Non-muscle Invasive Urothelial Carcinoma Research Articles

1974P A phase II trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder

1974P A phase II trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder

Sequential Endoluminal Gemcitabine and Cabazitaxel with Intravenous Pembrolizumab as a Bladder-Preserving Strategy for Docetaxel-Unresponsive Non-Muscle Invasive Urothelial Carcinoma Following Transurethral Resection of Bladder Tumor.

Growing evidence suggests that many patients with high-risk non-muscle invasive urothelial carcinoma (NMIUC) can undergo bladder-sparing management with salvage intravesical therapies. However, inherent or developed disease resistance, particularly after multiple lines of prior salvage therapy, implores the continued pursuit of new treatment combinations. Herein, we describe the outcomes of 26 patients (31 treated units; 24 lower tract, 7 upper tract) with high-risk NMIUC treated with sequential intravesical gemcitabine and cabazitaxel with concomitant intravenous pembrolizumab (GCP) at the University of Iowa from August 2020 to February 2023. Median (IQR) follow-up was 30 (IQR: 17-35) months. Treated units had a history of high-risk NMIUC with a median of four prior endoluminal inductions. Overall, 87% of units presented with CIS or positive urine cytology. The 1- and 2-year recurrence-free survival was 77% (CI: 58-88%) and 52% (CI: 30-70%), respectively. The 2-year progression-free and cancer-specific survival was 70% (CI: 44-85%) and 96% (CI: 75-99%), respectively. In total, 22/26 (85%) patients reported any adverse event and 5/26 (19%) reported a grade ≥3 adverse event; however, all patients tolerated a full induction course. These results suggest that GCP is an effective and tolerable treatment option for patients with recurrent high-risk NMIUC.

A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder.

Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as second-line therapy for patients with bacillus Calmette-Guérin (BCG)‒unresponsive nonmuscle-invasive urothelial carcinoma of the bladder (NMIBC). In the context of widespread BCG shortages, we performed a phase 2 prospective trial to assess GemDoce for BCG-naïve NMIBC. This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response, and key secondary end points included adverse events (AEs) and 12-month recurrence-free survival. Twenty-five patients were enrolled between August 2020 and August 2022 with median follow-up of 19.6 months. The pretreatment pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3). The 3-month complete response rate was 100% and recurrence-free survival at 12 months was 92%. Two patients with pretreatment HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had any radiographic evidence of progressive disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a grade 3 AE including hematuria and UTI. In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.

Prediction of Non-Muscle Invasive Papillary Urothelial Carcinoma Relapse from Hematoxylin-Eosin Images Using Deep Multiple Instance Learning in Patients Treated with Bacille Calmette-Guérin Immunotherapy.

The limited reproducibility of the grading of non-muscle invasive papillary urothelial carcinoma (NMIPUC) necessitates the search for more robust image-based predictive factors. In a cohort of 157 NMIPUC patients treated with Bacille Calmette-Guérin (BCG) immunotherapy, we explored the multiple instance learning (MIL)-based classification approach for the prediction of 2-year and 5-year relapse-free survival and the multiple instance survival learning (MISL) framework for survival regression. We used features extracted from image patches sampled from whole slide images of hematoxylin-eosin-stained transurethral resection (TUR) NPMIPUC specimens and tested several patch sampling and feature extraction network variations to optimize the model performance. We selected the model showing the best patient survival stratification for further testing in the context of clinical and pathological variables. MISL with the multiresolution patch sampling technique achieved the best patient risk stratification (concordance index = 0.574, p = 0.010), followed by a 2-year MIL classification. The best-selected model revealed an independent prognostic value in the context of other clinical and pathologic variables (tumor stage, grade, and presence of tumor on the repeated TUR) with statistically significant patient risk stratification. Our findings suggest that MISL-based predictions can improve NMIPUC patient risk stratification, while validation studies are needed to test the generalizability of our models.

Proliferation and immunohistochemistry for p53, CD25 and CK20 in predicting prognosis of non-muscle invasive papillary urothelial carcinomas.

