CIS of the Bladder: Significance and Implications for Therapy

Abstract

Purpose of the review: To review the most recent literature with regards to the pathogenesis, diagnostics, clinical implications and treatment strategies for Carcinoma in Situ (CIS) of the Bladder. Recent findings: There have been advancements in understanding the genetic composition and biochemical behavior of CIS. Technological advancements including Photodynamic Diagnosis (PDD) with Hexaminolevulinate (HVA) better detect CIS compared to traditional white light (WL) cystoscopy. Recently published single and multi-center studies have enabled better understanding of the impact of CIS on clinical and cancer related outcomes, including disease recurrence and patient survival. Alternative intravesical chemotherapeutic and immunotherapies for CIS have been investigated, especially in the setting of Bacillus Calmette-Guerin (BCG) unresponsive disease. While these demonstrate a great deal of promise, they have not garnered much success. Summary: The genetics of CIS is linked to aggressive, and at times resistant disease, with increased cancer progression and associated clinically worse cancer specific outcomes. New technologies have enabled a more effective diagnosis of CIS. The development of a standardized definition for clinical trials and greater disease understanding will enable us to develop better treatment options.

NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022

“…21 If untreated, 50% of CIS progresses to muscleinvasive disease within 5 years and, even with treatment, 30% to 40% progresses within 10 years. 22 Pembrolizumab is a PD-1 inhibitor that has been evaluated as treatment for BCG-unresponsive NMIBC with CIS in the single-arm, phase II KEYNOTE-057 study (pembrolizumab is also indicated for treatment of metastatic urothelial carcinoma, as described later). In the KEYNOTE-057 study, 101 patients who received previous BCG therapy and were either unable or unwilling to undergo cystectomy were treated with pembrolizumab 23 ; 96 patients were eligible for inclusion in the efficacy analysis.…”

Low-Cost, Label-Free Blue Light Cystoscopy through Digital Staining of White Light Cystoscopy Videos

“…For example, early-stage bladder tumors have small papillary structures or appear as a velvety patch on the bladder wall. 25 Under a quick glance, these small tumors may be missed due to the lack of contrast in WLC or distracting inflammation in larger regions of the bladder. However, distinct texture features (such as the velvety, carpet-like mucosa) and small changes in tissue color that are not apparent to human eyes are detectable by the machine learning model.…”