Micropapillary Urothelial Carcinoma Research Articles

Muscle-invasive and metastatic urothelial carcinoma of the urinary bladder : Current state of histopathologic, molecular, and immunologic prognostic and predictive factors

Muscle-invasive and metastatic urothelial carcinoma (UC) represents aheterogeneous disease entity with numerous morphological, molecular, and immunological phenotypes. This article aims to provide an overview of current histopathological, molecular, and immunological prognostic and predictive factors in muscle-invasive and metastatic UC. Muscle-invasive and metastatic UC exhibits awide range of divergent differentiations and histological subtypes. The correct diagnosis of these morphological variants is essential, as they may determine the clinical course and may also present specific and potentially therapeutically targetable molecular alterations (e.g., HER2 alterations in micropapillary UC). The morphological subtypes largely correlate with the six molecular consensus subtypes. Furthermore, morphological and molecular subtypes are associated with immunological properties that are relevant for modern immunotherapies, such as the PD-L1 status. Numerous immunotherapy studies in the setting of curatively treatable muscle-invasive UC will be reported in 2024 and 2025, likely leading to an increasing number of PD-L1 testing indications.

Early experience with sequential intravesical gemcitabine and docetaxel for micropapillary variant non-muscle invasive bladder cancer

BackgroundGuidelines lack clear recommendations regarding conservative management of micropapillary (MP) variant non-muscle invasive bladder cancer (NMIBC). Bladder-sparing therapy using intravesical Bacillus Calmette-Guerin (BCG) has been reported although there are concerns regarding recurrence and progression with this approach. Due to the ongoing BCG shortage, we have utilized sequential intravesical gemcitabine and docetaxel (Gem/Doce) as primary therapy for NMIBC, including some cases with limited MP urothelial carcinoma (MPUC). To compare oncologic outcomes of patients with non-muscle invasive MPUC and conventional UC treated with Gem/Doce. MethodsA secondary analysis of 138 patients with high-risk NMIBC treated with intravesical Gem/Doce from January 2011 to December 2021 was performed. Oncologic outcomes were compared in patients with or without MPUC using the Kaplan-Meier method. ResultsMedian follow-up (f/u) for all patients was 23 months (IQR 13–34). There were 129 patients with pure UC and 9 with MPUC. In those with MPUC, all were high-grade (HG), 8/9 were stage T1, 7/9 had a focal MP component (extent < 10%), 3/9 had concomitant CIS, and 2/9 had lymphovascular invasion. All MPUC tumors were re-resected, and 4 had T0, 3 had T1 HG, 1 had Ta HG, 1 had carcinoma in situ (CIS); none had residual MP or LVI tumors before Gem/Doce treatment. The 24-month high-grade recurrence-free survival was 89% and 80% in patients with MPUC and pure UC, respectively. Survival outcomes did not significantly differ between patients with and without MPUC. Four patients with MPUC experienced recurrent NMIBC after Gem/Doce, and all were treated successfully with rescue sequential intravesical valrubicin and docetaxel (Val/Doce). Pathology of these four recurrent patients revealed more aggressive histologic features in the original tumor including: multifocal tumor (3/4), T1 HG disease (4/4), concomitant CIS (2/4), and moderate MP variant extent (30%) (1/4). No patient with MPUC underwent cystectomy, experienced progression, or died at last follow-up (median f/u of 43 months). ConclusionsGem/Doce with Val/Doce rescue appears to have activity against carefully selected non-muscle invasive MPUC with favorable histology. Larger prospective trials are needed to validate these results.

Invasive micropapillary urothelial carcinoma of the renal pelvis presenting as nonfunctional kidney: A unique presentation and review of the literature.

Micropapillary urothelial carcinoma of the renal pelvis is a rare and aggressive variant and poses a diagnostic challenge, especially related to the site and histomorphology of the tumor. A 60-year-old female presented with right pelvic-ureteric junction obstruction and a nonfunctioning right kidney. She underwent a simple right nephrectomy. The microscopy examination revealed a high-grade tumor of the renal pelvis, predominant micropapillary architecture. The tumor infiltrated into the kidney, renal sinus, perinephric fat, adrenal gland, and Gerota's fascia. Extensive lymphovascular and perineural invasions were also noted. On immunohistochemistry, tumor cells were positive for GATA-binding protein 3, cytokeratin 7, and cytokeratin 20, while negative for paired box gene 8, cluster of differentiation 10, mammaglobin, and alpha-methylacyl-CoA racemase. The p63 was positive in the conventional areas and negative in the micropapillary pattern. We reported an additional case of micropapillary urothelial carcinoma of the renal pelvis, literature review, and discussed the differential diagnosis. Immunonegativity of p63 in the micropapillary component was an additional finding.

