Background

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.

Objective

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.

Intervention

Molecular subtype determined with established 35-gene expression classifier.

Outcome measurements and statistical analysis

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.

Results and limitations

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.

Conclusion

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.

Patient summary

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.

中文翻译：

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透明细胞肾细胞癌的分子亚型可在完全转移瘤切除后预后。

背景

转移性切除术通常在选定的转移性透明细胞肾细胞癌（ccRCC）患者中进行，以作为全身治疗的替代方法。在缺乏随机试验的情况下，尚不清楚患者选择的益处和最佳方法。早先，我们描述了四种分子ccRCC亚型（ccrcc1-4），它们对一线舒尼替尼或帕唑帕尼具有预后和预测价值。

客观的

评估完全转移灶后ccrcc1-4亚型的预后价值。（1）将预后良好的ccrccc2＆3肿瘤与预后中等/不良的ccrcc1＆4肿瘤的结果进行比较。（2）分别比较这四个亚型的结果。

设计，设置和参与者

单中心回顾性研究（1995-2017年），评估了43例未经系统治疗的ccRCC完全转移患者。

干涉

用已建立的35基因表达分类器确定分子亚型。

成果测量和统计分析

中位无病生存期（DFS），全身治疗时间，癌症转移治疗的癌症特异性（CSS）和总体生存期（OS），采用Kaplan-Meier方法进行评估，并与其他预测变量进行了多变量Cox回归检验。

结果与局限性

Ccrcc2＆3肿瘤的中位DFS为23 mo，而ccrcc1＆4肿瘤的中位DFS为9 mo（p  = 0.011，危险比[HR] = 2.6）。全身治疗的中位时间为92 mo与28 mo（p  = 0.003，HR = 3.3）。CSS的中位数为133 mo，而50 mo（p  <0.001，HR = 2.7）。中位OS为127 mo，而50 mo（p  = 0.011，HR = 2.5）。根据多变量分析，分类保持独立。当分别比较四种亚型时，结果仍然存在显着差异。表达谱的内在异质性是该方法的局限性。

结论

即使在临床患者选择之后，具有ccrcc1或ccrcc4肿瘤的患者在完全转移手术后仍具有较高的复发风险。患有ccrcc2或ccrcc3肿瘤的患者通常会经历较长的DFS。这些结果需要在更大的队列中进行验证，以将亚型确定为预后标记。

病人总结

对于某些转移性透明细胞肾癌患者，建议行转移灶切除术。但是，我们不知道谁会受益最大。我们显示，分子亚型增加了预测哪些患者转移瘤切除后有早期复发风险以及谁可能从其他治疗方案中受益的可能性的可能性。