Emerging treatment landscape of non-muscle invasive bladder cancer

ABSTRACT

Introduction

Non-muscle invasive bladder cancer (NMIBC) accounts for 70–75% of all bladder cancers and is a heterogeneous disease characterized by a wide spectrum of recurrences and progression. Adjuvant treatment for intermediate- and high-risk NMIBC is mainly represented by Bacillus Calmette Guerin (BCG). However, 20%–40% of patients develop disease recurrences or persistence following BCG treatment and are classified as “BCG unresponsive’ (BCGu), thus representing a therapeutic challenge due to their worse prognosis and unavailability of effective intravesical treatments.

Areas covered

We provide an overview of completed and ongoing clinical trials assessing the role of innovative immunological and target agents in patients with BCGu and BCG naive (BCGn) NMIBCs. New treatment options are emerging, demonstrating promising clinical activity, namely, pembrolizumab, atezolizumab, oportuzumab monatox, nadofaragene firadenovec, and N-803.

Expert opinion

The increasing number of newer therapeutic agents for patients with NMIBC poses challenges regarding the choice of the most suited treatment option for each patient and the best treatment sequence, given their diverse mechanisms of action and varying degrees of activity. Tailored treatment approaches are advocated, based on a deeper comprehension of disease features, available therapies, patient’s characteristics, and consequently, on the identification and validation of prognostic and predictive biomarkers.

KEYWORDS:

• BCG unresponsive
• immunotherapy
• non-muscle invasive bladder cancer
• target therapies
• biomarkers

Abbreviations

BCG, Bacillus Calmette-Guerine; BCGn, BCG naïve; BCGu, BCG unresponsive; CIS (or Tis), carcinomas in situ; CR, complete response; CV, cancer vaccine; DOR, duration of response; EBRT, External Beam Radiation Therapy; EFS, Event Free Survival; FDA, Food and Drug Administration; FGFR, fibroblast growth factor receptor; G, grade; GT, gene therapy; ICI, Immune Checkpoint Inhibitors; NMIBC, non muscle invasive bladder cancer; OV, oncolytic virus; PD-L1, programmed death ligand 1; PFS, progression free survival; RC: radical cystectomy; RS, risk score; RFR, Recurrence Free Rate; T1, tumors infiltrating the lamina propria; Ta, papillary non-invasive carcinomas; TRAE, treatment related adverse event; TURBT, transurethral resection of bladder tumor.

Declaration of interest

G Curigliano has served as consultant or advisor for Roche, Lilly, and Bristol Myers Squibb; served on the speakers bureau for Roche, Pfizer, and Lilly; received travel funding from Pfizer and Roche; and received honoraria from Roche, Pfizer, Lilly, Novartis, and Seagen all outside the submitted work. The authors have no other 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 apart from those disclosed.

Reviewer dislcosures

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

Supplementary material

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Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.