Background

Tumor budding (TB) is an adverse prognostic factor in colorectal cancer (CRC). International consensus on a standardized assessment method has led to its wider reporting. However, uncertainty regarding its clinical value persists. This study aimed to (1) confirm the prognostic significance of TB, particularly in stage II CRC; (2) to determine optimum thresholds for TB risk grouping; and (3) to determine whether TB influences responsiveness to chemotherapy.

Methods

TB was assessed in CRC sections from 1575 QUASAR trial patients randomized between adjuvant chemotherapy and observation. Optimal risk group cutoffs were determined by maximum likelihood methods, with their influence on recurrence and mortality investigated in stratified log-rank analyses on exploratory (n = 504), hypothesis-testing (n = 478), and final (n = 593) data sets.

Results

The optimal threshold for high-grade TB (HGTB) was ≥ 10 buds per 1.23 mm². High-grade TB tumors had significantly worse outcomes than those with lower TB: 10-year recurrence 36% versus 22% (risk ratio, 2.00 [95% CI, 1.62-2.45]; 2P < .0001) and 10-year mortality 50% vs. 37% (risk ratio, 1.53 [95% CI, 1.34-1.76]; 2P < .0001). The prognostic significance remained equally strong after allowance for other pathological risk factors, including stage, grade, lymphovascular invasion, and mismatch repair status. There was a nonsignificant trend toward increasing chemotherapy efficacy with increasing bud counts.

Conclusions

TB is a strong independent predictor of recurrence. Chemotherapy efficacy is comparable in patients with higher and lower TB; hence, absolute reductions in recurrence and death with chemotherapy should be about twice as large in patients with ≥ 10 than < 10 TB counts.

中文翻译：

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结直肠癌肿瘤出芽的预后和预测价值

背景

肿瘤出芽（TB）是结直肠癌（CRC）的不良预后因素。关于标准化评估方法的国际共识导致其报告范围更广。然而，关于其临床价值的不确定性仍然存在。本研究旨在 (1) 确认 TB 的预后意义，特别是在 II 期 CRC 中；(2) 确定结核病风险分组的最佳阈值；(3) 确定结核病是否影响对化疗的反应。

方法

对 1575 名 QUASAR 试验患者随机接受辅助化疗和观察的 CRC 切片进行了结核病评估。通过最大似然法确定最佳风险组截止值，并在探索性 (n = 504)、假设检验 (n = 478) 和最终 (n = 593) 数据的分层对数秩分析中研究它们对复发和死亡率的影响套。

结果

高级别结核病 (HGTB) 的最佳阈值是每 1.23 mm ² ≥ 10 个芽。高级别 TB 肿瘤的预后明显低于低级别 TB：10 年复发率分别为 36% 和 22%（风险比，2.00 [95% CI，1.62-2.45]；2 P < .0001）和 10 年死亡率50% 与 37%（风险比，1.53 [95% CI，1.34-1.76]；2 P < .0001）。在考虑其他病理危险因素（包括分期、分级、淋巴血管侵犯和错配修复状态）后，预后意义仍然同样强烈。随着芽数的增加，化疗疗效增加的趋势不显着。

结论

结核病是复发的强独立预测因子。较高和较低结核病患者的化疗效果相当；因此，在 ≥ 10 和 < 10 TB 计数的患者中，化疗后复发和死亡的绝对减少应该是两倍。