Carcinoma in Situ of the Bladder: Why Is It Underdetected?

José D. Subiela; Óscar Rodr&ıacute; guez Faba; Félix Guerrero-Ramos; Julia Aumatell; Alberto Breda; Joan Palou


Curr Opin Urol. 2020;30(3):392-399. 

In This Article

Abstract and Introduction


Purpose of review: The standard diagnosis of carcinoma in situ (CIS) of the bladder, based on white light cystoscopy and urine cytology, is limited because CIS can vary from normal-appearing mucosa to a lesion indistinguishable from an inflammatory process. Intravesical instillation of Bacillus Calmette–Guerin (BCG) remains first-line therapy; however, a significant proportion of cases persist or recur after BCG treatment. This review summarizes recent improvements in the detection and treatment of CIS.

Recent findings: The new optical technologies improve CIS detection, with a potential positive impact on oncological outcomes. The usefulness of MRI-photodynamic diagnosis fusion transurethral resection in CIS detection is unclear and further studies are needed. BCG instillation remains the first-line therapy in CIS patients and seems to improve recurrence and progression rates, especially with the use of maintenance. Intravesical device-assisted therapies could be effective in both BCG-naïve and BCG-unresponsive CIS patients, but further studies are ongoing to clarify their clinical benefit. A phase II clinical trial with pembrolizumab has shown the potential effectiveness of immune checkpoint inhibitors in BCG-unresponsive CIS patients and further trials are ongoing.

Summary: New optical techniques increase the CIS detection rate. BCG instillation remains the first-line treatment. Immune checkpoint inhibitors could be a future alternative in BCG-naïve and BCG-unresponsive CIS patients.


Carcinoma in situ (CIS) of the bladder is a high-grade flat lesion limited to the urothelial layer.[1] A recent meta-analysis in patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent random biopsies showed a pooled incidence of CIS of 17.35%.[2]

Histopathological and molecular analyses confirm that CIS presents morphometric features similar to muscle invasive bladder cancer (MIBC).[3] Without treatment, more than 50% of patients progress to MIBC at 5 years of follow-up.[4]

According to European Association of Urology (EAU) guidelines, CIS may be classified as: primary; CIS without a previous history of bladder cancer; concurrent; CIS in the presence of an exophytic tumor; or secondary; CIS detected during follow-up of a previous tumor that was not CIS.[5] However, the prognostic impact of this classification remains controversial.[6,7]

The diagnosis of CIS can be difficult since it can vary from normal-appearing mucosa to a lesion indistinguishable from an inflammatory process; therefore, a pathological report is required for the diagnosis.[1] However, the introduction of new optical technologies has been shown to improve detection.

The first-line treatment of bladder CIS is Bacillus Calmette–Guerin (BCG) instillation, which has been shown to decrease recurrence and progression, especially with the use of maintenance.[8] Clinical trials are ongoing to investigate the potential benefit of other agents such as immune checkpoint inhibitors.