Introduction

Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, it is unknown if this benefit persists in histological variants of bladder cancer. We aimed to assess the effect of neoadjuvant chemotherapy on overall survival (OS) and upstaging at radical cystectomy in the five most common histological variants.

Methods

Querying the National Cancer Data Base, we identified 1,555 patients with histological variants undergoing radical cystectomy for muscle-invasive bladder cancer between 2003-2011. Neoadjuvant chemotherapy was defined as multiagent systemic therapy administered within 180 days prior to surgery. Histological variants were categorized as pure neuroendocrine tumors, squamous cell carcinoma, and adenocarcinoma, or micropapillary and sarcomatoid differentiation. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Logistic regression models estimated the odds of pathological upstaging at radical cystectomy for each histological variant, stratified by the receipt of neoadjuvant chemotherapy.

Results

In multivariate analyses, an OS benefit for neoadjuvant chemotherapy was only found in neuroendocrine tumors (hazard ratio [HR]=0.64; 95% confidence interval [CI]=0.45-0.90; P=0.012). Neuroendocrine tumors (odds ratio [OR]=0.38; 95% CI=0.22-0.67; P=0.001), along with micropapillary (OR=0.16; 95% CI=0.05-0.47; P=0.001) and sarcomatoid differentiated tumors (OR=0.34; 95% CI=0.14-0.87; P=0.025), were less likely to be upstaged at radical cystectomy when treated with neoadjuvant chemotherapy. In squamous cell and adenocarcinoma, no favorable pathological outcomes were seen in patients receiving neoadjuvant chemotherapy vs. radical cystectomy alone (all P>0.08). Specifically, patients with squamous cell carcinoma even trended towards worse pathology (i.e. upstaging) at RC if they received neoadjuvant chemotherapy (OR=1.81; 95% CI=[0.93-3.52]; P=0.081) compared to patients undergoing RC alone.

Conclusions

Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better OS and lower rates of pathological upstaging at radical cystectomy. In micropapillary and sarcomatoid differentiated tumors, neoadjuvant chemotherapy decreased pathological upstaging at cystectomy. However, this favorable effect did not translate into a statistically significant OS benefit for these patients, potentially due to the aggressive tumor biology.

Funding

None