Urothelial Cancer Response to Neoadjuvant Chemo Varies by Histologic Variant

Certain histologic variants of urothelial bladder cancer benefit more from neoadjuvant chemotherapy, according to a new study. Patients with neuroendocrine tumors fared best with regard to the presence of non–organ-confined disease at the time of radical cystectomy, and were the only patients to derive an overall survival benefit from the treatment.

Previous research has shown benefit with neoadjuvant chemotherapy specifically in neuroendocrine tumors, but “its role remains uncertain for other non-pure urothelial histologic variants, such as those with micropapillary or sarcomatoid differentiation,” wrote study authors led by Malte W. Vetterlein, MD, of Brigham and Women’s Hospital in Boston.

The new study examined neoadjuvant therapy’s effect on those variants, based on patients in the National Cancer Data Base. It included a total of 2,018 patients, divided into six histologic categories: micropapillary differentiation (154 patients); sarcomatoid differentiation (304 patients); squamous cell carcinoma (810 patients); adenocarcinoma (357 patients); neuroendocrine tumors (269 patients); and other histology (124 patients).

A total of 369 patients received neoadjuvant chemotherapy prior to radical cystectomy, while the remaining 1,649 patients underwent radical cystectomy only. The results of the analysis were published online ahead of print in Cancer.

On a multivariate analysis, four of the six histologic variants had reduced odds of having non–organ-confined disease at radical cystectomy with neoadjuvant chemotherapy. The biggest effect was seen in neuroendocrine tumors, with an odds ratio (OR) of 0.16 (95% CI, 0.08–0.32; P < .001), followed by adenocarcinoma with an OR of 0.24 (95% CI, 0.06–0.91; P = .035), micropapillary tumors with an OR of 0.30 (95% CI, 0.10–0.95; P = .041), and sarcomatoid tumors with an OR of 0.40 (95% CI, 0.17–0.94; P = .035). Neither squamous cell carcinoma (OR, 0.74; 95% CI, 0.36–1.55; P = .4) nor those with other histology (OR, 0.64; 95% CI, 0.15–2.78; P = .5) showed benefit with neoadjuvant chemotherapy.

Those benefits with regard to non–organ-confined disease, however, did not translate into an overall survival benefit in most patients. The exception was those with neuroendocrine tumors, who had a median overall survival of 17.3 months with radical cystectomy only and 34.7 months with neoadjuvant chemotherapy, for a hazard ratio of 0.49 (95% CI, 0.33–0.74; P = .001). Though the median overall survival was numerically longer with neoadjuvant chemotherapy in each of the other histologic groups except the other histology group, none reached statistical significance.

“These findings should be interpreted within the context of the hypothesis-generating, retrospective study design,” the authors cautioned, noting the need for prospective evaluations of the role of systemic therapies in the various types of urothelial cancer. Still, the results suggest a tailoring of treatment based on histologic variation and other markers may be a good approach in the future.