Next-generation sequencing reveals potential predictive biomarkers and targets of therapy for urothelial carcinoma in situ of the urinary bladder.

Next-generation sequencing reveals potential predictive biomarkers and targets of therapy for urothelial carcinoma in situ of the urinary bladder. Am J Pathol. 2019 Nov 14;: Authors: Garczyk S, Ortiz-Brüchle N, Schneider U, Lurje I, Guricova K, Gaisa NT, Lorsy E, Lindemann-Docter K, Heidenreich A, Knüchel R Abstract Bacillus Calmette-Guérin instillation following removal of the tumor is the first-line of treatment for urothelial carcinoma in situ (CIS), the precursor lesion of most muscle-invasive bladder cancers. Bacillus Calmette-Guérin therapy fails in>50% of cases and second-line radical cystectomy is associated with overtreatment and drastic lifestyle consequences. Given the need for alternative bladder-preserving therapies, we identified genomic alterations (GAs) in urothelial CIS having the potential to predict response to targeted therapies. Laser-capture microdissection was applied to isolate 30 samples (25 CIS and five muscle controls) from 26 fresh-frozen cystectomy specimens. Targeted next-generation sequencing of 31 genes was performed. The panel comprised genes frequently affected in muscle-invasive bladder cancer of non-papillary origin, focusing on potentially actionable GAs described to predict response to approved targeted therapies or drugs that are in registered clinical trials. Ninety-two percent of CIS patients harbored at least one potentially actionable GA, which were were identified in TP53/cell cycle p...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research

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SummaryA  substantial increase in the number of elderly patients with muscle invasive bladder cancer (MIBC) is expected in upcoming years due to demographic changes and the peak incidence of bladder cancer in the 8th decade of life. The management of these patients is mainly driven by chronological age, co morbidities, tumor characteristics (unifocality, multifocality, concomitant carcinoma in situ, depth of invasion) and the presence of tumor-related symptoms (hematuria, pain, bladder dysfunction). A potential algorithm for the treatment of elderly patients with MIBC is presented. Ideally these pati ents ar...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
Bacillus Calmette-Gu érin instillation following removal of the tumor is the first-line of treatment for urothelial carcinoma in situ (CIS), the precursor lesion of most muscle-invasive bladder cancers. Bacillus Calmette-Guérin therapy fails in>50% of cases and second-line radical cystectomy is associated with overtreatment and drastic lifestyle consequences. Given the need for alternative bladder-preserving therapies, we identified genomic alterations (GAs) in urothelial CIS having the potential to predict response to targeted therapies.
Source: American Journal of Pathology - Category: Pathology Authors: Tags: Regular Article Source Type: research
CONCLUSIONS: The presence of detrusor muscle in TURB specimen, the absence of concomitant carcinoma in situ and the en-bloc resection were able to predict a negative histology at re-TURB, opening the door to the possibility to avoid it in an extremely well-selected cohort of patients. External validations and prospective studies are urgently needed. PMID: 31526650 [PubMed - as supplied by publisher]
Source: Urologic Oncology - Category: Urology & Nephrology Authors: Tags: Urol Oncol Source Type: research
ConclusionOur study showed no differences in per-patient tumour detection between WLI and NBI. Although NBI has significant benefits for detecting individual lesions overlooked by WLI-cystoscopy, this did not positively affect recurrence-free survival after transurethral resection.
Source: World Journal of Urology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 20 August 2019Source: European UrologyAuthor(s): Marko Babjuk, Maximilian Burger, Eva M. Compérat, Paolo Gontero, A. Hugh Mostafid, Joan Palou, Bas W.G. van Rhijn, Morgan Rouprêt, Shahrokh F. Shariat, Richard Sylvester, Richard Zigeuner, Otakar Capoun, Daniel Cohen, José Luis Dominguez Escrig, Virginia Hernández, Benoit Peyronnet, Thomas Seisen, Viktor SoukupAbstractContextThis overview presents the updated European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS).ObjectiveTo provide ...
Source: European Urology - Category: Urology & Nephrology Source Type: research
Urothelial carcinoma in situ (CIS) is a high-grade noninvasive malignancy with a high tendency of progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Urothelial CIS is histologically characterized by replacement of the urothelium by cells which fulfill the morphologic criteria of malignancy including nuclear pleomorphism, hyperchromasia, prominent nucleoli, and increased numbers of normal and abnormal mitoses. Urothelial CIS may be categorized as primary when it is not associated with any past or present urothelia...
Source: Advances in Anatomic Pathology - Category: Pathology Tags: Review Articles Source Type: research
This study aimed at determining the relationship between classification according to the papillary tumor pattern of carcinoma in situ (CIS) of the bladder and prognosis, as this has not yet been well established.MethodsThis study comprised a consecutive cohort of 254 patients (primary CIS: 66 patients, stage Ta-CIS: 52 patients, and stage T1-CIS: 136 patients) with CIS-associated bladder cancer. We classified CIS according to the pathological pattern of papillary tumors and analyzed prognostic factors, including CIS classification, for progression. We evaluated progression using two endpoints: infiltrative tumors detected ...
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
áñez José Luis Ruiz-Cerdá Patients with non-muscle invasive bladder cancer (NMIBC) undergo lifelong monitoring based on repeated cystoscopy and urinary cytology due to the high recurrence rate of this tumor. Nevertheless, these techniques have some drawbacks, namely, low accuracy in detection of low-grade tumors, omission of pre-neoplastic lesions and carcinomas in situ (CIS), invasiveness, and high costs. This work aims to identify a urinary metabolomic signature of recurrence by proton Nuclear Magnetic Resonance (1H NMR) spectroscopy for the follow-up of NMIBC patients. To do this, chang...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
The live attenuated mycobacterial strain BCG, in use as vaccine against tuberculosis, is considered the gold standard for primary therapy of carcinoma in situ of the bladder. Despite its limitations, to date it has not been surpassed by any other treatment. Our group has developed a recombinant BCG strain expressing the detoxified S1 pertussis toxin (rBCG-S1PT) that proved more effective than wild type BCG (WT-BCG) in increasing survival time in an experimental mouse model of bladder cancer, due to the well-known adjuvant properties of pertussis toxin. Here, we investigated the capacity of rBCG-S1PT to stimulate human immu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsThese findings provide strong evidence that the systemic administration of an immunocytokine consisting of a tumor-targeting Ig through recognition of DNA and DNA-histone complexes coupled to muIL-12 can effectively target the bladder TME; this significantly reduces the myeloid cellular compartment and reverts an immunosuppressive to an immunopermissive TME, ultimately resulting in antitumor effects. These studies provide further rationale for the employment of NHS-IL12 as an immunomodulator and clinical immunotherapeutic for NMIBC.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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