Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients and Methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85),p< 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53),p< 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98),p= 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18),p< 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant. Conclusion: Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes.
转移性结直肠癌（mCRC）是一种异质性疾病，可能导致同一患者体内不同病灶对治疗产生不一致的反应。实体瘤疗效评价标准（RECIST）未考虑这种反应异质性。本研究探索并建立了基于病灶的测量反应标准，以评估其对总生存期（OS）的预后影响。患者与方法：纳入17项一线临床试验中基线期至少存在2个病灶、并在12周内接受再分期扫描的mCRC患者。根据12周扫描结果，将每位患者的病灶分为进展病灶（PL：最长径增加>20%）、缓解病灶（RL：最长径减少>30%）或稳定病灶（SL：既非PL也非RL）。为每位患者定义基于病灶的反应标准：仅PL、仅SL、仅RL及混合反应（RL、SL和PL并存）。采用分层多变量Cox模型分析病灶反应标准与OS的相关性，并使用C统计量评估OS与分类标准的一致性。结果：在来自17项一线研究的10,551例mCRC患者中，51.6%的患者存在混合反应，其中3.3%在12周时出现RL/PL并存。在RL/SL并存的患者中，52%按RECIST 1.1标准评估为疾病稳定（SD），其OS（中位OS=19.9个月）长于仅SL患者（中位OS=16.8个月，HR=0.81[0.76-0.85]，p<0.001），但短于仅RL患者（中位OS=25.8个月，HR=1.42[1.32-1.53]，p<0.001）。在SL/PL并存的患者中，74%按RECIST 1.1评估为SD，其OS（中位OS=9.0个月）长于仅PL患者（中位OS=8.0个月，HR=0.75[0.57-0.98]，p=0.040），但短于仅SL患者（中位OS=16.8个月，HR=1.98[1.80-2.18]，p<0.001）。这些关联在不同治疗方案亚组中保持一致。基于病灶的反应标准与OS的一致性略高于RECIST 1.1，但无统计学显著性。结论：接受一线治疗的mCRC患者在首次再分期时出现混合反应较为常见。本研究建立的基于病灶的测量标准能更好地区分死亡风险，可能为治疗决策提供信息并影响患者预后。
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