Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.
Inserm, UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, IUH, Paris, France.
Eur Urol. 2018 Oct;74(4):474-480. doi: 10.1016/j.eururo.2018.01.042. Epub 2018 Feb 17.
Metastasectomy is routinely performed in selected patients with metastatic clear-cell renal cell carcinoma (ccRCC) as an alternative to systemic therapy. In the absence of randomized trials, the benefit and best way of patient selection remain unclear. Earlier, we described four molecular ccRCC-subtypes (ccrcc1-4) that have a prognostic and predictive value upon first-line sunitinib or pazopanib.
Assess the prognostic value of ccrcc1-4 subtypes after complete metastasectomy. (1) Compare outcomes of good-prognosis ccrccc2&3-tumors with intermediate/poor-prognosis ccrcc1&4-tumors. (2) Compare outcomes of the four subtypes separately.
DESIGN, SETTING, AND PARTICIPANTS: Single-center retrospective study (1995-2017), assessing 43 ccRCC patients undergoing complete metastasectomy without systemic treatment.
Molecular subtype determined with established 35-gene expression classifier.
Median disease-free survival (DFS), time to systemic therapy, cancer-specific (CSS) and overall survival (OS) from metastasectomy, estimated with Kaplan-Meier method and tested against other predictors with multivariable Cox regression.
Median DFS was 23 mo for ccrcc2&3-tumors versus 9 mo for ccrcc1&4-tumors (p=0.011, hazard ratio [HR]=2.6). Median time to systemic therapy was 92 mo versus 28 mo (p=0.003, HR=3.3). Median CSS was 133 mo versus 50 mo (p<0.001, HR=2.7). Median OS was 127 mo versus 50 mo (p=0.011, HR=2.5). The classification remained independent upon multivariable analysis. Outcomes remained significantly different when comparing four subtypes separately. The intrinsic heterogeneity of expression profiles is a limitation of this approach.
Even after clinical patient selection, patients with a ccrcc1- or ccrcc4-tumor are at a higher risk of relapse after complete metastasectomy. Patients with a ccrcc2- or ccrcc3-tumor usually experience a long DFS. These results need validation in a larger cohort to establish the subtypes as prognostic marker.
Metastasectomy is recommended for some patients with metastatic clear-cell kidney cancer; however, we do not know who will benefit the most. We show that molecular subtypes increase the possibility to predict which patients are at risk for early relapse after metastasectomy and who may benefit more from other treatment options.
在选定的转移性透明细胞肾细胞癌（ccRCC）患者中，转移切除术通常作为系统治疗的替代方法。在没有随机试验的情况下，其获益和最佳患者选择方法仍不清楚。我们之前描述了四种分子 ccRCC 亚型（ccrcc1-4），它们在一线舒尼替尼或帕唑帕尼治疗中具有预后和预测价值。
评估完全转移切除术后 ccrcc1-4 亚型的预后价值。（1）比较预后良好的 ccrccc2&3-肿瘤与中/差预后的 ccrcc1&4-肿瘤的结果。（2）分别比较四种亚型的结果。
设计、地点和参与者：单中心回顾性研究（1995-2017 年），评估 43 例接受完全转移切除术且未接受系统治疗的 ccRCC 患者。
采用已建立的 35 基因表达分类器确定分子亚型。
无复发生存期（DFS）、转移切除术至系统治疗时间、癌症特异性（CSS）和总体生存期（OS）的中位数，用 Kaplan-Meier 法估计，并与多变量 Cox 回归中的其他预测因素进行比较。
ccrcc2&3-肿瘤的中位 DFS 为 23 个月，而 ccrcc1&4-肿瘤为 9 个月（p=0.011，风险比[HR]=2.6）。中位至系统治疗时间为 92 个月与 28 个月（p=0.003，HR=3.3）。中位 CSS 为 133 个月与 50 个月（p<0.001，HR=2.7）。中位 OS 为 127 个月与 50 个月（p=0.011，HR=2.5）。多变量分析仍显示分类独立。当分别比较四种亚型时，结果仍有显著差异。表达谱的内在异质性是该方法的一个局限性。
即使在临床选择患者后，完全转移切除术后 ccrcc1-或 ccrcc4-肿瘤的患者复发风险仍然较高。ccrcc2-或 ccrcc3-肿瘤患者通常具有较长的 DFS。这些结果需要在更大的队列中进行验证，以确立亚型作为预后标志物。
转移性透明细胞肾癌患者推荐进行转移切除术；然而，我们尚不清楚哪些患者获益最大。我们表明，分子亚型增加了预测哪些患者在转移切除术后有早期复发风险的可能性，以及哪些患者可能从其他治疗选择中获益更多。
