A Single-Arm, Phase II Study of Thoracoscopic Lung Cancer Staging with the Use of Intraoperative Ultrasound at the Time of Definitive Resectio

INTRODUCTION: Lung cancer is the leading cause of cancer deaths in the United States. The 5-year survival rate for late-stage (stages III and IV) patients is less than 10%. Survival is directly related to stage and as such, treatment of lung cancer is stage-based. The evaluation of nodal metastases represents an important decision point. In patients who present with N2 positive disease based on imaging, and confirmed by tissue diagnosis, treatment is primarily systemic. A small subset of stage I-II patients, who have been evaluated prior to resection and are found at the time of surgery to have microscopic metastases to their N2 nodal stations, are upstaged to IIIA and receive postoperative systemic therapy. Although the incidence of pathologic upstaging is low (7.6% for standard thoracotomy with lobectomy), if these patients are not detected at the time of surgery they will be misclassified as stage I-II based on tumor size and may not receive any additional therapy after surgery. This will result in the increased risk of nodal and systemic recurrence, with impact on the stage-based survival. VATS lobectomy is associated with potentially missed N2 nodal disease during surgical resection of presumed early-stage lung cancer. This may in part be due to the diminished ability of the surgeon to palpate the tissues and directly examine nodes. Recent review of national data demonstrates the occurrence of pathologic upstaging during standard thoracotomy in 7.6% of resections, compared with 2.3% of VATS cases. The addition of intraoperative imaging during nodal assessment may increase the diagnostic yield and improve the sensitivity and specificity of the evaluation. METHODS: Subjects with previously untreated, clinically early-stage, lung cancer will undergo standard-of- care surgical resection by current thoracoscopic techniques (VATS). After the conclusion of the standard oncologic resection and lymph node evaluation, an independent operator will screen the mediastinal lymph nodes using intraoperative ultrasound. Additional nodes detected will be retrieved and labelled as additional sample to allow for determination of upstaging using ultrasound, sensitivity and specificity of the test. STATISTICAL DESIGN: The primary endpoint is upstaging rate. A Simon’s two-stage optimum design is employed to test the null hypothesis that the upstaging rate is 2% which is seen in usual VATS procedures. The two stage design will employ a total of 70 patients to detect an upstaging rate of 8% with a type I error rate of 5% and 80% power. Interim analysis at 34 patients will allow conclusion of the trial if no additional patients are upstaged, with the data at that point supporting the null hypothesis. EXPECTED OUTCOMES: This study will answer the question as to the effectiveness and accuracy of the surgical staging of patients undergoing VATS resection for lung cancer and whether or not ultrasound can improve this.