Resection Of Bladder Tumor Specimens Research Articles

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.

PT1 Subclassification Predicts Progression-Free Survival in En Bloc Resection of Bladder Tumor Specimens.

The pathologic diagnosis of pT1 substage in conventional transurethral resection of bladder tumor specimens is inaccurate and has low interobserver reproducibility owing to fragmentation and cauterization of the specimens. En bloc resection of bladder tumor is a novel surgical procedure that improves diagnostic feasibility and accuracy in the pathologic diagnosis of bladder cancer, including depth and extent of invasion. To examine the prognostic value of multiple pT1 subclassification methods, using only en bloc resection specimens. We examined 106 patients with T1 bladder cancer who underwent en bloc resection. The pT1 substages were assigned by 3 different subclassification methods by using the muscularis mucosae or stalk of the papillary lesion as diagnostic landmarks or millimetric depth of invasion. Intergroup differences in progression-free survival and recurrence-free survival rates were analyzed. The prognostic values of clinicopathologic factors for progression/recurrence were analyzed by using multivariate analysis. The pT1 substage was evaluable in all cases. Tumors with invasion into/beyond the muscularis mucosae and those beyond the stalk of the papillary lesion were associated with worse progression-free survival (P = .002 and P = .01, respectively). Notably, no patient with invasion confined to the stalk had disease progression during the 23-month median follow-up period. Only the pT1 subclassification method using the muscularis mucosae was an independent prognosticator of progression in multivariate analysis (P = .03). Precise pathologic subclassification of invasion using en bloc resection specimens may enable accurate prognosis and assessment in patients with bladder cancer with suspicious shallow invasion.

PD44-01 ACCURACY OF ACTUAL STAGE PREDICTION USING VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) BEFORE RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023PD44-01 ACCURACY OF ACTUAL STAGE PREDICTION USING VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) BEFORE RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA Si Hyun Kim, Jang Hee Han, Seung-Hwan Jeong, Hyeong Dong Yuk, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, and Ja Hyeon Ku Si Hyun KimSi Hyun Kim More articles by this author , Jang Hee HanJang Hee Han More articles by this author , Seung-Hwan JeongSeung-Hwan Jeong More articles by this author , Hyeong Dong YukHyeong Dong Yuk More articles by this author , Chang Wook JeongChang Wook Jeong More articles by this author , Cheol KwakCheol Kwak More articles by this author , Hyeon Hoe KimHyeon Hoe Kim More articles by this author , and Ja Hyeon KuJa Hyeon Ku More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003354.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies using the vesical imaging reporting and data system (VI-RADS) to predict muscle-invasive bladder cancer had some limitations. Most studies were performed with transurethral resection of bladder tumor specimens with few samples. This study was conducted to address these shortcomings and confirm the accuracy of VI-RADS for bladder cancer. METHODS: This study used data from the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer–Radical Cystectomy (SUPER-UC-Cx). Patients who underwent multiparametric magnetic resonance imaging (mp-MRI) before radical cystectomy were included in this study between March 2020 and March 2022. All images were reported by radiologists and reviewed by two urologists. The patient characteristics and clinical information were blinded during the review. The performance of qualitative and quantitative variables in predicting muscle layer invasion or perivesical fat infiltration was verified by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 208 patients, 182 (87.5%) underwent mp-MRI before radical cystectomy. Twenty-three patients with non-urothelial carcinoma, inappropriate MRI scans, and bladder filling were excluded. Cut-off for muscle invasion, VI-RADS score of 4 had the highest area under the curve (AUC) (sensitivity 0.84; specificity 0.93; accuracy 0.90; positive predictive value (PPV) 0.84; negative predictive value (NPV) 0.93, and AUC 0.88). Cut-off for perivesical fat invasion and VI-RADS score of 5 had the highest AUC (sensitivity, 0.78; specificity, 0.99; accuracy, 0.95; PPV, 0.96; NPV, 0.95; and AUC, 0.89). CONCLUSIONS: VI-RADS is a good predictor of bladder cancer staging before radical cystectomy and is especially helpful in predicting muscle invasion and perivesical fat infiltration. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1124 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Si Hyun Kim More articles by this author Jang Hee Han More articles by this author Seung-Hwan Jeong More articles by this author Hyeong Dong Yuk More articles by this author Chang Wook Jeong More articles by this author Cheol Kwak More articles by this author Hyeon Hoe Kim More articles by this author Ja Hyeon Ku More articles by this author Expand All Advertisement PDF downloadLoading ...

