Shorter Surgery Gap, Better Outcomes: New Insights into Immunochemotherapy for Esophageal Cancer
A Look into New Treatment Strategies for a Difficult Disease
Esophageal cancer (EC) is among the most aggressive and deadly cancers worldwide. It ranks seventh in cancer incidence and sixth in mortality. Often diagnosed at an advanced stage, EC presents challenges for curative surgery due to local tumor invasion and lymph node spread. Standard treatment for resectable cases has long involved surgery following neoadjuvant chemoradiotherapy (nCRT). While nCRT improves overall survival and the rate of complete tumor removal (R0 resection), it carries significant drawbacks — including toxicity, adverse events, and postoperative risks, especially in esophageal squamous cell carcinoma (ESCC).
To address these issues, researchers have turned to neoadjuvant immunochemotherapy (nICT). This approach combines chemotherapy with immune checkpoint inhibitors (ICIs), aiming to activate the body’s immune system against cancer cells while reducing the side effects associated with radiotherapy. Although clinical trials have shown promise, real-world data and consistent conclusions have been limited.
A recent retrospective study from Anyang Tumor Hospital in China helps fill this gap. The research team, led by Xiaomin Wang and colleagues, analyzed data from 99 patients with resectable EC who received nICT followed by surgery. Their goal was to evaluate safety, effectiveness, and prognostic factors — including the potential role of blood immune markers in predicting tumor regression.
High Resection Rates and Encouraging Survival
One of the most promising findings was the R0 resection rate of 99%. This suggests that nICT can effectively reduce tumor burden and improve the chances of complete surgical removal. For comparison, previous studies like the NEOCRTEC5010 trial reported R0 rates of around 97% in nCRT-treated groups.
The one-year overall survival (OS) rate was 91.6%, and the one-year disease-free survival (DFS) rate was 49.3%. Although longer follow-up is needed to assess three- or five-year survival, these early results are encouraging.
“These findings suggest that nICT not only significantly improves the R0 resection rate but may also reduce the technical difficulty for surgeons in achieving complete resection,” the authors write.
Safety Profile: Fewer Serious Complications
The safety of nICT was another focus. During neoadjuvant treatment, 21.2% of patients experienced grade ≥3 adverse events (AEs). Most common were gastrointestinal symptoms (16.2%) and bone marrow suppression (4.0%). Notably, no deaths, surgical delays, or treatment interruptions were reported due to AEs.
In the postoperative phase, 10.1% experienced grade ≥3 surgical complications, with anastomotic leakage being the most frequent (6.1%). This rate is lower than that observed in some nCRT studies, suggesting better tolerability.
Timing Matters: The Importance of a Shorter Interval Before Surgery
A critical takeaway from this study is the importance of timing surgery within 34 days of the final nICT dose. Patients who underwent surgery within this window had significantly better overall survival compared to those with a longer interval.
The researchers propose that this may relate to how long the immune system remains activated after immunotherapy. A shorter interval may take advantage of peak immune responses, while delays could allow tumors to adapt or evade immune detection.
Which Drugs Make the Difference?
All patients received PD-1 inhibitors, with sintilimab being the most common (75.8%). However, the choice of PD-1 drug did not significantly impact survival outcomes.
On the other hand, the choice of chemotherapy mattered. Regimens combining paclitaxel and platinum-based agents, particularly cisplatin or nedaplatin, were associated with better survival than those involving oxaliplatin or other drugs.
Blood Markers as Predictive Tools
Another aspect of the study explored whether routine blood tests could help predict how well tumors respond to nICT. Two markers stood out:
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Neutrophil-to-lymphocyte ratio (NLR)
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Lymphocyte-to-monocyte ratio (LMR)
Patients with favorable NLR and LMR after treatment were more likely to show tumor regression. While the predictive power of these markers was moderate, the findings highlight their potential use in guiding treatment and surgical timing.
Practical Implications and Future Research
This study supports the use of nICT as a viable alternative to traditional nCRT for resectable EC. The high resection and early survival rates, combined with a more manageable safety profile, suggest a potential shift in clinical practice — particularly for patients who may not tolerate radiotherapy well.
Importantly, the findings also emphasize that treatment logistics, such as drug selection and surgical scheduling, can have a real impact on outcomes. Incorporating blood-based immune indicators could further refine patient selection and personalize therapy.
However, the authors caution that further research is needed. The study was retrospective, with a limited sample size and short follow-up. Large-scale, prospective trials are essential to confirm the findings and explore additional markers or treatment refinements.
Conclusion
Neoadjuvant immunochemotherapy shows promise as an effective and safe approach for patients with resectable esophageal cancer. With a 99% complete resection rate, a favorable safety profile, and emerging evidence on prognostic markers, nICT may soon become an important part of the treatment landscape.
As researchers and clinicians continue to fine-tune regimens, surgical timing and chemotherapy selection appear especially important. Meanwhile, tools like NLR and LMR could help guide future decisions — pointing toward a more personalized, data-driven future for esophageal cancer care.
