Abstract：
BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor.
METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098.
RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm.
CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.
METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098.
RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm.
CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.
摘要：
背景：在回顾性分析中，前期原发肿瘤切除（PTR）与同步不可切除转移性结直肠癌（mCRC）患者的总生存期（OS）更长相关。CAIRO4研究的目的是调查在全身治疗中增加前期PTR是否会导致无严重原发肿瘤症状的同步mCRC患者的生存获益。
方法：这项随机3期试验在荷兰和丹麦的45家医院进行。合格标准包括以前未经处理的mCRC，无法切除的转移，原发肿瘤没有严重症状.患者被随机（1：1）接受前期PTR，然后进行全身治疗或无前期PTR的全身治疗。全身治疗包括两组均采用基于氟嘧啶的一线化疗和贝伐单抗。主要终点是意向治疗人群的OS。这项研究在ClinicalTrials.gov注册，NCT01606098。
结果：从2012年8月到2021年2月，206例患者被随机分组。在意向治疗分析中，纳入204例患者(n=103，无前期PTR，n=101，前期PTR），其中116为男性（57％），中位年龄为65岁（IQR59-71）。中位随访时间为69.4个月。无前期PTR臂的中位OS为18.3个月（95％CI16.0-22.2），而前期PTR臂为20.1个月（95％CI17.0-25.1）（p=0.32）。在没有前期PTR的情况下，3-4级事件的数量为71（72％），在前期PTR的情况下为61（65％）（p=0.33）。在没有前期PTR的手臂中报告了3例可能与治疗有关的死亡（3％），在前期PTR手臂中报告了4例（4％）。
结论：在没有严重原发肿瘤症状的同步mCRC患者中，预先PTR治疗姑息性全身治疗不会导致生存获益。这种做法不应再被视为护理标准。
方法：这项随机3期试验在荷兰和丹麦的45家医院进行。合格标准包括以前未经处理的mCRC，无法切除的转移，原发肿瘤没有严重症状.患者被随机（1：1）接受前期PTR，然后进行全身治疗或无前期PTR的全身治疗。全身治疗包括两组均采用基于氟嘧啶的一线化疗和贝伐单抗。主要终点是意向治疗人群的OS。这项研究在ClinicalTrials.gov注册，NCT01606098。
结果：从2012年8月到2021年2月，206例患者被随机分组。在意向治疗分析中，纳入204例患者(n=103，无前期PTR，n=101，前期PTR），其中116为男性（57％），中位年龄为65岁（IQR59-71）。中位随访时间为69.4个月。无前期PTR臂的中位OS为18.3个月（95％CI16.0-22.2），而前期PTR臂为20.1个月（95％CI17.0-25.1）（p=0.32）。在没有前期PTR的情况下，3-4级事件的数量为71（72％），在前期PTR的情况下为61（65％）（p=0.33）。在没有前期PTR的手臂中报告了3例可能与治疗有关的死亡（3％），在前期PTR手臂中报告了4例（4％）。
结论：在没有严重原发肿瘤症状的同步mCRC患者中，预先PTR治疗姑息性全身治疗不会导致生存获益。这种做法不应再被视为护理标准。
