Patel Mann, Moore Kyle, Lichtbroun Benjamin L, Stephenson Ryan D, Mayer Tina, Saraiya Biren, Golombos David, Jang Thomas, Packiam Vignesh T, Ghodoussipour Saum
Division of Urology, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Section of Urologic Oncology, Rutgers Cancer Institute, New Brunswick, NJ, USA.
Transl Cancer Res. 2024 Nov 30;13(11):6413-6429. doi: 10.21037/tcr-24-726. Epub 2024 Nov 11.
A standard of care for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Given recent improvements in NAC and the morbidity associated with RC, bladder-sparing therapy has been investigated as a promising treatment for patients with MIBC who experience a complete clinical response (CCR) to systemic therapy. However, clinical staging is unreliable, making it challenging to determine ideal candidates for bladder-sparing therapy. Our primary objective is to review the efficacy of NAC, strategies for determining a CCR as a surrogate for a complete pathologic response, and the emerging role of imaging, tumor genomics, and biomarkers in selecting candidates for bladder-sparing therapy.
We surveyed the literature for studies investigating the outcomes of current treatment modalities for MIBC and methods for determining a CCR following systemic therapy as well as the impact this has on pathologic staging. Studies employing imaging, tumor biomarkers, and genomics were included.
Clinical staging with cystoscopy or transurethral resection shows significant discordance with final pathology, with high rates of understaging. Multiparametric magnetic resonance imaging (mpMRI) has shown strong utility in determining the presence of MIBC, but it has yet to reliably identify CCR. Meanwhile, somatic DNA damage repair mutations and biomarkers such as circulating and urinary tumor DNA are strong predictors of recurrence, showing promise in predicting and monitoring a CCR to systemic therapy. Multiple ongoing trials are currently assessing the use of biomarkers and genomic analyses in determining eligibility for bladder-sparing therapy.
While no one method has reliably demonstrated the ability to detect a true CCR, a multimodal approach involving imaging, biomarkers, and genomic analyses holds promise. We eagerly await the results of clinical trials investigating these tools, which may allow for the safe recommendation of bladder-sparing therapy.
肌肉浸润性膀胱癌（MIBC）的标准治疗方案是基于顺铂的新辅助化疗（NAC），随后进行根治性膀胱切除术（RC）。鉴于NAC的近期进展以及与RC相关的发病率，对于经全身治疗获得完全临床缓解（CCR）的MIBC患者，膀胱保留疗法已被研究作为一种有前景的治疗方法。然而，临床分期不可靠，这使得确定膀胱保留疗法的理想候选者具有挑战性。我们的主要目的是回顾NAC的疗效、将CCR作为完全病理缓解替代指标的确定策略，以及成像、肿瘤基因组学和生物标志物在选择膀胱保留疗法候选者中的新兴作用。
我们检索了文献，以研究调查MIBC当前治疗模式的结果、全身治疗后确定CCR的方法及其对病理分期的影响。纳入了采用成像、肿瘤生物标志物和基因组学的研究。
膀胱镜检查或经尿道切除术的临床分期与最终病理结果存在显著不一致，分期不足的发生率很高。多参数磁共振成像（mpMRI）在确定MIBC的存在方面显示出强大的效用，但尚未可靠地识别CCR。同时，体细胞DNA损伤修复突变以及循环和尿液肿瘤DNA等生物标志物是复发的强预测指标，在预测和监测全身治疗的CCR方面显示出前景。目前多项正在进行的试验正在评估生物标志物和基因组分析在确定膀胱保留疗法资格方面的应用。
虽然没有一种方法能可靠地证明检测真正CCR的能力，但一种涉及成像、生物标志物和基因组分析的多模式方法具有前景。我们热切期待研究这些工具的临床试验结果，这可能允许安全推荐膀胱保留疗法。
