Temozolomide as a salvage therapy in aggressive pituitary adenomas and pituitary carcinomas: a systematic review and meta-analysis

Objectives Aggressive pituitary adenomas (APAs) and pituitary carcinomas (PCs) are rare, highly invasive tumors characterized by rapid growth, therapeutic resistance, and frequent recurrence. Temozolomide (TMZ) has emerged as a systemic treatment option; however, data on its efficacy and outcomes, remain limited. This meta-analysis aims to assess the role of TMZ in these tumors by synthesizing clinicopathological characteristics, prior therapies, biomarkers, and by pooling survival, mortality, and outcomes to identify determinants of treatment response and prognosis. Methods This systematic review and meta-analysis were prospectively registered in PROSPERO (Registration number: CRD420261285267) and conducted according to PRISMA guidelines. A comprehensive literature search of major medical databases was performed to identify English-language studies published between 2000 and 2024 evaluating TMZ in APAs and PCs, with extraction of patient, tumor, treatment, and outcome variables. Study quality was assessed using Joanna Briggs Institute and Newcastle–Ottawa tools, and pooled outcomes were analyzed using random-effects models. Results Narrative synthesis shows that patients with APA and PC were (n=1,049) were predominantly male (61 %) with a mean age of 47.1 years. Most patients had received prior surgery (98 %) and radiotherapy (92 %). Tumors were often invasive macroadenomas or rare aggressive subtypes, with high proliferative indices and variable MGMT expressions. TMZ demonstrated partial or complete tumor responses, particularly in cases with low MGMT expression, though clinical outcomes varied widely. Meta analysis demonstrated that survival rates were 26.3 % (95 % CI: 18.9–35.1 %) for APA and 17.3 % (95 % CI: 10.5–27.3 %) for PC. Mortality was 5.9 % (95 % CI: 3.2–10.5 %) for APA and 21.9 % (95 % CI: 14.3–32.3 %) for PC, while recurrence rates were 13.8 % (95 % CI: 8.9–20.7 %) and 13.4 % (95 % CI: 8.1–21.6 %), respectively. Conclusions TMZ demonstrates meaningful clinical benefit in APA and PC, with improved survival and acceptable mortality and recurrence outcomes. Treatment response is influenced by tumor biology, prior surgery and radiotherapy, and MGMT expression. These findings support temozolomide as an effective salvage therapy and emphasize the need for standardized treatment protocols and prospective studies.