Surgical Management of Odontogenic Keratocyst and Recurrence: A Multicenter Retrospective Study

Background: Odontogenic keratocysts (OKC) recur frequently. We evaluated surgical outcomes and predictors of recurrence in OKC, using orthokeratinized odontogenic cysts (OOC) as a comparison group. Methods: In this multicenter retrospective study, 113 consecutive patients (54 OKC, 59 OOC) treated in four northwestern Italian centres in 2015–2025 were included. Recurrence-free survival was analysed with Kaplan–Meier and Cox methods (107 patients with ≥12 months’ follow-up); initial treatment was compared within OKC, and a sensitivity analysis excluded patients operated on before 2015. Results: Median follow-up was 4 years. A first recurrence occurred in 40/54 OKC (74.1%; 95% CI 60.3–85.0%) and 7/59 OOC (11.9%); 5-year recurrence-free survival was 37.0% versus 70.9% (p < 0.001), and OKC histotype was the only independent predictor (hazard ratio 5.76; 95% CI 2.47–13.45). Within OKC, initial treatment was not associated with recurrence (p = 0.810); in the incident cohort, the recurrence rate was 72.5%. None of the eight patients treated with adjuvant therapy (three OKC with topical 5-fluorouracil) recurred after a median follow-up of 2.5 years. Conclusions: In this real-world series, three-quarters of OKC recurred, and histotype was the dominant prognostic factor; the absence of recurrence after adjuvant therapy is hypothesis-generating and requires prospective confirmation with long-term follow-up.