Expert Commentary: Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology

Neoadjuvant chemotherapy is a standard of care for patients with urothelial muscle-invasive bladder cancer. Histologic variants of bladder cancer are less common but often clinically aggressive. Understanding whether neoadjuvant chemotherapy results in the same benefit in histological variants as in urothelial bladder cancer is crucial.

A recent study published in the journal Cancer by Vetterlein et al. examined the National Cancer Data Base to examine the outcomes of patients with histological variants who underwent radical cystectomy for bladder cancer between 2003 and 2012. Interestingly, patients with neuroendocrine, micropapillary, sarcomatoid, and adenocarcinoma seemed to have lower frequencies of non-organ-confined disease at the time of radical cystectomy when treated with neoadjuvant chemotherapy. However, this observation did not translate into longer overall survival benefit except in patients with neuroendocrine tumors treated with neoadjuvant chemotherapy (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]).

As the authors note, an important limitation of this study is that histologic variants were identified based on coding and not central pathological slide review. This is a key point because even in expert hands, the identification of these variants is variable. This important study adds to the growing body of literature on this topic but more carefully designed prospective trials are needed. Finally, a deeper understanding of the true biological differences between these variants and conventional urothelial carcinoma is required to understand the root causes of aggressive clinical behavior and to identify variant-specific therapeutic strategies. 

Written By: Bishoy Faltas MD

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References: 
Vetterlein MW, Wankowicz SAM, Seisen T, Lander R, Löppenberg B, Chun FK, Menon M, Sun M, Barletta JA, Choueiri TK, Bellmunt J, Trinh QD, Preston MA. Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

Cancer. 2017 Jul 25. doi: 10.1002/cncr.30907. [Epub ahead of print]
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