Repeat Transurethral Resection of Muscle-invasive Bladder Cancer Prior to Radical Cystectomy is Prognostic but Not Therapeutic.

We sought to evaluate the impact of repeat transurethral resection of bladder tumor prior to radical cystectomy on oncologic outcomes in a contemporary cohort at a tertiary care center. An Institutional Review Board approved review of 657 patients diagnosed with muscle-invasive bladder cancer who underwent radical cystectomy at our institution for clinical stage T2 urothelial carcinoma between 2005 and 2017 was performed. Patients with and without repeat transurethral resection of bladder tumor were matched 1-to-1 by propensity score. Matching was done by age, gender, receipt of neoadjuvant chemotherapy, preoperative hydronephrosis, variant histology, lymphovascular invasion, or carcinoma in situ on index transurethral resection of bladder tumor. A total of 548 patients with muscle-invasive bladder cancer were included after matching (2 groups of 274 patients). Kaplan-Meier estimates of recurrence-free and overall survival demonstrated no significant difference based upon performance of repeat transurethral resection of bladder tumor (P = 1.0 and P = .3, respectively). When outcomes were stratified by pathology of repeat transurethral resection of bladder tumor specimens, those with pT0 had superior recurrence-free and overall survival compared to those with residual muscle invasive disease (P < .001 and P = .001, respectively). Notably, more than 60% of patients who were pT0 on repeat transurethral resection of bladder tumor had residual disease at the time of radical cystectomy. Repeat transurethral resection of bladder tumor prior to radical cystectomy, irrespective of receipt of neoadjuvant chemotherapy, was not associated with improved survival outcomes in this propensity score matched muscle-invasive bladder cancer cohort. The absence of residual tumor on pathological evaluation of repeat transurethral resection of bladder tumor specimen was prognostic and was associated with improved survival outcomes. However, a large percentage of patients with pT0 disease on repeat transurethral resection of bladder tumor had residual disease on radical cystectomy pathology.

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.

Prospective Validation of Vesical Imaging-Reporting and Data System Using a Next-Generation Magnetic Resonance Imaging Scanner-Is Denoising Deep Learning Reconstruction Useful?

The Vesical Imaging Reporting and Data System (VI-RADS) was launched in 2018 to standardize reporting of magnetic resonance imaging for bladder cancer. This study aimed to prospectively validate VI-RADS using a next-generation magnetic resonance imaging scanner and to investigate the usefulness of denoising deep learning reconstruction. We prospectively enrolled 98 patients who underwent bladder multiparametric magnetic resonance imaging using a next-generation magnetic resonance imaging scanner before transurethral resection of bladder tumor. Tumors were categorized according to VI-RADS, and we ultimately analyzed 68 patients with pathologically confirmed urothelial bladder cancer. We used receiving operating characteristic curve analyses to assess the predictive accuracy of VI-RADS for muscle invasion. Sensitivity, specificity, positive/negative predictive value, accuracy and area under the curve were calculated for different VI-RADS score cutoffs. Muscle invasion was detected in the transurethral resection of bladder tumor specimens of 18 patients (26%). The optimal cutoff value of the VI-RADS score was determined as ≥4 based on the receiver operating curve analyses. The accuracy of diagnosing muscle invasion using a cutoff of VI-RADS ≥4 was 94% (AUC 0.92). Additionally, we assessed the utility of denoising deep learning reconstruction. Combination with denoising deep learning reconstruction significantly improved the AUC of category by T2-weighted imaging, and of the 4 patients who were misdiagnosed by the final VI-RADS score 3 were correctly diagnosed by T2-weighted imaging+denoising deep learning reconstruction. In this prospective validation study with a next-generation magnetic resonance imaging scanner, VI-RADS showed high predictive accuracy for muscle invasion in patients with bladder cancer before transurethral resection of bladder tumor. Combining T2-weighted imaging with denoising deep learning reconstruction might further improve the diagnostic accuracy of VI-RADS.