Clinicopathologic Analysis of Micropapillary Urothelial Carcinoma of the Upper Urinary Tract: Implications for HER2-Targeted Therapy.

Introduction/Background To determine the clinical significance of micropapillary urothelial carcinoma (MPUC) of the upper urinary tract (UTUC) and a potential therapeutic strategy. Patients and Methods A retrospective cohort study was conducted to examine the incidence of micropapillary UTUC from 2010 to 2018 and its clinicopathological characteristics. Clinical outcomes and cancer-specific survival (CSS) were compared between MPUC and conventional UTUC matched by stage within a 6-month variation of receiving surgery. Results A total of 24 MPUC cases were identified out of 901 cases (2.7%) of urothelial carcinoma (UC) of the renal pelvis and ureter. MPUC was significantly smaller (<3 cm) and associated with nodal metastasis compared with conventional UTUC (P=.017 & 0.021, respectively); however, no significant difference was observed for lymphovascular invasion, distant metastasis, or CSS (P > 0.50, respectively) compared with match controls. Six MPUC patients (25%) developed metastasis to the liver, lymph nodes, and lung during follow-up. Patients with HER2-positive MPUC (3 of 4) had a significantly higher risk of metastasis compared with HER2-negative MPUC (3 of 20; P=0.035). Conclusions MPUC is an aggressive variant of UTUC and usually presents as a small locally advanced disease. HER2 immunohistochemistry may identify the subset of patients with micropapillary UTUC that are candidates for targeted therapy.

MP69-18 EVALUATING THE ROLE OF LYMPHVASCULAR INVASION AS AN INDICATOR FOR ADVERSE OUTCOMES IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA AND ITS HISTOLOGICAL SUBTYPES

You have accessJournal of UrologyCME1 Apr 2023MP69-18 EVALUATING THE ROLE OF LYMPHVASCULAR INVASION AS AN INDICATOR FOR ADVERSE OUTCOMES IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA AND ITS HISTOLOGICAL SUBTYPES Ivan Rakic, Matthew Davis, Nicholas Corsi, Alexander Stephens, Sohrab Arora, Nikola Rakic, Taylor Malchow, Chase Morrison, Rafe Affas, Akshay Sood, Craig Rogers, and Firas Abdollah Ivan RakicIvan Rakic More articles by this author , Matthew DavisMatthew Davis More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Alexander StephensAlexander Stephens More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Nikola RakicNikola Rakic More articles by this author , Taylor MalchowTaylor Malchow More articles by this author , Chase MorrisonChase Morrison More articles by this author , Rafe AffasRafe Affas More articles by this author , Akshay SoodAkshay Sood More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymphvascular invasion (LVI) is recognized as an adverse prognostic factor in many cancers. However, its utility in upper tract urothelial carcinoma (UTUC) has not been well-defined. Our aim is to assess the prognostic ability of LVI in UTUC urothelial carcinoma (UC) and micropapillary urothelial carcinoma (MPUC) subtypes as a predictor of overall survival (OS) using a large North American cohort. METHODS: Our cohort included 9750 cM0 UTUC patients who underwent a radical nephroureterectomy (RNU), between 2004 and 2015, within the National Cancer Database (NCDB). The main variable of interest was LVI status, and its interaction with pathological nodal (pN) status. Kaplan-Meier curves were used to estimate the OS. Cox regression analysis tested the impact of LVI status on OS after accounting for covariates: age, sex, race, year of diagnosis, Charlson Comorbidity Index, income, treatment center type, insurance status, pathological tumor, and pN status. RESULTS: Mean (SD) age was 70.90±10.9 years. Overall, 14.4% had LVI, and 6.77% had pN+ (pN1-3) disease. The rate of advanced stage (pT3 or higher), and pN+ disease was 78.8%% and 18.1% in patients with LVI vs. 34.7% and 3.32% in patients without LVI. The histological subtypes were UC, pure squamous, sacromatoid/spindle cell carcinoma, and MPUC in respectively 49.8%, 0.608%, 0.708%, and 48.9% of patients. The mean (SD) follow-up was 42.9±35.3 months. In patients with UC at 5-years post-RNU, the OS rates were 60.2%, 29.9%, 28.9%, and 20.8% in patient with pN0 without LVI, pN0 with LVI, pN+ without LVI, and pN+ with LVI, respectively (p<0.001). In patients with MPUC at 5-years post-RNU, the OS rates were 65.3%, 40.2%, 54.7%, and 36.5% in patient with pN0 without LVI, pN0 with LVI, pN+ without LVI, and pN+ with LVI, respectively (p<0.001). On multivariable analysis, LVI was an independent predictor of less favorable OS outcomes, as those with LVI had a 1.82-fold higher risk of death (95% CI: 1.21-1.54, p<0.001), when compared to their counterpart without LVI. CONCLUSIONS: To the best of our knowledge, our report is the first to examine the impact of LVI on OS in a large North American nationwide cohort. Our results indicate that LVI is associated with less favorable survival outcomes in patient with UTUC who are treated surgically, and can be utilized for counseling after RNU and as a risk-stratification tool for future clinical trials. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e972 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ivan Rakic More articles by this author Matthew Davis More articles by this author Nicholas Corsi More articles by this author Alexander Stephens More articles by this author Sohrab Arora More articles by this author Nikola Rakic More articles by this author Taylor Malchow More articles by this author Chase Morrison More articles by this author Rafe Affas More articles by this author Akshay Sood More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

