Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher’s exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher’s exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

中文翻译：

---

微小残留病分析可预测食管鳞状细胞癌的病理完全缓解

准确的术前预测病理完全缓解（pCR）可以指导治疗决策，有可能避免不必要的手术并提高癌症患者的生活质量。我们开发了一种具有增强敏感性和特异性的微小残留病 (MRD) 分析方法，用于从游离 DNA (cfDNA) 中检测最小肿瘤 DNA。该方法在两个独立的食管鳞状细胞癌（ESCC）队列中得到了验证。在接受新辅助、手术和辅助治疗的队列（NAT 队列）中，术前 MRD 状态精确预测了 pCR。所有MRD阴性病例（10/10）均通过对切除组织的病理评估证实为pCR。相反，MRD 阳性病例包括所有 27 例非 pCR 病例和仅 1 例 pCR 病例（10/10 vs 1/28，P < 0.0001，Fisher 精确检验）。在确定性放疗队列（dRT 队列）中，dRT 后 MRD 状态与患者预后密切相关。所有 MRD 阴性患者 (25/25) 在随访期间均保持无进展，而 26 名 MRD 阳性患者中有 23 名出现疾病进展（25/25 vs 3/26，P < 0.0001，Fisher 精确检验；无进展生存期，P < 0.0001，对数秩检验）。 MRD 分析方法有效地预测了通过手术达到 pCR 的 ESCC 患者以及无需手术即可保持无进展的患者。这表明这些 MRD 阴性患者的癌细胞已被有效消除，他们可能是观察等待策略的合适候选者，有可能避免不必要的手术。