Introduction & Objectives: Although recommended in international guidelines, the survival benefit of neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) remains controversial. As a result, practice variation is expected. We evaluated guideline adherence and assessed practice variation between hospitals in NAC use and its effect on survival.

Materials & Methods: In this nationwide study based on the Netherlands Cancer Registry, we identified 1,025 patients newly diagnosed with non-metastatic MIBC between November 2017 and November 2019 who underwent radical cystectomy. Patients with ECOG performance status 0-1 and creatinine clearance ≥50 mL/min/1.73m2were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. The association between hospital-specific probabilities of NAC and survival was evaluated using a Cox proportional hazards model. All analyses were stratified by disease stage (cT2 versus cT3-4a).

Results: In total, 809 patients were considered NAC-eligible, but only 277 (34%) received NAC. Guideline adherence for NAC in cT2 was lower compared to T3-T4a disease (26% versus 55%) and interhospital variation was larger (7-57% versus 31-62%). For cT2-disease, adjusted two-year OS seems in favor of patients treated in hospitals with higher probability to administer NAC (HR 0.59, 95%CI 0.33-1.05) although not statistically significant. For cT3-4a, no significant effect was observed (HR 0.71, 95%CI 0.25-2.04).

Conclusions: Guideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Our data suggest that hospitals more likely to give NAC in T2-disease perform slightly better concerning survival, although results should be interpreted with care as this was not statistically significant. Further research is warranted to elucidate the underlying mechanism. As literature is clear concerning the potential survival benefit of NAC in patients with cT3-4a disease, our data shows that guideline adherence could be improved.

**Introduction & Objectives**: Although recommended in international guidelines, the survival benefit of neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) remains controversial. As a result, practice variation is expected. We evaluated guideline adherence and assessed practice variation between hospitals in NAC use and its effect on survival.

**Materials & Methods**: In this nationwide study based on the Netherlands Cancer Registry, we identified 1,025 patients newly diagnosed with non-metastatic MIBC between November 2017 and November 2019 who underwent radical cystectomy. Patients with ECOG performance status 0-1 and creatinine clearance ≥50 mL/min/1.73m2were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. The association between hospital-specific probabilities of NAC and survival was evaluated using a Cox proportional hazards model. All analyses were stratified by disease stage (cT2 versus cT3-4a).

**Results**: In total, 809 patients were considered NAC-eligible, but only 277 (34%) received NAC. Guideline adherence for NAC in cT2 was lower compared to T3-T4a disease (26% versus 55%) and interhospital variation was larger (7-57% versus 31-62%). For cT2-disease, adjusted two-year OS seems in favor of patients treated in hospitals with higher probability to administer NAC (HR 0.59, 95%CI 0.33-1.05) although not statistically significant. For cT3-4a, no significant effect was observed (HR 0.71, 95%CI 0.25-2.04).

**Conclusions**: Guideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Our data suggest that hospitals more likely to give NAC in T2-disease perform slightly better concerning survival, although results should be interpreted with care as this was not statistically significant. Further research is warranted to elucidate the underlying mechanism. As literature is clear concerning the potential survival benefit of NAC in patients with cT3-4a disease, our data shows that guideline adherence could be improved.

Low guideline adherence to recommended use of neoadjuvant chemotherapy in patients with non-metastatic muscle-invasive bladder cancer