Response to Neoadjuvant Chemotherapy and Survival in Micropapillary Urothelial Carcinoma: Data From a Tertiary Referral Center and the Surveillance, Epidemiology, and End Results (SEER) Program - Beyond the Abstract

Micropapillary urothelial carcinoma is a relatively rare neoplasm comprising 0.6-6% of all urothelial carcinomas. Given its rarity, the evidence is scarce regarding the efficacy of neoadjuvant chemotherapy before radical cystectomy which is the cornerstone of treatment in conventional urothelial carcinoma. Historically, micropapillary has been considered to be more aggressive than conventional urothelial, presenting at advanced stage, as well as associated with worse survival outcomes, based on data from observational studies. Further, the role of neoadjuvant chemotherapy has not been well defined in that setting. In our study, we aimed to investigate patterns of pathologic response to neoadjuvant chemotherapy in a cohort of 46 patients diagnosed with micropapillary urothelial carcinoma, as well as their outcomes in comparison with a cohort of 457 patients with conventional urothelial carcinoma. In addition, we presented epidemiologic, clinicopathologic, and survival data from SEER-Medicare database for a cohort of patients with micropapillary carcinoma. Patients in all cohorts underwent radical cystectomy.



In our institutional cohort, we found that micropapillary had a predilection for lymphovascular spread, with approximately twice the rates of pN1-3 stage and lymphovascular invasion at radical cystectomy in comparison to conventional urothelial. These findings may explain the propensity for earlier recurrence as well as inferior overall survival noted in that group. In particular, median recurrence-free survival was 24 months for patients with micropapillary urothelial when compared to 84 months for those with conventional urothelial, while median overall survival was 44 and 105 months respectively. In a similar fashion, we noted a median OS of only 25 months in the SEER-derived micropapillary cohort. It should be noted that in multivariate analysis, micropapillary histology was not independently associated with shorter overall survival, while stage remained a well-known prognostic factor. This could indicate that the defining driver behind inferior outcomes in patients with micropapillary disease is the higher stage of presentation.

Pathologic complete response rate was comparable between micropapillary and conventional urothelial (33% vs 35%) in the institutional cohort, however, we did not notice a significant difference in median overall between patients who received neoadjuvant chemotherapy vs. those treated with upfront radical cystectomy (but with limited sample size). Of note, patients with micropapillary who achieved ypT0N0 had prolonged overall survival, with only one death noted in that subgroup (non-cancer related). Likewise, in the SEER-derived micropapillary cohort, we did not identify a significant association between neoadjuvant chemotherapy receipt and overall survival.

Our findings suggest that micropapillary urothelial has poorer outcomes than conventional urothelial mainly due to its advanced stage at presentation. This variant likely has a similar sensitivity to neoadjuvant chemotherapy in comparison to conventional urothelial, with the greatest benefit noted in patients who achieved pathologic complete response. However, we did not discern a significant overall survival benefit in the entire group that received neoadjuvant treatment, but our study may have been underpowered for that particular analysis. Overall, there is a need for validation of biomarkers enabling optimal selection of the ideal chemotherapy candidates who respond better to neoadjuvant chemotherapy. We believe that a cisplatin-based regimen before radical cystectomy remains the standard of care for patients with muscle-invasive urothelial cancer, including micropapillary variants, in cisplatin-fit patients. At the same time, we are evaluating a chemo-immunotherapy combination before radical cystectomy in patients with localized, resectable predominant, or pure non-urothelial histology in a novel clinical trial (NCT04383743) trying to also interrogate tumor biology and its micro-environment.

Written by: Leonidas Diamantopoulos, MD,1 Jonathan Wright, MD, MS, FACS,2 and Petros Grivas, MD, PhD3

  1. Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
  2. Professor, Medical Director, University of Washinton Medical Center Urology Clinic, Seattle, WA
  3. Associate Professor, Clinical Director, Genitourinary Cancers Program, University of Washinton, Seattle, WA
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