Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma

Abstract

IMPORTANCEThe prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival.OBJECTIVE To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC. DESIGN, SETTING, AND PARTICIPANTSThe Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020.INTERVENTIONS Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m 2 of vinorelbine on days 1 and 8 and 75 mg/m 2 of cisplatin on day 1 or 25 mg/m 2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization. MAIN OUTCOMES AND MEASURESThe primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival.RESULTS A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC.

Comparison of outcomes between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in patients with locally advanced esophageal cancer: A network meta-analysis

“… [45] , [46] , [47] One newly published trial that only reported short-term outcomes with one year's follow up was excluded, [45] while two trials from our included studies (the NEOCRTEC5010 trial [5] and the CROSS trial [6] ) with updated long-term outcomes were included in the analysis. [ 46 , 47 ] Supplementary figure 12 summarized the network meta-analysis of OS on all included patients [ [9] , [10] , [11] , [12] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , 46 , 47 ], ESCC subpopulation [ [9] , [10] , [11] , [12] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , 46 , 47 ], and EAC subpopulation. [ [9] , [10] , [11] , 27 , 34 , 44 …”

“…[45À47] One newly published trial that only reported short-term outcomes with one year's follow up was excluded, [45] while two trials from our included studies (the NEO-CRTEC5010 trial [5] and the CROSS trial [6]) with updated long-term outcomes were included in the analysis. [46,47] Supplementary figure 12 summarized the network meta-analysis of OS on all included patients [9À12,27À43,46,47], ESCC subpopulation [9À12,27À43,46,47], and EAC subpopulation. [9À11, 27,34,44,47] Here, network meta-analysis on OS in all included patients shows that NCRT is superior to NCT (HR: 0¢83, 95%CrI: 0¢69À0¢99) and surgery (HR: 0¢72, 95%CrI: 0¢63À0¢82).…”

Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer

“…Although it is not difficult to conclude from the CROSS trial that the effects of nCRT on SCC seem larger than AC, it is hard to widely extrapolate this result because of the small fraction of SCC patients. The recently published NEOCRTEC5010 trial randomized 451 patients with SCC to receive either nCRT plus surgery or surgery alone [13]. The results showed that nCRT improved the 5-year survival compared to surgery alone group (59.9% vs. 49.1%, p = 0.025), which was more favorable than those of the CROSS trial [13].…”

“…The recently published NEOCRTEC5010 trial randomized 451 patients with SCC to receive either nCRT plus surgery or surgery alone [13]. The results showed that nCRT improved the 5-year survival compared to surgery alone group (59.9% vs. 49.1%, p = 0.025), which was more favorable than those of the CROSS trial [13]. Moreover, the R0 resection rate was higher in the nCRT group than surgery alone (98.4% vs. 91.2%, p = 0.002) and the pCR rate reached 43.2%.…”

“…The clinical outcome to different neoadjuvant therapy was also associated with the histological subtypes [9,10]. Despite nCRT and nCT exhibiting a high tumor response to patients with squamous cell carcinoma (SCC) and adenocarcinoma (AC), the nCRT group showed higher sensitivity and significant improvement of survival in SCC patients, while the tumor response was not translated to survival advantages in AC patients [9,[11][12][13]. In addition to the efficiency, the treatment protocols of nCT and nCRT also need to consider the toxicity and complications risk.…”