Internal Medicine, University of California, Davis, Sacramento, CA, 95817, USA.
Division of Hematology and Oncology, Department of Medicine, Helen Diller Family Cancer Center, University of California San Francisco, 550 16th Street, Office 6811, Box 3211, San Francisco, CA, 94158, USA.
Curr Treat Options Oncol. 2023 Sep;24(9):1213-1230. doi: 10.1007/s11864-023-01113-z. Epub 2023 Jul 10.
There is an acute unmet need to develop novel treatment regimens in the perioperative setting since many patients with muscle-invasive bladder cancer (MIBC) are not eligible for the current standard of care (SOC) neoadjuvant treatment with cisplatin-based chemotherapy. The introduction of immune checkpoint inhibitors (ICIs), both as monotherapy and in combination regimens with other ICIs, chemotherapy, or targeted drugs, may provide safe and clinically effective treatment options that could revolutionize current standard of care. In the neoadjuvant setting, compelling data from phase II clinical trials suggests that single-agent immunotherapy, as well as dual-checkpoint blockade, may emerge as reasonable alternatives to traditional cisplatin-based chemotherapy. Prospective studies combining ICIs with chemotherapy or with antibody-drug conjugates have also demonstrated robust outcomes. However, these studies are not yet practice changing and data from larger randomized studies are needed to confirm this benefit. In the adjuvant setting, nivolumab is the FDA-approved treatment based on a disease-free survival benefit relative to placebo in a randomized trial. However, it will be important to confirm an overall survival benefit of this treatment and to better identify patients who need additional adjuvant treatment based on novel biomarker data. The treatment of muscle-invasive bladder cancer is moving toward the individualization of treatment options based on specific tumor and patient characteristics and away from the one-size-fits-all approach that has dominated this space for the last couple of decades. Emerging biomarker data, such as with ctDNA, suggests that immunotherapy may confer greater benefit to selected patients. Identifying who those patients are will be of paramount importance since additional treatments always come with additional toxicities. On the other hand, the more favorable toxicity profiles of certain immunotherapy-based regimens may make them superior options for some patients who would otherwise be unable to tolerate other systemic regimens. In the near future, it is likely that subsets of patients with MIBC will be receiving treatments with predominantly immunotherapy-based regimens while many patients may still be treated with regimens containing a cisplatin-based chemotherapy backbone. Currently ongoing clinical trials will help to better define patient populations optimized for each treatment.
目前，迫切需要开发新的治疗方案，因为许多肌层浸润性膀胱癌（MIBC）患者不符合当前以顺铂为基础的化疗作为新辅助治疗的标准治疗方案（SOC）。免疫检查点抑制剂（ICI）的应用，无论是作为单一药物治疗还是与其他ICI、化疗或靶向药物联合应用，都可能提供安全有效的治疗选择，从而彻底改变当前的标准治疗方法。在新辅助治疗中，来自 II 期临床试验的有力数据表明，单一药物免疫治疗以及双重检查点阻断可能成为传统以顺铂为基础的化疗的合理替代方案。将 ICI 与化疗或抗体药物偶联物联合使用的前瞻性研究也显示出了强大的疗效。然而，这些研究尚未改变实践，需要更大规模的随机研究数据来证实这一益处。在辅助治疗中，纳武单抗是基于随机试验中无疾病生存获益相对于安慰剂的 FDA 批准的治疗药物。然而，确认这种治疗方法的总生存获益并根据新的生物标志物数据更好地识别需要额外辅助治疗的患者将非常重要。肌层浸润性膀胱癌的治疗正在朝着基于特定肿瘤和患者特征的个体化治疗方案发展，而不是过去几十年中主导这一领域的一刀切方法。新兴的生物标志物数据，如 ctDNA，表明免疫治疗可能对某些患者有更大的获益。确定这些患者是谁将至关重要，因为额外的治疗总会带来额外的毒性。另一方面，某些基于免疫治疗的方案具有更好的毒性特征，这可能使它们成为某些无法耐受其他全身治疗方案的患者的更好选择。在不久的将来，可能会有一部分 MIBC 患者接受以免疫治疗为基础的治疗方案，而许多患者可能仍会接受以顺铂为基础的化疗方案。目前正在进行的临床试验将有助于更好地确定每种治疗方法的优化患者人群。
