Department of Urology, Icahn School of Medicine at The Mount Sinai Hospital, New York, New York, USA.
Curr Opin Urol. 2024 Nov 1;34(6):464-470. doi: 10.1097/MOU.0000000000001221. Epub 2024 Sep 3.
Tumor-informed circulating tumor DNA (ctDNA) is an emerging biomarker in urothelial carcinoma. Recent clinical trials have investigated the integration of ctDNA into clinical decision-making in patients with muscle-invasive bladder cancer, their findings suggest that ctDNA may potentially revolutionize the way we stratify patients to different treatment modalities.
ctDNA informed from TURBT specimens was found to be prognostic of disease outcomes among patients with localized nonmetastatic bladder cancer. Detectable precystectomy ctDNA status was associated with worse survival outcomes. Additionally, ctDNA status was predictive of adverse disease on radical cystectomy, including the likelihood of disease upstaging, lymph node involvement, and having a locally advanced disease (≥pT3a). In the postcystectomy minimal residual disease (MRD) period, ctDNA status may refine patient selection to adjuvant therapy, and if validated by ongoing clinical trials, patients with undetectable postcystectomy ctDNA status may forgo adjuvant treatment, regardless of pathological stage. On the contrary, patients with pre or postcystectomy detectable ctDNA status may benefit from treatment intensification.
The integration of ctDNA in clinical decision-making has the potential to revolutionize the way we manage urothelial carcinoma by refining patient selection to different treatment modalities. This approach could ultimately lead to personalization of oncological care, with the potential to reduce both treatment-related and financial toxicity.
肿瘤相关循环肿瘤 DNA(ctDNA)是尿路上皮癌中一种新兴的生物标志物。最近的临床试验已经研究了 ctDNA 在肌层浸润性膀胱癌患者临床决策中的整合,他们的研究结果表明,ctDNA 可能会彻底改变我们对不同治疗方式的患者分层方式。
从 TURBT 标本中获得的 ctDNA 被发现与局限性非转移性膀胱癌患者的疾病结局具有预后意义。术前可检测到的 ctDNA 状态与较差的生存结果相关。此外,ctDNA 状态可预测根治性膀胱切除术后的不良疾病,包括疾病升级、淋巴结受累和局部进展性疾病(≥pT3a)的可能性。在术后微小残留疾病(MRD)期间,ctDNA 状态可能会细化辅助治疗的患者选择,如果正在进行的临床试验得到验证,那么术后 ctDNA 状态不可检测的患者可能无需接受辅助治疗,无论病理分期如何。相反,术前或术后可检测到 ctDNA 状态的患者可能受益于治疗强化。
ctDNA 在临床决策中的整合有可能通过改进对不同治疗方式的患者选择来彻底改变我们管理尿路上皮癌的方式。这种方法最终可能会实现肿瘤治疗的个体化,有可能降低治疗相关毒性和经济毒性。