Mediastinal downstaging after induction treatment is not a significant prognostic factor to select patients who would benefit from surgery: the clinical value of the lymph node ratio

Abstract

Objectives: Multimodal management of N2 non-small-cell lung cancer is still a matter of debate. In particular, the place of surgery for persistent N2 after induction treatment is controversial and surgery is usually reserved for patients experiencing a mediastinal downstaging (pN1 and pN0). We aimed to evaluate whether there might exist subgroups of pN2 according to the lymph node ratio (LNR).

Methods: Between 1996 and 2012, we retrospectively reviewed the data from 152 potentially resectable cN2 patients who underwent an induction treatment before surgery.

Results: The median follow-up time was 32 months (2-112). The average age at the time of diagnosis was 58.52 ± 10.47 years. In univariate analysis, overall survival (OS) was significantly influenced by extracapsular spread (32 ± 5.33 vs 24 ± 12.73 months, P = 0.01), pN after surgery (65 ± 2.45 months for pN0, 44 ± 2.14 months for pN1 and 19 ± 1.72 months for pN2, P <0.0001) and LNR ≥ 1/3 (30 ± 3.77 months vs 16 ± 1.39 months, P <0.0001). When pN0 and pN1 patients were staged according to the LNR, the OS was divided by two for pN1 patients with an LNR ≥ 1/3 (48 ± 2.64 months vs 26 ± 5.65 months, P <0.001), whereas it decreased from 26 ± 0.87 to 15 ± 1.85 months (P <0.0001) for pN2 patients. OS was significantly better with adjuvant radio-chemotherapy than with chemotherapy or radiation therapy alone (P <0.0001). In multivariate analysis, mediastinal downstaging {Hazard Ratio (HR): 0.184 (95% confidence interval (CI): 0.084-0.403), P <0.0001} and LNR [HR: 0.359 (95% CI: 0.194-0.665], P = 0.001) remained significantly independent prognostic factors.

Conclusions: The LNR may potentially identify subgroups of pN+ patients and allow enhancement of adjuvant treatments. Because pN2 with a low LNR had an equivalent survival to pN1 with a high LNR, mediastinal downstaging does not seem to be a sufficient prognostic factor to exclude patients after induction treatment from surgery.

Keywords: Induction treatment; Lymph node ratio; Lymph nodes; Mediastinal downstaging; Non-small-cell lung cancer; Persistent N2.