Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial

Abstract

NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.

18F FDG-PET/CT evaluation of histological response after neoadjuvant treatment in patients with cancer of the esophagus or gastroesophageal junction

“…show an clear link between pCR and short term survival, furthermore patients AC demonstrated a trend towards lower long-term survival, possibly as a result of mortality related to the treatment, and the opposite in patients with SCC (20). The same results were later observed in regard to long term survival where no significant differences were observed between the two treatment arms (21).…”

Machine learning to predict early recurrence after oesophageal cancer surgery

“…In this cohort, although the postoperative pathology was considerably more favourable after NACRT, the rate of early recurrence was no less, and tended to be higher (NACRT 35·5 per cent, NACT 27·5 per cent; P = 0·061 ( Table S2 , supporting information)). This suggests that, although postoperative pathology is more favourable with NACRT, this does not translate to better outcome; hence ypT3 N1 R0 status after NACT does not have the same meaning as a ypT3 N1 R0 result after NACRT, at least in the early phase after treatment. This is important in postoperative discussions with patients.…”

Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis

“…Whether neoadjuvant chemotherapy (NAC) is inferior in esophageal SCC compared to nCRT is yet unknown. The NeoRes trial with 181 AC and SCC patients compared NAC to nCRT but found no significant subgroup difference between histological subtypes [83]. Ongoing RCTs, like the Japanese NExT study (JCOG1109), will help elucidate if nCRT is preferred over NAC [131].…”

“…Prognostic factors for the curative treatment of esophageal cancer identified from OS multivariate analyses in at least one RCT. In total, there were 28 RCTs contributing to Figure 3 with 16 investigating neoadjuvant therapy [10,11,54,58,61,62,64,65,66,69,70,73,74,76,80,83], seven definitive chemoradiotherapy [57,60,71,72,75,82,98], three adjuvant therapy [67,77,79], and two radiotherapy alone [63,68]. * Potentially clinically relevant factors according to the criteria described in the method section.…”