Long-term survival outcomes did not differ between neoadjuvant chemoradiotherapy followed by surgery and surgery followed by adjuvant therapy among patients with locally advanced esophageal squamous cell carcinoma, according to findings from a phase 3 randomized clinical trial.
Following a median follow-up of 59 months, 5-year overall survival was 59% in both treatment groups, and 5-year disease-free survival exceeded 50% in each group. However, patients who achieved a pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (NCRT) had markedly better outcomes, with a 5-year overall survival of 77% compared with 52% among those who did not achieve pCR.
The trial was conducted at Sichuan Cancer Hospital in China between January 2018 and April 2020. Eligible patients were aged 18 to 75 years and had histologically confirmed, locally advanced thoracic esophageal squamous cell carcinoma (ESCC) staged as cT1N+M0 or cT2–4aNxM0. Patients were randomly assigned to receive NCRT followed by surgery or upfront surgery followed by adjuvant therapy selected by a multidisciplinary team.
Of 254 patients initially assessed, 230 were included in the final analysis, with 118 assigned to the NCRT group and 112 to the adjuvant therapy group. Baseline characteristics were balanced between groups. Most patients were male, and more than 90% of tumors were located in the middle or lower third of the esophagus.
Pathologic findings differed between treatment groups despite similar clinical staging at enrollment. More than half of patients who received NCRT were classified as pathologic stage I following surgery, while most patients in the adjuvant therapy group were classified as pathologic stage III. Rates of lymph node involvement, vascular invasion, and neural invasion were lower among patients who received NCRT. Among 118 patients in the NCRT group, 34 (29%) achieved pCR.
Safety outcomes were largely comparable. Overall rates of treatment-related adverse events and postoperative complications were similar between groups. Hematologic toxic effects, including leukopenia and neutropenia, were more frequent among patients who received NCRT, as were gastrointestinal toxic effects such as anorexia and vomiting. Most adverse events were mild to moderate, and severe toxic effects were uncommon. Complete tumor resection with negative margins was achieved in more than 95% of patients in both groups, and one patient in each group died within 30 days following surgery.
The researchers noted that the findings suggest surgery followed by adjuvant therapy remains a reasonable treatment option for patients with resectable disease, particularly for those less likely to achieve a meaningful response to NCRT. The survival benefit associated with neoadjuvant treatment was concentrated among patients who achieved pCR.
Strengths of the study included its randomized design and extended follow-up period. Limitations included its single-center setting and modest sample size. The researchers concluded that NCRT should not necessarily be universally recommended for all patients with locally advanced ESCC and that treatment strategies should account for the likelihood of achieving pCR.
The researchers reported no conflicts of interest.
Source: JAMA Network Open