The translation of the preceding English text in Chinese:
手术间隔越短，治疗效果越佳：免疫化疗治疗食管癌的新进展
探索食管癌治疗的新策略
食管癌（EC）是全球范围内侵袭性和致死率最高的癌症之一。其发病率排名第七，死亡率排名第六。由于诊断时常为晚期，局部肿瘤浸润和淋巴结转移使得根治性手术具有挑战性。长期以来，可切除病例的标准治疗方案是在术前接受新辅助放化疗（nCRT）。尽管nCRT能提高总体生存率和完全切除率（R0切除），但副作用明显，尤其对食管鳞状细胞癌（ESCC）患者而言，毒性、不良反应及术后风险较高。
为了解决这些问题，研究人员探索了新辅助免疫化疗（nICT）。这种方法将化疗与免疫检查点抑制剂（ICIs）结合，旨在激活身体的免疫系统攻击癌细胞，同时减少放疗相关的副作用。尽管临床试验表现出良好前景，但实际数据和一致的结论仍然有限。
中国安阳肿瘤医院最近的一项回顾性研究填补了这一空白。研究团队由王晓敏等人带领，分析了99名接受nICT后手术治疗的可切除食管癌患者的数据，评估其安全性、有效性和预后因素，包括血液免疫标志物在预测肿瘤退缩中的潜在作用。
切除率高、生存率令人鼓舞
研究发现最鼓舞人心的结果之一是99%的R0切除率。这表明nICT能有效减轻肿瘤负荷，提高手术完全切除的机会。相较之下，以往的研究如NEOCRTEC5010试验报道nCRT组R0切除率约为97%。
研究的一年总生存率（OS）为91.6%，一年无病生存率（DFS）为49.3%。尽管还需要更长的随访以评估三年或五年生存率，这些早期结果已十分令人鼓舞。
作者指出：“这些发现提示nICT不仅显著提高了R0切除率，还可能降低外科医生实现完全切除的技术难度。”
安全性分析：严重并发症较少
nICT的安全性也是研究重点之一。在新辅助治疗阶段，21.2%的患者经历了3级或更严重的不良反应，最常见的是胃肠道症状（16.2%）和骨髓抑制（4.0%）。值得注意的是，没有患者因不良反应导致死亡、手术延迟或治疗中断。
术后阶段，10.1%的患者出现了3级或更严重的手术并发症，最常见的是吻合口瘘（6.1%）。这一比率低于部分nCRT研究所报道的结果，表明nICT的耐受性可能更好。
时机至关重要：缩短治疗到手术的间隔
本研究的重要结论之一是手术应在nICT最后一次给药后的34天内进行。在此时间窗内接受手术的患者，其总生存率明显优于间隔较长的患者。
研究人员推测，这可能与免疫系统在免疫治疗后的活化持续时间有关。较短的间隔可利用免疫反应的峰值，而延迟可能让肿瘤适应或逃避免疫检测。
药物选择的重要性
所有患者均接受了PD-1抑制剂治疗，最常用的是信迪利单抗（75.8%）。不过，PD-1抑制剂的选择对生存结果并无显著影响。
然而，化疗方案的选择则有明显影响。使用紫杉醇联合顺铂或奈达铂的方案，其疗效优于奥沙利铂或其他药物。
血液标志物的预测价值
研究还探索了常规血液检测是否能预测肿瘤对nICT的反应效果。中性粒细胞与淋巴细胞比值（NLR）和淋巴细胞与单核细胞比值（LMR）两个指标显著：治疗后有良好NLR和LMR的患者更可能出现肿瘤退缩。虽然这些标记物的预测能力中等，但这些发现强调了它们在指导治疗和手术时机方面的潜力。
实际应用与未来研究
这项研究支持了nICT作为可切除食管癌传统nCRT替代方案的可行性。高切除率和早期生存优势，加上更易管理的安全性，预示着临床实践可能发生转变，尤其对无法耐受放疗的患者而言。
重要的是，研究还强调了药物选择和手术时机等治疗细节对结果的真实影响。加入基于血液的免疫指标可能进一步优化患者选择和个性化治疗。
不过，研究者提醒需进一步研究。本研究为回顾性研究，样本量有限且随访时间短。未来需开展大规模前瞻性试验，以验证这些结果并探索更多标记物和治疗细化策略。
结论
新辅助免疫化疗展现出良好的疗效和安全性，有望成为治疗可切除食管癌的重要方法之一。其99%的完全切除率、良好的安全性及新兴的预后标志物证据，表明nICT可能很快将融入食管癌的治疗体系。
随着研究人员和临床医生继续优化方案，手术时机和化疗药物选择显得尤为重要。同时，NLR和LMR等工具有助于指导未来的治疗决策，推动食管癌护理进入更加个性化和数据驱动的时代。
Reference:
Xiaomin Wang, Bingxu Li, Zhiyong Zheng, Weijie Wang
Neoadjuvant immunochemotherapy for resectable esophageal cancer: A study on efficacy and safety.
Biomol Biomed [Internet]. 2025 Apr. 1 [cited 2025 May 27];
Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/11806
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