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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.

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BeTTer Outcomes Workgroup Health Quality Initiative to optimize bone health for prostate cancer patients in the British Columbia Cancer System

Introduction: Bone-targeted therapies (BTTs) are integral to the management of bone metastases in metastatic castration-resistant prostate cancer (mCRPC). BTTs vary considerably in referral and drug access pathways and optimal BTT use requires multi-specialty consultation and supervision. Health quality improvement (HQI) has become the predominant framework to improve patient care in multidisciplinary settings. Methods: HQI initiatives on use of BTT in mCRPC were developed and evaluated in five centers of a provincial cancer center network using Plan-Do-Study-Act (PDSA) methodology. Multidisciplinary teams (MDTs) completed a common quality assessment form and an HQI template and then implemented an HQI initiative. Feedback and findings were shared and discussed at regional events. It was subsequently determined whether to adopt, adapt, or abandon initiatives. Results: Patterns of unmet needs varied across type of BTT. Gaps in use of radium-223 were mostly referral and education issues that could be directly addressed at the local level by participating clinician teams. Conversely, most supportive BTT gaps were related to coverage and resourcing support. HQI initiatives selected by each site consisted of implementation or expansion of local MDT meetings, referral documents, databases, and improvement charters. The main HQI initiative was completed in four sites and was adapted or adopted in three. Improvements in BTT use were observed in two of three centers with data on HQI process measures. Conclusions: Despite the overall heterogenous structure of the groups and metrics used, this study demonstrated that the PDSA framework provides the needed structure for improvements in BTT use in mCRPC across multiple sites.

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Adjuvant therapy for renal cell carcinoma

Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.

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