2018 Congress of the Mexican Association of Oncological Urology

Optimizing BCG Therapy for NMIBC

Acapulco, GRO, Mexico (UroToday.com) Dr. Kamat starts his conference stating that bladder cancer immunotherapy treatment, including written literature, seems only to include systemic therapy and not BCG. Actually BCG is the original cancer immunotherapy, the most effective for NMIBC and approximately 1.2 million doses are used globally.

Six myths were explained and discussed, in order to achieve a better understanding about the use of BCG and optimize its use. He demonstrated that BCG reduces both recurrence and progression rates in NMIBC (Myth #1), but progression is only reduced when maintenance is used (2002, meta analysis of 24 RCT of BCG – 4863 pts). BCG has a 32% advantage over mitomycin C when maintenance is used, instead of induction alone (suboptimal therapy).

Optimal schedule of BCG is unknown (Myth #2). It’s stated that the SWOG (induction for 6 weeks plus 3 weekly instillations at the third and sixth month, and then every 6 months for up to 3 years) protocol shows clear benefit over induction alone. In a BCG naïve bladder, cytokines continuously rise in the weeks 1 to 6, however in patients with previous BCG treatment, cytokines rise up to the 3rd week and more BCG is given after that, it will suppress the immune system. Dr. Kamat emphasized that maintenance treatment duration is more important than dosage (3 year @ full dose: 64.2%, 3 year @1/3rd dose: 62.6%, 5 year disease free rate).

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BCG maintenance is only indicated for high risk patients (Myth #3). It is also indicated for intermediate risk, EORTC (30911) reported that BCG in these patients reduces deaths (n=497, HR 0.35, p value 0.020), recurrence, metastatic disease and there is an improved overall survival.

Intravesical BCG is not well tolerated (Myth #4). EORTC and International IPD Survey reported respectively that <10% and 5.2% patients discontinued maintenance therapy due to toxicity. Strategies for optimizing intravesical BCG are: inspect voided urine for visible hematuria, catheterize atraumatically, minimize lubricant amount (to avoid BCG clumping), avoid lidocaine (acidity degrades BCG), use of antispasmodics and 1 dose of quinolone 6 hours after BCG [Recommendations Urol Clin North Am].

Older patients have lower efficacy with intravesical immunotherapy rather than no efficacy (Myth #5). Patients > 70 years had shorter time to progression, worse overall survival and NMIBC specific survival, but similar time to recurrence compared with younger patients. In spite of theses characteristics, BCG is still a better option than other chemotherapies.

Myth #6: BCG is all the same, everywhere. Dr. Kamat opinion differs and expressed that a better response to local BCG (from the patient´s country) instead of international BCG has been reported; the explanation is that the epitopes of the BCG strain that mount a robust immune response are secondary to previous exposure (TB or mycobacterial linked).

Presented by: Dr. Ashish M. Kamat, Professor of Urologic Oncology, MD Anderson Cancer Center, Houston, TX

Written by: Eduardo Gonzalez-Cuenca, MD, medical writer for UroToday.com and Ashish Kamat, MD, Professor of Urology and Director of Urologic Oncology Fellowship at M.D. Anderson Cancer Center, at the Mexican Urologic Oncology Association Meeting - July 26 - 28, 2018