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Patients with muscle-invasive urothelial carcinoma and a minor variant histology component are treated with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) similar to conventional urothelial carcinoma. There are no definitive data to guide the therapy of those with a major (>50%) or pure variant component since most urothelial carcinoma trials have excluded such patients. However, the role of the proportion of variant histology in determining outcomes and therapy has not been systematically studied. Some histological variants are associated with poor outcomes, particularly micropapillary, plasmacytoid and small cell histology. Other data suggest that only the pure variants or predominant micropapillary or small cell and not predominant squamous, adenocarcinoma, sarcomatoid and lymphoepithelioma components are associated with poor outcomes. There is evidence supporting NAC with cisplatin and etoposide for neuroendocrine/small cell tumors. Nested variant histology appears associated with advanced stage at RC but when matched with conventional urothelial carcinoma, no differences have been noted in survival. The pathologic response to NAC has appeared to be poor in small studies. In the patient described above, the grade 1 nephrotoxicity and rash that appeared with NAC have resolved and do not preclude the resumption of NAC from that standpoint. However, given muscle-invasive disease and extensive nested variant histology, my recommendation would be to proceed with RC now. If the nested variant was a minor component of the disease, I would recommend continuing and completing NAC followed by RC. Indeed, a survival benefit of adjuvant chemotherapy has also not been identified for patients with urothelial carcinoma with predominant variant or pure variant histology.
1. Linder BJ, Frank I, Tarrell RF, et al. Outcomes Following Radical Cystectomy for Nested Variant of Urothelial Carcinoma: A Matched Cohort Analysis. J Urol 2013;189:1670-5.
2. Wasco MJ, Daignault S, Shah RB, et al. Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases. Hum Pathol 2010;41:163-71.
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