Non-Small Cell Lung Cancer With N1 Involvement or Skip Metastases Presents the Same Survival Outcome: Results From a Multicentric Study.

BACKGROUND: The prognostic difference among patients affected by NSCLC with hilar metastases only or mediastinal nodes metastases without hilar involvement (skip metastases) is still unclear. Aim of this study is to analyse if prognostic difference are present or if the two groups present the same survival outcome. MATERIALS AND METHODS: Data on NSCLC patients from 7 high volume centres (2004-2014) were collected and retrospectively reviewed. Histology different from adenocarcinoma(ADC) or squamous cell carcinoma(SCC), patients without data on lymphadenectomy, who underwent neoadjuvant treatment, with distant metastases or incomplete resection were excluded, selecting patients with hilar involvement or with skip metastases. Different prognostic factors such as Tstage, histology, pathological stage, nodal characteristics and adjuvant therapy administration were correlated to overall survival (OS) by the Kaplan-Meier product-limit method. The log-rank test was used to assess differences between subgroups. A multivariable Cox proportional hazard model was developed using stepwise regression to compare the prognostic power of different factors. RESULTS: The final analysis was conducted on 480 adenocarcinoma/squamous cell carcinoma patients. Five-year OS (5YOS) resulted 53.9%. No significant differences in OS were detected comparing pN1 vs. pN2 patients or stage IIB vs. stage IIIA-B patients. Univariable confirmed as favourable prognostic factors young age (P<.001), T1-2 tumors (P=.030), number of resected nodes≥10 (P=.040), lymph node ratio (P=.026). Multivariable analysis confirmed as independent negative prognostic factors T≥3 (HR:1.385, 95%CI:1.037-1.851, P=.027) and age≥68 years (HR1.637, 95%CI:1.245-2.152). CONCLUSION: Patients with N1 involvement or skip metastases present a similar prognosis, suggesting that N2 involvement in these cases may be related to a direct lymphatic drainage to the mediastinal stations.

Survival Analysis in Single N2 Station Lung Adenocarcinoma: The Prognostic Role of Involved Lymph Nodes and Adjuvant Therapy.

BACKGROUND: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. METHODS: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics together with adjuvant therapy (AD) and node (N) status classifications (number of resected nodes (#RN), number of metastatic nodes (#MN), and node ratio (#MN/#RN = NR) were analyzed. RESULTS: Univariable analysis confirmed that age (0.009), #MN (0.009), NR (0.003), #N1 involved stations (p = 0.003), and skip metastases (p = 0.005) were related to overall survival (OS). Multivariable analysis confirmed, as independent prognostic factors, age <66 years and NR with a three-year OS (3YOS) of 78.7% in NR < 10% vs. 46.6% in NR > 10%. In skip metastases, NR (HR 2.734, 95% CI 1.417-5.277, p = 0.003) and pT stage (HR2.136, 95% CI 1.001-4.557, p = 0.050) were confirmed as independent prognostic factors. AD did not influence the OS of patients with singular positive lymph nodes (p = 0.41), while in patients with multiple lymph nodes and AD, a significantly better 3YOS was demonstrated, i.e., 49.1% vs. 30% (p = 0.004). In patients with N2 + N1 involvement, age (p = 0.002) and AD (p = 0.022) were favorable prognostic factors. CONCLUSIONS: Adenocarcinoma patients with single N2 station involvement had a favorable outcome in the case of skip metastases and low NR. Adjuvant therapy improves survival with multiple nodal involvement, while its role in single node involvement should be clarified.

Prognostic score for survival with pulmonary carcinoids: the importance of associating clinical with pathological characteristics.

OBJECTIVES: Lung carcinoids (LCs) are staged using the non-small-cell lung cancer tumour/node/metastasis staging system; the possibility of an LC-specific staging system is still being debated. The goal of our study was to construct a composite prognostic score for LC. METHODS: From January 2002 to December 2014, data from 293 patients who underwent surgical treatment for LC in 7 research institutes were retrospectively analysed. A panel of established prognostic factors in addition to lymph node metastasis patterns (single/multiple N1-N2 station, skip metastasis, lobe specific), numbers of lymph nodes resected and the ratio between the numbers of metastatic lymph nodes and the numbers of lymph nodes resected (node ratio) were correlated to overall survival (OS) and disease-free survival (DFS). The log-hazard ratio (HR), obtained from the Cox model, was used to derive weighting factors for a continuous prognostic index, designed to identify differential outcome risks. The score was dichotomized according to maximally selected log-rank statistics. RESULTS: Pathological analysis showed typical carcinoids in 223 (76.1%) and atypical carcinoids in 70 (23.9%) patients; the tumour/node/metastasis pattern was stage I in 72.4%, stage II in 18.1%, stage III in 9.5% and stage IV in 0.03% cases. The median numbers of lymph nodes resected was 12 (range 0-53); hilar and mediastinal node metastases were identified in 14% and 6.8% of cases, respectively. Overall, the 5-year OS and 5-year DFS rates were 90.6% and 76.7%, respectively. At multivariable analysis, sex, age, pathological T stage and node ratio were significantly related to a better OS; age, histological type, pathological T stage and node ratio were related to DFS. These factors were used to generate the prognostic score, which showed statistically significant differences between the high-risk and low-risk groups: 5-year OS = 96.6% if score <3.1 vs 63.5% if score ≥3.1 [P < 0.0001; HR 17.56, 95% confidence interval (CI) 5.45-56.53]; 5-year DFS 92.3% if score <1.5 vs 52.5% if score ≥ 1.5 (P < 0.0001; HR 7.95, 95% CI 3.48-18.16). CONCLUSIONS: The proposed prognostic scores seem to be effective in predicting outcomes for patients with LCs.