Current advances in BCG-unresponsive non-muscle invasive bladder cancer

ABSTRACT

Introduction: The current first line therapy for high grade (HG) non-muscle invasive bladder cancer (NMIBC) is intravesical Bacillus Calmette–Guerin (BCG). Patients who recur or progress despite BCG are recommended to undergo radical cystectomy or participate in clinical trials. There is an urgent need for alternative therapies in the BCG-unresponsive NMIBC realm.

Areas covered: We queried clinicaltrials.gov and pubmed.gov for current and recently completed early clinical trials pertaining to investigational agents used for the treatment of BCG-unresponsive NMIBC. These included intravesical chemotherapy, immunotherapy, vaccines, gene therapy, viruses, and agents used with novel drug delivery methods. In this article, we discuss the treatment guidelines for non-muscle invasive bladder cancer and therapeutic approaches under investigation in clinical trials.

Expert opinion: The FDA is currently allowing single-arm studies as a pathway for approval in BCG-refractory patients with CIS. Although many agents are currently undergoing testing, none have been approved since Valrubicin. Hopefully, we will identify therapies sufficiently effective and durable to achieve FDA approval. Other considerations in this realm include the use of biomarkers in NMIBC to identify patients who will most likely respond to specific interventions. In addition, as systemic agents such as checkpoint inhibitors, are studied further, a multidisciplinary approach may be needed to treat this subset of patients

KEYWORDS:

• BCG-refractory
• BCG-unresponsive
• clinical trials
• non-muscle invasive bladder cancer

Article Highlights

• There is a paucity of options available for HG NMIBC who fail BCG-treatment.

• Current options for BCG-unresponsive disease include radical cystectomy or enrollment in clinical trials. Valrubicin remains the only agent that is FDA approved in BCG-refractory patients with CIS.

• Most agents currently under investigation are immune-mediated (with systemic checkpoint inhibitors currently enrolling in early clinical trials) or targeted therapies.

• The FDA is currently allowing single-arm studies as a pathway for approval in this realm but limiting approval to patients with CIS.

• Combination therapies may play a larger role in the future, although it will take time to determine the most active agents prior to studying combinatorial approaches.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose