Background: The impact of the change in the neutrophil-to-lymphocyte ratio (NLR) during neoadjuvant chemotherapy (NAC) on outcomes in patients with muscle-invasive bladder cancer (MIBC) is poorly understood. Objective: To evaluate the prognostic impact of the change in NLR during NAC for patients with MIBC. Methods: Patients referred to academic, community, and quaternary referral centres in Alberta, Canada from 2005 to 2015, Ontario, Canada from 2005 to 2013, and Southampton, UK from 2004 to 2010 were evaluated. 376 eligible patients were treated with NAC for clinical T2-4aN0M0 disease, and 296 were evaluable for the change in NLR. A high NLR was defined as being an NLR > 3. Relationships between the change in NLR from baseline to mid-NAC (pre-cycle 3) and outcomes were analyzed using multivariable Cox regression. Kaplan-Meier analysis was used with the log-rank test for group comparisons. Results: Median follow-up was 22.0 months (95% confidence interval [CI]: 14.9–30.0). Patients with a sustained high NLR had a median disease-free survival (DFS) of 12.6 months, compared to 34.8 months for those with a sustained low NLR (log-rank test p = 0.0025; hazard ratio [HR] 0.61 [95% CI: 0.44–0.84]). Median overall survival (OS) was 19.4 months for patients with a sustained high NLR, compared to 44.0 months for patients with a sustained low NLR (log-rank test p = 0.0011; HR 0.54 [95% CI: 0.38–0.77]). Conclusions: A sustained high NLR from baseline to mid-NAC is an independent prognostic factor for patients with MIBC.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. As a result of recent Canadian funding for SG in advanced hormone receptor (HR)-positive breast cancer and triple-negative breast cancer (TNBC), experience with using SG and managing adverse events (AEs) has grown. This review presents a summary of evidence and adverse event recommendations derived from Canadian experience, with SG use in metastatic TNBC for extrapolation and guidance in all indicated settings. SG is dosed at 10 mg/kg on day 1 and day 8 of a 21-day cycle. Compared to treatment of physicians’ choice (TPC) the phase III ASCENT and TROPiCS-02 studies demonstrated favorable survival data in unresectable locally advanced or metastatic TNBC and HR-positive HER2 negative metastatic breast cancer, respectively. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.

Despite a high disease burden, real-world data on treatment patterns in patients with unresectable locally advanced or metastatic urothelial carcinoma (la/mUC) in Canada are limited. This retrospective, longitudinal cohort study describes treatment patterns and survival in a population of patients with de novo unresectable la/mUC from Alberta, Canada, diagnosed between 1 January 2015 and 31 December 2019, followed until mid-2020. The outcomes of interest were systemic therapy treatment patterns and overall survival (OS). Of 206 patients, most (65.0%, n = 134) did not receive any systemic therapies. Of 72 patients (35.0%) who received first-line systemic therapy, the median duration of treatment was 2.8 months (IQR 3.3). Thirty-five patients (48.6% of those who received first-line therapy) received subsequent second-line therapy, for a median of 3.0 months (IQR 3.3). In all patients (n = 206), the median OS from diagnosis was 5.3 months (95% CI, 4.5–7.0). In patients who received treatment, the median OS from the initiation of first-line and second-line systemic therapy was 9.1 (6.4–11.6) and 4.6 months (3.9–19.2), respectively. The majority of patients did not receive first-line systemic therapy, and, in those who did, survival outcomes were poor. This study highlights the significant unmet need for safe and efficacious therapies for patients with la/mUC in Canada.

Introduction: Approximately 25% of patients diagnosed with bladder cancer have muscle-invasive disease (MIBC). While real-world data have highlighted opportunities to improve curative-intent treatment rates, comprehensive population-level data in Canada are limited. This study aimed to assess patterns of care and outcomes in a real-world cohort of MIBC in Canada. Methods: This retrospective, observational study describes baseline characteristics, treatment patterns, and overall survival (OS) of individuals with de novo MIBC diagnosed between 2010 and 2020 in Alberta, Canada. Data from adult patients with MIBC (T2-4N0-1M0) were obtained from administrative databases and analyzed using basic statistics, multivariate regression analyses, and the Kaplan-Meier method. Results: We identified 1292 patients with de novo MIBC. Of these, 76% were male with a median age of 73 years, 68% had cT2, and 76% had cN0 disease; approximately half had a Charlson comorbidity index (CCI) ≥1. Overall, 25% did not receive active treatment while 58% received curative-intent treatment (49% underwent radical cystectomy [RC] and 9% received chemoradiotherapy) and 17% received some form of non-curative-intent treatment. Of those who underwent RC, 45% received neoadjuvant chemotherapy (NAC). Median overall survival (mOS) in the entire cohort was 2.1 years (95% confidence interval 1.92.4). Key predictors of inferior survival were age ≥76 years, CCI score of ≥1, T4 tumor stage, or not receiving NAC. Conclusions: This real-world analysis highlights opportunities to improve outcomes for patients with MIBC. Increasing access to curative-intent treatments, particularly in the elderly and those with comorbidities, is likely to enhance patient care and outcomes.

388 Background: Patients with locally advanced urothelial cancer with regional lymph node involvement (LN+) have a poor prognosis. Surgical management of these patients is controversial and practice patterns vary. We evaluated the outcomes of patients with LN+ disease treated with pre-operative chemotherapy and cystectomy, cystectomy and post-operative chemotherapy, and chemotherapy alone. Methods: Patients with urothelial cancer with TxN1-3M0 disease treated with chemotherapy in Alberta from 2005 to 2015 were evaluated. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Cox regression analysis was performed to evaluate the impact of age, gender, T stage, and N stage on survival. Results: 184 patients with LN+ disease treated with chemotherapy were evaluable for outcomes; 42 underwent pre-operative chemotherapy (Group A), 92 underwent post-operative chemotherapy (Group B), and 50 received chemotherapy alone (Group C). The median age at diagnosis was 65 years (range 31-89) and most patients (83%) were male. The median follow-up time was 23.2 months. A higher T stage was seen in patients in Group A, while patients in Group C had a higher N stage. The median number of chemotherapy cycles delivered was equal in all arms at 4. Patients in Group A or B had significantly better PFS and OS compared with patients in Group C (Table). When adjusting for age, gender, T stage, and N stage, patients in Group C had significantly lower OS compared with those patients in Group A (HR 1.87, 95% CI 1.09 – 3.18, p=0.02). Conclusions: In this real-world analysis of patients with LN+ urothelial cancer, patient outcomes were improved with surgical resection of disease in combination with pre-operative chemotherapy. After chemotherapy in fit patients with LN+ disease, surgical management is a reasonable consideration. [Table: see text]