Invasive poorly differentiated adenocarcinoma of the bladder following augmentation cystoplasty: a multi-institutional clinicopathological study

Augmentation cystoplasty is a surgical procedure used in the management of patients with neurogenic bladder. This procedure involves anastomosis of the bladder with gastrointestinal grafts, including portions of ileum, colon, or stomach. A rare but important complication of augmentation cystoplasty is the development of malignancy. The majority of malignancies arising in this setting have been described in case reports. A search for cases of non-urothelial carcinoma following augmentation cystoplasty was conducted through the urological pathology files of four major academic institutions. Ten cases were identified, including six cystoprostatectomy/cystectomy, two partial cystectomy, and two transurethral resection of bladder tumour specimens. The mean patient age at diagnosis was 47 years (range 27-87 years). The male:female ratio was 4:6. The tumours tended to present at an advanced stage; four cystoprostatectomy/cystectomy cases were categorised as pT3a, one was categorised as pT3b, and one was categorised as pT4a. Lymph node metastases were present in all cases which had lymph node excision (range 1-16 positive nodes per case). The majority of cases (90%) were predominantly characterised by a poorly differentiated adenocarcinoma with signet ring cell features. Other morphological features included mucinous features (30%), plasmacytoid features (20%), enteric/villous architecture (10%), and large cell undifferentiated morphology (10%). This is the largest study to date on the clinicopathological features of invasive non-urothelial carcinoma of the bladder following augmentation cystoplasty. The tumours are typically poorly differentiated adenocarcinoma, with diffuse signet ring cell features, aggressive, and present at high stage. Further molecular characterisation may provide additional insights into the pathogenesis of this entity.

Assessing the Impact of the Absence of Detrusor Muscle in Ta Low-grade Urothelial Carcinoma of the Bladder on Recurrence-free Survival

BackgroundObtaining detrusor muscle (DM) in transurethral resection of bladder tumor (TURBt) specimen is considered a surrogate marker of resection quality. However, evidence was principally investigated in high-risk tumors. Therefore, DM sampling for low-grade (LG) urothelial carcinoma (UC) remains poorly investigated and certainly requires further investigation. ObjectiveTo assess whether the absence of DM in TURBt specimen has a negative impact on recurrence-free survival (RFS) in patients with a Ta LG UC. Design, setting, and participantsA multicenter TURBt database was queried for “LG, Ta, UC of the bladder.” All patients treated between 1996 and 2018 with tumor grade assessed according to both 1973 World Health Organization and 2004 WHO/International Society of Urological Pathology grading classifications and with a minimum follow-up of 1 yr were included. Patients with a previous history of high-grade UC, upper urinary tract UC, or bladder tumor differentiations other than UC were excluded. InterventionTURBt. Outcome measurements and statistical analysisBaseline demographic, clinical, and pathologic data were analyzed. The European Organization for Research and Treatment of Cancer (EORTC) risk group was recorded. Kaplan-Meier analysis was performed to assess the predictive role of clinical and pathologic data for RFS. Univariable and multivariable Cox regression analyses were performed to identify the predictors of recurrence. Results and limitationsOverall, 521 patients were included. At Kaplan-Meier analysis, the low-risk cohort displayed significantly higher RFS than the intermediate-risk cohort (1-yr RFS 87% vs 79%; log-rank p = 0.007). At univariable Cox regression analysis, only gender, multiple tumors, tumor diameter ≥3 cm, and EORTC risk group were significant predictors of recurrence. Absence of DM had no impact on RFS. Multivariable Cox regression analysis confirmed gender and EORTC risk group as independent predictors of recurrence. ConclusionsAbsence of DM in TURBt specimen has negligible role in RFS of patients with Ta LG tumors of the bladder. Patient summaryIn this study, we assessed the role that detrusor muscle (DM) in transurethral resection of bladder tumor specimen has in recurrence-free survival, in patients with a Ta low-grade urothelial carcinoma of the bladder. Absence of DM has no impact on tumor recurrence; therefore, it does not require additional attention.

