Incidental diffuse low-grade gliomas: A systematic review and meta-analysis of treatment results with correction of lead-time and length-time biases.

Background: Better overall survival (OS) reported in patients with incidental diffuse low-grade glioma (iLGG) in comparison to symptomatic LGG (sLGG) may be overestimated by lead-time and length-time.

Methods: We performed a systematic review and meta-analysis of studies on adult hemispheric iLGGs according to the PRISMA statement to adjust for biases in their outcomes. Survival data were extracted from Kaplan-Meier curves. Lead-time was estimated by 2 methods: Pooled data of time to become symptomatic (LTs) and time calculated from the tumor growth model (LTg).

Results: We selected articles from PubMed, Ovid Medline, and Scopus since 2000. Five compared OS between patients with iLGG (n = 287) and sLGG (n = 3117). The pooled hazard ratio (pHR) for OS of iLGG to sLGG was 0.40 (95% confidence interval [CI] {0.27-0.61}). The estimated mean LTs and LTg were 3.76 years (n = 50) and 4.16-6.12 years, respectively. The corrected pHRs were 0.64 (95% CI [0.51-0.81]) by LTs and 0.70 (95% CI [0.56-0.88]) by LTg. In patients with total removal, the advantage of OS in iLGG was lost after the correction of lead-time. Patients with iLGG were more likely to be female pooled odds ratio (pOR) 1.60 (95% CI [1.25-2.04]) and have oligodendrogliomas (pOR 1.59 [95% CI {1.05-2.39}]). Correction of the length-time bias, which increased the pHR by 0.01 to 0.03, preserved the statistically significant difference in OS.

Conclusions: The reported outcome in iLGG was biased by lead-time and length-time. Although iLGG had a longer OS after correction of biases, the difference was less than previously reported.