Minimally invasive interventions for atrophic acne scars: a PubMed/PMC-based systematic evidence review and exploratory network meta-analysis toward phenotype-guided interpretation.

BACKGROUND: Atrophic acne scars represent heterogeneous structural problems rather than a single treatment indication. This review compared minimally invasive, energy-based, and regenerative interventions and discussed, at a conceptual level, how sparse comparative evidence might generate phenotype-aware hypotheses for future trials. METHODS: This PROSPERO-registered PubMed/PMC-based review (CRD420261471957) searched PubMed/MEDLINE and PMC open-full-text records from inception to 20 June 2026. The database-limited strategy was chosen to prioritize records with verifiable source tables and reproducible aggregate data for exploratory network meta-analysis. Reference lists and accessible trial-registry records were checked for supplementary verification, but Embase, CENTRAL, Web of Science, Scopus, ClinicalTrials.gov, WHO ICTRP, and grey-literature sources were not systematically searched; therefore, eligible studies outside the PubMed/PMC-accessible evidence base may have been missed. Randomized and split-face randomized trials reporting extractable clinical scar-severity outcomes were synthesized using frequentist random-effects network meta-analysis; clinical heterogeneity was assessed by node definitions, treatment protocols, device platforms, outcome scales, and effect modifiers, with sensitivity analyses varying assumed within-person correlations for split-face trials. RESULTS: Nine randomized trials, 19 treatment arms, 11 direct comparisons, and 10 nodes formed a sparse connected network. Compared with laser monotherapy, numerically lower post-treatment severity point estimates were observed for laser plus PLLA (SMD -0.69, 95% CI -1.55-0.18; 95% prediction interval -1.80-0.42), laser plus PRP (SMD -0.20, 95% CI -0.81-0.40; 95% prediction interval -1.12-0.72), and microneedling plus chemical peel (SMD -0.14, 95% CI -1.34-1.07; 95% prediction interval -1.53-1.25), although all confidence and prediction intervals crossed the null. No closed loop from independent designs was available for formal inconsistency testing. Heterogeneity was moderate to substantial (tau2 = 0.124; I2 = 65.3%, 95% CI 0.0% to 92.1%), most nodes were supported by one or two studies, and sensitivity analyses changed the top-ranked treatment; therefore, P-scores were treated only as descriptive exploratory statistics and a reliable treatment ranking does not currently exist. CINeMA rated comparisons as low or very low confidence. No included trial reported treatment effects by scar morphology, so phenotype-based comparative efficacy could not be tested. CONCLUSIONS: Some combination strategies had numerically lower point estimates, but the network is too sparse and uncertain to support a dependable treatment hierarchy or any definitive between-treatment claim. Because included trials did not report phenotype-stratified results, the phenotype-guided component should be read only as a conceptual, hypothesis-generating interpretation and not as phenotype-specific treatment guidance. EVIDENCE CERTAINTY: Low to very low across network comparisons; exploratory therapeutic evidence synthesis rather than a definitive treatment-ranking claim. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD-420261471957, PROSPERO: CRD420261471957.