Molecular subtypes applied to a population-based modern cystectomy series do not predict cancer-specific survival

ObjectivesTo investigate the preoperative prognostic value of molecular subtypes in relation to clinical information, histopathological findings, and molecular markers for patients with bladder cancer treated with radical cystectomy. Patients and methodsAfter standard preoperative staging, a population-based cohort of 519 patients underwent radical cystectomy between 2006 and 2011. Following pathological review of all transurethral resection of bladder tumor specimens, tissue microarrays were constructed, and RNA was extracted from formalin-fixed tissue blocks. Immunohistochemistry (IHC) was performed using markers suggested to be relevant for prognosis (ZEB2, CCND1, CD3, CD68, CDH3, HER3, KRT14, CDKN2A(p16), TP63, FGFR3, EPCAM, GATA3, FOXA1, ERBB2, and EGFR). IHC- and gene-expression-based molecular classification was also conducted. Univariate and multivariate Cox proportional hazards regression were used for survival analyses. ResultsClinical T3 stage (Hazard Ratio [HR] 1.6, Confidence Interval [CI] 1.1–2.3), hydronephrosis (HR 1.7, CI 1.2–2.3), lymphovascular invasion (LVI) (HR 2.6, CI 1.9–3.6), extensive necrosis (HR 1.6, CI 1.1–2.5), and CD68/CD3-ratio >1 (HR 1.3, CI 1.1–1.5) in the transurethral resection of bladder tumor specimen was associated with worse cancer-specific survival (CSS) and progression-free survival (data not shown). In multivariate analysis, higher clinical T stage (HR 1.3, CI 1.1–1.7; P = 0.007) and presence of LVI (HR 2.4, CI 1.7–3.5; P = 1.8 × 10−6) were associated with worse CSS, whereas only LVI was associated with progression-free survival. Molecular subtypes (assessed by Lund taxonomy and the Consensus molecular subtypes of muscle-invasive bladder cancer) and published single IHC markers were not associated with survival. ConclusionsIn the present large population-based cystectomy series, LVI and clinical stage were independently associated with CSS. However, molecular subtypes determined by global gene expression showed no such association with CSS according to either the Consensus molecular subtypes of muscle-invasive bladder cancer or Lund taxonomy.

Individual patient risk of progression of urinary bladder papillary tumors estimated from biomarkers at initial transurethral resection of bladder tumor.

To determine if individual, instead of group, patient progression risk could be predicted using p53, Ki67 and CK20 biomarker percentage values at initial transurethral resection of bladder tumor specimens. This was an observational study where biomarkers were measured with no knowledge of tumor outcome. Initial bladder tumor specimens were classified as non-invasive and invasive to sub-epithelium (pT1). Percentages of stained biomarker cells were tested as progression predictors from non-invasive to pT1 and pT1 to pT2. Progression probability was correlated with biomarker percentages resulting in a regression equation. We studied 112 patients (median age = 67, range 37-91, males 83/112 (73%), with median follow-up of 39months (range 1.7-140). Mean biomarker values were higher in stage pT1 than in non-invasive (all p < 0.001). Cut-off points separating progression from non-progression groups in stage pT1 were higher than in non-invasive for all biomarkers. Correlation R values for progression probability vs. biomarker percentages varied from 0.7 to 0.9 (all p < 0.001), regression slopes from 0.1 to 0.8 and intercepts from 11 to 35. A novel individual progression probability was calculated as the product of biomarker percentage of stained cells and slope, plus the prevalence-adjusted intercept. Identification of individual risk of progression in patients with non-muscle-invasive bladder tumors was possible using p53- and Ki67-derived progression probability using a regression equation. Combining biomarker-derived progression probability to tumor stage pT1 improves progression to pT2 predictive accuracy.

