Impact of systemic inflammatory markers on the response to Hyperthermic IntraVEsical Chemotherapy (HIVEC) in patients with non-muscle-invasive bladder cancer after bacillus Calmette–Guérin failure

Objectives: To evaluate the impact of pre- and post-treatment systemic inflammatory markers on the response to Hyperthermic IntraVEsical Chemotherapy (HIVEC) treatment in a cohort of patients with high-grade non-muscle-invasive bladder cancer with bacillus Calmette–Guérin (BCG) failure or intolerance who were unsuitable or unwilling to undergo early radical cystectomy. As a secondary endpoint, we assessed the influence of some demographic, clinical and pathological factors on the response to chemo-hyperthermia. Patients and methods: Between March 2017 and December 2019, 72 consecutive patients were retrospectively analysed. Patients with diseases or conditions that could interfere with systemic inflammatory status or full blood count were excluded. The HIVEC protocol consisted of six weekly intravesical treatments with 40 mg Mitomycin-C diluted in 50 mL distilled water. The drug was heated to a temperature of 43°C. Association of categorical variables with response to HIVEC was evaluated using Yates’ chi-squared test and differences in continuous variable were analysed using the Mann–Whitney test. Logistic regression analysis was performed to define independent predictors of response to HIVEC. Results: Patients who failed HIVEC were more likely to have multiple tumours (P = 0.039) at transurethral resection of bladder and a recurrence rate of >1/year (P = 0.046). Lower post-HIVEC inflammatory indices [C-reactive protein (P = 0.021), erythrocyte sedimentation rate (P = 0.027)] and lower pre- (P = 0.014) and post-treatment (P = 0.004) neutrophil-to-lymphocyte ratio (NLR) values were significantly associated with the response to the HIVEC regimen (no bladder cancer recurrence or progression). In the multivariate analysis, patients with a recurrence rate of >1/year were eight-times more likely to experience failure of HIVEC (P = 0.007). Higher pre- (P = 0.023) and post-treatment NLR values (P = 0.046) were associated with a worse response to the HIVEC regimen. Conclusions: The recurrence rate and systemic inflammatory response markers could be useful tools to predict the likelihood of obtaining a response with the HIVEC regimen. These markers might help to guide patients about the behaviour of the tumour after BCG failure, predicting failure or success of a conservative treatment. Abbreviations: CHT: chemo-hyperthermia; CIS: carcinoma in situ; CRP: C-reactive protein; EAU: European Association of Urology; ESR: erythrocyte sedimentation rate; HG: high grade; HIVEC: Hyperthermic IntraVEsical Chemotherapy; ICD: immunogenic cell death; IL: interleukin; MMC: Mitomycin-C; NK: natural killer; NLR: neutrophil-to-lymphocyte ratio; NMIBC: non-muscle-invasive bladder cancer; PLR: platelet-to-lymphocyte ratio; RC: radical cystectomy; SIR: systemic inflammatory response; TURB: transurethral resection of bladder