Small Cell Carcinoma Of Bladder Research Articles

POU2F3-positive small cell carcinoma of the bladder: A clinicopathologic analysis of 4 cases and literature review

POU class 2 homeobox 3 (POU2F3)-positive small cell bladder carcinoma (SCBC) is an extremely rare entity, and its clinicopathologic features have not been fully described. Here, we investigated the clinicopathologic features of 4 cases of POU2F3-positive small cell bladder carcinoma (SCBC) and reviewed the literature. We collected 12 cases of SCBC from our departmental archives and detected the expression of POU2F3 by immunohistochemical (IHC) staining. Selected cases with or without POU2F3 expression were subjected to gene expression analysis between two different groups using DESeq2 software. We identified 4 POU2F3-positive SCBC patients, 2 males and 2 females, with a mean age of 77 years. Three patients had hematuria, and 1 patient had dysuria. Radiologic findings showed a bladder mass. Pathologic diagnosis showed that 3 cases were pure SCBC and 1 was mixed urothelial cancer (UC). Histopathologically, four POU2F3-positive SCBC tumors were composed of small round cells with sparse cytoplasm, the nuclei were salt-and-pepper-like or finely granular. Tumor cells showed characteristic cytoplasmic staining with punctate positive signals for cytokeratin. Syn and CD56 were diffusely positive in all the 4 patients. CgA was positive in only one patient. POU2F3-positive SCBC showed higher expression levels of POU2F3, HMGA2 and PLCG2 genes by RNA-Seq. Our data showed the specific clinicopathologic features of 4 rare POU2F3-positive SCBC cases, and the distinct molecular feature was observed between POU2F3-positive and negative SCBC in the limited number of cases.

Multidisciplinary treatment for small cell carcinoma of the bladder: a case report.

Small cell carcinoma (SCC) of the urinary bladder is a rare and highly aggressive subtype of bladder cancer. Most cases are diagnosed at advanced stages, and its therapeutic strategy remains unestablished. Here, we report a case of bladder SCC in which multidisciplinary treatment has resulted in relatively long-term survival. A 68-year-old man presented with gross hematuria. A cystoscopy revealed an invasive bladder tumor. A transurethral resection of bladder tumor (TURBT) was performed, and the pathological diagnosis was SCC. After systemic chemotherapy using etoposide and carboplatin and subsequent TURBT, a radical cystectomy and ileal conduit were performed. Three months postoperatively, the patient had a recurrence in the para-aortic lymph node. Systemic combination chemotherapy with carboplatin plus irinotecan (CBDCA + CPT-11) was administered, followed by amrubicin and an immune checkpoint inhibitor. In addition to this treatment, radiation therapy for the metastatic region led to the reduction of pain and shrinkage of the metastatic lesion. The patient survived for 2years after the initial diagnosis. Our report indicates that multidisciplinary treatment can be effective for SCC of the bladder, and a therapeutic strategy including the identification of novel biomarkers should be established.

Primary Small Cell Neuroendocrine Carcinoma of Bladder – A Rare Diagnostic Entity

Primary small cell carcinoma of the bladder is very rare pathological entity, follows an aggressive course and carries poor prognosis. The literature carrying these articles are scarce and due to which it poses a diagnostic challenge to the radiologist and urologists. Herein, we present a case of small cell carcinoma of urinary bladder in a 75 year old male patient initially reported as poorly differentiated urothelial carcinoma on transurethral resection of bladder tumor specimen to emphasize its rarity as well as the role of immunohistochemistry to differentiate between the two.

Comparison of clinicopathological characteristics, gene expression profiles, mutational analysis, and clinical outcomes of pure and mixed small-cell carcinoma of thebladder.

