Adjuvant Chemotherapy in Early-Stage Non–Small Cell Lung Cancer Improves Overall Survival
The use of adjuvant chemotherapy in early-stage non–small cell lung cancer (NSCLC) patients improves overall survival and 5-year overall survival rates in patients with tumor sizes ranging from 3 to 7 cm. These findings were published by Morgensztern et al in the Journal of Thoracic Oncology.
Several studies have found that patients with stage II or III NSCLC who had adjuvant chemotherapy following complete surgical resection lived longer than those who had surgery without chemotherapy. However, in early-stage NSCLC patients, there is not enough evidence to support the use of chemotherapy following complete resection, even though stage I lung cancer recurs either locally or at distant sites in roughly one-third of patients with early-stage disease.
Exploratory analysis of the use of adjuvant chemotherapy in early-stage NSCLC showed improved overall survival for patients whose tumors were < 4 cm. Consequently, a thorough investigation of the clinical benefits and survival of the use of adjuvant chemotherapy in early-stage patients is warranted to improve current treatment recommendations.
Study Details
A group of investigators analyzed a large cohort of patients (N = 29,908) with pathologic stage T2,N0,M0 NSCLC, diagnosed from 2003 to 2010, and who underwent complete (R0) resection to evaluate the role of adjuvant chemotherapy in early-stage disease. The patients were identified from the National Cancer Database (NCDB) using the International Classification of Diseases for Oncology, 3rd Edition, and pathologic staging was based on the American Joint Committee on Cancer, 7th Edition staging criteria.
Patients who died within 30 days after surgery were excluded from the study. Patients were categorized into two cohorts: those who received adjuvant chemotherapy (n = 5,209; 17.4%) and those who did not (n = 24,699; 82.6%). The cohorts were further divided into four groups based on tumor size: 3 to 3.9 cm, 4 to 4.9 cm, 5 to 5.9 cm, and 6 to 7 cm.
Findings
Results demonstrated that adjuvant chemotherapy was associated with improved median overall survival and 5-year overall survival rate compared to the observation group in both univariate and multivariate analyses. In the univariate analysis, the 5-year overall survival for patients not receiving adjuvant chemotherapy was inversely related to tumor size, decreasing from 58% in those with tumors measuring 3 to 3.9 cm to 46.9% in those with 6- to 7-cm tumors. However, in patients who received adjuvant chemotherapy, the 5-year overall survival rate was nearly identical for the 4- to 4.9-cm, 5- to 5.9-cm, and 6- to 7-cm groups.
Furthermore, all patients receiving adjuvant chemotherapy, regardless of tumor size, showed improved median overall survival (95.6 vs 67.0 months, hazard ratio [HR] = 0.64; 95% confidence interval [CI] = 0.61–0.68, P < .0001) and 5-year overall survival rate (67.9% vs 54.6%, P < .0001) compared to the observation group. The multivariate analysis, which took into account various characteristics (ie, age, histology, type of surgery) also demonstrated a benefit from adjuvant chemotherapy for all patient groups, with hazard ratio for mortality inversely related to tumor size, ranging from 0.75 in the 3- to 3.9-cm group to 0.62 in the 6- to 7-cm group.
The authors commented:
There are several limitations to our data including the retrospective nature of the study, with limited information on the reasons for the choice between chemotherapy and observation. Furthermore, there is no data on staging procedures prior to the surgical resection or type of chemotherapy regimens used. Another potential limitation is the presence of selection bias since patients had to survive long enough to have the adjuvant chemotherapy administered. However, our data suggest that there is a benefit from adjuvant chemotherapy in patients with completely resected stage T2N0M0 NSCLC regardless of tumor size. Assuming similar biases for the use of chemotherapy in all tumor size subgroups, the elimination of patients with early surgical mortality and the confirmed benefit from adjuvant chemotherapy in multivariable analysis, our study suggests that the postulated benefit from adjuvant chemotherapy in patients with stage T2N0M0 NSCLC may be extended to 3–3.9 cm tumor size. Therefore, if this hypothesis is either confirmed or not further evaluated in prospective trials, the current exclusion of stage IB tumors < 4 cm in adjuvant NSCLC trials should be revisited.
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