Non-muscle invasive papillary urothelial carcinoma is a prevalent disease with a high recurrence tendency. Good prognostic and reproducible biomarkers for tumor recurrence and disease progression are lacking. Currently, WHO grade and tumor stage are essential in risk stratification and treatment decision-making. Here we present the prognostic value of proliferation markers (Ki67, mitotic activity index (MAI) and PPH3) together with p53, CD25 and CK20 immunohistochemistry (IHC). In this population-based retrospective study, 349 primary non-muscle invasive bladder cancers (NMIBC) were available. MAI and PPH3 were calculated manually according to highly standardized previously described methods, Ki-67 by the semi-automated QPRODIT quantification system, p53 and CD25 by the fully automated digital image analysis program Visipharm® and CK20 with the help of the semi-quantitative immunoreactive score (IRS). Survival analyses with log rank test, as well as univariate and multivariate Cox regression analyses were performed for all investigated variables. Age and multifocality were the only significant variables for tumor recurrence. All investigated variables, except gender, were significantly associated with stage progression. In multivariate analysis, MAI was the only prognostic variable for stage progression (p<0.001).

Granulomatous myocarditis arising from intravesical Bacillus Calmette–Guérin therapy leading to death diagnosed by postmortem examination: a case report

BackgroundIntravesical Bacillus Calmette–Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach.Case presentationWe present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus.ConclusionGranulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.

Human epidermal growth factor receptor 2/neu expression in urothelial carcinomas.

Urothelial carcinomas of the bladder are more common in males, making them the sixth-most common cancer in men and the tenth-most common cancer overall, worldwide. Current guidelines do not recommend routine testing for human epidermal growth factor receptor (HER2/neu) expression on the biopsy specimens of patients with urothelial carcinoma. This study was aimed at determining the expression pattern of HER2/neu and its usefulness in muscle-invasive and nonmuscle-invasive urothelial carcinoma. HER2/neu expression was assessed in 89 specimens of urothelial cancer by immunohistochemistry (IHC), and equivocal cases were subjected to fluorescent in situ hybridization (FISH). On IHC for HER2/neu, 17.9% (7/39) of the muscle-invasive bladder cancers (MIBCs) showed a 3+ expression, whereas 22% (11/50) of the non-muscle invasive cancers were positive with a score of 3+. A significant correlation between HER2/neu status and muscle invasion could not be established in the current study (P = 0.74, Fisher's exact test). Three cases of muscle-invasive (7.7%) and 2 cases (4%) among nonmuscle invasive cancers showed equivocal expression. All the cases with equivocal (2+) expression on IHC were subjected to FISH and none showed gene amplification on hybridization and were considered as negative. Overexpression of HER-2/neu was seen in 17.9% of MIBCs and 22% of non-MIBCs. There are no norms for routine testing of HER2/neu expression in the biopsy specimens of urothelial carcinoma. There is an unmet need to establish guidelines for HER2/neu scoring, similar to that for breast and gastric cancers, to determine the proportion of positive cases and help in identification of those who may benefit from targeted therapies.

Endoscopic excision versus radical nephroureterectomy for non-muscle invasive upper tract urothelial carcinoma: A population-based large cohort study

BackgroundAs an important kidney-sparing treatment for upper urothelial carcinoma (UTUC), whether endoscopic excision can be performed without sacrificing oncologic outcomes remains indefinite. This study aimed to investigate the prevalence and efficacy of endoscopic excision, in patients with non-muscle invasive UTUC (NMIUTUC) and compare them to those of radical nephroureterectomy (RNU). MethodsUsing the Surveillance, Epidemiology, and End Results database, we reviewed 4347 cases with NMIUTUC (cTis/Ta/T1-N0-M0,≤ 5.0 cm) between 2004 and 2020. Surgical treatment modalities included endoscopic excision and RNU. Propensity score matching analysis was used to minimize the selection bias between endoscopic excision and RNU, selecting 1:1 matched patients in the two group. ResultsA total of 794 patients with NMIUTUC were included after matching (397:397). Patients who underwent endoscopic excision had worse survival outcomes compared with those of patients who underwent RNU (5-year OS: 65.3 % vs. 80.3 %, p < 0.0001; 5-year DSS: 83.2 % vs. 94.0 %, p = 0.00021). After stratification by anatomical sites, the effect of endoscopic excision for NMI renal pelvis cancer was worse than RNU (5-year OS, 62.9 % vs. 82.8 %; 5-year DSS, 78.8 % vs. 91.6 %), while in NMI ureteral cancer, there is no statistically significant difference in OS and DSS between endoscopic excision and RNU. Further stratification according to tumor grade revealed equivalent tumor control effects of endoscopic excision and RNU in low-grade NMI ureteral cancer (5-year OS: 67.7 % vs. 72.5 %, p = 0.23; 5-year DSS: 87.2 % vs. 93.1 %, p = 0.17); while for renal pelvis tumor and high-grade ureteral tumor, endoscopic excision was related with significantly inferior prognosis. ConclusionsOnly for low-grade NMI ureteral cancer, endoscopic excision and RNU are oncologically equivalent, indicating that endoscopic excision might be an effective option for low-grade NMI ureteral cancer. This result needs to be further verified in randomized controlled trials.

