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利用分子特征预测基于顺铂的新辅助化疗后肌肉浸润性尿路上皮膀胱癌的反应:一项前瞻性临床研究。

Predictors of Response Following Neoadjuvant Cisplatin-Based Chemotherapy for Muscle Invasive Urothelial Bladder Cancer Using Molecular Profile: A Prospective Clinical Study.

作者信息

Elkarta Ahmed, Awadalla Amira, El-Hefnawy Ahmed, Mosbah Ahmed, Abolenein Hassan, Shokeir Ahmed

机构信息

Urology department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Center of Excellence of Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

出版信息

Clin Genitourin Cancer. 2024 Apr;22(2):38-46.e1. doi: 10.1016/j.clgc.2023.08.003. Epub 2023 Aug 10.

DOI:10.1016/j.clgc.2023.08.003
PMID:37758560
Abstract

OBJECTIVES

To predict response of patients with muscle invasive bladder cancer (MIBC) to neoadjuvant chemotherapy (NAC) through analysis of molecular profile assessed clinically (radiologically and by pathological examination of transurethral resection biopsy [TURBT] specimens) and definitively with histopathological examination after radical cystectomy (RC).

METHODS

In a prospective study, tumor biopsies were obtained from patients with urothelial MIBC (T2-4a N0-2 M0) during TURBT. Patients were eligible for RC received 4 cycles of cisplatin-based NAC. DNA repair genes (BRACA1, ERCC1) & CTR gene m-RNA expression levels were assessed in resected tissue. The response to chemotherapy was assessed clinically (radiologically & TURBT) following NAC. Response was re-assessed for 64 patients who underwent RC and predictors of cancer-free survival (CFS) were calculated. Receiver operating characteristic (ROC) curve was used to delineate cutoff value copes with the best sensitivity and specificity for prediction of response to NAC.

RESULTS

The study included 104 patients, 42 (40.4%) responded well to NAC clinically. Out of 64 patients who underwent RC, 26 (40.6%) showed good response to NAC. CFS at 18 months for patients who underwent RC was 60%. Statistical analysis showed that molecular profile was an independent predictor of good response to NAC both clinically and pathologically and also predicted better CFS.

CONCLUSION

Molecular profile could play a decisive role in early detection of patients with MIBC who will get benefit from preoperative NAC.

摘要

目的

通过分析临床评估(影像学以及经尿道膀胱肿瘤电切术[TURBT]标本的病理检查)的分子特征,并在根治性膀胱切除术后(RC)通过组织病理学检查最终确定,预测肌肉浸润性膀胱癌(MIBC)患者对新辅助化疗(NAC)的反应。

方法

在一项前瞻性研究中,在TURBT期间从尿路上皮MIBC(T2-4a N0-2 M0)患者获取肿瘤活检标本。符合RC条件的患者接受4个周期的基于顺铂的NAC。在切除的组织中评估DNA修复基因(BRACA1、ERCC1)和CTR基因的mRNA表达水平。NAC后通过临床(影像学和TURBT)评估化疗反应。对64例行RC的患者重新评估反应,并计算无癌生存率(CFS)的预测指标。采用受试者工作特征(ROC)曲线确定预测对NAC反应具有最佳敏感性和特异性的临界值。

结果

该研究纳入104例患者,42例(40.4%)临床对NAC反应良好。在64例行RC的患者中,26例(40.6%)对NAC显示良好反应。行RC患者18个月时的CFS为60%。统计分析表明,分子特征在临床和病理上都是对NAC良好反应的独立预测指标,并且还预测了更好的CFS。

结论

分子特征在早期检测将从术前NAC中获益的MIBC患者中可能起决定性作用。

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