Small cell bladder carcinoma (SCBC) is a rare, divergent form of urothelial carcinoma (UC). We aimed to determine whether pure (n=16) and mixed (SCBC and UC; n=30) tumours differed in pathology, gene expression characteristics, genetic alterations, and clinical outcomes. Forty (87%) patients received first-line chemotherapy. Twenty-nine patients had no metastatic disease at diagnosis and underwent radical cystectomy. There were no differences in age, sex, race distribution, tumour size, stage at presentation, therapy response with pathological downstaging to ≤ypT1N0, or overall or progression-free survival (PFS) between pure and mixed tumours. There was a longer PFS among downstaged chemotherapy-responding tumours ≤ypT2N0M0 than among unresponsive tumours ≥ypT2 ≥ yN1M1 (P=0.001). Patients who achieved pathological downstaging with neoadjuvant chemotherapy (n=10) were stage cT2N0M0 at the time of diagnosis and were alive at the last follow-up (median 37months), while 46% of patients who failed to achieve pathological downstaging were alive at the last follow-up (median 38months; P=0.008). RNA sequencing showed that the UC of mixed SCBC had similar neural expression signatures to pure SCBC. DNA sequencing revealed alterations in TERT (83%), P53 (56%), ARID1A (28%), RB1 (22%), and BRCA2 (11%). Immunohistochemistry for RB1 showed loss of expression in 18/19 (95%) patients, suggesting frequent pathway downregulation despite a low prevalence of RB1 mutation. Patients with pure and mixed SCBC have similar outcomes and these outcomes are determined by the pathological stage at RC and are best among patients who have pathological downstaging after NAC.

Long-term complete response in small cell bladder carcinoma treated with carboplatin, etoposide, and atezolizumab

BackgroundSmall cell bladder carcinoma (SCBC) is a rare and aggressive malignant tumor with no established treatment guidelines. Its treatment algorithm has been based on the small cell lung cancer (SCLC) guidelines. Metastatic SCBC has poor prognosis (even when treated with platinum-based chemotherapy, which is usually used for extensive-disease SCLC).Case presentationHerein, we report a case of a 71-year-old man with SCBC who underwent radical cystectomy and received adjuvant chemotherapy with gemcitabine and cisplatin. However, recurrent tumors were found 6 months postoperatively. The patient was then treated with carboplatin, etoposide, and atezolizumab and achieved complete response. He continues receiving maintenance therapy with atezolizumab monotherapy without any evidence of recurrence over the 12 months follow up.ConclusionTo our knowledge, this is the first case of metastatic SCBC where carboplatin, etoposide, and atezolizumab achieved long-term complete response.

Surgical resection of mediastinal metastasis from small cell carcinoma of bladder: case report

BackgroundIsolated mediastinal metastasis from a malignant tumor and small cell carcinoma of the bladder are both very rare.Case presentationA 76-year-old woman who had undergone surgery for bladder cancer twice was referred to our hospital for a right paracardiac mass noted in chest computed tomography findings, and resection of the tumor was performed. Histological analysis of the mediastinal tumor revealed it to be a metastatic small cell carcinoma of the bladder. At 4 months after surgery, multiple metastatic lesions were found in the chest and liver, and chemotherapy for small cell carcinoma was started.ConclusionsWe present this case of mediastinal metastasis of small cell carcinoma of the bladder, which is very rare, to show the importance of surgical resection of an isolated mediastinal tumor. Such a procedure should be considered, as histological diagnosis of the tumor could be useful for determining therapeutic options.

Long-term Outcomes of Local and Metastatic Small Cell Carcinoma of the Urinary Bladder and Genomic Analysis of Patients Treated With Neoadjuvant Chemotherapy.

