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      Metastatic Urothelial Cancer: a rapidly changing treatment landscape

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          Abstract

          Despite significant progress, metastatic urothelial cancer remains an incurable condition with a limited life expectancy. Platinum-based chemotherapy is still the mainstay of treatment for metastatic disease, but immunotherapy, antibody drug conjugates, and targeted agents have shown encouraging results in several recent practice changing trials. In this review, we discuss the standard of care, recent therapeutic advances, ongoing clinical trials, and future perspectives in metastatic urothelial carcinoma.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.

            Naiyer A Rizvi, Matthew Hellmann, Alexandra Snyder … (2015)
            Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti-PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti-PD-1 therapy. Copyright © 2015, American Association for the Advancement of Science.
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              Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion.

              Robert D. Schreiber, Lloyd J. Old, Mark J. Smyth (2011)
              Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying cancer cells or inhibiting their outgrowth but also promote tumor progression either by selecting for tumor cells that are more fit to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor outgrowth. Here, we discuss a unifying conceptual framework called "cancer immunoediting," which integrates the immune system's dual host-protective and tumor-promoting roles.
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                Author and article information

                Contributors
                Carlos Stecca:
                ORCID: https://orcid.org/0000-0001-9103-9119
                Osama Abdeljalil
                Srikala S. Sridhar
                Journal
                Journal ID (nlm-ta): Ther Adv Med Oncol
                Journal ID (iso-abbrev): Ther Adv Med Oncol
                Journal ID (publisher-id): TAM
                Journal ID (hwp): sptam
                Title: Therapeutic Advances in Medical Oncology
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Print): 1758-8340
                ISSN (Electronic): 1758-8359
                Publication date (Electronic): 30 September 2021
                Publication date Collection: 2021
                Volume: 13
                Electronic Location Identifier: 17588359211047352
                Affiliations
                [1-17588359211047352]Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
                [2-17588359211047352]Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
                [3-17588359211047352]Professor, University of Toronto, Medical Oncologist, Princess Margaret Cancer Center, Chair, GU Medical Oncologists of Canada, 7-625 -700 University Avenue, Toronto, ON M5G 2M9, Canada
                Author notes
                Author information
                https://orcid.org/0000-0001-9103-9119
                Article
                Publisher ID: 10.1177_17588359211047352
                DOI: 10.1177/17588359211047352
                PMC ID: 8488509
                PubMed ID: 34616491
                SO-VID: e4e375c7-4199-44f2-be51-8ca252f4aa52
                Copyright © © The Author(s), 2021
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 17 May 2021
                Date accepted : 1 September 2021
                Categories
                Subject: Review
                Custom metadata
                cover-date January-December 2021
                typesetter ts1

                Keywords: antibody-drug conjugate,bladder cancer,fgfr,immunotherapy,immune checkpoint inhibitors,metastatic urothelial carcinoma
                Data availability:
                Keywords: antibody-drug conjugate, bladder cancer, fgfr, immunotherapy, immune checkpoint inhibitors, metastatic urothelial carcinoma

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