Prognostic value of metabolic tumor volume on [F]FDG PET/CT in addition to the TNM classification system of locally advanced non-small cell lung cancer.

Purpose: Staging of non-small cell lung cancer (NSCLC) is commonly based on [F]FDG PET/CT, in particular to exclude distant metastases and guide local therapy approaches like resection and radiotherapy. Although it is hoped that PET/CT will increase the value of primary staging compared to conventional imaging, it is generally limited to the characterization of TNM. The first aim of this study was to evaluate the PET parameter metabolic tumor volume (MTV) above liver background uptake as a prognostic marker in lung cancer. The second aim was to investigate the possibility of incorporating MTV into the TNM classification system for disease prognosis in locally advanced NSCLC treated with chemoradiotherapy.

Methods: Retrospective evaluation of 235 patients with histologically proven, locally advanced NSCLC from the multi-centre randomized clinical PETPLAN trial and a clinical cohort from a hospital registry. The PET parameters SUVmax, SULpeak, MTV and TLG above liver background uptake were determined. Kaplan-Meier curves and stratified Cox proportional hazard regression models were used to investigate the prognostic value of PET parameters and TNM along with clinical variables. Subgroup analyses were performed to compare hazard ratios according to TNM, MTV, and the two variables combined.

Results: In the multivariable Cox regression analysis, MTV was associated with significantly worse overall survival independent of stage and other prognostic variables. In locally advanced disease stages treated with chemoradiotherapy, higher MTV was significantly associated with worse survival (median 17 vs. 32 months). Using simple cut-off values (45 ml for stage IIIa, 48 ml for stage IIIb, and 105 ml for stage IIIc), MTV was able to further predict differences in survival for stages IIIa-c. The combination of TNM and MTV staging system showed better discrimination for overall survival in locally advanced disease stages, compared to TNM alone.

Conclusion: Higher metabolic tumor volume is significantly associated with worse overall survival and combined with TNM staging, it provides more precise information about the disease prognosis in locally advanced NSCLC treated with chemoradiotherapy compared to TNM alone. As a PET parameter with volumetric information, MTV represents a useful addition to TNM.