Invasive Micropapillary Urothelial Carcinoma: an Uncommon and Underreported Variant in Cystectomy Specimens.

Conventional urothelial carcinoma is the most common histological type of urinary bladder carcinoma. The latest edition of the WHO classification of tumours of the urothelial tract lays special emphasis on the ability of urothelial tumours to exhibit divergent differentiation with multiple histologic variants and a diverse genomic landscape. The presence of a micropapillary component (MPC) in urothelial carcinoma is associated with high-grade disease and poor response to intravesical chemotherapy. The present study aims to enumerate the clinicohistological features of urothelial carcinomas with micropapillary differentiation. Slides from 144 radical cystectomy specimens received over 6 years were reviewed independently by two pathologists. A predominant histological pattern along with co-existing pathology was noted. Of these, five cases were pure micropapillary carcinomas, four had conventional urothelial carcinoma with a MPC, one had a microscopic tumour at the mucosal surface, and two cases showed micropapillary histology in the lymph node metastasis, following transurethral resection of bladder tumour and Bacillus Calmette-Guerin therapy. The tumours with pure micropapillary carcinoma presented with a higher pathological stage and poor overall survival. Organ and lymph node metastasis was noted in five and eight cases, respectively, of which six showed a micropapillary pattern in the lymph nodes. Micropapillary urothelial carcinoma is a rare and aggressive variant of urothelial carcinoma with unique histologic features. This variant is often missed and underreported in biopsy and surgical resection specimens. Since the presence of MPC confers a poorer prognosis, the identification and reporting of this entity are important.

PREVALANCE OF UROTHELIAL CARCINOMA, ITS HISTOLOGICAL GRADE AND TYPE IN URINARY BLADDER OVER A PERIOD OF 2 YEARS: A STUDY IN A TERTIARY HOSPITAL IN CENTRAL INDIA

BACKGROUND:-Urinary bladder carcinoma is well known to show many histological divergent differentiation. The histological variants have important diagnostic, prognostic and therapeutic implications. The aim of the study was to find the prevalence of urothelial carcinoma in a tertiary care centre and to find the proportion of different histological grades and types of urothelial carcinoma. MATERIAL AND METHODS:- A retrospective monocentric study was done between April 2020 and April 2022 which includes 37 bladder biopsies which were received in the histopathology section of the Department of Pathology, Gajra raja medical college. Patients who refuse to give consent and those having cystitis were excluded from the study. RESULTS AND OBSERVATIONS :- Out of total 37 cases which were reviewed, the mean age was 62 years, with a male predominance (M:F ratio-3.16). Out of 37 cases, there were 8 cases each of highgrade urothelial carcinoma(21.6 %), high grade urothelial carcinoma with invasion ( 21.6 %) and high grade papillary urothelial carcinoma with invasion ( 21.6 %). There were 4 cases of high grade urothelial carcinoma with invasion with squamous differentiation ( 10.8 %), one case each of recurrent high grade urothelial carcinoma with invasion ( 2.7 %), well differentiated invasive glandular adenocarcinoma NOS (2.7%) and invasive micropapillary urothelial carcinoma with squamous differentiation ( 2.7 % ), two cases each of low grade urothelial carcinoma - 2 cases ( 5.4 %), low grade papillary urothelial carcinoma ( 5.4%) and papillary urothelial neoplasm of low malignant potential ( PUNLMP) ( 5.4 %). CONCLUSION Urinary bladder carcinoma is more common in male than females. Average age of presentation is 62 years in present study. High grade urothelial carcinoma ( 83.8 %) is more common compared to low grade ( 10.8% ). H&amp;E staining with ancillary techniques like immunohistochemistry or molecular it can be very effective in to analyse histological variants to better understand this invasive disease hence aiding in further management of patients.

