Dear Editor,

Surgery is the primary treatment modality for non-small cell lung cancer (NSCLC), but only approximately 20% of tumors are suitable for potentially curative resection and even after surgery, with a high percentage of recurrence probability.1, 2 Therefore, 5-year survival rates after surgery are disappointingly low2 and new strategies are needed to reduce mortality and recurrence rate in these patients. Stage IB NSCLC therapeutic approach remains a controversial issue. Adjuvant chemotherapy among this particular group of patients has never been demonstrated unequivocally as improving survival.1, 2

Based on recent evidence,3 the National Comprehensive Cancer Network (NCCN) guidelines1 included an indication for adjuvant chemotherapy for high-risk stage IB NSCLC patients. These high-risk factors include tumor >4 cm, poorly differentiated tumor, vascular invasion, visceral pleura involvement, wedge resection, and incomplete lymph node sampling (Nx). In order to evaluate the impact of adjuvant chemotherapy on stage IB NSCLC patients undergoing surgery, we reviewed our center experience with these patients.

All completely resected stage IB NSCLC patients observed during the period between January 2006 and December 2013 were included. Only patients with proven pT2N0 samples were consecutively enrolled. To ensure maximum homogeneity, patients who had received induction chemotherapy were excluded, even if their definitive staging was pT2N0.

We then analyzed the effect of adjuvant chemotherapy, irrespective of the indication, on survival data of all patients included and of a high-risk patients’ subgroup, as defined by the NCCN guidelines. The adjuvant chemotherapy regimen consisted of four courses of a platinum derivative and vinorelbine.

We analyzed 27 patients with a mean age of 65.3 ± 8.87 years and predominantly male (n = 18; 66.7%). Over 90% of patients had performance status ≤1 at diagnosis. There was no perioperative mortality (death within 30 days of surgery). General and high-risk subgroup population characteristics are presented in Table 1. Median follow-up time was 52.1 months.

Table 1. General population and high-risk subgroup population characteristics.

Recurrence was detected in 9 (33.3%) patients (5 in the adjuvant chemotherapy group and 4 in the non-adjuvant chemotherapy group). Mean disease-free time was 45.3 months for the adjuvant chemotherapy group and 33.6 months for the non-adjuvant chemotherapy group and there was no statistically significant difference between the two groups. Eight (29.6%) deaths occurred in the study group (3 in the adjuvant chemotherapy group and 5 in the non-adjuvant chemotherapy group). Mean survival time was 50.0 months for the adjuvant chemotherapy group and 36.4 months for the non-adjuvant chemotherapy group and again there was no statistically significant difference between the two groups.

As for the high-risk subgroup, 19 patients had at least one NCCN high-risk factor. Mean disease-free time was 43.3 months for the adjuvant group and 32.8 months for the non-adjuvant group, with no statistically significant difference between the two groups. Mean survival time was 48.9 months for the adjuvant chemotherapy group and 34.0 months for the non-adjuvant chemotherapy group. No statistically significant difference was found between the two groups.

Our study did not find any clear benefit for the NCCN's high-risk patients in terms of overall survival and disease-free survival, and the same holds for all NSCLC stage IB patients who underwent surgical treatment. Despite this evidence, we did find a non-significant difference in terms of overall survival and disease free survival between non-adjuvant chemotherapy and adjuvant chemotherapy group, with an improvement of both in the latter group. Although obviously limited by our sample size and by the fact that the non-adjuvant chemotherapy group had a higher ratio of pneumectomies, which is associated with poorer survival,5 this might indicate that adjuvant chemotherapy can play an important role in the treatment of these patients.

Unfortunately, adjuvant chemotherapy role in stage IB disease is not established yet. As in our study, subgroup stage IB analyses of larger trials have found a small but non significant overall survival benefit.1, 2 Recent evidence has demonstrated a significant benefit of adjuvant chemotherapy in stage IB patients with larger primary tumors (4.0 cm)3 and the same seems to hold for stage IB patients with vascular invasion.6 In spite of these results, at this point in time there is no available evidence to formally support routine use of adjuvant chemotherapy in stage IB.1, 2, 4

The authors certify that there were no potential conflicts of interest at the time of redaction of this article.

Daniel Coutinho, Ana Antunes and Ana Barroso conceived the project idea. Daniel Coutinho and Ana Gonçalves collected the data. Daniel Coutinho and Ana Antunes conducted the analyses. All authors interpreted and discussed the results. All authors wrote the manuscript. All authors have read and approved the final version.

Corresponding author. dpcoutinho@gmail.com