Clinical Study

Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma



Plasmacytoid urothelial carcinoma (PUC) is a rare, aggressive histologic variant of urothelial cancer characterised by a diffuse growth pattern and CDH1 mutation. We studied the efficacy of preoperative platinum-based chemotherapy in nonmetastatic PUC and immune checkpoint inhibitors (ICIs) in advanced PUC.


Cases of nonmetastatic PUC and advanced PUC treated with ICIs at our institution were identified. Outcomes were compared to those of a published cohort of patients with urothelial carcinoma not otherwise specified.


We identified 81 patients with nonmetastatic PUC. Of the patients with localised disease who underwent neoadjuvant chemotherapy, pathologic complete response and downstaging rates were 12 and 21%, respectively. Pathologic downstaging was not associated with significant improvement in clinical outcomes. Up to 18% of localised disease and 28% of locally advanced cases had unresectable disease at the time of surgery. ICI-treated advanced PUC (N = 21) had progression-free and overall survival of 4.5 and 10.5 months, respectively, and a 38% response rate. FGFR3 and DNA damage response gene alterations were observed in 3 and 15% of cases, respectively.


PUC is associated with high disease burden and poor chemosensitivity. Increased awareness and recognition of this disease variant will allow for new treatment strategies.

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Fig. 1: Consort diagram depicting the study population and subgroups for the primary clinical analysis.
Fig. 2: Recurrence-free and overall survival is reduced in plasmacytoid urothelial carcinoma.
Fig. 3: Genomic characterisation of plasmacytoid urothelial carcinoma.


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Sara DiNapoli provided editorial support for this manuscript.

Author information




M.Y.T. conceptualised and designed the study, acquired data, and drafted the manuscript. H.A.-A. conceptualised and designed the study, acquired data, and analysed and interpreted the data. K.S. drafted the manuscript and performed statistical analysis. C.T. acquired data. A.M.R. provided technical support and revised the manuscript. E.P., D.B.S., E.C., H.H., T.D., S.M.D., G.D., B.H.B., S.F., and D.F.B. acquired data and revised the manuscript. S.T. and V.R. acquired data. G.I. conceptualised the study, acquired data and revised the manuscript. I.O. performed statistical analysis. J.E.R. drafted the manuscript and supervised the study.

Corresponding author

Correspondence to Min Yuen Teo.

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Ethics approval and consent to participate

This study was approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board (#17–214). The need for informed consent was waived by the institutional review board. This study was performed in accordance with the Declaration of Helsinki.

Data availability

Anonymised data will be provided upon request.

Competing interests

MYT has received Research Support from Bristol Myers Squibb, Clovis and Pharmacyclics; DBS has consulted with/received honoraria from Pfizer, Loxo Oncology, Lilly Oncology, BridgeBio, Vividion Therapeutics, Scorpion Therapeutics and Illumina; SAF has received research support from AstraZeneca, Genentech/Roche, is a consultant/advisory board member for Merck, and owns stock in Urogen, Allogene Therapeutics, Neogene Therapeutics, Kronos Bio, and Inconovir; DFB has received research funding from Novartis, has received personal fees from Merck Sharp & Dohme, Eisai, Fidia Farmaceutici S.p.A., Lilly, and UroGen Pharma; and has received grants and personal fees from Bristol‐Myers Squibb, Roche/Genentech, and Novartis; and grants from Dendreon; GVI has received personal fees from Mirati Therapeutics and Janssen and research support from Novartis; JER has consulted for AstraZeneca, Bayer, Merck, BMS, Roche, Genentech, Seattle Genetics, Astellas, Boehringher Ingelheim, GSK, Mirati, Janssen, Lilly, and Pfizer. He has also received funding for clinical trials from Roche/Genentech, AstraZeneca, Bayer, Seattle Genetics and Astellas.

Funding information

This work was supported in part by the National Cancer Institute at the National Institutes of Health [P30 CA008748 to Memorial Sloan Kettering Cancer Center].

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Teo, M.Y., Al-Ahmadie, H., Seier, K. et al. Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma. Br J Cancer (2021).

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