A Novel Approach to Intraluminal Mitomycin C Instillation for Treatment of High Grade Nonmuscle Invasive Upper Tract Urothelial Carcinoma

Abstract Introduction and Objective: We present a novel technique for intrapelvicalyceal mitomycin C (MMC) instillation mixed with a contrast agent for treatment of high-grade nonmuscle invasive upper tract urothelial carcinoma in patients in whom nephroureterectomy would render them dialysis-dependent. Methods: After incomplete endoscopic resection, the patient underwent 3 intrapelvicalyceal instillations of MMC mixed with iopamidol, each 2 weeks apart. Results: Treatment has had a durable response for over 2 years after treatment. Conclusions: Intraluminal MMC mixed with iopamidol is an approach which helps to avoid pyelovenous backflow and provides visual confirmation that the drug is in adequate contact with the tumor.

Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy.

The treatment of metastatic urothelial carcinoma has dramatically changed over the past decade with the approval of several therapies from multiple drug classes including immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although next generation sequencing of urothelial carcinoma has revealed multiple recurring mutations, only one targeted therapy has been developed and approved to date. Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has been approved for treating patients with select FGFR2 and FGFR3 alterations and fusions since 2019. Since then, emerging data has demonstrated efficacy of combining erdafitinib with immunotherapy in treating FGFR-altered urothelial carcinoma. Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.

Ureteroureteral Fistula as a Rare Complication of Ileal Conduit Urinary Diversion: a Case Report

Long-term studies on ileal conduit have shown a complication rate of up to 66%. Fistulas are a rare late complication of ileal conduit. To our knowledge, no data about ureteroureteral fistulas has been published yet. We present the case of a 73-year-old man with non-muscle invasive high-grade urothelial carcinoma of the bladder who failed to BCG due to intolerance and developed a cripple bladder. He underwent a cystoprostatectomy, pelvic lymphadenectomy, and an ileal conduit urinary diversion. Four months after the surgery, a raised creatinine level was discovered. Sonography revealed bilateral hydro-ureteronephrosis. Shortly after, the stomal urinary production became minimal, and a nephrostomy was introduced to the right kidney. As a result, the right- as well as the left-sided hydronephrosis diminished, as assessed by ultrasound. Through a loopogram and anterograde pyelography, a stenosis at the ureteroileal anastomosis as well as a connection between the two ureters was proven. As an endoscopic intervention to resolve the obstruction failed, a re-laparotomy to make a neo-anastomosis from the ureters to the ileal conduit was performed. We suspect that total obliteration of the oral end of the ileal conduit caused fistula formation of the ureters. We would like to address this rare phenomenon as a complication of ileal conduit to be mentioned in the differential diagnosis if the outcome of urine is in question. It is not a simple stenosis of the distal portion of the ureters and demands an adapted surgical reconstructing technique as well.

Phase 2 trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder.

