UNLABELLED: Somatotroph-pituitary neuroendocrine tumors (PitNETs) represent one of the most prevalent functional pituitary adenoma subtypes. Achieving biochemical remission has been established as the primary determinant for improving quality of life in affected patients. Nevertheless, current clinical outcomes demonstrate suboptimal remission rates in cases of invasive somatotroph-PitNETs, predominantly attributable to cavernous sinus invasion and postoperative residual lesions. Our retrospective cohort study reveals that intraoperative identification of occult tumor invasion combined with extended resection of the medial wall of cavernous sinus (MWCS) significantly enhances biochemical control rates. OBJECTIVE: The purpose of this study was to investigate the therapeutic efficacy of extended resection of cavernous sinus medial wall and summarize current application status of this surgical strategy on Somatotroph-PitNETs. METHODS: We retrospectively analyzed consecutive patients with Somatotroph-PitNETs who underwent endoscopic transsphenoidal surgery (eTSS) in the Second Xiangya Hospital of Central South University between September 2016 and February 2024. Patients were stratified into two surgical groups based on intervention timeline: Group 1 (pre-October 2020) received conventional resection, whereas Group 2 (post-October 2020) underwent tumor resection with extended resection of MWCS. Comparative analysis included demographic profiles, postoperative biochemical remission rates and surgery-related morbidity. RESULTS: This study enrolled 101 consecutive patients with Somatotroph-PitNETs, stratified into Group 1 (n=45
pre-October 2020 cohort) and Group 2 (n=56
post-October 2020 cohort) based on surgical protocol evolution. Demographic analysis revealed comparable baseline profiles, with mean ages of 42.3±13.6 vs 44.9±11.1 years (P=0.147). Comparative outcomes demonstrated significantly higher biochemical remission rates in Group 2 versus Group 1 (85.7% vs 66.7%
P=0.023). This therapeutic advantage was magnified in Knosp grades 3-4 subgroups (77.8% vs 31.3%
P=0.014). Notably, data of surgery-related morbidity showed no significant intergroup difference, particularly in new-onset hypopituitarism (6.67% vs 3.57%
P=0.802) and cerebrospinal fluid leak (2.22% vs 3.57%
P=1.000). CONCLUSION: In somatotroph-PitNETs, intraoperative identification of occult invasion combined with extended resection of MWCS significantly improved biochemical remission rates, particularly in Knosp grade 3-4 subgroups. And this selective approach maintained a surgically validated safety profile without increasing overall surgical morbidity. However, MWCS resection should be judiciously avoided in lesions with intact pseudocapsular integrity or circumscribed by normal pituitary gland.