Muscle invasive bladder cancer: where is the field headed?

ABSTRACT

Introduction

The standard treatment for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy or upfront radical cystectomy for cisplatin-ineligible patients. In those who are ineligible for or refuse radical cystectomy, trimodal therapy with chemoradiation is offered. However, with the success of immune checkpoint inhibitors (ICI) and antibody-drug conjugates such as enfortumab vedotin in the metastatic setting, several trials are implementing these drugs in the neoadjuvant setting for cisplatin ineligible patients. Indeed, nivolumab is approved as adjuvant therapy for high-risk muscle-invasive urothelial carcinoma.

Areas covered

Clinical trials using ICI, ICI/ICI, and ICI/chemotherapy combination therapies in the perioperative setting have been completed. These clinical trials have demonstrated that neoadjuvant ICI are safe and have encouraging pCR, making them promising treatment options. Neoadjuvant enfortumab vedotin alone and in combination with pembrolizumab is also being studied, and preliminarily to have promising activity. ICI is also being combined with radiation therapy (RT) and early data indicate that ICI combined with RT or chemo-RT may be safe with promising activity.

Expert opinion

Biomarkers are urgently needed to identify appropriate treatment options for individual patients. The use of novel treatment approaches and biomarkers will help shape the future of precision therapy for MIBC and enable bladder preservation.

KEYWORDS:

• muscle invasive
• immunotherapy
• EV
• neoadjuvant
• adjuvant
• bladder cancer

Article highlights

• The neoadjuvant immune checkpoint inhibitor (ICI) therapy has demonstrated its safety and promising pathologic complete response rates in several clinical trials, indicating its potential as a viable treatment option in muscle-invasive bladder cancer.

• In single-arm studies comparing chemotherapy and ICI with neoadjuvant chemotherapy alone, showed comparable pathologic complete responses have been seen. However, randomized trials comparing combination therapy to neoadjuvant chemotherapy alone are still in progress.

• Additionally, the incorporation of novel agents such as enfortumab vedotin with or without ICI in the neoadjuvant setting is expected to be promising.

• Early findings from a clinical trial suggest that the combination of immune checkpoint inhibitors (ICI) with radiation therapy (RT) or chemoradiation (chemoRT) appears safe, with manageable side effects. While longer-term data is needed for a more comprehensive understanding, initial results show promising survival outcomes, suggesting this might be a viable option, particularly for frail patients who are ineligible for neoadjuvant chemotherapy (NAC) or cystectomy.

• Preserving the bladder is a significant strategy for the future advancement of treatment in muscle-invasive bladder cancer (MIBC). This can be achieved through the implementation of novel neoadjuvant therapies, the evolution of trimodal therapy by incorporating immune checkpoint inhibitors (ICI), and the utilization of biomarkers and improved clinical staging. By safely preserving the bladder, these approaches have the potential to enhance patients’ quality of life and improve clinical outcomes for individuals with MIBC.

Declaration of interest

G Sonpavde is on the advisory board for: Bristol-Myers Squibb, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, AstraZeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals, Lucence Health, IMV, Vial, Syapse, Tempus: is a consultant for/on the Scientific Advisory Board (SAB) for; Suba Therapeutics, Syapse, Servier, and Merck: has received research support to their institution, from; Sanofi (iaward), AstraZeneca, Gilead, Helsinn, Lucence, Bristol-Myers Squibb, EMD Serono, and Jazz Therapeutics; is a speaker for; BIO – INFORMAÇÃO BRASILEIRA DE ONCOLOGIA Ltda, OLE Forum (Mexico), Seagen, Gilead, Natera, Exelixis, Janssen: has received data safety monitoring committee honorarium from Mereo: their spouse is an employee of Myriad; and has received writing/Editor fees from Uptodate and Onviv. … 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 disclosures

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

Additional information

Funding

This paper was not funded.