Muscle invasive bladder cancer (MIBC) demonstrates neoadjuvant cisplatin-based chemotherapy (NAC) related changes in molecular subtype and immune infiltration.

443 Background: Defining the role of MIBC molecular subtypes and immune expression in determining clinical outcomes is an area of active investigation. However, changes in these transcriptomic profiles pre- and post-NAC have not been well characterized. Methods: This retrospective study reviewed 53 pts with MIBC treated with NAC, of whom 12 pts without complete pathological response had both pre- and post-NAC samples of sufficient quality. Post-NAC staging was &gt; = pT2 in 11 pts and pT1 in 1 pt. We performed RNA expression analysis of matched pre-NAC transurethral resection of bladder tumor specimens and post-treatment radical cystectomy primary bladder tumor specimens. We used a customized NanoString panel incorporating previously reported immune signatures (Ayers, JCI 2017; O’Donnell, ASCO 2017) and additional genes to assign basal ( CD14, CD44, PDGFC, KRT14, KRT5) and luminal ( GATA3, PPARG, SHH, CD24, FOXA1, WNT7B, ERBB2) molecular subtypes. Results: We first classified the bladder cancer cohort of The Cancer Genome Atlas into basal and luminal subtypes using the BASE47 signature (Damrauer, PNAS 2014) and the NanoString panel and there was good agreement (Rand Index = 0.72). We then assigned subtypes using the NanoString panel on matched pre- and post-NAC samples and found marked subtype shift (Table). We identified two robust clusters of samples according to immune expression with a 3-fold change of immune expression between them (FDR = 0.0008). We found that 4 pts switched from the low to the high cluster, while 2 switched from the high to the low cluster after NAC (Table). Conclusions: MIBC molecular subtype membership is dynamic and is influenced by NAC. NAC can induce both enhanced and suppressed immune activity. These findings have implications on future studies exploring the predictive value of RNA expression patterns for bladder cancer therapies as well as post-NAC immunotherapy. [Table: see text]

Dose dense MVAC prior to radical cystectomy: a real-world experience.

Our primary endpoint was to assess pathological response rate (pT0N0 and ≤pT1N0) for patients with BCa treated with the accelerated or dose dense MVAC (ddMVAC) chemotherapy followed by radical cystectomy (RC) in this real-word multi-institutional cohort. We retrospectively reviewed records of patients with urothelial cancer who underwent ddMVAC and RC at seven contributing institutions from 2000 to 2015. Patients with cT2-4a, M0 BCa were included. Presence of cT3-4 disease, hydronephrosis, lymphovascular invasion and/or existence of sarcomatoid, or micropapillary features on the initial transurethral resection of bladder tumor specimen was defined as high-risk disease. Logistic regression models for prediction of pT0N0 and ≤pT1N0 were generated for the entire cohort as well as for the cN0 subgroup. The multivariable Cox proportional hazards regression model for survival using post RC data was used to assess hazard ratios (HRs) for the variables of interest. A total of 345 patients received ddMVAC chemotherapy during the study period; 85% had high-risk features. The median number of chemotherapy cycles was 4 (IQR 4-4); >90% of patients completed all scheduled cycles. The observed rates of pT0N0 and ≤pT1N0 were 30.4 and 49.3%, respectively, among cN0 patients. On the multivariable regression model, the presence of more than one clinical high-risk element was associated with 70% [OR 0.30 95% CI (0.10-0.86); p=0.02] reduction in the odds of achieving partial pathological response. A complete response (pT0N0) was observed in one-third of patients after neoadjuvant ddMVAC therapy, and a partial response (≤pT1N0) was observed in nearly half of the cases in this real-world experience with this regimen. To our knowledge, this represents the largest experience outside clinical trial settings.

