Optimal management of locally advanced esophageal squamous cell carcinoma

The NEOCRTEC5010 trial, the largest multi-institutional trial, proved the long-term overall survival benefit of trimodality treatment for resectable locally advanced esophageal squamous carcinoma cell (LA-ESCC) (1). In the invited comment by Ceppa et al. (2), the transthoracic approach with 3-field lymphadenectomy was considered the key. Actually, the standard procedure of the NEOCRTEC5010 trial is McKeown or Ivor Lewis esophagectomy with 2-field lymphadenectomy (3). We offer the following comments with respect to the quality, reproducibility, and utility of the technique.

Firstly, among all the potential reasons, while the advantage of the extent of lymphadenectomy earned mixed reviews, the standardization of circumferential marginal status and pathologic evaluation is on the same page. Unfortunately, the circumferential histologic margins were not assessed in the NEOCRTEC5010 trial, so the interpretation of the results of the R0 resection rate (98.4% vs. 91.2%; P=0.002) must be cautious. The complete pathological response (pCR, ypT0N0) rate of the NEOCRTEC5010 trial was 43.2%, comparing with 49% of ESCC in the CROSS trial (4). However, the pCR rates of external cohorts with CROSS regimen were only 24.6% in the real-world setting (5) and 27.7% in the latest phase 3 prospective randomized controlled trial (RCT) (6).

Secondly, the issue of variability by surgical procedure types and quality is emphasized by previous RCTs, which may reduce the generalizability of results from such clinical trials (7). In the CROSS trial, transthoracic and transhiatal esophagectomy were justified for tumors located in-between, taking into account patient and tumor characteristics and local preferences. It is hardly understood that the surgical approach did not affect survival in both study arms (8).

Finally, it’s worth noting that vinorelbine used in the NEOCRTEC5010 trial has not been approved with an indication for treatment of esophageal cancer by the Chinese National Medical Products Administration (NMPA) or U.S. Food and Drug Administration (FDA). Currently, we are conducting three registered multicenter phase 3 RCTs to compare different perioperative treatments aiming to determine the optimal multimodality treatment for LA-ESCC, which are preoperative chemotherapy followed by surgery versus surgery alone (NCT02442440), perioperative anti-PD-1 plus chemotherapy versus neoadjuvant chemotherapy only followed by surgery (ChiCTR2000040034), and adjuvant anti-PD-1 plus chemotherapy versus anti-PD-1 alone for non-pCR LA-ESCC yielded after neoadjuvant therapy (ChiCTR2100045651).

In summary, ours is not the task of fixing the entire world all at once but stretching to mend the part within our reach. The search for optimal management of LA-ESCC is still on the way.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Editorial Office, Annals of Esophagus. The article did not undergo external peer review.

Peer Review File: Available at https://aoe.amegroups.com/article/view/10.21037/aoe-21-59/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoe.amegroups.com/article/view/10.21037/aoe-21-59/coif). JQ serves as an unpaid editorial board member of Annals of Esophagus from November 2018 to October 2022. YL serves as the Editor-in-Chief of Annals of Esophagus. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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