Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-invasive Bladder Carcinoma

Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting. We enrolled 389 patients who underwent cisplatin-based chemotherapy before radical cystectomy in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in radical cystectomy specimens by local pathologists. Central pathology review was conducted in 20% of cases, which were randomly selected. The major response was defined as ≤pT1N0. The remaining patients were grouped into partial responders (≥ypT2N0-3 and TRG 2) and nonresponders (≥ypT2N0-3 and TRG 3). TRG was successfully determined in all cases, and interobserver agreement in central pathology review was high (κ=0.83). After combining TRG and TNM, 47%, 15%, and 38% of patients were major, partial, and nonresponders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of overall survival (major responder: reference; partial responder: hazard ratio 3.5 [95% confidence interval: 1.8-6.8]; nonresponder: hazard ratio 6.1 [95% confidence interval: 3.6-10.3]). This discrimination was superior compared with TNM staging alone, supported by 2 goodness-of-fit criteria (P=0.041). TRG is a simple, re...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research

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ConclusionsThe updated PURE-01 results confirm the activity of neoadjuvant pembrolizumab in MIBC. Patients with SCC and LEL features may be suitable for neoadjuvant immunotherapy trials. CPS and TMB are the key response predictors irrespective of the histological subtypes.Patient summaryIn the PURE-01 study, we have preliminarily evaluated the activity of neoadjuvant pembrolizumab in patients with predominant variant histology (VH). Of these patients, those harboring squamous-cell carcinoma or a lymphoepithelioma-like variant feature had major, although preliminary, pathological responses compared with those with other pre...
Source: European Urology - Category: Urology & Nephrology Source Type: research
Abstract OBJECTIVES: Overexpression of aurora kinase A (AURKA) confers a poor prognosis in patients with urothelial carcinoma of the bladder. The prognostic value of high aurora kinase B (AURKB) expression in local bladder cancer is not well defined, and whether the prognostic value of either AURKA or AURKB is affected by the use of chemotherapy is unknown. We sought to characterize the impact of high AURKA and AURKB expression on clinical outcome in patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Immunohistochemistry for AURKA and AURKB ...
Source: Urologic Oncology - Category: Urology & Nephrology Authors: Tags: Urol Oncol Source Type: research
Conclusion: Neoadjuvant chemotherapy utilization continues to slowly increase in patients with MIBC. Patients with variant histology lag behind in terms of receiving NAC but appear to derive as much benefit as patients with pure urothelial cell bladder cancer.
Source: Indian Journal of Urology - Category: Urology & Nephrology Authors: Source Type: research
CONCLUSIONS: The epithelial-mesenchymal transition phenotype and actin-cytoskeleton remodeling are associated with pathologic progression on NAC. Chemotherapy induced an mesenchymal-epithelial transition phenotype and decreased cofilin phosphorylation, providing new insights into therapeutic resistance mechanisms. Primary tumors with high apoptosis rates exhibited favorable response to NAC and lower mortality rates, indicating that these tumors may be sensitized to therapy. Further validation will establish these novel signatures as predictors of therapeutic response. PMID: 31326313 [PubMed - as supplied by publisher]
Source: Urologic Oncology - Category: Urology & Nephrology Authors: Tags: Urol Oncol Source Type: research
Publication date: Available online 11 July 2019Source: European UrologyAuthor(s): Filippo Pederzoli, Marco Bandini, Alberto Briganti, Elizabeth R. Plimack, Günter Niegisch, Evan Y. Yu, Aristotelis Bamias, Neeraj Agarwal, Srikala S. Sridhar, Cora N. Sternberg, Ulka N. Vaishampayan, Christine Théodore, Jonathan E. Rosenberg, Lauren C. Harshman, Joaquim Bellmunt, Matthew D. Galsky, Andrea Gallina, Andrea Salonia, Francesco Montorsi, Andrea NecchiAbstractThe availability of new potent systemic therapies for urothelial carcinoma may change the way we use standard chemotherapy perioperatively. In particular, identify...
Source: European Urology - Category: Urology & Nephrology Source Type: research
In this report, we present familial cases of urothelial carcinoma. To investigate the possibility of hereditary urothelial cancer, we performed semiconductor-based next-generation DNA sequencing. A woman in her 80s who had bladder and left ureteral cancer was hospitalized in Sapporo Shirakaba-dai Hospital due to consciousness disturbance. Radiographic evaluation revealed multiple liver metastases and she died 38  days later. Needle necropsy was done for a left ureteral tumor that continued to her bladder tumor and for liver metastases. At the same time, her son in his 60s, who also had muscle-invasive bladder cancer, ...
Source: International Cancer Conference Journal - Category: Cancer & Oncology Source Type: research
Bladder cancer is a highly prevalent disease throughout the world usually encountered in older patients, and associated with substantial morbidity, mortality, and cost. The treatment of bladder cancer has remained unchanged for the last several decades. However, in recent years the availability of comprehensive genomic data from The Cancer Genome Atlas and other large projects have considerably improved our understanding of the pathogenesis of these tumors. These studies demonstrated that bladder cancers can be grouped into 2 broad categories namely basal and luminal molecular subtypes with recognizable subgroups in each o...
Source: Advances in Anatomic Pathology - Category: Pathology Tags: Review Articles Source Type: research
AbstractNeoadjuvant cisplatin‐based chemotherapy (NAC; 70 mg/m2) is standard of care for muscle‐invasive bladder carcinoma (MIBC). Many patients (pts) cannot receive cisplatin because of renal impairment, and administration of cisplatin 35 mg/m2 on day 1 + 8 or 1 + 2 (i.e., split schedule) is a commonly used alternative. In this retrospective analysis, we compared complete (pT0) and partial (
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Genitourinary Cancer Brief Communications Source Type: research
Publication date: Available online 12 May 2019Source: European UrologyAuthor(s): Yair Lotan, Stephen A. Boorjian, Jingbin Zhang, Trinity J. Bivalacqua, Sima P. Porten, Thomas Wheeler, Seth P. Lerner, Ryan Hutchinson, Franto Francis, Elai Davicioni, Robert S. Svatek, Chun-Liang Chen, Peter C. Black, Ewan A. GibbAbstractBackgroundUpstaging of clinical T1-T2 urothelial carcinoma (UC) to non-organ-confined (NOC) pathological stage ≥T3 or N+ at radical cystectomy (RC) is common. Tools for stratifying patients who may have NOC disease are limited.ObjectiveTo determine an association of a genomic subtyping classifier (GSC) wit...
Source: European Urology - Category: Urology & Nephrology Source Type: research
ConclusionsIn carefully selected patients of GB NECs, downsizing with NACT facilitates radical resection with negative margins.
Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
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