Impact of Different Mediastinal Staging Modalities on Target Volume Delineation in Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the Multicenter Randomized PET-Plan Trial

To evaluate the role of different invasive and non-invasive mediastinal staging methods in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with definitive chemoradiotherapy in the prospective XXX trial (XXX; NCTXXX) and to evaluate the impact of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy on target volume definition. Patients treated per-protocol (n = 172), all receiving isotoxically dose-escalated chemoradiotherapy, were included in this unplanned secondary analysis. Radiation treatment planning was based on an 18F-FDG PET/CT targeting all CT positive lymph nodes (i.e. short axis diameter > 10 mm), even if PET-negative, plus elective nodal irradiation (arm A) or targeting only PET-positive nodes (arm B). The concordance rate between different staging modalities and their impact on target volume delineation were calculated. The median follow-up time (95% confidence interval) was 41.1 (33.8-50.4) months. A total of 2,752 lymph node stations were evaluated non-invasively, 330 were examined invasively. Of 172 patients, 87 (50.6%) underwent at least one invasive staging modality. The number of different staging procedures per patient did not correlate with any of the primary endpoints (OS, PFS, or FFLP). The sensitivity of 18F-FDG PET/CT was 89.7% (78/87) and the specificity 67.5% (112/166) based on histology as assessed by EBUS. When using the results from mediastinoscopy, the sensitivity of PET was 82.6% (19/23) and the specificity 66.7% (36/54). Based on invasive staging methods, 13 lymph node stations in 9 patients (10.3%) were PET-negative while positive on invasive staging, thus leading to a significant adjustment of the target volume. In this unplanned secondary analysis of the XXX trial, the additional use of invasive staging resulted in relevant changes of the target volume in a tenth of patients. Invasive staging did not, however, have an effect on outcome in this trial, with a low rate of isolated out-of-field recurrences (6 in arm A versus 3 in arm B). Radiation treatment planning can thus be based on invasive staging in addition to non-invasive PET in patients undergoing definitive chemoradiotherapy for locally advanced NSCLC. Prospective randomized data are required to confirm these findings.