Kroeger Nils, Lebacle Cédric, Hein Justine, Rao P N, Nejati Reza, Wei Shuanzeng, Burchardt Martin, Drakaki Alexandra, Strother Marshall, Kutikov Alexander, Uzzo Robert, Pantuck Allan J
Institute of Urologic Oncology at the Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, USA; Department of Urology, University of Greifswald, Germany.
Institute of Urologic Oncology at the Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, USA; Department of Urology, University Hospital Bicetre, APHP, University Paris-Saclay, Le Kremlin Bicetre, France.
Eur J Cancer. 2022 Jun;168:68-76. doi: 10.1016/j.ejca.2022.03.023. Epub 2022 Apr 20.
To elucidate which patients with clear cell renal cell carcinoma have the highest risk for disease relapse after curative nephrectomy is challenging but is acutely relevant in the era of approved adjuvant therapies. Pathological and genetic markers were used to improve the University of California Los Angeles Integrated Staging System (UISS) for the risk stratification and prognostication of recurrence free survival (RFS).
Necrosis, sarcomatoid features, Rhabdoid features, chromosomal loss 9p, combined chromosomal loss 3p14q and microvascular invasion (MVI) were tested in univariable and multivariable analyses for their ability to improve the discriminatory ability of the UISS.
In the development cohort, during the median follow-up time of 43.4 months (±SD 54.1 months), 50/240 (21%) patients developed disease recurrence. MVI (HR: 2.22; p = 0.013) and the combined loss of chromosome 3p/14q (HR: 2.89; p = 0.004) demonstrated independent association with RFS and were used to improve the assignment to the UISS risk category. In the current UISS high-risk group, only 7/50 (14%) recurrence cases were correctly identified; while in the improved system, 23/50 (45%) were correctly prognosticated. The concordance index meaningfully improved from 0.55 to 0.68 to distinguish patients at intermediate risk versus high risk. Internal validation demonstrated a robust prognostication of RFS. In the external validation cohort, there was no case with disease recurrence in the low-risk group, and the mean RFS times were 13.2 (±1.8) and 8.2 (±0.8) years in the intermediate and high-risk groups, respectively.
Adding MVI and combined chromosomal loss3p/14q to the UISS improves the ability to define the patient group with clear cell renal cell carcinomawho are at the highest risk for disease relapse after surgical treatment.
阐明哪些透明细胞肾细胞癌患者在根治性肾切除术后疾病复发风险最高是一项具有挑战性的任务，但在批准辅助治疗的时代却极为重要。病理和基因标志物被用于改进加利福尼亚大学洛杉矶分校综合分期系统（UISS），以对无复发生存期（RFS）进行风险分层和预后评估。
对坏死、肉瘤样特征、横纹肌样特征、9号染色体缺失、3p14q联合染色体缺失以及微血管侵犯（MVI）进行单变量和多变量分析，以检验它们改善UISS鉴别能力的能力。
在开发队列中，中位随访时间为43.4个月（标准差±54.1个月），50/240（21%）例患者出现疾病复发。MVI（风险比：2.22；p = 0.013）和3p/14q染色体联合缺失（风险比：2.89；p = 0.004）与RFS呈独立相关，并被用于改进UISS风险分类的分配。在当前的UISS高危组中，仅7/50（14%）例复发病例被正确识别；而在改进后的系统中，23/50（45%）例被正确预后。一致性指数从0.55显著提高到0.68，以区分中危和高危患者。内部验证显示RFS具有可靠的预后评估。在外部验证队列中，低危组无疾病复发病例，中危组和高危组的平均RFS时间分别为13.2（±1.8）年和8.2（±0.8）年。
在UISS中加入MVI和3p/14q联合染色体缺失可提高定义透明细胞肾细胞癌患者组的能力，这些患者在手术治疗后疾病复发风险最高。