TPS4616 Background: For patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacille Calmette-Guerin (BCG), multi-agent intravesical trials have been limited. The goal of this Phase 2 study is to investigate the efficacy of intravesical chemotherapy consisting of sequential cabazitaxel, gemcitabine, and cisplatin (CGC) in the salvage setting. Phase 1 results reporting on 18 subjects demonstrated adverse events limited to local Grade 1 and 2 toxicities. Partial funding support for the trial was provided by a pharmaceutical company. Methods: This is a Phase 2 trial (NCT02202772) presently enrolling patients with BCG unresponsive NMIBC as defined by the FDA who refuse or are ineligible for radical cystectomy. All patients undergo pre-treatment transurethral resection of bladder tumor (TURBT) and a 6-week regimen of intravesical cisplatin (100mg), gemcitabine (2gm), and cabazitaxel (5mg). Each drug is instilled weekly except for cisplatin, which is given every other week. Complete response is defined as having no evidence of cancer on post-induction biopsy and negative urine cytology at 3 months. Complete responders proceed with monthly and bimonthly maintenance therapy without cisplatin in the first and second years, respectively, for a total of 24 months. Results: To date thirty-one patients have been enrolled (with target accrual of 33), of whom seven are female. One patient withdrew consent before first evaluation cystoscopy. Mean age thus far is 72 years. All patients have previously received at least two prior induction cycles of BCG, and meet FDA criteria for BCG unresponsive disease. All patients have biopsy proven high grade disease at enrollment; 8 (27%) have high grade T1 disease; and 20 (67%) patients have CIS. Conclusions: Salvage options for BCG unresponsive NMIBC are limited. The CGC protocol has been demonstrated to be safe in a previous Phase 1 study, and accrual for this Phase 2 is near completion. Clinical trial information: NCT02202772 .

UriFind assay and association with whole course management of urothelial carcinoma in a large multicentric, prospective China cohort.

e16588 Background: The gold standard to diagnose and monitor urothelial carcinoma is cystoscopy, which is invasive and painful. The currently available non-invasive methods to detect urothelial carcinoma are either of unsatisfying sensitivity or limited specificity in China. Previously, a DNA methylation assay, termed UriFind, was developed, and showed a compelling sensitivity and specificity in a retrospective cohort. This study aimed to further validate its performance in a large multicentric, prospective China cohort. Methods: Patients involved in the whole course of UC management were recruited in this cohort. The cohort contained 931 patients diagnosed with urothelial carcinoma (UC), and 994 controls with benign diseases and 78 healthy participants from 12 hospitals across China. Urine samples were collected before the therapy, and analyzed with quantitative PCR of ONECUT2 and VIM methylation (UriFind), FISH and urinary cytology. Sensitivity, specificity, accuracy, PPV and NPV of these assays were evaluated as compared to the diagnostic gold standard of cystoscopy, histology results or clinical diagnosis. Results: The UC group of the cohort consisted of 683 non-muscle invasive UC (73.4%), 203 muscle invasive UC (21.8%) and 45 unavailable stage (4.8%). The patients of low, high-grade UC and unavailable grade were 244(26.2%), 651(69.9%) and 36 (3.9%), respectively. Overall sensitivity, specificity, accuracy, PPV and NPV of UriFind was 82.3%, 91.2%, 87.3%, 88.1% and 86.7%, respectively. The specificity of healthy participants was 100%. The overall sensitivity and accuracy of UriFind were significantly higher than urine cytology (40% and 55.7%) and FISH (68.2% and 73.6%), while the specificity was similar to cytology (93.9%) and FISH (87.3%). Importantly, UriFind achieved a great improvement of sensitivity in whole course management, including low grade tumor (56.1%), small and single tumor (63.3%), residual tumor after therapy (71.4%) and recurrent tumor (84.3%). Conclusions: The performance of UriFind is well validated with significantly higher sensitivity and accuracy than urine cytology and FISH in UC detection in this cohort with 2003 cases. This assay facilitates whole course management of urothelial carcinoma, which may reduce the burden of cystoscopy and unnecessary second TURBT. Clinical trial information: NCT04314245 .

International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer. Working Group 1: Comparison of Bladder Cancer Grading System Performance.

