Surgery versus radiotherapy for limited-stage small cell esophageal carcinoma: a multicenter, retrospective, cohort study in China (ChiSCEC)

Abstract

Background: There is no standard management for small cell esophageal carcinoma (SCEC). The purpose of this multicenter, retrospective study (ChiSCER) was to investigate the treatment, outcomes, and risk factors impacting survival endpoints in patients with limited-stage SCEC (LS-SCEC).

Materials and methods: Consecutive patients with LS-SCEC from 14 institutions between 2000 and 2020 in China were enrolled. Survival curves were constructed using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate Cox regression models and propensity score matching (PSM) analysis were adopted in the prognostic analysis. Results were reported as hazard ratio (HR), 95% confidence interval (CI), and P value. Statistical significance was set as P value <0.05 in a two-tailed test.

Results: Among 458 LS-SCEC patients, the median age was 63 [interquartile range (IQR), 57-68] years, and 318 (69%) were males. Eighty-four (18%), 167 (36%), and 207 (45%) patients received chemotherapy (CT) alone, CT plus definitive radiotherapy (CT+RT), and CT plus radical surgery (CT+S), respectively. With a median follow-up time of 58.7 (95% CI 48.9-68.6) months, the median overall survival (OS) and 3-year OS rate for all patients 24.3 (95% CI 21.6-27) months and 37.3% (95% CI 32.8-42.5%), respectively. Multivariate analysis indicated that treatment modes, Karnofsky performance status (KPS), TNM stage, and CT cycle were independent prognostic factors for OS ( P <0.05). Compared with CT alone, patients treated with CT+RT (HR 0.57, 95% CI 0.41-0.8, P =0.001) or CT+S (HR 0.59, 95% CI 0.42-0.82, P =0.002) had an improved OS, with no significant survival differences between CT+S and CT+RT groups after multivariate and PSM analyses ( P >0.05). Subgroup analysis indicated that compared with CT+RT, patients with tumor location at lower 1/3 (HR 0.59, 95% CI 0.37-0.93, P =0.03) or tumor length >5 cm (HR 0.52, 95% CI 0.3-0.9, P =0.02) could obtain significant OS benefit from CT+S. Patients with tumor location at middle 1/3 (HR 1.55, 95% CI 1.03-2.36, P =0.04) or tumor length ≤5 cm (HR 1.49, 95% CI 1.02-2.17, P =0.04) favored CT+RT. Distant metastasis accounted for 73.7% of all treatment failures after multidisciplinary treatments.

Conclusion: Surgery and RT were equally effective local therapies for patients with LS-SCEC. The personalized decision of local therapy should be made after comprehensive considerations on tumor location, length, comorbidities, and organ preservation.

Figure 1

Multivariate Cox HR for OS and PFS in LS-SCEC. CT, chemotherapy; CT+RT, chemotherapy plus radiotherapy; CT+S, chemotherapy plus surgery; EP, etoposide plus cisplatin or carboplatin; HR, hazard ratio; KPS, Karnofsky performance status; LS-SCEC, limited-stage small cell esophageal carcinoma; OS, overall survival; PFS, progression-free survival.

Figure 2

Kaplan–Meier survival curves of different treatment modes in LS-SCEC. (A) OS of CT alone, CT+RT, and CT+S groups in unmatched population; (B) PFS of CT alone, CT+RT, and CT+S groups in unmatched population; (C) OS of CT+RT and CT+S groups in matched population; (D) PFS of CT+RT and CT+S groups in matched population. CT, chemotherapy; CT+RT, chemotherapy plus radiotherapy; CT+S, chemotherapy plus surgery; LS-SCEC, limited-stage small cell esophageal carcinoma; OS, overall survival; PFS, progression-free survival.

Figure 3

Multivariate Cox HR of CT+S versus CT+RT in different subgroups. CT, chemotherapy; CT+RT, chemotherapy plus radiotherapy; CT+S, chemotherapy plus surgery; EP, etoposide plus cisplatin or carboplatin; HR, hazard ratio; KPS, Karnofsky performance status; LS-SCEC, limited-stage small cell esophageal carcinoma; OS, overall survival; PFS, progression-free survival.