BOSTON — Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) may provide a survival advantage for patients with neuroendocrine tumors of the bladder, researchers revealed at the American Urological Association 2017 annual meeting.

Evidence of benefit exists for patients with localized pure urothelial muscle-invasive bladder cancer (MIBC), but it less clear for variant non-pure urothelial tumors, including the most common types: pure neuroendocrine tumors, squamous cell carcinoma, adenocarcinoma, micropapillary differentiation, and sarcomatoid differentiation.

To address the evidence gap, Malte Vetterlein, MD, of Brigham and Women’s Hospital in Boston, and colleagues compared overall survival and pathology between patients receiving RC with (210 patients) and without (1345 patients) NAC for MIBC cT2 and above (without lymph node involvement or metastasis) using the National Cancer Database 2003 to 2011. NAC was considered multi-agent systemic therapy given within 6 months of RC (single-agent chemotherapy was excluded).

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Results from multivariate analyses showed less upstaging at RC and a 36% greater overall survival benefit for neuroendocrine tumor patients receiving NAC versus surgery alone. The investigators adjusted survival results for pathologic tumor and lymph node stage, soft tissue surgical margin status, age, sex, Charlson-Deyo comorbidity index, and use of radiation therapy.

Patients who had tumors with micropapillary and sarcomatoid differentiation also showed a decrease in pathologic upstaging with NAC, but there were no significant improvements in survival.

“While neoadjuvant chemotherapy in neuroendocrine tumors seemed to be associated with a survival benefit, this was not in seen in micropapillary and sarcomatoid differentiated tumors, potentially due to the aggressive biology,” Dr Vetterlein told Renal & Urology News. “However, we observed less upstaging in patients with micropapillary and sarcomatoid variants who received neoadjuvant chemotherapy, which suggests that there might be a benefit in a specific subgroup of patients harboring those variant histologies.”

The investigators encouraged future studies on systemic therapy in histological variants: “Given that evidence for neoadjuvant chemotherapy in non-pure urothelial bladder cancer variants is scarce, we believe that our hypothesis-generating study might aid in underlining the importance of including histologic bladder cancer variants into prospective investigations,” Dr Vetterlein said. “Future studies should focus on including variant non-pure urothelial histologies into randomized controlled trials, given the known unfavorable survival outcomes compared with urothelial cancer.”

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Vetterlein MW, Mullane S, Seisen T, et al. Neoadjuvant Chemotherapy Prior to Radical Cystectomy for Muscle-Invasive Bladder Cancer with Variant Histology. Poster presented at the American Urological Association 2017 annual meeting in Boston on May 13, 2017. Poster MP34-11.