Postoperative Adjuvant Therapy Versus Surgery Alone for Stage IIB–III Esophageal Squamous Cell Carcinoma: A Phase III Randomized Controlled Trial

Abstract

Background. Retrospective studies have shown that adjuvant treatment improves survival of patients with stage IIB-III esophageal squamous cell carcinoma, but there is no evidence from prospective trials so far. Methods. Patients with pathological stage IIB-III esophageal squamous cell carcinoma were randomly assigned to receive surgery alone (SA), postoperative radiotherapy (PORT), or postoperative concurrent chemoradiotherapy (POCRT). PORT patients received 54 Gy in 27 fractions; POCRT group received 50.4 Gy in 28 fractions, plus concurrent chemotherapy with paclitaxel (135-150 mg/m 2 ) and cisplatin or nedaplatin (50-75 mg/m 2 ) every 28 days. The primary endpoint was disease-free survival (DFS), and secondary endpoint was overall survival (OS).Results. A total of 172 patients were enrolled (SA, n=54; PORT, n=54; POCRT, n=64). The 3-year DFS was significantly better in PORT/POCRT patients than in SA patients (53.8% vs. 36.7%; p = 0.020); the 3-year OS was also better in PORT/POCRT patients (63.9% vs. 48.0%; p = 0.025). The 3-year DFS for SA, PORT, and POCRT patients were 36.7%, 50.0%, 57.3%, respectively (p = 0.048). The 3-year OS for SA, PORT, and POCRT patients were 48.0%, 60.8%, 66.5%, respectively (p = 0.048). Conclusion. PORT/POCRT (especially POCRT) may significantly improve DFS and OS in stage IIB-III esophageal squamous cell carcinoma.Trial registration: clinicaltrials.gov (NCT02279134). The Oncologist 2021;9999:• • Implications for Practice: The results of this phase III study indicated that PORT/POCRT could significantly improve DFS and OS in stage IIB-III esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. In-field and out-of-field recurrences were comparable between the POCRT and PORT groups, which demonstrates the rationality and safety of the radiation field used in our study. The postoperative regimens in this trial might be accepted as a standard treatment options for pathological stage IIB-III esophageal cancer. Larger sample size prospective randomized trials to identify the value are warranted.

Severe radiation-induced lymphopenia during postoperative radiotherapy or chemoradiotherapy has poor prognosis in patients with stage IIB-III after radical esophagectomy: A post hoc analysis of a randomized controlled trial

“…According to the prospective randomized controlled trial by Ni et al. ( 43 ), for patients with pathological stage IIB–III esophageal squamous cell carcinoma after radical surgery, POCRT, which reduced the radiation field to 3 cm below the carina and reduced the radiation dose to 50.4 Gy, did not increase the in- or out-of-field recurrence. Additionally, the survival rate was more comparable than with the PORT.…”

Effectiveness evaluation of adjuvant concurrent chemoradiotherapy for patients with positron emission tomography‐staged esophageal squamous cell carcinoma after complete resection: A population‐based cohort study

“…Lv et al 6 reported 3‐year OS of 63% for ACCRT versus 51% for observation, whereas 65% versus 47% was observed in our study after PSW adjustment. In another recently published RCT (also limited by lack of mandatory PET), Ni et al 25 reported 3‐year OS of 66.5% for ACCRT versus 48% for observation ( p = 0.016). Hsu et al 26 reported the HR of death to be 0.63 when ACCRT was compared to observation, whereas we found the HR of death to be 0.58 in our study.…”

Genetic variant of ADH1C for predicting survival in esophageal squamous cell cancer patients who underwent postoperative radiotherapy

“…A phase III randomized controlled trial in China has demonstrated that postoperative treatment (PORT/POCRT) may significantly prolong the survival in these patients. The pathological TNM stage and treatment regimen can significantly affect the DFS and OS ( Ni et al, 2021 ). In our study, the TNM stage was also found as an independent prognostic factor for OS and DFS, but the predictive capability for survival was poor.…”

“…According to Xiao’s research conclusion, postoperative radiotherapy can effectively reduce the probability of locoregional recurrence for all patients and can improve the survival of stage III or positive lymph node metastatic esophageal carcinoma ( Xiao et al, 2003 ; Xiao et al, 2005 ). A randomized controlled trial of phase III suggested that postoperative radiotherapy, especially postoperative chemoradiotherapy, significantly improved DFS and OS in stage IIB–III esophageal squamous cell carcinoma ( Ni et al, 2021 ). Even for patients with relatively early-stage T2–3N0M0, it was also well documented that postoperative radiotherapy significantly increased the patients’ DFS and reduced the likelihood of the local regional recurrence rate ( Deng et al, 2020 ).…”