Achalasia is a rare esophageal motility disorder defined by impaired lower esophageal sphincter (LES) relaxation and complete aperistalsis of the esophageal body. Its incidence is estimated at ~1/100,000 per year, with a prevalence near 10/100,000. A recognized long-term complication is esophageal squamous cell carcinoma (ESCC), occurring at rates ranging from 0.4% to 9.2% and significantly exceeding that of the general population. Despite compelling evidence of elevated risk, international guidelines still do not recommend routine endoscopic surveillance for achalasia patients. This study quantifies ESCC risk in end-stage achalasia — defined by longstanding stasis and sigmoid-shaped megaesophagus — and evaluates whether surgical correction mitigates cancer risk. We report a single-center cohort of patients undergoing Laparoscopic Heller-Dor (LHD), supplemented by a systematic review and meta-analysis of published literature.

All consecutive patients with radiologically confirmed end-stage achalasia undergoing LHD at the University of Padova between 2000–2025 were enrolled. Pre-operative diagnostics included endoscopy, barium swallow, and manometry. Post-operative surveillance consisted of endoscopy one year after surgery and every two years thereafter, aimed at detecting malignant transformation. Cancer prevalence and incidence rates were calculated. We additionally conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library (from inception to January 2025) to identify studies reporting ESCC in achalasia. Pooled prevalence, pooled incidence, rate ratios, and 95% confidence intervals (CIs) were estimated according to PRISMA standards.

Among 1,782 patients who underwent LHD for achalasia, 115 exhibited radiological stage IV disease (median age 55 y, IQR 42–63). After a median follow-up of 8.2 years (IQR 5.1–15.6), 4 patients (3.47%) developed ESCC, only one at early stage despite systematic postoperative endoscopic surveillance (Table 1). Three cases arose more than 10 years after surgery, and one occurred in a patient with persistent dysphagia after failed surgical outcome. By contrast, no ESCC cases were detected among the remaining 1,667 patients with stage I–II–III disease (median follow-up 10.2 y).

The systematic review identified 26 eligible studies spanning 13 countries, comprising 12,962 achalasia patients. Overall ESCC prevalence in achalasia was ~2%, with an incidence of 173 cases per 100,000 patient-years. Stratified analysis demonstrated substantially higher risk in end-stage disease, with an incidence of 724 vs 114 cases per 100,000 patient-years (rate ratio 6.34; 95% CI 3.24–12.38). Most tumors occurred in males (81%) and predominantly in the mid-thoracic esophagus (52%).

Conclusion: Patients with end-stage achalasia and sigmoid megaesophagus exhibit a significantly elevated ESCC risk that persists even after surgical correction. These findings support reconsideration of current guidelines and emphasize the need for structured, targeted endoscopic surveillance in this high-risk subgroup. Further prospective studies are warranted to define evidence-based surveillance strategies and to refine risk-stratification thresholds for early detection.