Uniportal-VATS for Early-Stage NSCLC in Octogenarians: A Single-Center, Retrospective Study of Surgical and Short-Term Oncological Outcomes

<b>Background/Objectives:</b> This study aimed to assess the safety and efficacy of lung surgery for the treatment of early-stage non-small cell lung cancer (NSCLC) in octogenarians, with a specific focus on the Uniportal-VATS approach, evaluating surgical outcomes and short-term oncological results within a precision medicine perspective. <b>Methods</b>: This retrospective, single-center study included octogenarian patients who underwent surgical treatment for early-stage NSCLC between January 2018 and March 2024. Among 1329 patients treated during the study period, 136 octogenarians were carefully evaluated by a multidisciplinary board and selected for surgical management. <b>Results</b>: The mean age was 82.41 ± 2.72 years, with a prevalence of men (63.2%). In 107 (78.7%) cases, lung resection was performed using the Uniportal-video-assisted thoracic surgery (U-VATS) approach. Overall, 71 lobectomies (52.2%) and 65 segmentectomies or wedge resections (47.8%) were performed, balancing oncological radicality with comorbidities. Only minor complications occurred, such as atelectasis (2.9%), atrial fibrillation (4.4%), pneumonia (1.5%), or air-leakage (2.2%). Factors significantly associated with postoperative complications included open approach (<i>p</i> = 0.014), lobectomy as the extent of resection (<i>p</i> = 0.008), and chronic obstructive pulmonary disease (COPD) (<i>p</i> = 0.010). On multivariable analysis, lobectomy remained the only independent predictor for postoperative complications (OR: 5.95, 95% CI [1.24-28.62], <i>p</i> = 0.026). In-hospital and 90-day mortality were null. The median length of hospital stay in octogenarians was 6 days and was significantly shorter in the Uniportal-VATS group compared with the open surgery one (<i>p</i> < 0.001). All patients were discharged home independently. One- and three-year overall survival rates were 88% and 71%, respectively. No risk factor was associated with mortality in our series. <b>Conclusions</b>: Lung surgery, particularly the Uniportal-VATS approach, appears to be a safe and effective treatment option for octogenarian patients with early-stage NSCLC, provided that patient selection is carefully based on individual clinical characteristics within a multidisciplinary framework based on individualized risk stratification. When feasible, sublobar resection should be preferred in order to minimize postoperative complications.