Introduction
Patients with multiple Lugol-voiding lesions (mLVLs) in esophageal squamous cell carcinoma (ESCC) were known to have an increased risk of metachronous ESCC or pharyngeal and laryngeal squamous cell carcinoma (PLSCC) following endoscopic resection (ER), necessitating intensive endoscopic surveillance. The Japan Esophageal Cohort study, a multicenter prospective study evaluating the cumulative incidence of metachronous ESCC after esophageal ER, demonstrated that ER was selected as the initial treatment for most newly detected metachronous ESCC (72/74 patients). However, in clinical practice, ESCC or PLSCC outside the indications for ER are occasionally detected. Additionally, patients with mLVLs are known to have a high risk of developing other secondary primary cancers, nonetheless, the long-term clinical course in this population remains unclear.
Aims & Methods
The aim of this retrospective study was to evaluate the long-term prognosis of patients with mLVLs after endoscopic submucosal dissection (ESD) for superficial ESCC. This study included patients with mLVLs who underwent ESD for primary ESCC at our institution between April 2008 and August 2016. The exclusion criteria were patients with non-curative resection after ESD requiring additional treatment, such as submucosal invasion, positive vertical margins (pVM1), or lymphovascular invasion (LVI), and patients with a follow-up period of less than one year. After esophageal ESD, endoscopic surveillance was conducted every six months to one year, and metachronous cancers were considered for treated if detected. The cumulative incidence of metachronous ESCC and PLSCC, as well as the cumulative incidence of metachronous major ESCC and PLSCC, and overall survival (OS) were evaluated. Major ESCC were defined as lesions outside the indications for ER or those in which ER was performed resulting in a non-curative resection. Major PLSCC were defined as lesions outside the indications for ER or endoscopic laryngopharyngeal surgery (ELPS), or those in which ER or ELPS were performed resulting in pVM1 or LVI.
Results
A total of 140 patients were included, with a median age of 69 years (range: 47-86), and 30 patients (21.4%) had a history of head and neck cancer. During the median follow-up of 8.8 years (range: 1.2–15.5), 85 patients (60.7%) developed metachronous ESCC, all of whom were initially treated with ER, and 81 (95.3%) managed with ER alone, including repeated ER. Meanwhile, 35 patients developed metachronous PLSCC, 30 (85.7%) of whom were managed with ELPS alone. The cumulative incidence of metachronous ESCC and PLSCC at 5/10 years was 47.5%/67.1% for ESCC, and 13.8%/35.4% for PLSCC, respectively. The cumulative incidence of metachronous major ESCC and PLSCC at 5/10 years was 0.8%/2.8% for ESCC, and 1.5%/1.5% for PLSCC. Additionally, 30 (21.4%) patients died during follow-up, including progression of superficial metachronous ESCC (n=1) and superficial metachronous PLSCC (n=2) under observation after detection due to poor performance status, recurrences of previously treated PLSCC (n=7), aspiration pneumonia (n=4), hematological malignancies (n=3), tongue cancer (n=2), and others (n=11). The 5- and 10-year OS rates were 92.4%/ 79.5%.
Conclusion
In patients with mLVLs, endoscopic surveillance including pharyngo-laryngeal area following ESD for ESCC enabled early detection of metachronous lesions, the majority of which were successfully treated with ER. However, deaths from other causes were not negligible, highlighting the importance of careful long-term systemic monitoring.