Impact of neoadjuvant therapies on the risk for perioperative complications in patients with advanced thoracic oesophageal cancer

The phase III NExT study (JCOG 1109) compares the impact on perioperative complications of standard preoperative therapy with cisplatin plus 5-FU (CF) to that of docetaxel plus CF (DCF) or radiation with CF (CF-RT), in patients with potentially resectable, locally advanced oesophageal cancer. The three regimens used in this trial were associated with similar perioperative complication rates, although the RT-based therapy did seem to result in a higher rate of chylothorax.

Introduction

Preoperative treatments strategies for patients with advanced oesophageal cancer differ between continents. In Japan, preoperative cisplatin plus 5-fluorouracil (CF) before oesophagectomy and D2-3 lymphadenectomy has become the standard of care for advanced oesophageal cancer. In contrast, specialists in Western countries more frequently opt for preoperative chemoradiotherapy. However, to date there have not been any head-to-head comparison of both strategies. To address this issue, the phase III NExT study (JCOG 1109) looked at the incidence of perioperative complications in patients with potentially resectable, locally advanced oesophageal cancer treated with neo-adjuvant cisplatin plus 5-FU (CF), docetaxel plus CF (DCF) or radiation with CF (CF-RT).

Eligible patients (N= 546) were randomised to receive one of three preoperative therapies, followed by open or thoracoscopic oesophagectomy with regional lymphadenectomy. Surgical results, perioperative complications and clinical data were compared between the 3 treatments arms. Subsequently, uni- and multivariate analyses were used to look for potential risk factors for perioperative complications.

No increase in perioperative complications with DCF or CF-RT

Patient characteristics were well balanced between the 3 treatment arms. At the time of the presented analysis, the median number of harvested lymph nodes from patients who received CF-RT was significantly lower than that in patients who received CF (49 vs. 58, P <0.0001). Overall, the incidence of grade 2 perioperative complications was lower in patients who received DCF, compared to patients who received CF (44.8% vs. 56.2%, p= 0.036). In contrast, the incidence of grade 2 chylothorax was higher in patients who received CF-RT compared to those who received CF (5.1% vs. 1.1%, p= 0.032). However, the incidence of reoperation and intra-hospital deaths in patients who received DCF or CF-RT did not differ from rates observed in patients who received CF. Multivariate analyses further identified operation time and open oesophagectomy as independent risk factors for an increase in grade 2 perioperative complications. Also in this analysis, CF-RT was associated with an increase in occurrence of grade 2 chylothorax (RR: 4.84, P= 0.043).

Conclusions

The results of this trial show that, compared to preoperative CF,  DCF and CF-RT generally do not increase the risk for perioperative complications or mortality in patients with advanced oesophageal cancer receiving oesophagectomy. However, CF-RT did seem to be associate with a higher incidence of chylothorax.

Reference

Koyanagi K et al., Impact of preoperative therapy for locally advanced thoracic esophageal cancer on the risk of perioperative complications: Results from multicentre phase III trial JCOG 1109. Presented at ASCO GI 2021; Abstract no. 162.