Developments in conservative treatment for BCG-unresponsive non-muscle invasive bladder cancer

ABSTRACT

Introduction

To reduce the risk of disease recurrence and progression of intermediate and high-risk Non-Muscle Invasive Bladder Cancers (NMIBCs), intravesical adjuvant treatment with Bacillus Calmette-Guerin (BCG) represents the standard of care, although up to 50% of patients will eventually recur and up to 20% of them will progress to Muscle Invasive Bladder Cancer (MIBC). Radical Cystectomy (RC) is the treatment of choice in this setting; however, this represents a major and morbid surgery, thus meaning that not all NMIBCs patient could undergo or may refuse this procedure or may refuse. The search for effective bladder sparing strategies in NMIBCs BCG-unresponsive patients is a hot topic in the urologic field.

Areas covered

We aimed to review the most important bladder-preserving strategies for BCG unresponsive disease, from those used in the past, even though rarely used nowadays (intravesical chemotherapy with single agents), to current available therapies (e.g. intravesical instillation with Gemcitabine-Docetaxel), and to future upcoming treatments (Oportuzumab Monatox).

Expert opinion

At present, bladder-preserving treatments in BCG-unresponsive patients are represented by the use of intravesical instillations, systemic immunotherapies, both with good short-term and modest mid-term efficacy, and numerous clinical trials ongoing, with encouraging initial results, in which patients could be recruited.

KEYWORDS:

• BCG
• BCG-Unresponsive NMIBC
• bladder cancer
• immunotherapy
• intravesical instillation
• NMIBC

Article highlights

• Bladder-sparing strategies in BCG-Unresponsive patients are a hot topic in the urologic field.

• In the past years lots of bladder-sparing strategies have been evaluated, but most of them are not approved or recommended in international guidelines, except for intravesical Valrubicin.

• At present, intravesical instillations with Gemcitabine plus Docetaxel could be offered in patients refusing to undergo to radical cystectomy, with a 2 years RFS of 46%.

• Actual approved treatment in CIS BCG-Unresponsive patients, other than intravesical Valrubicin, are systemic Pembrolizumab (3 months CR of 41%) and Nadofaragene Firadenovec (3 months CR of 53%).

• There are lots of ongoing trials evaluating new bladder-sparing strategies (e.g. Oportuzumab Monatox, TAR-200) in this setting, with promising initial results, but long-term data are lacking so the real efficacy is yet to be known.

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.

Additional information

Funding

This paper was not funded.