Small cell carcinoma of the bladder (SCCB) is a rare variant of bladder cancer with poor outcomes. We evaluated long-term outcomes of nonmetastatic (M0) and metastatic (M1) SCCB and correlated pathologic response with genomic alterations of patients treated with neoadjuvant chemotherapy (NAC). Clinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed. One hundred and ninety-nine SCCB patients were identified. (M0: 147 [74%]; M1: 52 [26%]). Among M0 patients, 108 underwent radical cystectomy (RC) (NAC: 71; RC only: 23; adjuvant chemotherapy: 14); 14 received chemoradiotherapy; the rest received chemotherapy alone or no cancer-directed therapy. RC-only patients had a median follow-up of 9.1 years, and median disease-free survival (DFS) and overall survival (OS) were 1.1 and 1.2 years, respectively. NAC patients had pathologic response (<pT2pN0) and pathologic complete response (pT0pN0) rates of 48% and 38%, respectively, with median follow-up of 7.2 years, and median DFS and OS of 5.6 and 14.5 years, respectively. NAC responders (<ypT2N0) had superior median DFS (14.5 vs. 0.6 years, hazard ratio [HR] 0.24, P< .001) and OS (14.5 vs. 2.5 years, HR 0.31, P = .002). DFS rates for responders and nonresponders were 76% and 27% at 5 years, and 71% and 23% at 10 years, respectively. Local and central nervous system recurrences were infrequent. Median progression-free survival (PFS) and OS for M1 disease were 6.9 and 10.3 months, respectively. Genomic profiling was performed on 47 NAC patients. Loss of ERCC2 function was significantly enriched among those with pathologic complete response to NAC (mutations present in 50% of pathologic complete responders vs. 15% nonresponders, P = .045). M0 SCCB is chemo-sensitive and patients have excellent long-term survival following response to NAC. Patients with M1 disease have poor survival despite systemic therapy. Loss-of-function mutations of ERCC2 were associated with pathologic complete response to NAC.

889MO Comparative expression of driver transcription factors in extra-pulmonary small cell carcinoma

Extra-pulmonary small cell carcinomas (EPSCC) are aggressive neuroendocrine tumors that are clinicopathologically distinct from small cell lung cancer (SCLC). Recent data suggest that transcriptionally-defined SCLC subtypes exhibit different underlying biology and therapeutic vulnerabilities. With limited data available on the EPSCC transcriptomic landscape, we analyzed gene expression profiles and its correlation with clinical outcomes across EPSCC anatomic sites. DNA (592 genes/whole-exome) and RNA (whole transcriptome) sequencing were performed for 1070 small cell carcinoma (SCC) patient (pt) samples that underwent molecular profiling at Caris Life Sciences (Phoenix, AZ). Samples were stratified into 5 subtypes based on the relative expression of key transcription factors (TFs): ASCL1, NEUROD1, YAP1, POU2F3, and Mixed. Real-world survival information was available for 111 pts treated with etoposide+platinum (EP) therapy. Overall survival (OS) was obtained from insurance claims & Kaplan-Meier estimates. Statistical significance is determined by Chi-square & Wilcoxon rank sum tests. EPSCC comprised 28.8% (n=308) of SCCs evaluated; most common primary sites included gynecologic (GYN, 21.8%, n=67), prostate (16.6%, n=51), bladder (15.9%, n=49) and colorectal (10.1%, n=31). Each primary site had a unique distribution of molecular subtypes relative to SCLC. ASCL1 was less frequent in GYN and bladder SCC (13.4% and 16.3%) compared to SCLC (35.7%), with bladder SCC enriched in NEUROD1 and POU2F3 (30.6% and 22.4% vs SCLC 17.5% and 6.4%, P<0.05). YAP1 was most common in GYN SCC (35.8% vs SCLC 20.7%, P<0.05). For both SCLC and EPSCC, low YAP1 was associated with improved OS (SCLC HR 2.1, P=0.05; EPSCC HR 4.3, P=0.02), and high NEUROD1 trended towards improved OS (SCLC HR 0.6, P=0.12; EPSCC HR 0.4, P=0.10) from start of EP therapy. Our analysis revealed differential expression of key lineage-defining TFs in EPSCCs from various anatomic sites that looked distinct from SCLC. EPSCC and SCLC OS was similarly associated with TF expression, suggesting the underlying biology of SCLC and EPSCC subtypes might predict comparable therapeutic vulnerabilities.

Identification of potential biomarkers and novel therapeutic targets through genomic analysis of small cell bladder carcinoma and associated clinical outcomes.

