Clinical Outcomes of Nonsurgical Retreatment in Teeth With Persistent Apical Periodontitis: A Systematic Review.

Persistent apical periodontitis is a common cause of endodontic failure. While nonsurgical retreatment (NS-ReTx) is the typical first-line option used to manage this condition, its reported success varies depending on clinical, radiographic, and methodological factors despite recent advances that improve case management. This systematic review aimed to assess the clinical and radiographic outcomes of NS-ReTx in teeth with persistent apical periodontitis. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, the databases of PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, and grey literature were searched for randomized and non-randomized clinical studies and case series involving ≥10 teeth reporting outcomes after orthograde retreatment from January 1988 to September 2025. The primary outcome was periapical healing assessed through radiography and/or cone-beam computed tomography (CBCT), and secondary outcomes were tooth survival and prognostic factors. Risk of bias was appraised using the Cochrane Risk of Bias 2.0 (RoB 2) tool, ROBINS-I, or the Newcastle-Ottawa Scale, as appropriate, and findings were synthesized narratively due to heterogeneity in outcome definitions, imaging modalities, and follow-up intervals. Thirty studies, comprising randomized controlled trials (RCTs) and cohorts, met the inclusion criteria. Across these studies, reports using strict radiographic criteria or CBCT generally described lower apparent healing rates than those using looser criteria and 2D radiographs, although the magnitude of this difference could not be reliably quantified across studies. Additionally, a favorable prognosis was consistently associated with the absence of preoperative lesions, smaller lesion sizes, adequate obturation and coronal seals, and specialist operators. Overall, NS-ReTx provides favorable outcomes for persistent apical periodontitis. Future research should standardize outcome definitions using validated frameworks (such as periapical index (PAI)-based radiographic criteria and CBCT-specific scoring systems) and adopt longer, more uniform follow-up periods to enable robust quantitative synthesis.