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Case Reports
. 2020 Sep 7;13(3):1059-1066.
doi: 10.1159/000509747. eCollection 2020 Sep-Dec.

Major Durable Response of Pembrolizumab in Chemotherapy Refractory Small Cell Bladder Cancer: A Case Report

Olav Toai Duc Nguyen  1   2 , Stein Harald Sundstrøm  1   2 , Ganna Surzhykova Westvik  1 , Ane Karoline Stræte Røttereng  1 , Mona Røli Melhus  1 , Cecilie Bergseth  1 , Elisabeth Kvelstad Hallem  1 , Oluf Dimitri Røe  1   2
Affiliations
Case Reports

Major Durable Response of Pembrolizumab in Chemotherapy Refractory Small Cell Bladder Cancer: A Case Report

Olav Toai Duc Nguyen et al. Case Rep Oncol. .

Abstract

Small cell carcinoma of the urinary bladder is a rare subtype (incidence of 1-9/1,000,000), characterized by an aggressive behavior with early metastasis and poor prognosis. Chemotherapy, radiation, and surgery are the usual treatment options, but to date, no accepted standard treatment exists. Since small cell bladder cancer shares similar clinicopathological features with small cell lung cancer, the same type of chemotherapy has been used. Recently, immune checkpoint inhibitors have shown effect in small cell lung cancer, but data regarding small cell bladder cancer is insufficient. Here we present a case where a 73-year-old male with chemorefractory metastatic small cell bladder cancer received a successful treatment with immune checkpoint inhibitor pembrolizumab resulting in a major durable response and no side effects. To our knowledge, this is the second case report on successful treatment of the rare subtype of small cell bladder cancer with an immune checkpoint inhibitor, supporting the use of pembrolizumab as a therapeutic option for small cell bladder cancer. Serum neuron-specific enolase was a useful biomarker both for chemo- and immunotherapy response.

Keywords: Biomarkers; Immunotherapy; Liver metastasis; Small cell bladder carcinoma; Small cell carcinoma.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
A–D Pathology of bladder tumor. E–H Pathology of liver metastasis. A, E Hematoxylin and eosin staining of the biopsy specimen shows typical histopathological pattern with small epithelial cells and hyperchromatic nuclei. The cells grow in sheets with no specific structures. This pattern along with the immunohistochemical profile is typical for small cell carcinoma, independent of location and organ. B Immunostaining: cytokeratin AE1/AE3-antibody-positive bladder tumor cells. C Immunostaining: synaptophysin-antibody-positive bladder tumor cells. D Immunostaining: thyroid transcription factor 1 (TTF-1)-antibody-positive bladder tumor cells. F Immunostaining: cytokeratin AE1/AE3-antibody-positive tumor cells. G Immuno­staining: synaptophysin-antibody-positive tumor cells. H Immunostaining: chromogranin-antibody-positive tumor cells.
Fig. 2
Fig. 2
Serum levels of tumor marker NSE pre- and post-pembrolizumab treatment. NSE normal range 0–16 μg/L. NSE, neuron-specific enolase; ACO, doxorubicin, cyclophosphamide, and vincristine.
Fig. 3
Fig. 3
A–G Radiographic response to pembrolizumab. Red circle indicates area of bladder tumor. A, B April 2019: baseline computed tomography scan (CT) prior to therapy. C, D October 2019: response after 6 months of pembrolizumab treatment. E, F, G January 2020: PET-CT response 9 months after pembrolizumab treatment was initiated. H Illustration of the response in the liver by volume reduction of >2,000 cm3 from April 2019 to January 2020; the liver volumes (measured in cm3) are measured based on the CT images from April 2019 and PET-CT from January 2020 by the use of PACS Sectras's Volume Measurement Tool and General Electric's AW Software, respectively.
See this image and copyright information in PMC

References

    1. Ismaili N. A rare bladder cancer– small cell carcinoma: review and update. Orphanet J Rare Dis. 2011;6:75. - PMC - PubMed
    1. Mandelkow T, Blessin NC, Lueerss E, Pott L, Simon R, Li W, et al. Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder. Dis Markers. 2019;2019:2532518. - PMC - PubMed
    1. Wilde L, Ali SM, Solomides CC, Ross JS, Trabulsi E, Hoffman-Censits J, et al. Response to Pembrolizumab in a Patient With Chemotherapy Refractory Bladder Cancer With Small Cell Variant Histology: A Case Report and Review of the Literature. Clin Genitourin Cancer. 2017;15((3)):e521–e4. - PubMed
    1. Naito A, Taguchi S, Nakagawa T, Matsumoto A, Nagase Y, Tabata M, et al. Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder. World J Urol. 2017;35((1)):97–103. - PubMed
    1. Administration . FDA approves atezolizumab for extensive-stage small cell lung cancer. U.S. 2019. [cited 2019 March 19] Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-atez....

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