Small cell bladder carcinoma (SCBC) represents a rare histologic variant with a poor prognosis and for which no routine biomarkers exist. Limited reports of genomic sequencing in SCBC have demonstrated a high prevalence of TP53 and RB1 gene mutations, though the prognostic value of these and other gene variants in SCBC remains undefined. In this study, we performed targeted genomic sequencing on a cohort of SCBC patients and correlated genomic findings with clinical outcomes to identify potential novel biomarkers. Thirty-one patients with SCBC and available treatment-naïve tumor specimens were identified from an institutional database (23 limited stage [LS], 8 extensive stage [ES]). Small cell carcinoma specimens were microdissected and subjected to tumor next-generation whole-exon sequencing with a 592 gene panel. Kaplan-Meier techniques and Cox proportional hazards models were used to evaluate genomic aberration association with relapse-free survival (RFS) and overall survival (OS) in the limited stage cohort. The most common pathogenic gene variants included ARID1A (48%), TP53 (48%) and RB1 (48%). Mutations in genes with potential therapeutic targets not routinely evaluated in SCBC included BRCA1/2 (16%), POLE (13%), JAK2 (13%), PDGFB (13%) and FGFR3 (3%). Multiple novel biomarker candidates showed trends for improvements in OS in the LS subset including ERCC2 (HR 0.322, P = 0.122) and RB1 (HR 0.481, P = 0.182), while LS patients with TP53 mutations (HR 2.730, P = 0.056), and MCL1 gene amplification (HR 4.183, P = 0.018) suggested inferior OS. Additionally, gene or copy number variants with potential prognostic benefit included UBR5 and DAXX (P = 0.02, [hazard ratios nonestimable due to zero events in biomarker positive groups]). These results support the role for tumor genomic profiling in SCBC and identify multiple potential novel biomarkers and therapeutic targets in this rare disease. Efforts to validate these findings should lead to improved decision-making and treatment outcomes in SCBC.

Small cell carcinoma of the urinary bladder: Distinctive cytological characteristics and Cyto-histologic correlation

Preoperative diagnosis in liquid-based cytology preparation in voided urine specimen and cyto-histologic correlation of small cell carcinoma of the urinary bladder has not been described in detail in the literature. A 79-year old male presented at our institution with gross hematuria. He was accurately diagnosed with small cell carcinoma of the bladder on liquid-based cytology in urine. The patient subsequently proceeded to transurethral resection of the bladder tumor, confirming the diagnosis. In this article, we present a detailed report of primary urothelial carcinoma with dominant neuroendocrine differentiation of the bladder describing the cytologic and histologic morphologic features, its differential diagnosis with a review of the literature.

Primary Small Cell Neuroendocrine Carcinoma of Bladder – A Rare Diagnostic Entity

Primary small cell carcinoma of the bladder is very rare pathological entity, follows an aggressive course and carries poor prognosis. The literature carrying these articles are scarce and due to which it poses a diagnostic challenge to the radiologist and urologists. Herein, we present a case of small cell carcinoma of urinary bladder in a 75-year-old male patient initially reported as poorly differentiated urothelial carcinoma on transurethral resection of bladder tumor specimen to emphasize its rarity as well as the role of immunohistochemistry to differentiate between the two.

Primary Small Cell Neuroendocrine Carcinoma of Bladder – A Rare Diagnostic Entity

Primary small cell carcinoma of the bladder is very rare pathological entity, follows an aggressive course and carries poor prognosis. The literature carrying these articles are scarce and due to which it poses a diagnostic challenge to the radiologist and urologists. Herein, we present a case of small cell carcinoma of urinary bladder in a 75-year-old male patient initially reported as poorly differentiated urothelial carcinoma on transurethral resection of bladder tumor specimen to emphasize its rarity as well as the role of immunohistochemistry to differentiate between the two.

