterized. This study serves to investigate the association between postoperative opioid use and length of hospital stay after RC. The relationship between patient and surgical factors on LOS was also characterized. METHODS: We retrospectively reviewed all patients between 2009 and 2019 who underwent RC at our institution. Patient and perioperative variables were analyzed to determine the relationship between postoperative opioid use and LOS using multivariable linear regression analysis. RESULTS: We identified 240 patients for study inclusion with a median age of 70.0 years. Median LOS was 10.0 days, with median daily mg morphine equivalent use of 57.5 for patients. Daily mg morphine equivalent use was significantly associated with an increased LOS, as were previous pelvic radiation, postoperative ileus, and higher Clavien-Dindo grade complication during admission (all p<0.05). Median LOS increased by one day for each increase of 13.2 daily mg morphine equivalents received. CONCLUSIONS: Increased daily opioid use was associated with increased length of hospital stay after RC. Non-opioid-based pain management approaches may be effective in reducing LOS after RC.

Clinical utility of routine postoperative serial hemoglobin measurements in patients undergoing radical cystectomy for urothelial carcinoma.

INTRODUCTION: Routine measurements of serum hemoglobin (sHgb) are common after abdominal surgery; however, prolonged measurements may be associated with patient anxiety, increased costs, and longer hospitalization without clinical benefit. The objective of this study was to determine the utility of routine sHgb measurements after radical cystectomy (RC) and factors associated with transfusion of packed red blood cell (pRB C) beyond postoperative day (POD ) 2. METHODS: We retrospectively reviewed patients who underwent RC between 2009 and 2019 at a single academic tertiary care center. The number of sHgb measurements for each patient was examined and pRB C transfusion rates were calculated. Multivariable logistic regression was used to determine factors associated with transfusion beyond POD 2. RESULTS: The median number of sHgb measurements per patient during admission was nine (interquartile range [IQR] 7, 25). Overall, 69/240 (28.7%) patients received a postoperative transfusion, including 46/240 (19.2%) patients receiving a transfusion beyond POD 2. Among patients with a sHgb ≥100 g/L on POD 2, 7/85 (8.2%) went on to receive a transfusion beyond this day compared with 39/155 (25.2%) patients with sHgb <100 g/L. On multivariable analysis, risk factors associated with pRB C transfusion beyond POD 2 included older age, lower sHgb on POD 2, and longer length of stay in hospital. CONCLUSIONS: Transfusion of pRB Cs beyond POD 2 was found to be common; however, patients with sHgb ≥100 g/L on POD 2 were at low risk of requiring subsequent transfusion. Discontinuing further routine sHgb checks in these patients may serve to decrease patient anxiety, healthcare costs, and delays in hospital discharge.

Recommendations for the implementation of genetic testing for metastatic prostate cancer patients in Canada.

INTRODUCTION: Genetic testing in advanced prostate cancer is rapidly moving to become standard of care. Testing for genetic alterations in genes involved in DNA repair pathways, particularly those implicated in the homologous recombination repair (HRR) pathway, in patients with metastatic prostate cancer (mPCa) can inform selection of optimal therapies, as well as provide information about familial cancer risks; however, there are currently no consistent Canadian guidelines in place for genetic testing in mPCa. METHODS: A multidisciplinary steering committee guided the process of an environmental scan to define the current landscape, as well as the perceived challenges, through interviews with specialists from 14 sites across Canada. The challenges most commonly identified include limited testing guidelines and protocols, inadequate education and awareness, and insufficient resources. Following the environmental scan, an expert multidisciplinary working group with pan-Canadian representation from medical oncologists, urologists, medical geneticists, genetic counsellors, pathologists, and clinical laboratory scientists convened in virtual meetings to discuss the challenges in implementation of genetic testing in mPCa across Canada. RESULTS: Key recommendations from the working group include implementation of germline and tumor HRR testing for all patients with mPCa, with a mainstreaming model in which non-geneticist clinicians can initiate germline testing. The working group defined the roles and responsibilities of the various healthcare providers (HCPs) involved in the genetic testing pathway for mPCa patients. In addition, the educational needs for all HCPs involved in the genetic testing pathway for mPCa were defined. CONCLUSIONS: As genetic testing for mPCa becomes standard of care, additional resources and investments will be required to implement the changes that will be needed to support the necessary volume of genetic testing, to ensure equitable access, and to provide education to all stakeholders.

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.

Results from a Canadian consensus forum of key controversial areas in the management of advanced prostate cancer: Recommendations for Canadian healthcare providers.

INTRODUCTION: Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) has created areas where high-level evidence to guide practice is lacking. The Genitourinary Research Consortium (GURC) conducted its second Canadian consensus forum to address areas of controversy in the management of PCa and provide recommendations to guide treatment. METHODS: A panel of PCa specialists discussed topics related to the management of PCa. The core scientific committee finalized the design, questions, and analysis of the consensus results. Attendees then voted to indicate their management choice regarding each statement/topic. Questions for voting were adapted from the 2019 Advanced Prostate Cancer Consensus Conference. The thresholds for agreement were set at ≥75% for "consensus agreement," >50% for "near-consensus," and ≤50% for "no consensus." RESULTS: The panel was comprised of 29 PCa experts, including urologists (n=12), medical oncologists (n=12), and radiation oncologists (n=5). Voting took place for 65 predetermined questions and three ad hoc questions. Consensus was reached for 34 questions, spanning a variety of areas, including biochemical recurrence, treatment of metastatic castration-sensitive PCa, management of non-metastatic and metastatic castration-resistant PCa, bone health, and molecular profiling. CONCLUSIONS: The consensus forum identified areas of consensus or near-consensus in more than half of the questions discussed. Areas of consensus typically aligned with available evidence, and areas of variability may indicate a lack of high-quality evidence and point to future opportunities for further research and education.