Recognition and Treatment of BCG Failure in Bladder Cancer

Abstract

Patients with high-grade Ta, T1, or carcinoma in situ non–muscle-invasive bladder cancer (NMIBC) are at high risk for recurrence and, more importantly, progression. Thus, both the American Urological Association and European Association of Urology recommend initial intravesical treatment with bacillus Calmette-Guerin(BCG) followed by maintenance therapy for a minimum of 1 year. The complete response rate to BCG therapy in patients with high-risk NMIBC can be as high as ∼80%; however, most patients with high-risk disease suffer from recurrence. BCG failure can be further characterized into BCG refractory, BCG resistant, BCG relapsing, and BCG intolerant. Current recommendations include one further course of BCG or cystectomy. In patients who continue to fail conservative treatment and who refuse surgical therapy or are not surgical candidates, treatment options become even more complicated. In this setting, treatment options are limited and include repeat BCG treatment, an alternate immunotherapy regimen, chemotherapy, or device-assisted therapy. To date, however, further research is necessary for all secondary treatment options in order to determine which might be the most efficacious. All conservative treatments should be considered investigational. Currently, cystectomy remains the standard of care for high-risk patients who have failed BCG therapy.

Bacillus Calmette–Guérin‐unresponsive non‐muscle‐invasive bladder cancer: Its definition and future therapeutic strategies

“…Despite the potentially curative nature of RC, many physicians and patients refrain from RC in favor of preserving bladder function. Current conservative therapeutic options for BCG failure are limited and include repeated BCG therapy . O'Donnell and Boehle reviewed previous studies and reported that 35% of patients with BCG failure achieved durable success with the addition of another BCG therapy .…”

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

“…55 In tumours that do not respond to BCG anymore, conventional intravesical chemotherapy agents, such as doxorubicin, thiotepa and mitomycin, have limited activity. In addition, valrubicin, the only FDAapproved drug for BCGrefractory CIS, is only effective in <10% of patients at 2 years and none with coincident stage T1 disease.…”

“…For example, the use of initial chemotherapy followed by BCG, the reverse version or alternating application, as well as other novel chemotherapy regimens, have been investigated in small clinical studies. 55 In addition, several original approaches using electromotive accelera tion have been investigated. Kaasinen et al 75 conducted a study in 236 patients with recurrent Ta or T1 bladder tumours.…”

Multi-institutional analysis of sequential intravesical gemcitabine and mitomycin C chemotherapy for non–muscle invasive bladder cancer

“…Treatment options for patients following recurrence of NMIBC after BCG therapy who refuse cystectomy are limited and the majority are experimental. Options include repeat BCG treatment, an alternate immunotherapy regimen, chemotherapy, or device-assisted therapy (including electromotive intravesical administration of mitomycin C [MMC] and microwave hyperthermia and administration of MMC) [6]. …”