Neuroendocrine Carcinoma of Urinary Bladder: Extremely a Rare Entity

Neuroendocrine carcinoma or small cell carcinoma (SCC) of the bladder is a rare and aggressive tumor associated with a poor prognosis. It often presents at a later stage than urothelial carcinoma of the bladder, and comprises less than 1% of bladder malignancies. A number of treatment algorithms have been used to treat bladder SCC, including cystectomy, partial cystectomy, radiotherapy, chemoradiotherapy, chemotherapy alone, and neoadjuvant/adjuvant chemotherapy. Here we are presenting a case of, small cell variety of neuroendocrine carcinoma of the bladder, and its epidemiology, prognosis, and current treatment algorithms are reviewed.&#x0D; Bangladesh Journal of Urology, Vol. 22, No. 2, July 2019 p.166-169

Abstract 5434: Insulinoma-associated protein 1 (INSM1) expression in small cell neuroendocrine carcinoma of the urinary tract

Abstract Introduction Clinical guidelines including the American Urological Association (AUA) state that neoadjuvant chemotherapy should be administered prior to surgery in cases of muscle invasive urinary bladder small cell neuroendocrine carcinoma. Although the recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation in neuroendocrine tumors at several sites, its efficacy as a marker in urinary bladder small cell carcinoma has not been well established. This study aims to examine the immunohistochemical expression pattern of INSM1 on whole tissue sections of urinary bladder small cell neuroendocrine carcinoma and compare INSM1 expression to those of established markers of neuroendocrine differentiation. Methods Archived tissue from 32 cases of urinary bladder small cell neuroendocrine carcinoma were obtained from Rhode Island Hospital and The Miriam Hospital. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed. Staining was scored for intensity (0: no staining; 1: weak; 2: moderate; 3: strong) and proportion of cells stained (0: 0%; 1: &amp;gt;0 to 25%; 2: &amp;gt;25 to 50%; 3: &amp;gt;50 to 75%; 4: &amp;gt;75 to 100%). Results INSM1 was positive (intensity 1-3 or proportion 1-4) in 87% (28/32) of small cell neuroendocrine carcinoma cases (20 with intensity 2-3, 17 with proportion 3-4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. While the rate of positivity was high, INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. Conclusion INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary bladder. However, the findings in this study suggest that optimal utilization of INSM1 would be in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases. StainNegative [n (%)]Positive [n (%)]INSM14 (13)28 (87)CD568 (25)24 (75)Synaptophysin13 (40)19 (60)Chromogranin18 (56)14 (44) Citation Format: Isaac E. Kim, Ali Amin, Li Juan Wang, Liang Cheng, Carmen M. Perrino. Insulinoma-associated protein 1 (INSM1) expression in small cell neuroendocrine carcinoma of the urinary tract [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5434.

Small cell carcinoma of gall bladder: An uncommon histologic entity.

&lt;b&gt;Introduction:&lt;/b&gt; Gall bladder (GB) small cell carcinoma (SCC) comprises 0.5% of all gall bladder cancers. It carries a poor prognosis in view of its aggressive nature. &lt;br&gt;&lt;b&gt;Case report:&lt;/b&gt; We here report a case of small cell carcinoma of GB in a female who presented with obstructive jaundice. Examination revealed a hard lump in the right upper abdomen. Tumour markers showed raised CA 19-9. Staging CECT of the thorax and abdomen reported polypoidal enhancing wall thickening of the gall bladder with multiple metastatic deposits close to the pancreatic head encasing the main portal vein and common bile duct. Histopathology report was suggestive of small cell carcinoma, which was confirmed by immunohistochemistry. Patient was referred to the Oncology Department for palliative chemotherapy.

Small cell carcinoma of gall bladder: An uncommon histologic entity

Gall bladder small cell carcinoma (scc) comprises of 0.5% of all GB cancers. It carries a poor prognosis in view of its aggressive nature. We here report a case of small cell carcinoma GB 55-year old lady presented with features of obstructive jaundice with significant weight loss. Examination revealed hard lump in right upper abdomen with multiple scratch marks all over the body. Clinically she had jaundice. Blood investigations revealed hyperbilirubinemia. Tumour markers showed raised CA 19-9. Staging CECT thorax and Abdomen reported polypoidal enhancing wall thickening of gall bladder with multiple metastatic deposits close to pancreatic head encasing main portal vein and common bile duct. Histopathology was suggestive of small cell carcinoma. Patient was referred to Oncology department and is receiving palliative cisplatin-etoposide chemotherapy

Small Cell Carcinoma of Bladder; Still A Diagnostic and Therapeutic Challenge: Seven Years of Experience and Follow-up in A Referral Center.