Grade is a key prognostic factor in determining progression in nonmuscle invasive papillary urothelial carcinomas. The 2 most common grading methods in use worldwide are the World Health Organization (WHO) 2004 and 1973 schemes. The International Society of Urological Pathology (ISUP) organized the 2022 consensus conference in Basel, Switzerland on current issues in bladder cancer and tasked working group 1 to make recommendations for future iterations of bladder cancer grading. For this purpose, the ISUP developed in collaboration with the European Association of Urology a 10-question survey for their memberships to understand the current use of grading schemes by pathologists and urologists and to ascertain the areas of potential improvements. An additional survey was circulated to the ISUP membership for their opinion on interobserver variability in grading, reporting of urine cytology, and challenges encountered in grade assignment. Comprehensive literature reviews were performed on bladder cancer grading prognosis and interobserver variability along with The Paris System for urine cytology. There are notable differences in practice patterns between North American and European pathologists in terms of used grading scheme and diagnosis of papillary urothelial neoplasm of low malignant potential. Areas of common ground include difficulty in grade assignment, a desire to improve grading criteria, and a move towards subclassifying high-grade urothelial carcinomas. The surveys and in-person voting demonstrated a strong preference to refine current grading into a 3-tier scheme with the division of WHO 2004 high grade into clinically relevant categories. More variable opinions were voiced regarding the use of papillary urothelial carcinoma with low malignant potential.

MP63-07 SEQUENTIAL ENDOLUMINAL DOXORUBICIN AND GEMCITABINE ALTERNATING WITH SEQUENTIAL MITOMYCIN AND DOCETAXEL FOR MULTI-FAILURE NON-MUSCLE INVASIVE UROTHELIAL CARCINOMA OF THE UPPER AND LOWER URINARY TRACTS

You have accessJournal of UrologyCME1 Apr 2023MP63-07 SEQUENTIAL ENDOLUMINAL DOXORUBICIN AND GEMCITABINE ALTERNATING WITH SEQUENTIAL MITOMYCIN AND DOCETAXEL FOR MULTI-FAILURE NON-MUSCLE INVASIVE UROTHELIAL CARCINOMA OF THE UPPER AND LOWER URINARY TRACTS Ian M. Mcelree, Ryan L. Steinberg, Sarah L., Vignesh T. Packiam, and Michael A. O'Donnell Ian M. McelreeIan M. Mcelree More articles by this author , Ryan L. SteinbergRyan L. Steinberg More articles by this author , Sarah L. Sarah L. More articles by this author , Vignesh T. PackiamVignesh T. Packiam More articles by this author , and Michael A. O'DonnellMichael A. O'Donnell More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Sequential intravesical gemcitabine and docetaxel (Gem/Doce) has shown over 50% 2-year high-grade (HG) recurrence free survival in patients with BCG-unresponsive non-muscle invasive urothelial carcinoma (NMIUC) of the bladder. For those who recur, further bladder-sparing therapies are needed, particularly when cystectomy is refused or precluded. We report outcomes of patients treated with a novel regimen of sequential doxorubicin and gemcitabine alternating with sequential mitomycin C and docetaxel (Quad Chemo) as a rescue therapy for patients with recurrent high-grade (HG) NMIUC. METHODS: We retrospectively reviewed 27 patients (37 treated units; 27 lower tract, and 10 upper tract) treated with Quad Chemo from December 2007 to February 2021. Patients received 8 induction endoluminal instillations of sequential 50 mg doxorubicin and 1 g gemcitabine alternating weekly with sequential 40 mg mitomycin C and 37.5 mg docetaxel. Alternating monthly maintenance treatment was administered up to 24 months if disease free at 3-month surveillance. The primary outcome was recurrence-free survival (RFS) defined as no disease on bladder/upper tract wash cytology or for-cause biopsies. Progression events included development of muscle-invasive or metastatic disease and any death due to bladder cancer. Adverse events were reported per CTCAE v.5. RESULTS: Median follow-up was 36 months. Patients with lower tract disease had a median of 3 prior inductions and upper tract 1 prior induction course. Stage at induction was pure CIS or positive cytology in 29 (78%) units, CIS+papillary in 5 (14%), and pure HG papillary in 1 (2.7%). Two (5.4%) upper tract units received Quad Chemo following a suspicious cytology. Among all treated units, the 2-year RFS rate was 38%. If disease-free at first follow-up, median duration of response was 30 months. The 2-year cystectomy-free, progression-free, and cancer-specific survival rates were 82%, 87%, and 96%, respectively. Regarding adverse events, 7.4% (2/27) of patients had a grade 3 event, including bladder stone development, bladder ulceration, and de-novo hydronephrosis. 67% (18/27) of patients experienced a grade 1-2 event. Induction treatment was ended in 11% (3/27) of patients due to side effects. CONCLUSIONS: Quad Chemo shows efficacy in a heavily pretreated HG NMIUC cohort but with a more severe side effect profile. Further prospective evaluation is needed for this regimen and to evaluate the boundaries of intravesical therapy. Source of Funding: This work was supported by the John & Carol Walter Family Foundation and the Cancer Center Support Grant © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e873 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ian M. Mcelree More articles by this author Ryan L. Steinberg More articles by this author Sarah L. More articles by this author Vignesh T. Packiam More articles by this author Michael A. O'Donnell More articles by this author Expand All Advertisement PDF downloadLoading ...