Five-year survival stratification using “the Cancer Of the Bladder Risk Assessment” (COBRA) score for micropapillary and sarcomatoid urothelial carcinoma of the bladder variants.

e16534 Background: The Cancer of the Bladder Risk Assessment (COBRA) score is a validated risk stratification tool for patients with urothelial carcinoma of the bladder (UCB) after cystectomy. Radical cystectomy with or without neoadjuvant chemotherapy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Lymph node density and the presence of positive lymph nodes have been demonstrated to be critical prognostic tools. Our goal was to evaluate 5-year overall survival (OS) on UCB variants: micropapillary and sarcomatoid, stratified by COBRA score and the presence of lymph nodes. Methods: We sampled the National Cancer Database (NCDB) for bladder cancer patients diagnosed with de novo micropapillary and sarcomatoid UCB between 2004 and 2018 and treated with radical cystectomy. 5-year Kaplan-Meier survival plots were utilized to assess OS differences amongst different COBRA score groups and stratified by the presence of lymph nodes (LNs). A multivariable Cox regression model was used to compare hazard ratios, adjusting for significantly unbalanced factors. A p-value &lt; 0.05 was considered statistically significant. Results: A total of 1382 patients met the inclusion criteria. The average age was 68.10 + 10.31 years. 75% were male. Micropapillary represented 50.1% of selected histologies, followed by 49.5% sarcomatoid. For all combined histologies, 5-year OS percentage for patients with cystectomy and stratified by COBRA score (0-7) were 66% COBRA 0, 54% COBRA 1, 34% COBRA 2, 29% COBRA3, 15% COBRA &gt; 4) (p &lt; 0.001). 5-year OS for patients with cystectomy stratified by LN status was 54% for LN negative and 24% for LN positive (p &lt; 0.001). Substratification of the cohort according to the presence of LNs and COBRA score have shown a numerical drop in 5-year survival and a notable decrease in median survival amongst compared groups. The risk of death was almost 5 times higher in patients with a high COBRA score (&gt; 4) than in patients with a COBRA score of 0 (HR = 5.15, p &lt; 0.001). Conclusions: COBRA score could contribute to clinical decision-making as a risk stratification tool for patients with UCB variants, micropapillary and sarcomatoid. 5-year OS decreases with higher COBRA scores, and LN status plays a major role in 5-year OS for these two UCB variants.[Table: see text]

Pleural fluid metastasis of plasmacytoid urothelial carcinoma in comparison to micropapillary and conventional high-grade urothelial carcinoma: Cytologic and immuonohistochemical findings.

Plasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high-grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, and CD138, diminished or loss of E-cadherin membranous expression, negative expression for p63, p53, Epicam-BerEP4, Epicam-MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E-cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, p63, Epicam-BerEP4 (focal weak), and Epicam-MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.

MP56-13 ROLE OF RADICAL CYSTECTOMY AND LYMPH NODE DISSECTION IN PATIENTS WITH NON-METASTATIC CLINICALLY ADVANCED LYMPH NODAL (CN2/N3) BLADDER CANCER: AN ANALYSIS FROM NATIONAL CANCER DATABASE

