Immune Cell Infiltration Predicts Response to Neoadjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer - Expert Commentary

Incorporating neoadjuvant chemotherapy (NAC) into the management of patients with localized muscle-invasive bladder cancer (MIBC) improves survival. However, due to multiple factors, NAC is still not effectively used in real-life settings. Moreover, there is are established predictor biomarkers to guide clinicians to choose the most beneficial treatment with the least possible toxicities.

A recent study by Ikarashi et al. published in the British Journal of Cancer investigated the predictive value of tumor immune microenvironment (TME) to NAC response in patients with MIBC using multiplex fluorescence immunohistochemistry (mFIHC). The investigators evaluated 51 patients with MIBC retrospectively who underwent  NAC then radical cystectomy. Eligible subjects were <pT0, N0M0 and were divided into responders (>pT2) and non-responders ( ≤pT2). Three patients represented the control group, who underwent radical cystectomy alone. Samples were collected pretreatment in all patients and were assessed by hematoxylin/eosin and mFIHC. The patients were followed up to a median of 38 months.

Expectedly, patients who were responders (n=22) to NAC had a better prognosis than non-responders (n=29). Patients with tumors showing higher CD8+ tissue infiltration had a significantly shorter cancer-specific survival (CSS) than subjects with lower infiltration (P = 0.0238). Post-radical cystectomy subjects with higher CD204+ tissue infiltration were associated with shorter progression-free survival (PFS) and CSS compared with subjects showing lower infiltration (P = 0.0078, P = 0.0435, respectively). Non-responders showed higher densities of CD204+ and CD8+ cell infiltrates in pre-treatment samples than responders ( P = 0.0394, P = 0.0056, respectively) . Moreover, non-responders showed a significant increase in CD204+ cell infiltrates post-treatment (P = 0.0009), while responders had no significant change. Taken together, these findings indicate that TME is a predictor of NAC response in this patient population.

These results generate hypotheses that could guide precision neoadjuvant treatment plans to patients with MIBC, including developing neoadjuvant immunotherapy regimens in patients with tumors that are less likely to respond to NAC. The limitations of this study include its retrospective design and the relatively small number of subjects.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Ikarashi D, Kitano S, Tsuyukubo T, Takenouchi K, Nakayama T, Onagi H, et al. Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting. Br J Cancer. 2021 Nov 15. doi: 10.1038/s41416-021-01628-y. PMID: 34782748.

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