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Published in Bladder Cancer

Expert Opinion / Cases · October 01, 2021

Muscle-Invasive Bladder Cancer With Primarily Squamous Differentiation

Written by
Daniel E. Lage MD, MSc


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  • Guru Sonpavde

    Oct 21, 2021

    The role of neoadjuvant chemotherapy in predominant variant muscle-invasive bladder cancer remains unproven in a phase III trial, and these patients are generally taken to upfront surgery. Patients with a minor variant histology component are treated similar to conventional urothelial carcinoma, but there are no definitive data to guide the therapy of those with a major or pure variant component. Some histological variants are associated with adverse outcomes, particularly micropapillary, plasmacytoid and small cell histology. However, other data suggest that only the pure variants predominantly micropapillary or small cell and not mixed variant histologies mostly with squamous, adenocarcinoma, sarcomatoid and lymphoepithelioma components were associated with poor outcomes. The role of trimodality therapy (TMT) or chemoradiation in variant histology MIBC is also unclear. One retrospective analysis suggested no detrimental impact of mixed variant urothelial carcinoma histology (Krasnow et al, EUROPEAN UROLOGY 7 2 ( 2 0 1 7 ) 5 4 – 6 0). The role of adjuvant therapy is also unclear with predominant variant urothelial carcinoma histology. A large NCDB analysis (Berg et al, Cancer ) reported that only patients with pure urothelial carcinoma had an overall survival benefit associated with adjuvant chemotherapy, whereas no benefit was observed for those with variant histology. The adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection is approved by the US FDA. Thus, the use of adjuvant nivolumab with predominant urothelial histology and minor variant component is reasonable. The role of adjuvant nivolumab in those with predominant or pure variant histology needs further study. I would consider adjuvant nivolumab even in those with predominant variant urothelial carcinoma histology, especially if the PD-L1 expression is high (but not in pure variant carcinoma).

  • Aug 13, 2022

    Pending Moderator approval.

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