From the Guidelines
Carcinoma in situ (CIS) of the bladder with underlying endothelial cells is a high-grade, non-invasive bladder cancer that requires prompt treatment with intravesical BCG (Bacillus Calmette-Guérin) immunotherapy to prevent progression to muscle-invasive disease. The mention of "underlying endothelial cells" likely indicates that the pathology report is noting the presence of normal blood vessel lining cells beneath the cancerous tissue, which is a typical finding when the cancer has not invaded beyond the basement membrane. According to the most recent guidelines, intravesical BCG therapy is the treatment of choice for urothelial carcinoma in situ (CIS), as it has been shown to reduce the risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) after trans-urethral resection 1.
Key Considerations
- Complete transurethral resection of visible lesions should be performed before BCG therapy begins.
- CIS has a high risk of progression to muscle-invasive disease if left untreated, with approximately 50% of cases progressing within 5 years 1.
- Regular cystoscopic surveillance every 3-6 months is essential to monitor response to treatment and detect any recurrence or progression early.
- For patients who don't respond to BCG, alternative treatments include intravesical chemotherapy, clinical trials of novel agents, or radical cystectomy (surgical removal of the bladder) 1.
Treatment Approach
- Intravesical BCG therapy should be administered weekly for 6 weeks, followed by maintenance therapy for 1-3 years.
- Patients with high-risk disease (recurrent, large, deeply invasive, multifocal, poorly differentiated or with carcinoma in situ) can be treated with intravesical BCG therapy after initial TUR or radical cystectomy 1.
- Radical cystectomy is the standard treatment for patients with muscle-invasive bladder cancer, but bladder-preserving approaches with a complete TUR and radiotherapy alone or with concomitant chemotherapy are reasonable alternatives for patients who are medically unfit for surgery or seek an alternative 1.
From the Research
Carcinoma in Situ of the Bladder
- Carcinoma in situ (CIS) of the bladder is defined as a high-grade flat lesion confined to the mucosa 2.
- It is a unique clinical entity with a high rate of recurrence and progression, and its management remains complex and challenging 3.
Underlying Endothelial Cells
- Endothelial cells are not the primary target of bacillus Calmette-Guérin (BCG) in the treatment of CIS, as BCG has a low affinity for these cells compared to urothelial tumor cells 4.
- The binding of BCG to urothelial tumor cells is specific and dose-dependent, and it is not mediated by fibronectin, an adhesion molecule present in the bladder wall 4.
Detection and Treatment
- New optical imaging modalities have improved the detection rate of CIS, and intravesical BCG immunotherapy remains the first-line treatment for CIS 2, 5.
- BCG instillation has been shown to reduce the risk of recurrence and progression, but a significant proportion of patients do not respond to BCG treatment, highlighting the need for alternative therapies 3, 2.
- Immune checkpoint inhibitors, such as pembrolizumab, may be a future alternative for BCG-unresponsive CIS patients, but further studies are needed to clarify their clinical benefit 5.