Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction.

BACKGROUND: Neoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT. PATIENTS AND METHODS: This multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm. RESULTS: The trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms. CONCLUSION: The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival. CLINICALTRIALSGOV: NCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).