Tumor marker-based RecistTM is superior to RECIST as criteria to predict the long-term benefits of targeted therapy in advanced non-small-cell lung cancer with driver gene mutations

Abstract

Background: Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment.

Methods: We retrospectively analysed patients with stage IIIA-IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST.

Findings: The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS.

Interpretation: RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.

Keywords: Non-small-cell lung cancer; Overall survival; Progression-free survival; RECIST; RecistTM.

Fig. 1

Flow diagram of this study. NSCLC, non-small-cell lung cancer.

Fig. 2

Consistency test between RecistTM and RECIST (n = 206). Efficacy assessment of targeted therapy with RECIST and RecistTM. The consistency between the criteria was 36.9%. The Kappa test indicated poor consistency between the criteria. RECIST, Response Evaluation Criteria in Solid Tumors; RecistTM, Response Evaluation Criteria in Solid Tumors based on Tumor Markers; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; tmCR, tumor marker-related complete response; tmPR, tumor marker-related partial response; tmSD, tumor marker-related stable disease; tmPD, tumor marker-related progressive disease.

Fig. 3

Comparison of tumor marker-based progression-free survival (tmPFS) among different efficacy categories by RecistTM. RecistTM, Response Evaluation Criteria in Solid Tumors Based on Tumor Markers. tmCR, tumor marker-related complete response; tmPR, tumor marker-related partial response; tmSD, tumor marker-related stable disease; tmPD, tumor marker-related progressive disease.

Fig. 4

Differences in progression-free survival (PFS) among different efficacy categories by RecistTM (A) and RECIST (B). RecistTM, Response Evaluation Criteria in Solid Tumors Based on Tumor Markers; RECIST, Response Evaluation Criteria in Solid Tumors. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; tmCR, tumor marker-related complete response; tmPR, tumor marker-related partial response; tmSD, tumor marker-related stable disease; tmPD, tumor marker-related progressive disease.

Fig. 5

ROC curves predicting the risk of disease progression at 1 year, 2 years, and 3 years by RecistTM (A) and RECIST (B). ROC, receiver operating characteristic. AUC, areas under the curves. RecistTM, Response Evaluation Criteria in Solid Tumors Based on Tumor Markers. RECIST, Response Evaluation Criteria in Solid Tumors. PFS, progression-free survival.

Fig. 6

Differences in overall survival (OS) among different efficacy categories by RecistTM (A) and RECIST (B). RecistTM, Response Evaluation Criteria in Solid Tumors Based on Tumor Markers. RECIST, Response Evaluation Criteria in Solid Tumors. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; tmCR, tumor marker-related complete response; tmPR, tumor marker-related partial response; tmSD, tumor marker-related stable disease; tmPD, tumor marker-related progressive disease.

Fig. 7

Differences in overall survival (OS) between patients categorized by RecistTM, who were categorized as partial response (PR) (n = 131, A) and stable disease (SD) (n = 68, B) by RECIST. RecistTM, Response Evaluation Criteria in Solid Tumors Based on Tumor Markers. RECIST, Response Evaluation Criteria in Solid Tumors. tmCR, tumor marker-related complete response; tmPR, tumor marker-related partial response; tmSD, tumor marker-related stable disease; tmPD, tumor marker-related progressive disease.

Fig. 8

ROC curves predicting 1-year, 3-year, and 5-year overall survival (OS) by RecistTM (A) and RECIST (B). ROC, receiver operating characteristic curve; AUC, area under the curve. RecistTM, Response Evaluation Criteria in Solid Tumors Based on Tumor Markers. RECIST, Response Evaluation Criteria in Solid Tumors.

Fig. 9

Distribution of the difference in progression-free survival (△PFS) by RecistTM and RECIST. RecistTM, Response Evaluation Criteria in Solid Tumors Based on Tumor Markers. RECIST, Response Evaluation Criteria in Solid Tumors.