A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer.
A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer.
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在化学疗法的尿路上皮癌的分子分类中，预后的基因表达特征可以预测新辅助化学疗法的临床结局：剂量密度甲基二羟基甲氨蝶呤，vinblastine，doxorubibicin和cisplatin cisplatin convacizumab in revacizumab in erutothealial cancer cassplatin进行的2期试验。
DOI：
10.1016/j.eururo.2015.08.034
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发表时间：
2016-05
期刊：
影响因子：
23.4
通讯作者：
Siefker-Radtke AO
中科院分区：
文献类型：
--
作者：
McConkey DJ;Choi W;Shen Y;Lee IL;Porten S;Matin SF;Kamat AM;Corn P;Millikan RE;Dinney C;Czerniak B;Siefker-Radtke AO
基因表达谱（GEP）表明，肌层浸润性尿路上皮癌（UC）有三种亚型：预后最差的基底型; p53样型;管腔型。我们假设经尿道切除术（TUR）和膀胱癌标本的GEP可以预测可能从化疗中获益的亚型。探索接受剂量密集（DD）甲氨蝶呤、长春碱、多柔比星和顺铂（MVAC）和贝伐珠单抗（B）治疗的患者的临床结局以及UC亚型的影响。在2007年至2010年期间，60例患者入组了4个周期DDMVAC + B的新辅助治疗试验。分别从38例和23例患者以及49例接受围手术期MVAC治疗的患者的额外确认队列中获得了用于GEP的TUR和cytoplasmic标本。使用多变量考克斯回归和对数秩检验分析与结局的关系。化疗是积极的，pT 0 N 0和≤ pT 1 N 0的降级率分别为38%和53%，5年总生存率（OS）为63%。贝伐珠单抗对结局无明显影响。基底部肿瘤的生存率高于腔型和p53样肿瘤（5年OS分别为91%、73%和36%，对数秩p = 0.015），多变量分析结果相似。2年内骨转移仅与p53样亚型相关（p53样100%，管腔0%，基底0%; p ≤ 0.001）。肿瘤富含p53-样亚型在cyclic表明这种亚型的化疗耐药。另一个接受围手术期MVAC治疗的队列证实了UC亚型的生存获益（基础组5年OS为77%，管腔组为56%，p53样组为56%; p = 0.021）。局限性包括具有足够组织用于GEP的治疗前标本数量较少。GEP可预测临床UC结局。基础亚型与较好的生存率相关，p53样亚型与骨转移和化疗耐药相关。我们不能再将尿路上皮癌视为一种单一的疾病。基因表达谱鉴定尿路上皮癌的亚型，这些亚型在其自然史和对化疗的敏感性方面不同。
Gene expression profiling (GEP) suggests there are three subtypes of muscle-invasive urothelial cancer (UC): basal, which has the worst prognosis; p53-like; and luminal. We hypothesized that GEP of transurethral resection (TUR) and cystectomy specimens would predict subtypes that could benefit from chemotherapy. To explore clinical outcomes for patients treated with dose-dense (DD) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and bevacizumab (B) and the impact of UC subtype. Sixty patients enrolled in a neoadjuvant trial of four cycles of DDMVAC + B between 2007 and 2010. TUR and cystectomy specimens for GEP were available from 38 and 23 patients, respectively, and from an additional confirmation cohort of 49 patients treated with perioperative MVAC. Relationships with outcomes were analyzed using multivariable Cox regression and log-rank tests. Chemotherapy was active, with pT0N0 and ≤pT1N0 downstaging rates of 38% and 53%, respectively, and 5-yr overall survival (OS) of 63%. Bevacizumab had no appreciable impact on outcomes. Basal tumors had improved survival compared to luminal and p53-like tumors (5-yr OS 91%, 73%, and 36%, log-rank p = 0.015), with similar findings on multivariate analysis. Bone metastases within 2 yr were exclusively associated with the p53-like subtype (p53-like 100%, luminal 0%, basal 0%; p ≤ 0.001). Tumors enriched with the p53-like subtype at cystectomy suggested chemoresistance for this subtype. A separate cohort treated with perioperative MVAC confirmed the UC subtype survival benefit (5-yr OS 77% for basal, 56% for luminal, and 56% for p53-like; p = 0.021). Limitations include the small number of pretreatment specimens with sufficient tissue for GEP. GEP was predictive of clinical UC outcomes. The basal subtype was associated with better survival, and the p53-like subtype was associated with bone metastases and chemoresistant disease. We can no longer think of urothelial cancer as a single disease. Gene expression profiling identifies subtypes of urothelial cancer that differ in their natural history and sensitivity to chemotherapy.