You have accessJournal of UrologyCME1 May 2022MP56-13 ROLE OF RADICAL CYSTECTOMY AND LYMPH NODE DISSECTION IN PATIENTS WITH NON-METASTATIC CLINICALLY ADVANCED LYMPH NODAL (CN2/N3) BLADDER CANCER: AN ANALYSIS FROM NATIONAL CANCER DATABASE Harshit Garg, Furkan Dursun, Ahmed Elshabrawy, Hanzhang Wang, Michael Liss, Dharam Kaushik, Robert Svatek, and Ahmed Mansour Harshit GargHarshit Garg More articles by this author , Furkan DursunFurkan Dursun More articles by this author , Ahmed ElshabrawyAhmed Elshabrawy More articles by this author , Hanzhang WangHanzhang Wang More articles by this author , Michael LissMichael Liss More articles by this author , Dharam KaushikDharam Kaushik More articles by this author , Robert SvatekRobert Svatek More articles by this author , and Ahmed MansourAhmed Mansour More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002639.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of radical cystectomy in non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer is controversial. This study aims to compare the outcomes of patients undergoing radical cystectomy (RC) vs systemic therapy only in patients with non-metastatic bladder cancer with clinical N2/N3 disease. METHODS: We queried the National Cancer Database for patients with non-metastatic muscle-invasive bladder cancer (cT2-T4N2-3M0), who presented with advanced lymphadenopathy. Patients were classified as Group A: Those who received definitive surgery with or without neoadjuvant/ adjuvant therapy, Group B: Those who received systemic therapy alone and Group C: Those who did not receive any treatment. The predictive factors for undergoing definitive surgery were identified using multivariate regression analysis. Inverse probability propensity weighting was utilized to balance groups. The overall survival (OS) was evaluated using Kaplan Meir survival analysis and predictors for survival were studied using multivariate cox regression analysis. RESULTS: A total of 2,725 patients were identified and classified into Group A (n=1,366), Group B (n=2,372) and Group C (n=190). The predictive factors for undergoing RC were male gender (OR= 1.16, p=0.05), age below 70 years (OR=1.36, p=0.006), white race compared to black race (OR=1.38, p=0.009) and histology of micropapillary urothelial carcinoma (OR=2.37, p=0.004). The median (IQR) overall survival was 20 (10.5-66.8) months in Group A, 11.1(4.9-24.2) months in Group B and 6.1(3.2-12.4) months in Group C (p<0.001).13.2 (IQR). After weighted analysis, patients undergoing radical cystectomy had significantly higher 5-year OS as compared to systemic therapy group [25.9% vs 13.4%, p<0.001] [Figure 1]. Radical cystectomy was identified as an independent predictor for overall survival (compared to systemic therapy) [HR=0.58, p<0.001]. CONCLUSIONS: In clinically advanced non-metastatic lymph nodal disease (T2-T4,N2/N3) of bladder cancer, radical cystectomy offers superior survival benefit compared to systemic therapy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e977 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Harshit Garg More articles by this author Furkan Dursun More articles by this author Ahmed Elshabrawy More articles by this author Hanzhang Wang More articles by this author Michael Liss More articles by this author Dharam Kaushik More articles by this author Robert Svatek More articles by this author Ahmed Mansour More articles by this author Expand All Advertisement PDF DownloadLoading ...

Clinicopathological Review of Micropapillary Urothelial Carcinoma.

This review will discuss micropapillary urothelial carcinoma with respect to biology, histopathologic characteristics, genetic and molecular features, diagnosis, clinical management, and future directions of research. Recent consensus opinion study showed only moderate interobserver reproducibility in the diagnostic criteria. The most reproducible criteria with the highest consensus were multiple nests in the same lacunar spaces. There are recent reports of high rates of intratumoral heterogeneity of ERBB2 amplification within tumor containing both micropapillary and classic urothelial components. Micropapillary urothelial carcinoma is a well-documented highly aggressive variant of urothelial carcinoma with proven worse outcomes. Accurate recognition and reporting of this pattern is critical for optimal management. Newer therapeutic strategies related to the molecular and genetic findings seen in MPUC remain to be explored further.

Non-muscle invasive micropapillary urothelial carcinoma of the bladder: Variable use of initial cystectomy versus intravesical bacillus calmette-guérin

Introduction and Objective Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive histologic variant of bladder cancer. Treatment guidelines recommend forgoing Bacillus Calmette-Guérin (BCG) therapy in favor of early radical cystectomy for non-muscle invasive (NMI)-MPUC due to high rates of disease progression. We aimed to evaluate its management in patients with immediate cystectomy and BCG across various centers. Methods Patients with MPUC were identified from the National Cancer Database (2004-2017). Treatment trends and rates of pathological upstaging were identified. Bivariate and multivariate analyses were performed to assess differences in outcomes by treatment approach. Results 1,685 patients were diagnosed with MPUC during the study period with 531 identified with localized Ta, T1, or Tis disease. BCG was administered as an initial therapy in 24.1% of NMI-MPBC patients and in 16.3% of NMI-non-MPUC patients (p&lt;0.001). Cystectomy was performed as primary therapy for NMI disease in 29.9% of MPUC and in 2.7% of non-MPUC patients (p&lt;0.001). Of the patients who underwent primary cystectomy, upstaging from NMI-MPUC to T2-T4 disease was seen in 46.5% of the MPUC patients compared to 37.3% in patients with non-MPUC (p=0.025). Upstaging to pathologic N1-3 disease was observed in 33.1% of MPUC patients compared to 11.9% non-MPUC patients (p&lt;0.001). Cox regression analysis, adjusting for patient age, sex, race, comorbidities, and disease stage, care at academic cancer centers were associated with increased odds of having cystectomy as primary therapy compared to community cancer centers (OR = 4.29, 95% CI 2.73-6.76). Conclusion The current study lends evidence to current practice guidelines by reporting treatment patterns for patients with micropapillary bladder cancer across a broad spectrum of clinical practice. NMI-MPUC patients treated at academic cancer centers were more likely to receive radical surgery as primary treatment compared to patients at the community cancer centers.