To report clinical, histopathological, and treatment features of small cell carcinoma of (SmccB) bladder during 7 years in a referral center. The clinical, histopathological features, treatment modalities, and outcome of all patients with bladder SmccB treated between 2009 and 2016 who were managed in Hasheminejad Kidney Center (HKC) were retrospectively collected. Thirteen patients were diagnosed and managed with SmccB. The average age of patients was 64.92 years. For each patient, 8 markers were used for IHC staining on average. Neuroendocrine markers such as CD 56, Neuron Specific Enolase, Synaptophysin, and Chromogranin were found in a significant percentage of patients (69%, 38%, 54%, and 31% respectively). Patients were managed with TURBT alone (N=3), chemotherapy after TURBT (N=4), chemotherapy plus radical surgery (N=4) and radical surgery alone (N=2). The best clinical result was seen in chemotherapy received patients with or without radical surgery. The mean(SE) of survival rate in patients who received only chemotherapy alone was 42.4 (10.0) months, while in those who were managed with chemotherapy plus radical surgery it was 47.7 (10.1) months. In our center immunohistochemistry was needed for definitive diagnosis in 17/19 samples. Misdiagnosis happened in two samples without IHC request. We think that use of immunohistochemistry should be mandatory for diagnosis of SmccB to exclude misdiagnosis. Chemotherapy is the most important part of treatment and the addition of radical surgery can slightly improve patients' survival.

Comparative genomics of high grade neuroendocrine carcinoma of the cervix.

In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.

Abstract B13: A novel mouse model for small-cell carcinoma of bladder

Abstract Background: Molecular characterization studies suggest the neuronal subtype muscle invasive bladder cancer (MIBC) is associated with a high response rate to immune checkpoint inhibitor. We sought to establish a mouse model for small-cell carcinoma of bladder. Materials and Methods: Three canonical signaling pathways (TP53, RB1, and RTK/PI3K/AKT) are commonly altered in small-cell bladder cancer. Keratin 5 promoter-driven adenovirus Cre (Ad-K5-Cre, University of Iowa) was instilled into the bladder of female triple floxed (Trp53f/f:Pten f/f:Rb1 f/f) mice for 30 min. The mice were monitored for hematuria and bladder mass using ultrasound. Results: One Ad-K5-Cre:Trp53-/-: Pten-/-: Rb1-/- mouse died from urinary obstruction at 22 weeks. An obstructive tumor was noted in bladder trigone. Immunohistochemistry analysis of bladder tumor demonstrated negative cytokeratin 7 (CK7) expression and strong synaptophysin expression. Disseminated metastatic foci in lung were noted with positive synaptophysin expression as of primary tumor in the bladder. PCR demonstrated Cre mediated recombined alleles of the Trp53, Pten, and Rb1 in the tumor DNA but not in the tail DNA. The bladder tumor was dissociated to generate an organoid line. The organoid after 5 passages was tested for drug response of standard chemotherapy regimens. IC50 of cisplatin, etoposide, and gemcitabine were 3.1 μM, 0.8 μM, and 92.3 nM, respectively. Further characterization of more mice will address the limitation of small sample size. Conclusion: Inactivation of Trp53, Pten, and Rb1 is sufficient to induce metastatic small-cell carcinoma of bladder. This mouse model provides a powerful tool to study molecular mechanism of neuroendocrine differentiation and screen novel therapeutic drugs for small-cell carcinoma of bladder. Citation Format: Dongbo Xu, Qiang Cao, Li Wang, Yanqing Wang, Xiaojing Zhang, Yue Wu, Gary Smith, Bo Xu, David Goodrich, Qiang Li. A novel mouse model for small-cell carcinoma of bladder [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B13.

MP17-14 MOLECULAR CHARACTERIZATION AND RESPONSE TO THE IMMUNOTHERAPY OF SMALL CELL BLADDER CANCER

INTRODUCTION AND OBJECTIVE:Small cell bladder carcinoma (SCBC) is clinically-aggressive variant of urothelial carcinoma with advanced stage at presentation. Due to its rarity, its molecular charact...