Bacillus Calmette-Guérin unresponsiveness in non-muscle-invasive bladder cancer patients: what the urologists should know.

Transurethral resection of bladder (TURB) with adjuvant intravesical bacillus Calmette-Guérin (BCG) remains the gold standard therapy for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, this disease is burdened with a high risk of recurrence or progression. For this reason, we sought to review and summarize the current evidence with a non-systematic Medline/PubMed literature search, regarding optimal treatment in BCG failure patients. Radical cystectomy (RC) should be considered as the preferred option in patients who experience a BCG-failure, especially in case of Ta or T1 high grade recurrence which occurred within 3 months of start-date of induction or in early-intermediate BCG relapsing tumors or in case of recurrence after ≥1 maintenance course with a maintenance exposure ≤6 months. However, in BCG-intolerant patients and in patients unfit or who refuse RC, alternative treatments can be proposed. In particular in BCG intolerant patients a reduction of dwell-time, an increase of length of intervals between the doses, use of anti-inflammatory drugs and antibiotics can be practiced for reducing symptoms. In patients with a low-intermediate grade recurrence for primary intermediate-risk tumor or for CIS disease after a single course of induction, a second induction course of BCG (but not further) can be performed. Intravesical chemotherapeutic agents are considered suboptimal but can be proposed in patients unfit or who refuse RC. On the contrary, combination chemotherapy is not indicated in BCG failure patients. Several ongoing trials are testing with promising prospects the efficacy of cytotoxic agents, immunotherapeutic agents, target therapies, devices and other molecules in BCG-failure patients.