Non-muscle invasive micropapillary urothelial carcinoma of the bladder: Variable use of initial cystectomy versus intravesical bacillus calmette-guérin

Introduction and Objective Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive histologic variant of bladder cancer. Treatment guidelines recommend forgoing Bacillus Calmette-Guérin (BCG) therapy in favor of early radical cystectomy for non-muscle invasive (NMI)-MPUC due to high rates of disease progression. We aimed to evaluate its management in patients with immediate cystectomy and BCG across various centers. Methods Patients with MPUC were identified from the National Cancer Database (2004-2017). Treatment trends and rates of pathological upstaging were identified. Bivariate and multivariate analyses were performed to assess differences in outcomes by treatment approach. Results 1,685 patients were diagnosed with MPUC during the study period with 531 identified with localized Ta, T1, or Tis disease. BCG was administered as an initial therapy in 24.1% of NMI-MPBC patients and in 16.3% of NMI-non-MPUC patients (p&lt;0.001). Cystectomy was performed as primary therapy for NMI disease in 29.9% of MPUC and in 2.7% of non-MPUC patients (p&lt;0.001). Of the patients who underwent primary cystectomy, upstaging from NMI-MPUC to T2-T4 disease was seen in 46.5% of the MPUC patients compared to 37.3% in patients with non-MPUC (p=0.025). Upstaging to pathologic N1-3 disease was observed in 33.1% of MPUC patients compared to 11.9% non-MPUC patients (p&lt;0.001). Cox regression analysis, adjusting for patient age, sex, race, comorbidities, and disease stage, care at academic cancer centers were associated with increased odds of having cystectomy as primary therapy compared to community cancer centers (OR = 4.29, 95% CI 2.73-6.76). Conclusion The current study lends evidence to current practice guidelines by reporting treatment patterns for patients with micropapillary bladder cancer across a broad spectrum of clinical practice. NMI-MPUC patients treated at academic cancer centers were more likely to receive radical surgery as primary treatment compared to patients at the community cancer centers.

Prostate cancer nomenclature at diagnosis can affect treatment decisions.

Prostate cancer nomenclature at diagnosis can affect treatment decisions.

Dissecting patterns of care in patients with variant histology of bladder cancer and lymph node invasion

Objectives Lymph node invasion (LNI) is related to long-term survival in patients with muscle-invasive bladder cancer. However, in the case of variant histology (VH), data on pelvic lymph node dissection (PLND) and LNI are sparse. We described the pattern of care of PLND in patients with VHs of bladder cancer, exploring predictors of LNI. Methods Using the 2001–2016 SEER registry, 20 767 bladder cancer patients who underwent PLND were identified. Included histological variants were pure urothelial carcinoma (UC), micropapillary UC, sarcomatoid UC, lymphoepithelioma-like UC, adenocarcinoma, sarcoma, giant and spindle cell carcinoma, squamous cell carcinoma (SCC), and neuroendocrine tumor. Uni- and multivariable logistic regression analyses tested for LNI predictors. Cox regression was used to test for predictors of overall mortality (OM) among both LNI positive and LNI negative patients. Results Overall, 2464 (11.9%) harbored a VH. On multivariate analysis, only micropapillary UC was associated with higher risk (OR = 3.39) of LNI. This association was maintained when only the subset of patients treated without perioperative chemotherapy were analyzed (OR = 3.30). Similarly, higher T stage (T2 stage OR = 2.24; T3–4 stage OR = 9.44) and the use of chemotherapy (OR = 2.29) were associated with a higher risk of LNI. Among patients with LNI (5299, 25.5%), SCC (HR = 1.87), T3–4 stage (HR = 1.94), age at diagnosis (HR = 1.01) and geographic region (south) (HR = 1.22) were predictors of higher risk of OM. Conversely, chemotherapy (HR = 0.69) and number of removed LN (HR = −0.99) were associated with lower risk of OM. Finally, in a subgroup of patients without LNI, sarcomatoid UC (HR = 1.58) and giant and spindle cell carcinoma (HR = 1.83) were the only VH predictors of OM. Conclusions We described different patterns of care in patients with VHs of bladder cancer. Micropapillary UC was an independent risk factor for LNI. Among patients harboring LNI, those with SCC VH had higher OM compared to pure UC. Conversely, sarcomatoid UC and giant and spindle cell carcinoma were predictors of OM in patients without nodal involvement.

