This study aimed to measure the incidence of tumor progression among patients that underwent endoscopic transsphenoidal surgery for pituitary adenomas, as well as the performance of the molecular and radiological factors that are commonly associated with progression. Patients of both adult and pediatric populations with pituitary adenomas who were treated for the first time with endoscopic transsphenoidal surgery in a single tertiary care center, between June 2006 and December 2019, were included. Clinical features, laboratory results, imaging findings, and molecular test results were collected. Progression or recurrence was measured in a follow-up MRI. Eighty-eight patients were included. 19.5% presented gonadotroph adenomas and null-cell adenomas, followed by corticotrophs (17.2%) and somatotrophs (13.8%). 20.7% had cellular atypia, 26.2% had p53 expression, and up to 79.5% had Ki-67 under 3%. On postoperative MRI (available for 90.9% of patients), 43.8% had tumor residue. Tumor progression occurred in 32 patients (36.4%). The median progression-free survival time was 5.37 years (95% CI = 3.29–N/A). Cellular atypia, Ki-67 elevation, cavernous sinus invasion, and tumor residue were suggested as significant prognostic factors. Nonetheless, the multivariate time-to-event analysis identified tumor residue as the only factor significantly associated with progression: HR = 4.0, 95% CI = 1.56–10.31. Residual tumor in postoperative imaging aids as a predictor for tumor progression and the invasion of the cavernous sinus, presence of cellular atypia, and a proliferation index (Ki-67) above 3% influence the speed at which the progression appears, therefore not being a predictive factor but rather a modifier of the progression.
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