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Emerging role of checkpoint inhibition in localized bladder cancer.
Urol Oncol. 2016 12; 34(12):548-555.UO

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.

Authors+Show Affiliations

Division of Hematology and Oncology , Mayo clinic, Phoenix, AZ. Electronic address: drparminder.singh@me.com.Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

27776977

Citation

Singh, Parminder, and Peter Black. "Emerging Role of Checkpoint Inhibition in Localized Bladder Cancer." Urologic Oncology, vol. 34, no. 12, 2016, pp. 548-555.
Singh P, Black P. Emerging role of checkpoint inhibition in localized bladder cancer. Urol Oncol. 2016;34(12):548-555.
Singh, P., & Black, P. (2016). Emerging role of checkpoint inhibition in localized bladder cancer. Urologic Oncology, 34(12), 548-555. https://doi.org/10.1016/j.urolonc.2016.09.004
Singh P, Black P. Emerging Role of Checkpoint Inhibition in Localized Bladder Cancer. Urol Oncol. 2016;34(12):548-555. PubMed PMID: 27776977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Emerging role of checkpoint inhibition in localized bladder cancer. AU - Singh,Parminder, AU - Black,Peter, Y1 - 2016/10/21/ PY - 2016/06/11/received PY - 2016/08/27/revised PY - 2016/09/17/accepted PY - 2016/10/26/pubmed PY - 2018/1/13/medline PY - 2016/10/26/entrez KW - Bladder cancer KW - Checkpoint inhibitors KW - Clinical trials KW - Immune therapy KW - Urothelial carcinoma SP - 548 EP - 555 JF - Urologic oncology JO - Urol Oncol VL - 34 IS - 12 N2 - 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. SN - 1873-2496 UR - https://www.unboundmedicine.com/medline/citation/27776977/Emerging_role_of_checkpoint_inhibition_in_localized_bladder_cancer_ DB - PRIME DP - Unbound Medicine ER -