Utility of the laminin immunohistochemical stain in distinguishing invasive from noninvasive urothelial carcinoma.

To study the utility of the laminin immunostain in distinguishing invasive from noninvasive urothelial carcinoma (UC). The distinction is difficult but clinically significant as it can affect the decision to administer intravesical Bacillus Calmette-Guerin or can even lead to cystectomy. Representative sections of the transurethral resection of bladder tumor specimens from 25 cases of formalin-fixed paraffin-embedded invasive UCs and 25 cases of noninvasive UCs were selected for immunohistochemical (IHC) staining with laminin (Ventana, Oro Valley, AZ, USA). These cases were selected using a computer-assisted search of our laboratory information system (Cerner CoPath). Tissue from five paraffin-embedded tissue blocks containing unremarkable urothelial-lined bladder parenchyma was chosen as controls. All five control cases demonstrated crisp linear staining of the basement membrane underlying the unremarkable urothelium. Similar findings were also noted in the 25 cases of noninvasive UC. All 25 cases of the invasive UC demonstrated a complete absence of the staining around invasive and malignant urothelial cells. Laminin staining was also noted in both the muscularis mucosae and the detrusor muscle, although the pattern of staining in these areas was granular and was distinguishable from the crisp linear staining of the basement membrane. Laminin IHC staining can be useful in differentiating invasive from noninvasive UC.

Evaluating transurethral resection of bladder tumour specimens: an approach

Evaluating transurethral resection of bladder tumour specimens: an approach

MP49-08 PROGNOSTIC SIGNIFICANCE OF DEPTH OF INVASION IN TRANSURETHRAL RESECTION OF BLADDER TUMOR SPECIMENS.

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2016MP49-08 PROGNOSTIC SIGNIFICANCE OF DEPTH OF INVASION IN TRANSURETHRAL RESECTION OF BLADDER TUMOR SPECIMENS. Mahmut Akgul, Bream Matthew, Nafiseh Janaki, Hammad Tashkandi, Lee Ponsky, and Gregory MacLennan Mahmut AkgulMahmut Akgul More articles by this author , Bream MatthewBream Matthew More articles by this author , Nafiseh JanakiNafiseh Janaki More articles by this author , Hammad TashkandiHammad Tashkandi More articles by this author , Lee PonskyLee Ponsky More articles by this author , and Gregory MacLennanGregory MacLennan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.421AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Depth of invasion in transurethral resection of bladder (TURB) biopsies of T1 urothelial cancer has previously been evaluated for subclassification. This has been done by measuring depth of lamina propria (LP) invasion or by identifying muscularis mucosa invasion, however these are affected by tissue orientation, LP variation, and inconclusive presence of muscularis mucosa. Identifying tumor that is adjacent to detrusor muscle (TADM) is not affected by orientation or LP size and may be a better histologic indicator of advanced T1 disease. METHODS A language search of our departmental pathology archives from 1995-2015 using “transurethral resection” and “bladder” identified all 2786 TURB cases. Pathologic and clinical records were reviewed, and only those with T1 cancer at initial resection, urothelial histology, detrusor muscle (DM) present in the biopsy, and adequate clinical records were included. All available slides were reviewed, and patients were classified into two groups: LP invasion with TADM (group 1), or any other LP invasion without TADM (group 2). Further clinical data was obtained including, age, gender, treatment and disease course including all subsequent resections or cystectomy, and status of nodal or metastatic disease. Recurrence (subsequent resections with T1 or higher), progression (presence of T2 or higher or nodal/metastatic disease), and rates of cystectomy were compared using Fisher's exact and chi-square tests. RESULTS A total of 105 patients met inclusion criteria. The male:female ratio was 3.4:1, and median age was 74. Twenty patients had TADM (group 1), and 85 patients did not have TADM (group 2). Disease recurrence was higher in group 1 (15 of 20, 75%) compared to group 2 (32 of 85, 37%), p=0.005. Disease progression was higher in group 1 (14 of 20, 70%) compared to group 2 (19 of 85, 22%), p=0.04. Rates of lymph node positive disease at cystectomy or development of metastatic disease were significantly higher in group 1 (8 of 20, 40%) than in group 2 (9 of 85, 10%), p=0.003. The cystectomy rate was higher in group 1 than group 2, although the difference was not statistically significant [group 1: 8 of 20 (40%) vs group 2: 22 of 85 (25%), p=0.09]. CONCLUSIONS This retrospective analysis of T1 disease in TURB specimens showed that LP invasion with TADM is associated with higher rates of disease recurrence and progression to muscle invasion or nodal/metastatic disease. This means of subclassifying T1 bladder cancers is not affected by tissue orientation, variations in LP depth or presence of a muscularis mucosa layer, and may be a better prognostic tool. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e667 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Mahmut Akgul More articles by this author Bream Matthew More articles by this author Nafiseh Janaki More articles by this author Hammad Tashkandi More articles by this author Lee Ponsky More articles by this author Gregory MacLennan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

