Brännbäck Anna, Mustonen Ivan, Laajala Teemu D, Vainio Paula, Lindskog Magnus, Kjellman Anders, Lundgren Per-Olof, Jaakkola Panu M, Mattila Kalle E
Department of Clinical Science, Intervention and Technology, Karolinska Institute Karolinska University Hospital Stockholm Sweden.
Department of Oncology and Radiotherapy and Fican West Cancer Centre University of Turku and Turku University Hospital Turku Finland.
BJUI Compass. 2025 Jul 21;6(7):e70047. doi: 10.1002/bco2.70047. eCollection 2025 Jul.
Adjuvant pembrolizumab has improved overall survival after surgery for clear cell renal cell carcinoma (ccRCC) with an intermediate-high and high risk of recurrence according to the inclusion criteria of Keynote-564 study, but non-RCC mortality is common during postoperative follow-up. We aimed to evaluate the competing risk of death after surgery in patients with ccRCC stratified according to the risk of recurrence with Keynote-564, Three-feature and Leibovich models.
A total of 1108 patients with ccRCC operated with curative intent between 2005 and 2021 before the use of adjuvant immunotherapy were identified from two academic centres in Finland and Sweden. Patients with cytoreductive nephrectomy, multiple kidney tumours or non-ccRCC were excluded. Baseline characteristics and survival outcomes were described, and the Kaplan-Meier method was used to estimate overall survival.
During the median postoperative follow-up of 5.0 years, 134 (12%) patients had died from RCC with a median time to death of 3.7 years (IQR 1.6-6.6) while for 220 (20%) patients the cause of death was other than RCC, most commonly other cancers (n = 59, 5%) and cardiovascular diseases (n = 54, 5%). According to the Keynote-564 criteria, 34 (3%) patients were classified as having high risk of recurrence, 336 (30%) patients intermediate-high risk and 738 (67%) patients low risk of recurrence with 41% of RCC deaths observed in this subgroup. Limitations of this study include the lack of information on performance status, comorbidities and systemic treatments for recurrent RCC.
In addition to deaths from RCC, deaths from other cancers and cardiovascular diseases were common after surgery for ccRCC. As 41% of RCC deaths were observed among patients currently excluded from adjuvant therapy, more research on patient selection for perioperative immunotherapy is needed as well as interventions improving the treatment of comorbidities and lifestyle after nephrectomy.
根据KEYNOTE-564研究的纳入标准，辅助性帕博利珠单抗改善了中高复发风险和高复发风险的透明细胞肾细胞癌（ccRCC）患者术后的总生存期，但非肾细胞癌死亡率在术后随访期间很常见。我们旨在评估根据KEYNOTE-564、三特征模型和莱博维奇模型按复发风险分层的ccRCC患者术后死亡的竞争风险。
从芬兰和瑞典的两个学术中心确定了2005年至2021年期间在使用辅助免疫治疗之前接受了根治性手术的1108例ccRCC患者。排除了减瘤性肾切除术、多发性肾肿瘤或非ccRCC患者。描述了基线特征和生存结果，并使用Kaplan-Meier方法估计总生存期。
在术后中位随访5.0年期间，134例（12%）患者死于肾细胞癌，中位死亡时间为3.7年（IQR 1.6-6.6），而220例（20%）患者的死亡原因不是肾细胞癌，最常见的是其他癌症（n = 59，5%）和心血管疾病（n = 54，5%）。根据KEYNOTE-564标准，34例（3%）患者被归类为复发风险高，336例（30%）患者为中高风险，738例（67%）患者为复发风险低，该亚组中观察到41%的肾细胞癌死亡。本研究的局限性包括缺乏关于复发肾细胞癌的体能状态、合并症和全身治疗的信息。
除肾细胞癌死亡外，ccRCC患者术后其他癌症和心血管疾病死亡也很常见。由于在目前被排除在辅助治疗之外的患者中观察到41%的肾细胞癌死亡，因此需要对围手术期免疫治疗的患者选择进行更多研究，以及改善肾切除术后合并症治疗和生活方式的干预措施。
