High rate of detection of unsuspected distant metastases by PET in apparent Stage III non–small-cell lung cancer: implications for radical radiation therapy

Purpose: Most radical radiotherapy (RT) candidates with non–small-cell lung cancer (NSCLC) have Stage III disease and ultimately die with distant metastases. We tested the hypothesis that positron emission tomography (PET) using 18-F fluorodeoxyglucose (FDG) would detect more unsuspected metastases in apparent Stage III disease than in Stages I–II. Methods and Materials: Staging FDG-PET was performed for 167 NSCLC patients, with Stage I–III by conventional workup, who were candidates for curative therapy with surgery ( n = 8), radical chemo/RT or RT ( n = 156), or preoperative chemo/RT ( n = 3). Each patient was allocated a conventional “pre-PET stage” and a “post-PET stage” that relied on PET when discordance with conventional staging occurred. Results: Stage distribution pre-PET was n = 39 (Stage I), n = 28 (Stage II), and n = 100 (Stage III). In 32 patients (19%), PET detected distant metastasis, most commonly abdominal with 17 cases (adrenal, n = 7; liver, n = 4; other, n = 6). Other sites included lung ( n = 10) and bone ( n = 6). PET-detected metastasis increased with increasing pre-PET stage from I (7.5%) through II (18%) to III (24%, p = 0.016), and, in particular, was significantly higher in Stage III ( p = 0.039). Biopsy confirmation was not routine, but progression occurred at PET-detected metastatic sites or other metastatic sites in all but 3 of the 32 patients by last review. Conclusion: PET staging is recommended for radical RT candidates with NSCLC. The highest yield of unexpected distant metastases is observed in Stage III.