PD55-12 NEOADJUVANT CHEMOTHERAPY FOR VARIANT HISTOLOGY MUSCLE INVASIVE BLADDER CANCER: PATHOLOGIC DOWNSTAGING AND SURVIVAL OUTCOMES

You have accessJournal of UrologyBladder Cancer: Invasive IV (PD55)1 Sep 2021PD55-12 NEOADJUVANT CHEMOTHERAPY FOR VARIANT HISTOLOGY MUSCLE INVASIVE BLADDER CANCER: PATHOLOGIC DOWNSTAGING AND SURVIVAL OUTCOMES Nicholas Chakiryan, David Jiang, Kyle Gillis, Elizabeth Green, Ali Hajiran, Lee Hugar, Logan Zemp, Jad Chahoud, Jingsong Zhang, Rohit Jain, Brandon Manley, Wade Sexton, and Scott Gilbert Nicholas ChakiryanNicholas Chakiryan More articles by this author , David JiangDavid Jiang More articles by this author , Kyle GillisKyle Gillis More articles by this author , Elizabeth GreenElizabeth Green More articles by this author , Ali HajiranAli Hajiran More articles by this author , Lee HugarLee Hugar More articles by this author , Logan ZempLogan Zemp More articles by this author , Jad ChahoudJad Chahoud More articles by this author , Jingsong ZhangJingsong Zhang More articles by this author , Rohit JainRohit Jain More articles by this author , Brandon ManleyBrandon Manley More articles by this author , Wade SextonWade Sexton More articles by this author , and Scott GilbertScott Gilbert More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002089.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with variant histology muscle invasive bladder cancer (MIBC) have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy, the standard of care for pure urothelial MIBC, is associated with pathologic downstaging or improved overall survival for patients with variant histology. The primary objective is to assess for associations between receipt of neoadjuvant chemotherapy, pathologic downstaging, and overall survival for patients with variant histology MIBC. METHODS: This retrospective study identified patients in the National Cancer Database from 2004-2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histologic subgroup, and receipt or non-receipt of neoadjuvant chemotherapy. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathologic downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and overall survival. The main outcomes were pathologic downstaging, defined as pT0N0 or pT≤1N0, and overall survival from the time of diagnosis to date of death or censoring at last follow-up RESULTS: 31,218 patients were included in the final study population (Urothelial carcinoma (UC): 27,779; Sarcomatoid UC: 501; Micropapillary UC: 418; Squamous cell carcinoma (SCC): 1,141; Neuroendocrine carcinoma: 629; Adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathologic downstaging to pT0N0 in all histologic subgroups (UC: OR 5.1 [4.6-5.6]; Sarcomatoid UC: OR 13.8 [5.5-39.0]; Micropapillary UC: OR 9.7 [2.8-46.8]; SCC: OR 7.4 [2.1-24.5]; Neuroendocrine: OR 4.7 [2.6-9.2]; Adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved overall survival for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]), and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]). CONCLUSIONS: Neoadjuvant chemotherapy was associated with pathologic downstaging for all MIBC histologic variants, with improved overall survival for patients with UC, sarcomatoid variant UC, and neuroendocrine carcinoma. Source of Funding: NA © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1002-e1002 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Chakiryan More articles by this author David Jiang More articles by this author Kyle Gillis More articles by this author Elizabeth Green More articles by this author Ali Hajiran More articles by this author Lee Hugar More articles by this author Logan Zemp More articles by this author Jad Chahoud More articles by this author Jingsong Zhang More articles by this author Rohit Jain More articles by this author Brandon Manley More articles by this author Wade Sexton More articles by this author Scott Gilbert More articles by this author Expand All Advertisement Loading ...

Detection of HPV infection in urothelial carcinoma using RNAscope: Clinicopathological characterization.

BackgroundHuman papillomavirus (HPV) is a well‐established mucosotropic carcinogen, but its impact on urothelial neoplasm is unclear. We aimed to clarify the clinical and pathological features of HPV‐related urothelial carcinoma (UC).MethodsTissue samples of 228 cases of UC were obtained from the bladder, upper and lower urinary tract, and metastatic sites to construct a tissue microarray. The samples were analyzed for the presence of HPV by a highly sensitive and specific mRNA in situ hybridization (RISH) technique (RNAscope) with a probe that can detect 18 varieties of high‐risk HPV. We also conducted immunohistochemistry (IHC) for a major HPV capsid antibody and DNA‐PCR.ResultsThe HPV detection rates varied among the methods; probably due to low HPV copy numbers in UC tissues and the insufficient specificity and sensitivity of the IHC and PCR assays. The RISH method had the highest accuracy and identified HPV infection in 12 (5.2%) of the cases. The histopathological analysis of the HPV‐positive UC showed six cases of usual type UC, five cases of UC with squamous differentiation (UC_SqD), and one case of micropapillary UC. The HPV detection rate was six‐fold higher in the cases of UC_SqD than in the other variants of UC (odds ratio [OR] =8.9, p = 0.002). In addition, HPV infection showed a significant association with tumor grade (OR =9.8, p = 0.03) and stage (OR =4.7, p = 0.03) of UC. Moreover, the metastatic rate was higher in HPV‐positive than in negative UC (OR =3.4).ConclusionThese data indicate that although the incidence of HPV infection in UC is low, it is significantly associated with squamous differentiation and poor prognosis. Furthermore, our observations show that RNAscope is an ideal method for HPV detection in UC compared with the other standard approaches such as IHC and PCR assays.

