Treatment resistance in potentially malignant disorders—‘Nature’ or ‘Nurture’…?

Background Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate ‘high‐risk’ mucosal lesions. Although the majority of patients achieve disease‐free status post‐treatment, others develop further or persistent disease unresponsive to intervention. Methods A detailed, retrospective clinico‐pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO 2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). Results A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease‐free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia ( P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease‐free status ( P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision ( P = .027). Conclusion Despite clinico‐pathological profiling of treatment resistant patients, the precise inter‐relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure.