Prognostic Value of 68 Ga-NOTA-AE105 uPAR PET/CT in Resected Non–Small Cell Lung Cancer: A Single-Center Prospective Study

Non–small cell lung cancer shows wide variability in outcomes after curative-intent resection. 18F-FDG PET/CT is indispensable for staging but primarily reflects glucose metabolism rather than the invasion-related tumor biology that may contribute to recurrence. 68Ga-NOTA-AE105 PET/CT images the urokinase-type plasminogen activator receptor (uPAR), a cell-surface mediator of local invasion and metastatic spread. We assessed whether preoperative 68Ga-uPAR PET/CT is prognostic for postoperative recurrence. Methods: We conducted a single-center cohort study of patients with resectable lung adenocarcinoma or squamous cell carcinoma who were prospectively enrolled to undergo preoperative 68Ga-uPAR PET/CT in addition to standard-of-care 18F-FDG PET/CT. Primary tumor SUVmean and SUVmax were measured for both tracers, and tumor tissue uPAR expression was quantified by immunohistochemistry (H-score). Postoperative recurrence was the primary endpoint and was analyzed in a competing-risks framework with death as a competing event. The primary prognostic analyses evaluated 68Ga-uPAR SUVs, 18F-FDG SUVs, and uPAR H-score as continuous variables using univariable cause-specific Cox models. A 1.5-y horizon was used for exploratory Youden-derived high versus low groups, for which cumulative incidence of recurrence was estimated using the Aalen–Johansen method. Trial registration number is NCT02755675. Results: Thirty-seven patients comprised the analysis cohort, of whom 14 developed recurrence during a median follow-up of 2.38 y (interquartile range, 1.97–8.20 y). Four patients died without prior recurrence. 68Ga-uPAR uptake correlated with tumor tissue uPAR expression, whereas 18F-FDG uptake did not. As continuous prognostic factors, higher 68Ga-uPAR SUVmax (hazard ratio, 2.16; 95% CI, 1.34–3.49; P = 0.002) and higher uPAR H-score (hazard ratio, 1.04 per unit; 95% CI, 1.01–1.08; P = 0.017) were associated with recurrence; 68Ga-uPAR SUVmean showed borderline evidence of association (P = 0.053), whereas 18F-FDG uptake was not prognostic. Exploratory 1.5-y threshold analyses showed greater early recurrence in the high SUVmean and high H-score groups; the SUVmax comparison did not reach statistical significance. Conclusion: Preoperative 68Ga-uPAR PET uptake reflected tumor uPAR expression and was associated with early postoperative recurrence, whereas 18F-FDG uptake was not prognostic in this cohort. These findings suggest that uPAR PET captures invasion-related tumor biology that is not fully reflected by glucose metabolism imaging. External validation is required.