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.

Phase 1 Trial of Atezolizumab Plus Trimodal Therapy in Patients With Localized Muscle-Invasive Bladder Cancer.

PURPOSE: Immune checkpoint programmed death-ligand 1 inhibitor therapy has shown response in metastatic muscle invasive bladder cancer (MIBC). We evaluated the safety and tolerability of atezolizumab (anti-programmed death-ligand 1) in combination with trimodal therapy in patients with localized MIBC. METHODS AND MATERIALS: A prospective nonrandomized phase 1 study using a 3 + 3 design was conducted in patients with localized MIBC (T2-T4a N0M0) treated on a bladder preservation program. After transurethral resection of bladder tumor, patients received concurrent radiation therapy at a fixed dose of 50 Gy in 20 fractions, gemcitabine (100 mg/m2, intravenously once weekly for 4 weeks) and atezolizumab (1200 mg intravenously every 3 weeks for 16 cycles). The primary endpoint was safety/toxicity profile. RESULTS: Between May 2018 and March 2019, 8 patients (6 male and 2 female) were enrolled. The first 5 patients received atezolizumab at 1200 mg, 3 of whom developed grade 3 side effects (2 of them dose-limiting toxicity). Atezolizumab dose was reduced to 840 mg for 3 additional patients. The study was terminated due to the presence of 3 grade 3 adverse events (2 of which were dose-limiting toxicity) despite the reduced atezolizumab dose. Gastrointestinal events were the main toxicity. No grade 4 to 5 adverse effects were observed. CONCLUSIONS: Concurrent administration of atezolizumab with concomitant hypofractionated radiation therapy and gemcitabine appears to be associated with unacceptable gastrointestinal toxicity. Although the numbers studied are small, our results suggest considerable caution with its concurrent use with trimodal therapy for MIBC.