Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller

Abstract

Background: We sought to analyze the prognostic significance of the new International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) lung adenocarcinoma (ADC) classification for patients undergoing resection for small (≤2cm) lung ADC and to investigate whether histologic subtyping can predict recurrence after limited resection (LR) vs lobectomy (LO).

Methods: Comprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification on all consecutive patients who underwent LR or LO for small lung ADC between 1995 and 2009 at Memorial Sloan-Kettering Cancer Center. Clinical characteristics and pathologic data were retrospectively evaluated for 734 consecutive patients (LR: 258; LO: 476). Cumulative incidence of recurrence (CIR) was calculated using competing risks analysis and compared across groups using Grey's test. All statistical tests were two-sided.

Results: Application of IASLC/ATS/ERS lung ADC histologic subtyping to predict recurrence demonstrates that, in the LR group but not in the LO group, micropapillary (MIP) component of 5% or greater was associated with an increased risk of recurrence, compared with MIP component of less than 5% (LR: 5-year CIR = 34.2%, 95% confidence interval [CI] = 23.5% to 49.7% vs 5-year CIR = 12.4%, 95% CI = 6.9% to 22.1%, P < .001; LO: 5-year CIR = 19.1%, 95% CI = 12.0% to 30.5% vs 15-year CIR = 12.9%, 95% CI = 7.6% to 21.9%, P = .13). In the LR group, among patients with tumors with an MIP component of 5% or greater, most recurrences (63.4%) were locoregional; MIP component of 5% or greater was statistically significantly associated with increased risk of local recurrence when the surgical margin was less than 1cm (5-year CIR = 32.0%, 95% CI = 18.6% to 46.0% for MIP ≥ 5% vs 5-year CIR = 7.6%, 95% CI = 2.3% to 15.6% for MIP < 5%; P = .007) but not when surgical margin was 1cm or greater (5-year CIR = 13.0%, 95% CI = 4.1% to 22.1% for MIP ≥ 5% vs 5-year CIR = 3.4%, 95% CI = 0% to 7.7% for MIP < 5%; P = .10).

Conclusions: Application of the IASLC/ATS/ERS classification identifies the presence of an MIP component of 5% or greater as independently associated with the risk of recurrence in patients treated with LR.

Figure 1.

Study cohort flow chart. Between 1995 and 2009, 1421 patients with lung adenocarcinoma of 2cm or less were identified. After exclusion, 734 were included in the analysis, of whom 258 underwent limited resection (LR) and 476 underwent lobectomy (LO). H&E = hematoxylin and eosin; MSKCC = Memorial Sloan-Kettering Cancer Center.

Figure 2.

Five-year cumulative incidence of recurrence (CIR) by extent of resection and percentage of micropapillary (MIP) component. A and B) Five-year CIR for the training (A) and validation (B) sets, stratified by MIP percentage, in the limited resection group. C and D) Five-year CIR for the training (C) and validation (D) sets, stratified by MIP percentage, in the lobectomy group. CI = confidence interval

Figure 3. Five-year cumulative incidence of recurrence as a function of micropapillary percentage.

A) Five-year cumulative incidence of recurrence (CIR) among the training set, as a function of the micropapillary (MIP) percentage for each surgical treatment group. B) CIR among the training set for patients with tumors with an MIP component of less than 5%, 5% to 10%, or greater than 10% who underwent lobectomy, compared with those who underwent limited resection. CI = confidence interval; LO = lobectomy; LR = limited resection.