Low adherence to recommended use of neoadjuvant chemotherapy for muscle-invasive bladder cancer

Abstract

Purpose: To evaluate guideline adherence and variation in the recommended use of neoadjuvant chemotherapy (NAC) and the effects of this variation on survival in patients with non-metastatic muscle-invasive bladder cancer (MIBC).

Patients and methods: In this nationwide, Netherlands Cancer Registry-based study, we identified 1025 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/1.73 m² were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. A Cox proportional hazards model was used to evaluate the association between hospital specific probability of using NAC and survival. All analyses were stratified by disease stage (cT2 versus cT3-4a).

Results: In total, of 809 NAC-eligible patients, only 34% (n = 277) received NAC. Guideline adherence for NAC in cT2 was 26% versus 55% in cT3-4a disease. Interhospital variation was 7-57% and 31-62%, respectively. A higher hospital specific probability of NAC might be associated with a better survival, but results were not statistically significant (HR_cT2 = 0.59, 95% CI 0.33-1.05 and HR_cT3-4a = 0.71, 95% CI 0.25-2.04).

Conclusion: Guideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Although not significant, our data suggest that survival of patients diagnosed in hospitals more inclined to give NAC might be better. Further research is warranted to elucidate the underlying mechanism. As literature clearly shows the potential survival benefit of NAC in patients with cT3-4a disease, better guideline adherence might be pursued.

Keywords: Bladder carcinoma; Guideline adherence; MIBC; Muscle-invasive bladder cancer; Neoadjuvant chemotherapy; Radical cystectomy; Variation in healthcare.

Fig. 1

The probability of platinum-eligible patients to receive NAC per hospital* overall, for cT2-disease only and for cT3-4a disease only, observed and adjusted for case-mix factors. NAC neoadjuvant chemotherapy, MDTM multidisciplinary team meeting. *Hospitals with < 5 cases were excluded from analysis. a: The multilevel model for all disease stages (cT2–4a) included: age at diagnosis, comorbidity and disease stage, based on 52 hospitals; b: the multilevel model for cT2-disease only included: age at diagnosis and BMI, based on 47 hospitals; c: the multilevel model for cT3-4a disease only included: age at diagnosis and comorbidity, based on 18 hospitals