What is the management approach for a patient with mild atypia on follow-up biopsy after BCG (Bacillus Calmette-Guérin) induction for bladder cancer?

From the Guidelines

For a patient with mild atypia on follow-up biopsy after BCG induction for bladder cancer, continued surveillance with close monitoring is the recommended approach rather than immediate aggressive intervention. The patient should undergo repeat cystoscopy with cytology in 3 months, followed by regular surveillance every 3-6 months for the first two years if findings remain stable. Mild atypia alone does not necessarily indicate treatment failure or disease recurrence, as BCG therapy itself can cause reactive changes in the urothelium that may appear as mild atypia 1. These changes often represent an inflammatory response to the immunotherapy rather than persistent or recurrent malignancy. If subsequent evaluations show progression to high-grade dysplasia, carcinoma in situ, or invasive disease, then additional BCG maintenance therapy, alternative intravesical agents like valrubicin or gemcitabine, or more aggressive surgical approaches should be considered 1. Throughout this surveillance period, urinary cytology should accompany each cystoscopy to help detect any cellular changes that might not be visually apparent. Some key points to consider in the management of non-muscle invasive bladder cancer include:

• The use of intravesical BCG or mitomycin C as adjuvant therapy after transurethral resection of bladder tumor (TURBT) 1
• The consideration of maintenance BCG therapy for one year in intermediate-risk patients who completely respond to induction BCG 1
• The importance of close surveillance and monitoring for recurrence and progression, with regular cystoscopy and urinary cytology 1
• The potential use of alternative intravesical agents or more aggressive surgical approaches in cases of recurrence or progression 1
• The need for patient education on the importance of completing the full surveillance schedule, given the high recurrence rate of bladder cancer even after successful initial treatment 1

From the Research

Management Approach for Mild Atypia on Follow-up Biopsy after BCG Induction

• The management approach for a patient with mild atypia on follow-up biopsy after BCG induction for bladder cancer is largely based on the clinical presentation and outcome of urothelial atypia on biopsy of the bladder 2.
• Studies have shown that urothelial atypia, including reactive urothelial atypia (RUA) and urothelial atypia of unknown significance (AUS), have a benign clinical course, and further intervention or surveillance may be unnecessary 2.
• However, it is essential to consider the context of BCG treatment and the potential for BCG-induced irritation or inflammation, which can lead to erythematous lesions that may harbor significant malignancies 3.
• In cases where erythematous lesions are present, voided urine cytology can be a useful tool for assessing the need for biopsy, with a sensitivity of 59%, specificity of 76%, and negative predictive value of 94% 3.
• The decision to perform a biopsy should be based on a combination of clinical factors, including cystoscopy findings, urine cytology results, and patient history 4, 5.
• For patients with a history of non-muscle-invasive bladder cancer treated with BCG, routine biopsy may not be necessary if cystoscopy and urine cytology results are normal 4.
• However, patients with carcinoma in situ or high-risk non-muscle-invasive tumors may require more frequent surveillance and biopsy to monitor for recurrence or progression 6.

Diagnostic Considerations

• Urine cytology can be a useful diagnostic tool for detecting recurrence or malignancy in patients with a history of bladder cancer, particularly in cases where erythematous lesions are present 3.
• However, the accuracy of urine cytology can be impaired in the recurrence-free interval after BCG treatment, and biopsy may be necessary to confirm the presence of malignancy 5.
• Enhanced cystoscopy, including technology used to improve the detection of tumors, can reduce the risk of recurrence and improve diagnostic accuracy 6.

Treatment Implications

• The treatment approach for patients with mild atypia on follow-up biopsy after BCG induction will depend on the clinical context and the presence of any suspicious lesions or abnormalities 6.
• Patients with high-risk non-muscle-invasive tumors or carcinoma in situ may require more aggressive treatment, including intravesical therapy or radical cystectomy, to prevent recurrence or progression 6.
• The use of immunotherapy, including checkpoint inhibitors, targeted therapies, and antibody-drug conjugates, is being explored for the treatment of advanced bladder cancer, and may offer new options for patients with recurrent or refractory disease 6.