Depth of invasion: Surgical management and outcomes for non-functioning pituitary neuroendocrine tumors in the cavernous sinus KNOSP 3 and 4.

[BACKGROUND] Nonfunctioning Pituitary Neuroendocrine Tumors (NFPitNETs) account for 14 %-54 % of all pituitary tumors and 10-15 % of primary intracranial tumors. Unlike functioning pituitary tumors, NFPitNETs are not associated with hormonal hypersecretion but can cause symptoms due to mass effects. These tumors may extend into critical areas, especially into the cavernous sinus, presenting surgical challenges. Subtotal resection, therefore, may occur and potentially lead to regrowth in 10 %-20 % of cases. This systematic review and meta-analysis aims to assess the safety and efficacy of surgical approaches for management of NFPitNETs classified as KNOSP grades 3 and 4, where significant or definite cavernous sinus invasion complicates surgical resection.

[METHODS] A search was conducted in Medline, Cochrane, Web of Science, and Embase. We have restricted our selection to articles published from 2000 to November 2023. Eligible studies included randomized and non-randomized studies with ≥5 patients reporting NFPitNETs Knosp III and IV with cavernous sinus invasion treatment efficacy and safety outcomes and studies reporting the endonasal endoscopic approach (EEA). Statistical analyses were carried out using R Studio, employing a random effects model and presenting results as proportions with 95 % confidence intervals.

[RESULTS] Fourteen studies were analyzed, encompassing 899 patients aged 15 to 81 years. The avarage follow-up time is 43.32 months. The gross total resection (GTR) rate was 31 % (95 % CI: 0.17 to 0.45, I = 97 %), and the subtotal resection rate was 69 % (95 % CI: 0.55 to 0.83, I = 97 %). The recurrence rate was 32 % (95 % CI: 0.32 to 0.67, I = 92 %). The CSF leak rate was 2 % (95 % CI: 0.00 to 0.05, I = 11 %), CN VI transient deficits rate of 1 % (95 % CI: 0.02 to 0.03, I = 0 %). Permanent diabetes insipidus rate was 3 % (95 % CI: 0.00 to 0.07, I = 20 %).

[CONCLUSION] Attempting GTR in Knosp 3-4 tumors is technically challenging and successful in a minority of cases, though serious complications are relatively low. The high rate of subtotal resections and recurrences suggests that many patients may require additional treatments, such as reoperation or radiotherapy. These findings highlight the complexity of managing advanced NFPitNETs and the need for further research to optimize surgical strategies and improve long-term tumor control.