摘要:
Kenmotsu et al 1 have reported the results of the first randomized phase III study on adjuvant chemotherapy in high-grade neuroendocrine carcinoma (HGNEC). From 2013 to 2018, 221 patients evaluated with stage I-IIIA HGNEC were randomly assigned 1:1 to either cisplatin-etoposide or cisplatin-irinotecan. Unfortunately, the adjusted primary end point relapse-free survival did not show superiority for irinotecan. As the authors discuss in the publication, data on adjuvant treatment of small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) are scarce. Whereas the choice of platinum-etoposide may be well-accepted for SCLC, we would like to put forward this is less clear for LCNEC. Although LCNEC and SCLC are commonly grouped together as HGNEC, the question arises whether they should be evaluated as a single entity in a clinical trial. For example, we recently have reported that LCNEC rather should be considered a unique clinical entity because these tumors more commonly present with local (regional) disease compared with SCLC, 2 have radiologic features comparable with non–small-cell lung cancer (NSCLC), 3 and are often recognized on the initial biopsy specimen as NSCLC. 4 In addition, in case of local-regional disease (N1 or single-level N2) a preoperative NSCLC (mis)diagnosis may argue for surgical resection, whereas in SCLC any local-regional disease will likely result in concurrent chemoradiation therapy. This argument is reflected by the equal number of patients with SCLC and LCNEC enrolled in the trial but would not be expected based on the low incidence of LCNEC versus SCLC (1%-3% v 15%). Therefore, although the trial stratified for histology (ie, [combined] SCLC 53% and [combined] LCNEC 47%), bias might be introduced by differences in TNM classification with inclusion of more LCNEC with a higher TNM classification. Although a clinical stage IIIa was not an exclusion criteria for SCLC, none were included, whereas several cT3-4 (10%) and/or cN