Clinical staging to differentiate T2 and T3 esophageal squamous cell carcinomas—essential details or just noise?

In a recent issue of the Journal of Thoracic Disease, Leng and colleagues presented a roundtable discussion between surgeons, medical and radiation oncologists, endoscopists, and pathologists on the challenges of differentiating cT2 from cT3 esophageal squamous cell carcinomas (ESCC) (1). Several salient points deserve discussion.

First, as detailed in their roundtable discussion, accurate clinical staging is essential to allocate ESCC patients to the most appropriate treatment algorithm. Unfortunately, the sum of the evidence in the literature suggests that current staging modalities (alone or in combination) are limited by poor accuracy for staging T2 tumors. While endoscopic ultrasound (EUS), computed tomography (CT) of the chest, abdomen and pelvis, and positron emission tomography (PET) play a critical role in esophageal cancer staging, each has its inherent limitations and hence can individually contribute to the inaccuracy of clinical staging. Though it is superior for T staging than either PET/CT or CT (2,3), EUS has limited accuracy for T2 tumors. One study using the Society of Thoracic Surgeons Database found that among patients with cT2N0 carcinoma who underwent upfront surgery, 46.7% were upstaged at esophagectomy (T3–4N0 or Tany N1–3) (4), a finding confirmed by other studies (3,5). Therefore, treatment decisions must take these inaccuracies into consideration when weighing the risk of undertreatment vs. overtreatment.

These difficulties in achieving accurate clinical T staging have important implications, because differentiating cT2N0M0 from cT3N0M0 ESCC impacts treatment decisions. While current National Comprehensive Cancer Network Guidelines suggest neoadjuvant therapy for cT3N0M0 ESCC, preoperative therapy does not benefit all patients with cT2N0M0 tumors, especially those with low-risk features [tumors <3 cm, well-differentiated tumors and no lymphovascular invasion (LVI)] (6,7). Indeed, both a systematic review and meta-analysis (7) and data from a multi-institutional collaboration of 26 high-volume esophageal centers (The Esophageal Cancer Study Group) (8) found no difference in recurrence rates or survival with neoadjuvant therapy, as compared with upfront surgery. However, given the inherent inaccuracies in staging cT2N0 tumors, one must weigh the risk of understaging (potential) T3 tumors and undertreating (occult) lymph node metastasis for tumors with high-risk features if upfront esophagectomy is entertained vs. the risk of overtreatment if the tumor is truly a low-risk pT2N0 tumor. Dysphagia and bulky tumor noted on cross sectional imaging are clues that a tumor is more than T2.

A more critical point than differentiating T2 from T3 is the need to accurately detect lymph node metastasis in the pretreatment setting, as most patients cannot tolerate a full course of adjuvant therapy after esophagectomy (9,10). Tumor size is one important factor that can be taken into consideration when assessing the risk of nodal disease. Indeed, a multi-institutional study from the Esophageal Cancer Study Group found that longitudinal tumor length was independently associated with 2.2-fold increased odds of lymph node metastasis on multivariable analysis (8). Radiographic and endoscopic modalities can be used to complement the use of high-risk tumor characteristics to predict lymph node metastasis. Similar to T staging, the strengths and limitations of these modalities for N staging must be appreciated. While PET is more sensitive than CT for detecting lymph node metastases (11,12), especially for distant nodal disease (13), EUS is superior for detecting regional nodal disease. Therefore, the combination of PET/CT and EUS is most useful. To further augment the accuracy of the combination of EUS and PET/CT, the maximum standardized uptake value of the primary tumor may be utilized as a predictive factor for occult nodal disease (5).

Multidisciplinary discussions are essential to allocate cancer patients to the most appropriate treatment plan. Such discussions, should take into consideration the strengths and limitations of existing modalities used in the clinical staging of ESCC patients. In the future, radiomics and artificial intelligence may further enhance our ability to accuracy stage ESCC patients.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article has undergone external peer review.

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-491/prf

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-491/coif). S.S.G. reports that he is a proctor for Intuitive Surgical Inc. and received speaker and proctoring honoraria from that company. The author has no other conflicts of interest to declare.

Ethical Statement: The author is 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.

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