Bladder Sparing Therapy for BCG Failures – I – Intravesical Immunotherapy

Between 15 and 20% of patients with newly diagnosed urothelial cancer (UC) of the bladder will have high grade (HG) non-muscle invasive (NMI) disease including carcinoma-in-situ (CIS) and stage Ta and T1 tumors [1]. After transurethral resection of the cancer (TURBT), patients may undergo re-TURBT, but if no muscle invasive (MI) cancer is found most will receive an induction course of 6 weekly intravesical instillations of Bacillus Calmette Guerin (BCG). If at the first post BCG surveillance cystoscopy no cancer is found, they usually receive 3 weekly instillations of BCG every 6 months for 3 years [2]. If persistent or recurrent NMI cancer is found, they will usually receive another 6 week re-induction course of BCG without [3] or with alpha interferon [4]. Persistence or recurrence of any HG cancer at 6 months after the initial TURBT (termed “BCG unresponsive or resistant” disease) is generally an indication for cystectomy. However, bladder cancer is a disease of the elderly, and usually arises in patients with numerous comorbidities [5]. Thus, some UC patients are not candidates for cystectomy, and some patients who are medical “candidates” decline to undergo it. Treatment options for these patients are limited. Only Valrubicin has been approved by the US Food and Drug Administration (FDA) for salvage intravesical therapy for patients with CIS after BCG, even though 20% or fewer patients so treated remained recurrence-free by 12 months [6]. Studies of bladder preservation therapies for BCG unresponsive or “relapsing” (recurrence of HG NMI UC after