Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis

Ferdinand Roelfsema, Nienke R. Biermasz, Alberto M. Pereira

To study the currently available data of recurrence rates of functioning and nonfunctioning pituitary adenomas following surgical cure and to analyze associated predisposing factors, which are not well established. A systematic literature search was conducted using Medline, Embase, Web of Science and the Cochran Library for studies reporting data on recurrence of pituitary adenoma after surgery, in nonfunctioning adenoma (NF), prolactinoma (PRL) acromegaly (ACRO) and Cushing's disease (CUSH). Of 557 initially retrieved potential relevant studies 143 were selected. Recurrence in NFA was defined as reappearance of tumor on MRI or CT. Increase of hormone levels above normal limits as set by the authors after initial remission was used to indicate recurrence in the functioning tumor types. Remission percentage was lowest in NFA compared with other tumor types (P < 0.001). Surgery-related hypopituitarism was more frequent in CUSH than in the other tumors (P < 0.001). Recurrence, expressed as percentage of the cured population or as ratio of recurrence and total patient years of follow-up was highest in PRL (P < 0.001). The remission percentage did not improve over 3 decades of publications, but there was a modest decrease in recurrence rate (P = 0.04). Recurrences peaked between 1 and 5 years after surgery. Most of the studies with a sufficient number of recurrences did not apply multivariate statistics, and mentioned at best associated factors. Age, gender, tumor size and invasion were generally unrelated to recurrence. For functioning adenomas a low postoperative hormone concentration was a prognostically favorable factor. In NFA no specific factor predicted recurrence. Recurrence rate differs between pituitary adenomas, being highest in patients with prolactinoma, with the highest incidence of recurrence between 1 and 5 years after surgery in all adenomas. Patients with NFA have a lower chance of remission than patients with functioning adenomas. The postoperative basal hormone level is the most important predictor for recurrence in functioning adenomas, while in NFA no single convincing factor could be identified.