MP63-18 UriFIND ASSAY FACILITATES WHOLE COURSE MANAGEMENT OF UROTHELIAL CARCINOMA IN A LARGE MULTICENTRIC, PROSPECTIVE CHINA COHORT

MP63-18 UriFIND ASSAY FACILITATES WHOLE COURSE MANAGEMENT OF UROTHELIAL CARCINOMA IN A LARGE MULTICENTRIC, PROSPECTIVE CHINA COHORT

CD8+ Cell Density Gradient across the Tumor Epithelium-Stromal Interface of Non-Muscle Invasive Papillary Urothelial Carcinoma Predicts Recurrence-Free Survival after BCG Immunotherapy.

Bacille Calmette-Guerin (BCG) immunotherapy is the first-line treatment in patients with high-risk non-muscle invasive papillary urothelial carcinoma (NMIPUC), the most common type of bladder cancer. The therapy outcomes are variable and may depend on the immune response within the tumor microenvironment. In our study, we explored the prognostic value of CD8+ cell density gradient indicators across the tumor epithelium-stroma interface of NMIPUC. Clinical and pathologic data were retrospectively collected from 157 NMIPUC patients treated with BCG immunotherapy after transurethral resection. Whole-slide digital image analysis of CD8 immunohistochemistry slides was used for tissue segmentation, CD8+ cell quantification, and the assessment of CD8+ cell densities within the epithelium-stroma interface. Subsequently, the gradient indicators (center of mass and immunodrop) were computed to represent the density gradient across the interface. By univariable analysis of the clinicopathologic factors, including the history of previous NMIPUC, poor tumor differentiation, and pT1 stage, were associated with shorter RFS (p < 0.05). In CD8+ analyses, only the gradient indicators but not the absolute CD8+ densities were predictive for RFS (p < 0.05). The best-performing cross-validated model included previous episodes of NMIPUC (HR = 4.4492, p = 0.0063), poor differentiation (HR = 2.3672, p = 0.0457), and immunodrop (HR = 5.5072, p = 0.0455). We found that gradient indicators of CD8+ cell densities across the tumor epithelium-stroma interface, along with routine clinical and pathology data, improve the prediction of RFS in NMIPUC.

Prognostic value of galectin-1 and galectin-3 expression in localized urothelial bladder cancer.

Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins with a wide range of biological activity, including regulation of cellular adhesion, proliferation, and apoptosis in solid tumors. Prior small studies have reported that Gal-3 expression is associated with progression of disease in urothelial carcinoma (UC), from non-muscle invasive UC progression to muscle invasive UC. We assessed Gal-1 and Gal-3 protein expression H-score utilizing a tissue microarray (TMA) created from 301 cystectomy specimens. Immunohistochemistry for Gal-1 and Gal-3 was performed on TMA generated from tumor blocks from chemotherapy naïve cystectomy specimens. The variable of interest, H-score, was defined as the product of the percentage of cells staining positive (0-100) and intensity score (0-3) scored by a single pathologist. Survival end points were analyzed using Kaplan-Meier and Cox Proportional Hazards methods. Clinical data including Charlson Comorbidity Index (CCI), pathologic tumor (T) stage, tumor size, node stage, and surgical margins, were included in multivariable analysis. We found that Gal-1 and Gal-3 expression correlated with intratumoral T stage (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, P<0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, P<0.01). However, the highest intratumoral H-score per cystectomy core did not independently predict for recurrence-free survival (RFS) (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.65) or OS (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.72) in this cohort. Significant intratumoral heterogeneity was present for both Gal-1 and Gal-3, with an average difference between the highest and lowest H score was 95 for Gal-1 and 109 for Gal-3 for cystectomy specimens with more than one biopsy. Gal-1 and Gal-3 H-score per bladder did not independently predict for RFS or OS. Intra-tumoral Gal-1/Gal-3 heterogeneity complicates the use of Gal-1 and Gal-3 expression as a prognostic biomarker. Future studies should consider the evaluation of serum and urinary galectins as an approach to mitigate tumor heterogeneity.

