ypN0: Does It Matter How You Get There? Nodal Downstaging in Esophageal Cancer

Abstract

Natural N0 and downstaged N0 patients are different clinical entities: downstaging cN+ with induction treatment producing downstaged N0 improves survival only if there is concomitant primary cancer downstaging to ypT0. Intermediate survival is seen in downstaged N0 patients with complete tumor response. Natural N0 patients experience intermediate survival with incomplete response (ypT+). Complete response in natural N0 patients produces the best survival. Means of obtaining ypN0 status matters and requires a complete response for downstaged N0 patients to benefit from induction treatment.

Evaluation of the American Joint Committee on Cancer 8th edition staging system for gastric cancer patients after preoperative therapy

“…Kim et al reported that survival of ypT0N1 patients was similar to that of stage II patients rather than that of stage I patients [13]. Zanoni et al reported that cN-positive status was associated with diminished survival among patients with ypN0 status, indicating that downstaged ypStage does not guarantee survival similar to that of ypStage without downstaging [14]. Verlato et al also reported that persistent ypN-positive status was associated with poor survival, regardless of pathological response in the primary tumor (tumor regression grade) [15].…”

Reliability of clinical nodal status regarding response to neoadjuvant chemoradiotherapy compared with surgery alone and prognosis in esophageal cancer patients

“…Even with current sophisticated diagnostic methods, preoperative LN staging remains uncertain with considerable high false negative rates [5,6]. In this study we found a nodal downstaged ratio of 56% after nCRT, including a 'true' downstaging due to the neoadjuvant treatment and the socalled 'natural' nodal downstaging through overestimation of cN stage [25]. Surgery alone provided a nodal downstaging of 25%, indicating that a substantial part of the post-nCRT nodal downstaging attributes to the inadequacy of pretreatment (a) (b) Figure 2.…”

“…The downstaging effect was even higher in cT1/T2 tumors (50%), but comparable to the nodal up and downstaging in cT3/T4 after nCRT, suggesting a generally high nodal overstaging and probably less CRT sensitivity in these advanced tumors. This potential overestimation of response might contribute to the reported large variety (25-42%) of complete responses [16,25,27].…”

“…Patients with pCR including a node-negative status (ypT0N0), have a lower recurrence risk and higher survival. While omission of surgery and a wait-and-see strategy have been suggested, predicting prognosis in clinical complete responders remains difficult, as ypT0N0 patients with nodal downstaging (cNþ to ypN0) appeared to have a lower survival compared with true equal staged (cN0 ¼ ypN0) patients [25,28]. This was also expressed in our study by a significant better prognosis of patients with nodal downstaging than those with nodal upstaging in both groups, probably due to true nodal negative tumors (Figure 2).…”

“…Nodal downstaging from cNþ to ypN0 can only be considered as potential sterilized effect of nCRT (true treatment response), but this may lead to a false treatment response in the true cN0 group (cN0 ¼ ypN0), which is partially based on incorrect assessment. This concept of nodal misstaging based on up-and downstaging is also influenced by histologic type and clinical T stage [25].…”