Conversion Surgery Following Immunochemotherapy in Initially Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma—A Real-World Multicenter Study (RICE-Retro)

Abstract

PurposeThe present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and MethodsIn this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.ResultsOne hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.ConclusionOur results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Comparison of immunochemotherapy and chemotherapy alone in conversion therapy for locally advanced unresectable esophageal squamous cell carcinoma

“…This study found that in patients with cT 4b ESCC, the induction regimen of preoperative PD-1 inhibitor combined with albumin-bound paclitaxel + cisplatin resulted in a better pCR rate than did the chemotherapy regimen of albumin-bound paclitaxel + cisplatin alone (23.1% vs. 6.7%). Our findings are consistent with the results reported by Huang ( 17 ) et al., which both confirm that immunochemotherapy results in a better pCR rate (22.4% vs. 6.7%) than does chemotherapy alone in the conversion treatment of cT 4b ESCC. The pCR rate after induction with preoperative chemotherapy in a previous study was 4% ( 9 ), which is similar to 6.7% for chemotherapy alone observed in this study.…”

Neoadjuvant chemoimmunotherapy for locally advanced esophageal squamous cell carcinoma: Data from literature review and a real‐world analysis

“…After searching for full‐text articles, 51 articles were further excluded because of duplicate publications, a lack of relevant subgroups, incomplete data, or other reasons (e.g., non‐English language). Finally, 27 articles published between 2017 and 2022, 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 were eligible for this meta‐analysis.…”

Immunotherapy for esophageal cancer: Where are we now and where can we go

“…Recent trials have indicated the utility of other ICIs targeting PD-1, and further, use of ICI combination therapy in the perioperative settings may enable high PCR rate, complete resection rate, and thus lead to better survival outcomes. Furthermore, due to the high PCR rate, ICI combination induction therapy may enable curative resection for initially unresectable cases[ 22 , 23 ], and may overcome the treatment results of the current standard chemoradiotherapy.…”