The BCG shortage: No short-term solution!

April 25, 2019

"Bacillus Calmette-Guerin (BCG) intravesical immunotherapy is the most effective treatment for management of our patients with non-muscle invasive bladder cancer. What do we do without it, and how do we explain the current worldwide BCG shortage to our patients?" writes Adele M. Caruso, DNP, CRNP.

Dr. Caruso is a nurse practitioner at the University of Pennsylvania Health System, Philadelphia. Opinions expressed by bloggers are their own, and do not necessarily reflect the views of Urology Times or its parent company, MultiMedia Healthcare.

Bacillus Calmette-Guerin (BCG) intravesical immunotherapy is the most effective treatment for management of our patients with non-muscle invasive bladder cancer (NMIBC). What do we do without it, and how do we explain the current worldwide BCG shortage to our patients?

BCG intravesical immunotherapy is indicated in the form of intravesical installations for intermediate- and high-risk tumors following transurethral resection of the bladder tumor (TURBT). BCG significantly reduces bladder cancer recurrence rates while also impacting early progression rates. A risk-stratified approach is outlined in both the AUA/Society of Urologic Oncology and European Association of Urology guidelines for NMIBC according to low-, intermediate-, and high-risk tumors.

 

AUA/SUO, EAU recommendations

Per the AUA/SUO and EAU guidelines, post-TURBT mitomycin-C or epirubicin is recommended for low- and intermediate-risk patients. Additional induction intravesical therapy is not recommended for low-risk patients, post TURBT. In intermediate-risk patients, chemotherapy and immunotherapy is recommended. BCG immunotherapy is the recommended therapy for high-risk patients newly diagnosed with carcinoma in situ (CIS), high-grade T1, or high-risk bladder cancer.

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In intermediate-risk patients responsive to chemotherapy or BCG, maintenance chemotherapy or BCG is recommended. The recommendation for high-risk patients is induction BCG and for BCG responders, a 3-year BCG maintenance regimen is recommended as tolerated. BCG induction without maintenance is associated with an 11% progression rate at 5 years (Eur Urol 2011; 60:32-6).

 

What can we offer?

In the absence of full availability, one would like to offer an effective alternative that optimizes patient access. Patients can be offered a one-third dose of BCG for induction and maintenance courses up to 1 year. This approach is based on a randomized trial by the European Organization for Research and Treatment of Cancer that showed no difference in progression rates between a full dose and one-third dose of BCG (Eur Urol 2015; 67:359-60; Eur Urol 2013; 63:462-72). Conservation of the medication requires three patients to be treated simultaneously, and coordination of this approach requires some administrative effort. Ideally, and for optimal efficacy, an induction of BCG course should be followed by maintenance if the drug is available. This is not generally not feasible during this current shortage. Other agents may be offered if BCG is unavailable or if administering one-third dose is not possible.

 

Therapeutic options other than BCG

Alternatives to BCG include alternate intravesical immunotherapy and chemotherapy agents. One may consider an alternate immunotherapy agent such as intravesical interferon, which alone and in combination with BCG has demonstrated efficacy against bladder cancer. Chemotherapy alternatives to BCG include intravesical gemcitabine, mitomycin-C, and valrubicin (See AUA/Society of Urologic Oncology guideline and European Association of Urology guideline and "Alternatives to BCG Immunotherapy for Bladder Cancer Treatment During Drug Shortages.")

Next:Triage of patientsTriage of patients

A triage process is essential during this time of shortage. In a group practice, this requires a weekly review of the panel of bladder cancer patients in entirety. Patients are categorized by their pathology and assigned BCG therapy according to severity. Initiation of BCG maintenance therapy may not be an option during this time. If the patient is currently on maintenance, the recommendation is that BCG maintenance be stopped after 1 year, and for those high-risk patients with CIS, consider offering a reduced dose for years two and three (Eur Urol 2015; 67:359-60). Maintenance BCG can be omitted for intermediate-risk patients and not utilized for low-risk patients. Patients not assigned BCG therapy are offered alternate therapies.

 

Availability

Will other strains eventually become available? The FDA is exploring opportunities to approve other strains; however, Merck is currently the sole maker and supplier, since Sanofi Pasteur suspended production in 2012. Companies in Japan, Canada, and Europe are working towards the development of new strains to thwart future supply shortages. (See "SWOG Now Searches for BCG Replacement," "BCG Shortage Info," and "BCG: What to do when there is a shortage."

 

Patient perception and anxiety

Many of our patients are in disbelief about the BCG shortage. The shortage is a major source of anxiety for them in addition to their bladder cancer diagnosis and disease management. How can we help our patients and offer them reassurance?

Read: Shared decision-making presents opportunity for APPs

Open dialogue with your patients is the best way to offer support and reassurance and reduce patient anxiety. Provide the most up-to-date, evidence-based information regarding disease management and alternate therapeutic treatment options if BCG intravesical immunotherapy is not immediately available to them.

It may also be helpful to refer them to online resources such as the AUA and Bladder Cancer Advocacy Network websites. Moreover, the AUA’s website has a section called “BCG Shortage Info” that includes a “frequently asked questions” portion for your patients. This document provides clear and concise information. I recommend that you have this information readily available in printed form in your clinic. Additionally, the website provides an “office phone script” to assist staff with patient inquiries.

Merck, the only approved and sole supplier of BCG in the United States, expects the shortage to continue throughout 2019. Merck and their wholesalers and distributers adopted a distribution model based on supply and historical purchasing patterns, according to information on the AUA’s “BCG Shortage Info” page. This model is currently utilized when filling physician and hospital orders.

As always, please feel free to share your perspective by emailing me at UT@advanstar.com.