AUA 2016: What’s so Difficult about A New Approach Post-BCG? - Session Highlights

San Diego, CA USA ( In today’s society of basic urological research meeting at the 2016 AUA, Dr. Michael O’Donnell discussed a new approach post-BCG for patients with NMIBC. Traditional categories of BCG failure have been refractory, relapsing, resistant, and intolerant. These terms were unworkable and poorly adopted, thus leading to the use of the term “BCG Unresponsive.”

In particular, high risk patients included T1 HG disease at first evaluation following BCG induction and those with persistent or recurrent HG disease within 6 months of receiving at least 2 courses of BCG (at least 5 of 6 induction and 2 of 3 maintenance).

It remains unclear why BCG fails in certain patients. This may be due to inadequate or insufficient immune response or intrinsic tumor resistance to immune killing.

The “safe” time window to treat after BCG failure is less than 2 years. This conclusion is drawn from data on median time to progression across 14 series, which is 24 months. Untreated CIS has an annual 5% progression rate but since 50% fail, this annual rate doubles to 10%. Mortality is approximately 1% at 1 year. Those patients who undergo cystectomy for T1 disease after BCG failure have a 92% DSS at less than 2 years, but 55% DSS at greater than 2 years.

Before embarking on “rescue therapy,” it is imperative that the patient is properly staged with thorough cystoscopy with re-resection, imaging, and exam under anesthesia. Treatment options in the rescue setting include conventional chemotherapy (valrubicin), BCG+IFN, “new” single agent chemotherapy such as gemcitabine or docetaxel, and combination chemotherapy.

Pooled data for repeat BCG after failure x 1 demonstrates a 35% NED rate at 2 years. BCG+IFN is an option but is not recommended in patients with CIS who have failed x 1, failure x 2, and has decreased efficacy in multifocal disease, large tumors, and elderly patients. Quad immunotherapy is an option (BCG + IFN + IL-2 + subsequent GMCSF) that showed 53% RFS at 42 months median follow-up. Gemcitabine has CR rates of 40-50% in BCG refractory CIS but only 7% show a durable response at 2 years. When added to Mitomycin, this rate improves to 38% at 2 years. Intravesical docetaxel is another alternative which has demonstrated 25% RFS at 39 months.

Modern studies in BCG unresponsive patients support the safety margin for attempting rescue therapy. Pooled data shows a 5 year DSS for eacly cystectomy of 83%. With this in mind, the FDA has made it favorable to enter the market for testing agents with the indication of BCG failure. As such, there are 16+ agents that are currently in the pipeline.

Dr. O’Donnell summarized that rescue therapy requires careful selection and risk discussion, along with thorough re-staging. BCG+IFN for late relapsers, single agent novel drugs, and sequential combination chemotherapeutics for higher-risk patients have shown some degree of promise. With continued investigation of new agents, we can take advantage of the 2 year window of opportunity to provide less invasive treatment for BCG-unresponsive patients.


Presented By: Michael A. O'Donnell, MD


Written By: Nikhil Waingankar, MD; Fox Chase Cancer Center, Philadelphia, PA., at the 2016 AUA Annual Meeting - May 6 - 10, 2016 – San Diego, California, USA

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