Rationale and Objectives
To evaluate the prognostic significance of maximum standardized uptake value (SUVmax) at 18 F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography in patients with stage IIIA non-small-cell lung cancer (NSCLC) who underwent surgical resection after neoadjuvant chemoradiotherapy, focused on the relationship between SUVmax values and tumor histology.
Materials and Methods
We retrospectively evaluated the initial SUVmax of 205 patients (112 adenocarcinomas, 82 squamous cell carcinomas [SCCs], and 11 of other histology) with a stage IIIA NSCLC who underwent surgical resection after neoadjuvant chemoradiotherapy, and who were followed for up to 6 years. Clinical data, including histologic type, pathologic response, and treatment, were reviewed, and the relationship between the SUVmax and patient overall survival was examined.
Results
Overall, the 2-year survival rate was 68%. Between the two histologic subtypes of adenocarcinoma and SCC, we noted significant differences in all variables of gender (male predominance in SCC), initial SUVmax (greater in SCC), pathologic response (more complete remission in SCC), and overall survival (better in SCC) (all P values, < .05). SUVmax remained as a sole independent factor for survival in multivariate analysis in whole series (SUVmax cutoff, 13; median survival, 3.0 years vs. 4.0 years; P = .016) and in adenocarcinomas (SUVmax cutoff, 11.5; median survival, 2.6 years vs. 3.6 years; P = .045), but not in SCCs.
Conclusion
The initial SUVmax is a sole significant prognostic factor in patients with a surgically resected NSCLC after neoadjuvant chemoradiotherapy, particularly in patients with an adenocarcinoma.
The effect of preoperative induction therapy (neoadjuvant therapy) for locally advanced non-small-cell lung cancer (NSCLC) on tumor staging, surgery, and patient survival has been described in previous clinical reports . The maximum standardized uptake value (SUVmax) of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) has been investigated fairly extensively, and has proven effective in the prediction of patient prognosis after surgical treatment . Moreover, a recent systematic review and meta-analysis conducted by the European Lung Cancer Working Party for the work of International Association for the Study of Lung Cancer lung cancer staging project concluded that the primary SUVmax is a prognostic factor in NSCLC patients .
However, NSCLC consists of heterogeneous diseases of several histologic subtypes that may show different biological behaviors and levels of clinical aggressiveness . Although measuring the SUVmax of a primary lung cancer at PET-CT has already been proven effective in predicting prognosis, there remain many unresolved questions associated with the use of SUVmax as a prognostic marker, particularly with regard to the optimal threshold value for prognostic determination and its relationship with the different histologic subtypes of NSCLC . For these reasons, more accurate and widely applicable biologic surrogate markers may be required to identify patients with locally advanced NSCLC who might still benefit from neoadjuvant chemoradiotherapy.
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Materials and methods
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Patients
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Table 1
Demographic Data Including Patient Characteristics ( n = 205)
Characteristics Number (%) Sex Males 156 (76) Females 49 (24) Age (year) Median (range) 58 (31–76) Clinical stage IIIA 205 (100) IIIB 0 Type of operation Segmentectomy 3 (1) Lobectomy 181 (88) Pneumonectomy 21 (11) Histologic subtypes Adenocarcinoma 112 (55) Squamous cell 82 (40) Large cell or neuroendocrine 6 (3) Pleomorphic carcinoma 1 (0) Non small cell, not specified 4 (2) Adjuvant chemotherapy 205 (100) Pathologic response Complete remission 34 (16) Partial remission 171 (84)
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PET Imaging
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Pathologic Evaluation
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Treatment and Follow-up Studies
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Data Analysis
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Results
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Table 2
Comparison between Adenocarcinoma and Squamous Cell Carcinoma
Adenocarcinoma ( n = 112) Squamous Cell Carcinoma ( n = 82)P Value ∗ Sex Male 68 78 .000 Female 44 4 Tumor at initial PET-CT Size 4.0 ± 1.7 4.7 ± 1.9 .013 SUVmax 11.9 ± 5.2 14.5 ± 6.1 .002 Pathologic response CR 9 18 .000 PR 103 64 Survival Mean 3.1 ± 0.3 4.1 ± 0.3 .046 † 95% CI 2.6–3.6 3.5–4.7
CR, complete remission; CT, computed tomography; PET, positron emission tomography; PR, partial remission.
Data are mean values ± standard deviations.
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Survival Analysis
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Table 3
Univariate and Multivariate Analyses for Factors Affecting Patient Survival
Univariate Analysis Cutoff Hazard Ratio 95% Confidence Interval_P_ Values ∗ Age, year ≤60 vs. >60 0.92 0.56–1.52 .750 Gender, No. Male vs. female 1.36 0.80–2.31 .221 Tumor Size on CT, cm ≤4.2 vs. >4.2 0.95 0.57–1.59 .844 SUVmax ≤13 vs. > 13 0.57 0.35–0.92 . 021 Histologic subtypes Adenocarcinoma vs.
squamous cell carcinoma 0.59 0.37–0.96 . 041 Pathologic complete remission No vs. yes 2.44 1.21–4.92 .069
Multivariate Analysis_P_ Values † SUVmax ≤13 0.38 0.24–0.60.018
P values of <.05 are shown as bold face type.
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Discussion
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