Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

Abstract

SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved.

8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice

“…That prognostication based on cTNM differs from that based on pTNM reflects inaccuracies of obtaining cancer facts by current clinical staging modalities. These inaccuracies result in dissimilar stage group composition and survival profiles of cTNM vs. pTNM groups (2,(5)(6)(7).…”

“…The use of G, particularly the finding of cG3, which is associated with reduced survival, may facilitate decision-making and prognostication (6,21). cN EUS, CT, and fluorodeoxyglucose positron emission tomography (FDG-PET) afford regional lymph node imaging and are the principal non-invasive modalities for cN determination.…”

“…Clinical staging: prognostication Survival according to cTNM stage groups is "pinched together" compared with pathologic stage groups (2,3,5,6). …”

“…Staging of cancer of the esophagus and esophagogastric junction (EGJ), presented in chapter 16 of the 8th edition American Joint Committee on Cancer (AJCC) Cancer Staging Manual (1), was derived from a machine-learning analysis of data from six continents from the Worldwide Esophageal Cancer Collaboration (WECC) (2)(3)(4)(5)(6)(7). The purpose of this manuscript is to review staging in the 8th edition, which now includes clinical (cTNM), pathologic (pTNM), and postneoadjuvant therapy (ypTNM) stage groupings, and examine its application to clinical practice.…”

Cancer of the esophagus and esophagogastric junction: an 8th edition staging primer

“…The data driven analysis, however, indicates that discriminating outcomes for cT2N0 tumours is aided by differentiation with G1 tumours having a better prognosis than G2 or G3 for both histologic subtypes and may be a useful discriminator in clinical practice (17).…”