ObjectiveTo evaluate the clinical significance of lymphovascular invasion (LVI) on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.MethodsThis retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS) and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.ResultsLVI was detected in a total of 34 patients (21.9%). While LVI was associated with high-grade tumors (P<0.001) and intravesical therapy (P=0.009). Correlations with age (P=0.227), sex (P=0.376), tumor size (P=0.969), tumor multiplicity (P=0.196), carcinoma in situ (P=0.321), and smoking (P=0.438) were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of recurrence. The hazard ratios (95% confidence interval) were 2.042 (1.113–3.746, P=0.021), 1.817 (1.014–3.256, P=0.045), and 2.079 (1.172–3.687, P=0.012), respectively.ConclusionThe presence of LVI in transurethral resection of bladder tumor specimens is significantly associated with higher recurrence rate and shorter RFS time in patients with newly diagnosed T1 urothelial carcinoma of the bladder. It is an independent prognostic predictor for disease recurrence. Thus, patients with LVI should be followed up closely.

Does desmin immunohistochemistry have a role in assessing stage of urothelial carcinoma in transurethral resection of bladder tumor specimens?

Context: Pathological stage is the most important determinant of clinical outcome of bladder carcinoma patients. pT 1 carcinoma is defined by invasion into lamina propria, including muscularis mucosae (MM), but not into muscularis propria (MP) (pT 2 ). However, pathological staging of the tumor is a complicated task for pathologists. Splitting of MP or hypertrophy of MM caused by tumor invasion are important causes of interpretation subjectivity leading to intra-pathologist variation and disagreement. The aim of the study was to prospectively evaluate the utility of desmin immunohistochemical expression for evaluation of muscle invasion in transurethral resection of bladder tumor (TURBT) specimens. Materials and Methods: A total of 40 TURBT cases was taken. Specimens were processed, stained with H and E, graded and evaluated to determine whether MP invasion was present. Desmin immunohistochemistry (IHC) was used to assess muscle invasion and compare the result with H and E stained sections. Tumors with radiological evidence of gross invasion and those of stage T is were excluded. Results: Among 40 TURBT cases, there were 37 cases of transitional cell carcinoma. Among them, 17 were high grade and 20 were low grade. On H and E, 17/37 cases showed MP invasion, 8/37 cases showed no MP invasion and the rest 12/37 had questionable MP invasion. Desmin staining intensity was graded from 0 to 3+. MM showed negative (0) and moderate (2+) staining in one case each, mainly (35/37) showed mild (1+) staining intensity. MP showed moderate (2+) (3/37) to strong (3+) (34/37) staining intensity. Among 12/37 questionable cases (on H and E) desmin staining showed definite MP invasion in eight cases. Conclusions: Although morphology remains the gold standard, desmin IHC has diagnostic utility in the evaluation of questionable MP invasion and hence in staging of urothelial carcinoma.

