Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
JAMA Surg. 2021 Dec 1;156(12):1093-1101. doi: 10.1001/jamasurg.2021.4992.
The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR.
To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality.
DESIGN, SETTING, AND PARTICIPANTS: CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible.
Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab.
The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol.
A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics.
Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited.
ClinicalTrials.gov Identifier: NCT01606098.
对于同时患有转移性结直肠癌（mCRC）且无法切除转移灶且原发肿瘤症状轻微或不存在的患者，原发肿瘤切除术（PTR）的作用尚不清楚。研究术后死亡率低的亚组可能有助于确定可能从 PTR 中受益的患者。
确定随机分配至单纯全身治疗组与 PTR 后全身治疗组之间 60 天死亡率的差异，并探讨与 60 天死亡率相关的危险因素。
设计、地点和参与者：CAIRO4 是一项于 2012 年启动的随机 3 期临床试验，其中 mCRC 患者被随机分配至单纯全身治疗组或 PTR 后全身治疗组（姑息性）。这项多中心研究由丹麦和荷兰结直肠癌小组在丹麦和荷兰的普通和学术医院进行。符合条件的患者包括 2012 年 8 月至 2019 年 12 月间经组织学证实的结直肠癌、不可切除的转移灶和症状轻微或不存在的原发性肿瘤患者。
全身治疗，包括基于氟嘧啶的化疗联合贝伐珠单抗与 PTR 后基于氟嘧啶的化疗联合贝伐珠单抗。
本分析的目的是比较两组治疗后的 60 天死亡率。次要目的是确定两组治疗中与 60 天死亡率相关的危险因素。这些目标在研究方案中没有预先设定。
共有 196 名患者纳入意向治疗分析（112 名男性[57%]；中位[IQR]年龄 65[59-70]岁）。单纯全身治疗组的 60 天死亡率为 3%（95%CI，1%-9%），PTR 组为 11%（95%CI，6%-19%）（P=0.03）。在符合方案分析中，60 天死亡率为 2%（95%CI，1%-7%）与 10%（95%CI，5%-18%；P=0.048）。随机分配至 PTR 后全身治疗的血清乳酸脱氢酶、天冬氨酸转氨酶、丙氨酸转氨酶和/或中性粒细胞升高的患者，60 天死亡率显著高于无这些特征的患者。
随机分配至 PTR 后全身治疗的 mCRC 患者 60 天死亡率高于随机分配至全身治疗的患者。特别是随机分配至 PTR 组且血清乳酸脱氢酶、中性粒细胞、天冬氨酸转氨酶和/或丙氨酸转氨酶升高的患者，术后死亡率风险较高。仍需等待总体生存的最终研究结果。
ClinicalTrials.gov 标识符：NCT01606098。