Clinicopathological analysis of micropapillary urothelial carcinoma of the bladder

收集2013—2019年间21例膀胱微乳头尿路上皮癌（MPUC）及同期117例膀胱非特殊型浸润性尿路上皮癌的临床病理资料，探讨MPUC临床病理学特征，并比较两组病例临床病理特征及预后的差异。MPUC患者男女比17∶4，中位年龄67岁，微乳头成分占5%~70%，12例（12/21，57.1%）有脉管侵犯。10例（47.6%，10/21）MPUC HER2阳性。MPUC脉管侵犯率、T分期、HER2阳性率显著高于非特殊型浸润性尿路上皮癌。MPUC、年龄大于69岁、T2-4期与预后差显著相关。膀胱MPUC是尿路上皮癌的一种侵袭性亚型，易侵犯脉管，预后差。MPUC的高HER2阳性率提示HER2靶向治疗可能是潜在的治疗方向。.

P-120 Catenin is a Useful Diagnostic Biomarker for Distinguishing Plasmacytoid and Sarcomatoid Variants From Conventional Urothelial Carcinoma.

Plasmacytoid urothelial carcinoma (PC-UC) is an aggressive variant of urothelial carcinoma (UC), characterized by loss of E-cadherin (E-Cad)-mediated intercellular adhesion. Loss of E-Cad by immunohistochemistry can help diagnose PC-UC; however, sensitivity is limited. Expression of other cadherin-catenin adhesion complex members, that is, p-120 catenin (p-120) and β-catenin (B-Cat), which are diagnostically useful for lobular breast carcinoma, remains unknown in UC. To determine the utility of p-120 and B-Cat in conventional and variant UC. E-cadherin, B-Cat, and p-120 immunohistochemistry was performed in 25 conventional UCs and 33 variant UCs, including 22 PC-UCs, 6 sarcomatoid UCs (SUCs), and 5 micropapillary UCs. Membranous staining for all biomarkers was considered normal; however, any cytoplasmic staining or an absence of staining was considered diagnostically abnormal. Next-generation sequencing was performed on 8 PC-UC cases. E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17 of 22; 77%) with an additional 2 of 22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21 of 22 cases (95%). Most SUCs showed an absence of E-Cad (5 of 6; 83%) and cytoplasmic or negative p-120 in 5 of 6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive. p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC.

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.

Micropapillary urothelial carcinoma (MPC) is a rare urothelial carcinoma variant with conflicting data guiding clinical practice. In this study, we explored oncologic outcomes in relation to neoadjuvant chemotherapy (NAC) in a retrospective cohort of patients with MPC, alongside data from Surveillance, Epidemiology, and End Results (SEER)-Medicare. We retrospectively identified patients with MPC or conventional urothelial carcinoma (CUC) without any variant histology undergoing radical cystectomy (RC) in our institution (2003-2018). SEER-Medicare was also queried to identify patients diagnosed with MPC (2004-2015). Clinicopathologic data and treatment modalities were extracted. Overall survival (OS) was estimated with the Kaplan-Meier method. Mann-Whitney-Wilcoxon and chi-square tests were used for comparative analysis and Cox regression for identifying clinical covariates associated with OS. Our institutional database yielded 46 patients with MPC and 457 with CUC. In SEER-Medicare, 183 patients with MPC were identified, and 63 (34%) underwent RC. In the institutional cohort, patients with MPC had significantly higher incidence of cN+ (17% vs. 8%), pN+ stage (30% vs. 17%), carcinoma-in-situ (43% vs. 25%), and lymphovascular invasion (30% vs. 16%) at RC versus those with CUC (all P< .05). Pathologic complete response (ypT0N0) to NAC was 33% for MPC and 35% for CUC (P= .899). Median OS was lower for institutional MPC versus CUC in univariate analysis (43.6 vs. 105.3 months, P= .006); however, MPC was not independently associated with OS in the multivariate model. Median OS was 25 months in the SEER MPC cohort for patients undergoing RC, while NAC was not associated with improved OS in that group. Pathologic response to NAC was not significantly different between MPC and CUC, while MPC histology was not an independent predictor of OS. Further studies are needed to better understand biological mechanisms behind its aggressive features as well as the role of NAC in this histology variant.