Expression of Nucleoside Transporters and Deoxycytidine Kinase Proteins in Muscle Invasive Urothelial Carcinoma of the Bladder: Correlation with Pathological Response to Neoadjuvant Platinum/Gemcitabine Combination Chemotherapy

In pancreatic cancer, deoxycytidine kinase and the human equilibrative nucleoside transporter 1 have been validated as predictive markers for benefit from gemcitabine therapy. Gemcitabine is used with cisplatin or carboplatin as neoadjuvant chemotherapy for muscle invasive urothelial cancer of the bladder before radical cystectomy and patients rendered disease-free at surgery tend to have better outcomes. In this trial we examined if nucleoside transporter or deoxycytidine kinase protein abundance in biopsy specimens before chemotherapy is related to the response to neoadjuvant chemotherapy. A total of 62 consecutive patients undergoing neoadjuvant chemotherapy with platinum/gemcitabine at a single institution were accrued. Initial transurethral resection of bladder tumor specimens and cystectomy specimens were collected, and scored for nucleoside transporter and deoxycytidine kinase expression. Pathological response rates and survival data were collected. Of the 62 patients 17 (27%) achieved a complete pathological response (pT0) to neoadjuvant chemotherapy. Nucleoside transporter and deoxycytidine kinase protein expression in the transurethral resection of bladder tumor specimens did not predict for pT0 status to neoadjuvant chemotherapy. Median overall survival was not reached for the group achieving pT0 status and was 46 months for those with persistent cancer at definitive surgery (p = 0.07). Median followup for the cohort was 30 months. Nucleoside transporter and deoxycytidine kinase expression in transurethral resection of bladder tumor samples do not predict for response to gemcitabine and platinum neoadjuvant chemotherapy. Patients should continue to be offered neoadjuvant chemotherapy before radical cystectomy based on clinical and pathological staging.

Does the presence of muscularis propria on transurethral resection of bladder tumour specimens affect the rate of upstaging in cT1 bladder cancer?

OBJECTIVE • To determine how the presence of MP on T1 biopsy specimens affects the outcome of patients undergoing RC as compared to when no MP is identified in the TURBT specimen. • Patients were retrospectively identified from the Columbia University Urologic Oncology Database. • From January 1986 to October 2009, 114 patients diagnosed with cT1N0M0 bladder cancer who underwent RC within 4 months of their last biopsy were identified. • Patients were stratified based on the presence of MP on T1 biopsy, and upstaging was defined as any tumor T2 or greater, N+, or M+ at the time of radical cystectomy. • The rate of upstaging was assessed using univariate and multivariate regression models; Kaplan meier curves were also extrapolated for each cohort to compare disease specific and overall survival patterns. • Of the 114 patients evaluated in this study, 24 (20.2%) did not have MP on their T1 biopsy before RC. The rate of upstaging (>=pT2) stratified by the presence of MP on biopsy was 50% and 78%, respectively (p = 0.017). • On univariate analysis, lack of MP on biopsy was associated with an increased risk of upstaging (HR 3.52, p = 0.021, CI 1.2-10.3), however did not reach significance as an independent predictor (HR 2.9, p = 0.056, CI 0.97-8.9). • At a mean follow-up of 33.5 months, there was no difference in disease specific (p = 0.41) and overall survival (p = 0.68) between groups. • The lack of MP on TURBT for high grade cT1N0M0 bladder cancer portends a high likelihood of upstaging at RC, although this risk did not translate into a detectable increased risk of disease specific mortality.