From Interferon to Checkpoint Inhibition Therapy—A Systematic Review of New Immune-Modulating Agents in Bacillus Calmette–Guérin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC)

Cancers, 2022 · DOI: 10.3390/cancers14030694 · Published: January 29, 2022

Simple Explanation

In Bacillus Calmette–Guérin (BCG) refractory non-muscle-invasive bladder cancer (NMIBC), radical cystectomy is the gold standard. Immune-modulating (IM) therapies can offer a chance for bladder preservation in the treatment of NMIBC. This systematic review includes four full-text articles and four congress abstracts with IM agents in this setting.

Study Duration

Not specified

Participants

406 articles were identified, with 4 full-text articles and 4 congress abstracts included in the review.

Evidence Level

Systematic Review

Key Findings

1
Durvalumab plus Oportuzumab monatox, Pembrolizumab, and Nadofaragene ﬁradenovec (NF) show complete response (CR) rates of 41.6%, 40.6%, and 59.6% after 3 months.
2
Instillations with oncolytic viruses such as NF and CG0070 show good efﬁcacy without triggering signiﬁcant immune-mediated systemic adverse events.
3
Recombinant BCG VPM1002BC could prove to be valid as an alternative to BCG in the future.

Research Summary

The urinary bladder is an immunogenic organ. The occurrence of BC permanently alters the immune landscape of the bladder. Immunizing therapies, either as bladder instillation or as intravenously or orally administered therapies, may offer a chance for bladder-preserving treatment. Ultimately, we need more research, including basic research on the complex interactions of the urinary bladder immune system, in order to offer patients a well-established alternative to RC and not to compromise oncological outcome.

Practical Implications

Bladder-Preserving Treatment Options

Immunizing therapies offer a potential bladder-preserving treatment for high-risk NMIBC patients who have failed BCG therapy, reducing the need for radical cystectomy.

Advancements in Immunotherapy

New immunomodulatory agents, such as checkpoint inhibitors and virus vector-mediated therapies, show promising results in treating BCG-refractory NMIBC.

Personalized Treatment Strategies

Further research is needed to understand the complex interactions of the urinary bladder immune system and identify predictive biomarkers for treatment response, enabling personalized treatment strategies.

Study Limitations

1
The available number of studies on the topic is small.
2
Many data, especially phase 3 studies, are still in their early phases.
3
In some studies, it is unclear how the criterion BCG refractory (or “unresponsive”) is deﬁned.

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