Supplementary Material for: Natural History of Postoperative Nonfunctioning Pituitary Adenomas: A Systematic Review and Meta-Analysis

Objective: Previous studies attempting to define the natural history of postoperative nonfunctioning pituitary adenomas (pNFPAs) were somewhat limited by selection bias and/or small numbers and/or lack of consistency among the study findings. The aim of this study was to scrutinize the literature in order to analyze the natural history of pNFPAs. Methods: Electronic database including MEDLINE, PubMed and Cochrane CENTRAL were searched. The literature relating to the patients with pNFPAs without postoperative radiotherapy and pharmacotherapy was collected. Eligible studies reported on the rate of tumor recurrence, the tumor growth-free survival rate (TGFSR) at 5 and 10 years, and/or the residual tumor volume doubling time (TVDT). Results: 19 studies met the criteria. The pNFPAs were divided into two groups: the pooled recurrence rate of group I without detectable residual tumor (371 patients) was 12% (95% CI 6–19%), the TGFSR at 5 and 10 years were 96% (95% CI 89–99%) and 82% (95% CI 65–94%), respectively. The pooled recurrence rate of group II with residual tumor (600 patients) was 46% (95% CI 36–56%), the TGFSR at 5 and 10 years were 56% (95% CI 41–71%) and 40% (95% CI 27–53%), respectively. The mean TVDT was 3.4 years (95% CI 2.4–4.5 years). Conclusions: pNFPAs, with or without detectable residual tumor, need stratification of treatment and radiological/endocrinological follow-up strategy. According to the TVDT, residual tumor regrowth is very slow, which permits an extensive and safe follow-up program for most patients.