Recurrence in silent corticotroph adenomas after primary treatment: A systematic review and meta-analysis.

CONTEXT: 2017 WHO Classification of Pituitary Tumors grades silent corticotroph adenomas (SCAs) as "high-risk adenomas" due to their aggressive clinical behavior (high probability of recurrence). However, studies comparing recurrence rates of SCAs with other non-functioning pituitary adenoma (NFPAs) subtypes have provided conflicting results. OBJECTIVE: Estimate recurrence rates of SCAs after primary treatment (surgery±radiotherapy) and recurrence rate ratios (RRR) between SCAs and other NFPA subtypes. METHODS: Systematic review of published literature reporting on outcomes of SCAs up to October 31, 2017 was conducted. Recurrence rates, RRRs, 95% confidence intervals (CIs) were estimated from each study and pooled using random effects meta-analysis model. RESULTS: For determination of SCAs recurrence rates, 14 studies (low risk of bias, 297 patients) were selected; recurrence rate was 5.96 (95% CI, 4.3-7.84) per 100 person-years. Based on studies with mean follow-up <5 or ≥5 years, 25% (cumulative incidence 0.25; 95% CI, 0.13-0.38) and 31% (cumulative incidence 0.31; 95% CI, 0.23-0.40) of SCAs had recurrence, respectively. Recurrence rates after surgery or surgery+radiotherapy were 5.41 (95% CI, 3.28-7.96) and 4.88 (95% CI, 0.67-11.54) cases per 100 person-years, respectively. Analysis of 10 eligible studies (moderate risk of bias, 244 SCAs, 1622 NFPAs) showed no significant RRR (1.44; 95% CI, 0.9-2.33, p=0.130) between the groups. Focus on tumors treated solely by surgery also revealed no significant RRR (1.17; 95% CI, 0.79-1.75, p=0.429). CONCLUSIONS: Based on studies with mean follow-up ≥5 years, 31% of SCAs have recurrence. No evidence supporting higher recurrence risk of SCAs compared with other NFPA subtypes was found.