| Summary: | Respiratory–digestive tract fistulas are fatal complications that occur in esophageal cancer treatment. Interdisciplinary treatment strategies are still evolving, especially in anatomical treatment stratification. Thus, this study aims to evaluate general therapeutic strategies for this rare condition. Medical records were reviewed for esophageal cancer-associated respiratory–digestive tract fistula patients treated between January 2008 and September 2021. Fistulas were classified according to being surgery- and tumor-associated. Treatment strategies, clinical success, and survival were analyzed. A total of 51 patients were identified: 28 had tumor-associated fistulas and 23 surgery-associated fistulas. Risk factors for fistula development such as radiation (OR = 0.290, p = 0.64) or stent implantation (OR = 1.917, <i>p</i> = 0.84) did not correlate with lack of symptom control for RDF patients. In contrast, advanced lymph node metastasis as another risk factor was associated with persistent symptoms after treatment for RDF patients (OR = 0.611, <i>p</i> = 0.01). Clinical success significantly correlated with bilateral fistula repair in surgery-associated fistulas (<i>p</i> = 0.01), while tumor-associated fistulas benefited the most from non-surgical (<i>p</i> = 0.04) or combined surgical and non-surgical intervention (<i>p</i> = 0.04) and a bilateral fistula repair (<i>p</i> = 0.02) in terms of overall survival. The therapeutic strategy should aim for bilateral fistula closure. A multidisciplinary, stepwise approach might have the best chance for restoration or symptom control with optimized overall survival in selected patients.
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