Role of magnetic resonance imaging in urinary bladder carcinoma: A tertiary care experience

Background: Bladder cancer is the most common malignancy of the urinary tract. Pre-operative tumour staging and grading play a significant role in treatment planning and prognosis estimation for bladder cancer. Aims and Objectives: This study aims to evaluate the utility of multiparametric-magnetic resonance imaging (mp-MRI) in detecting and staging bladder cancers and hence its role in final management. Materials and Methods: A total of 40 patients with documented urinary bladder mass undergoing mp-MRI before transurethral resection of bladder tumours for primary bladder cancer were identified and compared with post-operative histopathological reports. The data were collected and analysed using SPSS software. Results: The mean age in the study population was 53.68 ± 13.2 years, including 7 (17.5%) females and 33 (82.5%) males. Twenty-three (57.5%) of our patients had muscle invasion on the MRI pelvis. In muscle-invasive urothelial carcinoma, there were significantly more patients with Vesical Imaging-Reporting and Data System (VIRADS) 3, VIRADS 4 and VIRADS 5 than in non-muscle invasive urothelial carcinoma. The proportion of patients with VIRADS 1 and VIRADS 2 on MRI pelvis was significantly lower in muscle-invasive urothelial carcinoma than in non-muscle-invasive urothelial carcinoma (P = 0.0001). Histopathology and muscle invasion on the MRI pelvis agree well in the current study (κ = 0.742; P = 0.0001). There was an overall concordance rate of 87.5% and an overall discordance rate of 12.5% between histopathology and muscle invasion on the MRI pelvis. The sensitivity, specificity, area under the curve, positive predictive value, negative predictive value and diagnostic accuracy of the mp-MRI scan were 87.5%, 87.5%, 0.88, 91.3%, 82.35% and 87.50%, respectively. Conclusion: The mp-MRI and VIRADS scoring is an effective comprehensive tool with satisfactory sensitivity, specificity and diagnostic value for detecting muscle invasiveness of primary bladder cancer. We recommend VIRADS scoring for all bladder cancer patients for better pre-operative staging and overall management.

Oncological safety of simultaneous transurethral resection of high-grade urothelial carcinoma of the bladder and benign prostatic hyperplasia

ABSTRACT Objectives To examine the oncological safety of simultaneous resection of bladder tumor and prostate in the presence of non-muscle invasive high-grade urothelial carcinoma of the bladder (UCB). Materials and Methods Between 2007 and 2019, 170 men with high–grade UCB who had a follow-up of at least 12 months were included in the study, including 123 with transurethral resection of bladder tumor (TURBT) only and 47 with simultaneous TURBT and transurethral resection of the prostate (TURP). We recorded and compared patients' clinicopathological parameters, recurrence, and progression rates during the follow–up period, as well as time to UCB recurrence in the bladder and the prostatic urethra/fossa. Results Baseline demographic and pathological characteristics were comparable between the groups. At a median follow-up of 31 months in both groups, there were no significant differences in recurrence rates in the bladder and the prostatic urethra/fossa in either group (34.1% and 7.3% vs. 36.2 and 6.4%, p=0.402, p=0.363). No statistically significant differences were found between the two groups in terms of follow-up time, elapsed time to recurrence, or and progression in the bladder or prostatic urethra/fossa. Conclusions Simultaneous TURBT and TURP in the presence of high-grade UCB appears to be oncologically safe in selected patients.