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Clinical Trial
. 2021 Mar;124(7):1214-1221.
doi: 10.1038/s41416-020-01244-2. Epub 2021 Jan 21.

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

Min Yuen Teo  1 , Hikmat Al-Ahmadie  2 , Kenneth Seier  3 , Christopher Tully  4 , Ashley M Regazzi  5 , Eugene Pietzak  6 , David B Solit  7 , Satish Tickoo  2 , Victor Reuter  2 , Eugene K Cha  6 , Harry Herr  6 , Timothy Donahue  6 , Sherri M Donat  6 , Guido Dalbagni  6 , Bernard H Bochner  6 , Samuel Funt  5 , Gopakumar V Iyer  5   7 , Dean F Bajorin  5   8 , Irina Ostrovnaya  3 , Jonathan E Rosenberg  5   8
Affiliations
Clinical Trial

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

Min Yuen Teo et al. Br J Cancer. 2021 Mar.

Erratum in

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1. Consort diagram depicting the study population and subgroups for the primary clinical analysis.
PUC plasmacytoid urothelial carcinoma.
Fig. 2
Fig. 2. Recurrence-free and overall survival is reduced in plasmacytoid urothelial carcinoma.
Recurrence-free survival (a) and overall survival (b) of patients with plasmacytoid urothelial carcinoma (PUC) and urothelial carcinoma, not otherwise specified (UC NOS) treated with neoadjuvant chemotherapy. Survival is compared between responders (those with pathologic complete response, defined as <pT2 pN0 disease on pathologic evaluation) and nonresponders.
Fig. 3
Fig. 3. Genomic characterisation of plasmacytoid urothelial carcinoma.
Oncoprint of 33 plasmacytoid urothelial carcinoma cases. Left, the prevalence of alterations in genes commonly altered in urothelial carcinoma, not otherwise specified, per The Cancer Genome Atlas analysis. Right, the prevalence of alterations in selected DNA damage response genes.
See this image and copyright information in PMC

Comment in

References

    1. Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur. Urol. 2016;70:106–119. doi: 10.1016/j.eururo.2016.02.028. - DOI - PubMed
    1. Nigwekar P, Tamboli P, Amin MB, Osunkoya AO, Ben-Dor D, Amin MB. Plasmacytoid urothelial carcinoma: detailed analysis of morphology with clinicopathologic correlation in 17 cases. Am. J. Surg. Pathol. 2009;33:417–424. doi: 10.1097/PAS.0b013e318186c45e. - DOI - PubMed
    1. Kaimakliotis HZ, Monn MF, Cheng L, Masterson TA, Cary KC, Pedrosa JA, et al. Plasmacytoid bladder cancer: variant histology with aggressive behavior and a new mode of invasion along fascial planes. Urology. 2014;83:1112–1116. doi: 10.1016/j.urology.2013.12.035. - DOI - PubMed
    1. Al-Ahmadie HA, Iyer G, Lee BH, Scott SN, Mehra R, Bagrodia A, et al. Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer. Nat. Genet. 2016;48:356–358. doi: 10.1038/ng.3503. - DOI - PMC - PubMed
    1. Cockerill PA, Cheville JC, Boorjian SA, Blackburne A, Thapa P, Tarrell RF, et al. Outcomes following radical cystectomy for plasmacytoid urothelial carcinoma: defining the need for improved local cancer control. Urology. 2017;102:143–147. doi: 10.1016/j.urology.2016.09.053. - DOI - PubMed

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