Improving the role of immune checkpoint inhibitors in the management of advanced urothelial carcinoma, where do we stand?
(2022) Translational Oncology — Vol. 19, p. 101387 (2022)
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- Abstract
- Immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with metastatic uro-thelial cancer (mUC). If these agents were first used in monotherapy after failure of platinum-based chemo-therapy, new strategies have been evaluated in the last years, including association of ICIs, ICI plus chemotherapy association or maintenance therapy. This maintenance concept allows a better management of mUC, which is particularly interesting in cisplatin-ineligible patients. This paper aims to review the current knowledge of ICIs in urothelial carcinoma as well as the new indications of these agents in mUC. Introduction Bladder cancer is the seventh most common cancer with more than 350,000 newly diagnosed cases, and approximately 150,000 deaths each year worldwide [1]. Urothelial carcinoma (UC) histology accounts for more than 90% of bladder cancer; other histologies include squa-mous carcinoma, adenocarcinoma and neuroendocrine carcinoma [1,2]. Around 75% of patients present with localized and non-muscle invasive tumor (NMIUC) and are treated in a curative intent with different modalities , including surgical resection, intravesical chemotherapy and/or intravesical injection of bacillus Calmette-Guerin (BCG) [3]. Muscle-invasive UC (MIUC) requires multimodal strategy including cystectomy and perioperative chemotherapy [4]. Despite this aggressive management, more than 50% of MIUC patients develop metastases with a poor prognosis. For decades, cisplatin-based chemotherapy remained the standard treatment in first-line metastatic UC (mUC), improving progression free survival (PFS) and overall survival (OS) of these patients. Two regimens, methotrexate/vinblastine/adriamycin/cisplatin (M-VAC) and cisplatin/ gemcitabine (CG), have shown greater activity over cisplatin alone in the first-line setting with an objective response rate (ORR) of 40-49%, a PFS ranging from 7.7 to 10 months and an OS not exceeding 14.8 months [5]. Due to its better tolerability and safety profile, the CG combination remains thus the standard of care for mUC patients in first-line setting. A proportion of patients are ineligible for cisplatin due to poor performance status and renal failure and are treated with carboplatin-gemcitabine regimen, with inferior efficacy, ORR not exceeding 36%, PFS 5 months and OS 9 months [4-6]. Platinum-based chemotherapy does not cure patients and progression occurs in more than 90% of patients. Second-line options are limited and include mainly immune checkpoint inhibitor (ICI) in mon-otherapy with only a limited percentage of patients presenting durable benefit [7-9]. Further therapeutic options are available, including paclitaxel, docetaxel and vinflunine, but these agents do not improve significantly outcome of these patients [10-12]. Advances in immuno-oncology field has considerably improved outcome of patients in different cancer types, including UC. These treatments allow innovative strategies including maintenance treatment and tailored treatment. We describe in this review the recent advances in mUC management with ICIs. Rational for immunotherapy in bladder cancer Retrospective analysis showed that patients with increased tumor-infiltrating CD8+ lymphocytes (TILs) within advanced UC (pT2, pT3, or pT4) have better disease-free survival and OS than patients with similar-staged UC and fewer intra-tumoral CD8+ TILs, suggesting that this lymphocyte infiltration is associated with better outcome [13,14]. This highlights the role of immune system in controlling evolution of UC cells, which is indirectly confirmed by the fact that intravesical in-stillations of bacillus Calmette-Guerin (BCG) prevent recurrences of high-risk NMIUC [15].
- Affiliations
Centre Hospitalier de Jolimont, Rue Ferrer 159, 7100 Haine Saint Paul, Belgium Department of Medical Oncology
Citations
Houssiau, H., & Seront, E. (2022). Improving the role of immune checkpoint inhibitors in the management of advanced urothelial carcinoma, where do we stand? Translational Oncology, 19, 101387. https://doi.org/10.1016/j.tranon.2022.101387 (Original work published 2022)