Aggressive resection of non-contrast-enhanced tumor provides varying benefits to glioblastoma, IDH-wildtype patients based on different clinical characteristics.

Supramaximal resection in glioblastoma, concerning non-contrast-enhancing (nCE) tumors, exhibited additional survival benefits. However, whether all patients can benefit from supramaximal resection of nCE tumors and the optimal resection target remains unclear, especially for the glioblastoma, IDH-wildtype under the new WHO CNS tumor classification. Clinical and surgical characteristics were collected from 155 patients with newly diagnosed glioblastoma, IDH-wildtype from the Chinese Glioma Genome Atlas, and a prospective cohort of 128 patients was enrolled for external validation. Recursive partitioning analysis was used to identify risk groups considering the effects of residual nCE tumor volume (RnTV) and clinical factors on overall survival (OS). Age, preoperative Karnofsky Performance Score (KPS), MGMT promoter status, and postoperative RnTV were independently associated with patient survival. Four risk groups with distinct prognoses were identified: Group 1 (median OS: 13.4 months), RnTV >43.27 ml; Group 2 (median OS: 17.8 months), RnTV ≤43.27 ml, KPS ≤90, and age ≥60; Group 3 (median OS: 22.3 months), RnTV 5.27-43.27 ml, age <60; Group 4 (median OS: 38.2 months) including 4a, KPS 100 and RnTV ≤43.27 ml; and 4b, KPS ≤90, age <60, and RnTV ≤5.27 ml. These results were retained regardless of MGMT promoter methylation status and validated in the external prospective validation cohort. Supramaximal nCE tumor resection enhances survival outcomes in glioblastoma, IDH-wildtype, but depending on clinical characteristics. In young symptomatic patients, supramaximal resection should be recommended with the RnTV ≤5.27 ml; in symptomless patients or elder patients, keeping the RnTV ≤43.27 is recommended to obtain the survival benefit from tumor resection surgery.