Discussion
esophageal cancer, DFS, hypoproteinemia, ESCC, anastomotic leakage, hypokalemia
ESOPHAGEAL CANCER, CARDIAC ARRHYTHMIAS, OESOPHAGEAL CANCER, HYPOPROTEINEMIA, COMPLICATION, SURGICAL COMPLICATIONS, PRIMARY TUMOR
In the first Phase II randomized controlled study of PD-L1 inhibitor plus chemotherapy in the neoadjuvant treatment of locally advanced ESCC, treatment with socazolimab in combination with nab-paclitaxel and cisplatin demonstrated a better antitumor effect, with an MPR rate of 69.0% at the primary tumor site and an increase of 6.9% compared to chemotherapy alone, although there was no significant difference. This result is comparable to the MPR rate of 63.4% resulting from concurrent chemoradiotherapy with paclitaxel and cisplatin reported in a recently reported Phase III randomized controlled study [Currently, neoadjuvant concurrent chemoradiotherapy followed by surgery remains the primary treatment option for locally advanced ESCC. In this study, the pCR rate in the Socazolimab + TP group reached 41.4%, a level comparable to results reported for concurrent chemoradiotherapy in the CROSS and NEOCRTEC5010 studies [The pCR rate of the socazolimab plus nab-paclitaxel and cisplatin group was comparable to the rates reported in several Phase II studies of neoadjuvant therapy with PD-1 inhibitors for the treatment of esophageal cancer, indicating comparable efficacy of chemotherapy with PD-1 or PD-L1 inhibitors. For example, in the NIC-ESCC (2019) study, in which 51 ESCC patients were treated with a neoadjuvant therapy program consisting of camrelizumab in combination with nab-paclitaxel and carboplatin, the pCR rate was 39.2% [Fan et al., in a single-arm Phase II study, reported that only 13.3% of patients with locally advanced ESCC who underwent neoadjuvant chemotherapy (nab-paclitaxel combined with cisplatin) reached pCR [The median number of cycles of neoadjuvant treatment, proportion of patients receiving reduced dosage, and the overall incidence of Grade 3 or 4 AEs in the Socazolimab + TP group was comparable to that in the Placebo + TP group, although Grade 1 and 2 AEs were somewhat more prevalent in the Socazolimab + TP group than in the Placebo + TP group. There was a higher frequency of hypokalemia and hypoproteinemia in the Socazolimab + TP group than in the Placebo + TP group, possibly because of an increased incidence of gastrointestinal side effects and inadequate supportive care. In addition, irAE incidence was 25.0% in the Socazolimab + TP group, similar to levels (26.0%) reported in a Phase III study of pembrolizumab plus chemotherapy for treatment of esophageal cancer [In view of the complexity of esophageal cancer surgery and the possible confounding factors associated with different surgical procedures, we designed strict inclusion criteria, and all cases were uniformly treated by video-assisted thoracoscopic and laparoscopic surgery with three incisions for esophageal cancer (McKeown). Two-field lymph nodes (including the left and right para-laryngeal recurrent nerve lymph nodes) were completely dissected, and the surgical procedure was performed with strict quality control and recorded by video. An enhanced recovery after surgery (ERAS) protocol was applied, and the major surgical complications were counted, excluding cardiac arrhythmias. We harvested more dissected lymph nodes (the maximum numbers of lymph nodes dissected in the experimental and control groups were 69 and 99, respectively) and achieved a lower complication rate than reported in previous studies (3.4% patients with anastomotic leakage in our study compared with 22.0% in the CROSS study), which were closely related to minimally invasive esophagectomy with strict quality control after neoadjuvant chemoimmunotherapy and ERAS implementation.Our findings demonstrated that the rate of change in PET/CT metabolic parameters (specifically, SUVmax-DR) before and after neoadjuvant treatment had high predictive value for the effectiveness of neoadjuvant treatment for esophageal cancer. SUVmax-DR can be used to accurately identify the majority of patients achieving pCR and MPR, leading to more informed preoperative decisions. Multiple studies have demonstrated that SUVmax-DR and SUVmax after neoadjuvant treatment can predict DFS. We did not analyze the prognostic value of SUVmax-DR because of the limited follow-up time. However, due to the substantial overlap in SUVmax-DR, PET/CT was unable to discriminate pCR from MPR, as was also reported in a previous study [As a Phase II clinical trial, this study had several limitations. First, there is the possibility of bias due to the limited sample size, and thus, the results need to be further validated in a Phase III trial. Second, follow-up data are lacking, and whether the impressive pCR and MPR rates attained through this therapeutic approach translate into higher DFS or OS rates needs to be explored in future work. Finally, as this was the first study to focus on the combination of socazolimab with nab-paclitaxel and cisplatin as a treatment for esophageal cancer, comparison of our results to those of previous research was problematic because of the lack of preexisting evidence.