Emerging role of checkpoint inhibition in localized bladder cancer

Parminder - Singh, Peter Black

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Objective Checkpoint inhibitors have rapidly become a standard treatment option for metastatic urothelial carcinoma. A wave of enthusiasm for these drugs has pushed them also into the setting of localized bladder cancer, including both non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive disease bladder cancer (MIBC). Here, we aimed to review the emerging role of checkpoint inhibition in localized bladder cancer. Methods We reviewed the current treatment landscape for both NMIBC and MIBC and established a significant unmet clinical need for novel therapies. We have compiled the evidence that supports the investigation of checkpoint blockade in localized bladder cancer and have reviewed the corresponding clinical trial׳s landscape. Results The success of checkpoint inhibitors in metastatic bladder cancer offers the most compelling rationale for testing checkpoint blockade in localized disease. The established benefit of intravesical Bacillus Calmette–Guérin provides precedent for immune therapy in bladder cancer. Immune dysfunction has been described in bladder cancer, and we know that checkpoint molecules are expressed in these tumors. Furthermore, the high neoantigen burden of bladder cancer and results from preclinical studies suggest that checkpoint blockade deserves testing in earlier stage disease. Multiple trials are either planned or underway in almost all bladder cancer disease states. Conclusion Ongoing trials would determine in the next several years whether checkpoint inhibitors can have a similar effect in localized disease as they have had in metastatic bladder cancer. They would also determine if patients with earlier disease would tolerate the toxicity of systemic therapy. The future holds promise for predictive biomarkers to guide individualized use of these agents and for effective combination therapies to overcome resistances.

Original languageEnglish (US)
Pages (from-to)548-555
Number of pages8
JournalUrologic Oncology: Seminars and Original Investigations
Volume34
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Urinary Bladder Neoplasms
Muscle Neoplasms
Therapeutics
Urinary Bladder Diseases
Bacillus
Biomarkers
Clinical Trials
Carcinoma

Keywords

  • Bladder cancer
  • Checkpoint inhibitors
  • Clinical trials
  • Immune therapy
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Emerging role of checkpoint inhibition in localized bladder cancer. / Singh, Parminder -; Black, Peter.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 34, No. 12, 01.12.2016, p. 548-555.

Research output: Contribution to journalReview article

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abstract = "Objective Checkpoint inhibitors have rapidly become a standard treatment option for metastatic urothelial carcinoma. A wave of enthusiasm for these drugs has pushed them also into the setting of localized bladder cancer, including both non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive disease bladder cancer (MIBC). Here, we aimed to review the emerging role of checkpoint inhibition in localized bladder cancer. Methods We reviewed the current treatment landscape for both NMIBC and MIBC and established a significant unmet clinical need for novel therapies. We have compiled the evidence that supports the investigation of checkpoint blockade in localized bladder cancer and have reviewed the corresponding clinical trial׳s landscape. Results The success of checkpoint inhibitors in metastatic bladder cancer offers the most compelling rationale for testing checkpoint blockade in localized disease. The established benefit of intravesical Bacillus Calmette–Gu{\'e}rin provides precedent for immune therapy in bladder cancer. Immune dysfunction has been described in bladder cancer, and we know that checkpoint molecules are expressed in these tumors. Furthermore, the high neoantigen burden of bladder cancer and results from preclinical studies suggest that checkpoint blockade deserves testing in earlier stage disease. Multiple trials are either planned or underway in almost all bladder cancer disease states. Conclusion Ongoing trials would determine in the next several years whether checkpoint inhibitors can have a similar effect in localized disease as they have had in metastatic bladder cancer. They would also determine if patients with earlier disease would tolerate the toxicity of systemic therapy. The future holds promise for predictive biomarkers to guide individualized use of these agents and for effective combination therapies to overcome resistances.",
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