Recurrence of Silent Corticotroph Adenomas After Primary Treatment: A Systematic Review and Meta-Analysis

Context: The 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 nonfunctioning pituitary adenoma (NFPA) subtypes have provided conflicting results. Objective: To estimate recurrence rates of SCAs after primary treatment (surgery followed, or not, by radiotherapy) and recurrence rate ratios (RRRs) between SCAs and other NFPA subtypes. Methods: A systematic review of published literature reporting on SCA outcomes up to 31 October 2017 was conducted. Recurrence rates, RRRs, and 95% CIs estimated from each study were pooled using a random-effects meta-analysis model. Results: For determination of SCA recurrence rates, 14 studies (n = 297 patients) were selected; the recurrence rate was 5.96 (95% CI, 4.3 to 7.84) per 100 person-years. Based on studies with mean follow-up of <5 or >= 5 years, 25% (cumulative incidence, 0.25; 95% CI, 0.13 to 0.38) and 31% (cumulative incidence, 0.31; 95% CI, 0.23 to 0.40) of SCAs had recurrence, respectively. Recurrence rates after surgery or surgery and radiotherapy were 5.41 (95% CI, 3.28 to 7.96) and 4.88 (95% CI, 0.67 to 11.54) cases per 100 person-years, respectively. Analysis of 10 eligible studies (n = 244 SCAs; n = 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). Conclusion: Based on studies with mean follow-up >= 5 years, 31% of SCAs recur. No evidence supporting higher recurrence risk of SCAs compared with other NFPA subtypes was found.