Epithelial thickness as a new predictor of recurrence in oral leukoplakia after photodynamic therapy: a retrospective cohort study

Background Recent studies have reported encouraging clinical efficacy of photodynamic therapy (PDT) for oral leukoplakia (OLK), yet limitations remain, including inconsistent outcomes across centers, incomplete analysis indicators, and insufficient prognostic accuracy. This retrospective cohort study aimed to evaluate the efficacy of PDT for OLK and to explore potential influencing factors. Methods A total of 60 patients with clinically and pathologically confirmed OLK were enrolled. All patients received one or more sessions of PDT with 5-aminolevulinic acid (5-ALA). Initial response was assessed at 1 ~ 3 weeks after the first session, and short-term efficacy was evaluated at 4 weeks after the final session. All patients were subsequently followed up to monitor lesion recurrence and malignant transformation. Univariate and multivariate logistic regression models were used to identify factors associated with treatment response. Kaplan–Meier survival analysis with log-rank test and Cox proportional hazards regression models were applied to analyze risk factors for recurrence. Results Assessment after the first treatment demonstrated a mean lesion area reduction of 40.3%, with an initial total response (ITR) rate of 78.3%. After the final treatment, the mean reduction in lesion area was 74.4%. Complete response (CR), partial response (PR), and no response (NR) were achieved in 30.0%, 60.0%, and 10.0% of patients, respectively, resulting in a total response (TR) rate of 90.0%. During a mean follow-up of 10.8 months, recurrence occurred in 26 patients (48.1%), and two patients (3.3%) developed malignant transformation. Multivariate Cox analysis identified that lesions with epithelial thickness ≥ 400 μm (HR: 6.88, p = 0.005), non-smoking status (HR: 0.18, p = 0.025), and lesion location in a dangerous region (HR: 8.62, p = 0.027) were associated with an increased risk of recurrence. Conclusion ALA-PDT is an effective treatment for OLK, demonstrating favorable efficacy in both initial and short-term response. Epithelial thickness is a novel predictor for recurrence risk, alongside established factors such as smoking history and lesion location in a dangerous region. Nevertheless, vigilant long-term monitoring remains essential due to a non-negligible rate of recurrence. Trial registration chictr.org.cn, identifier ChiCTR2500099540 (March 25, 2025).