So-called “skip metastasis” of lung cancer to the lymph nodes – when the cancer “skips” over the N1 bronchopulmonary or hilar stage to N2 ipsilateral mediastinal metastasis – may be associated with distinct histological characteristics that can further help understand its association with longer survival and better prognosis in advanced resectable lung adenocarcinoma, according to a small study from China.
Researchers at Fudan (Shanghai ) University Cancer Center published their findings online ahead of print for the October issue of the Journal of Thoracic and Cardiovascular Surgery (2015 July 6 [ doi: 10.1016/j.jtcvs.2015.03.067 ]). In all, they enrolled 177 patients with N2 adenocarcinoma, 45 (25.4%) of whom had skip N2 metastasis.
They reported that patients with skip metastasis had considerably better 5-year recurrence-free survival rates of 37.4% vs. 5.7% and better overall survival rates of 60.7% vs. 32.1% when compared with those with non-skip involvement.
“There are distinct differences in clinicopathological features and prognosis in patients with or without skip N2 metastasis,” Dr. Haiquan Chen and his colleagues said. “Considering the results of our study, subclassifications of mediastinal lymph nodes metastases would have potential clinical significance for patients with lung adenocarcinoma.”
Dr. Chen and his colleagues sought to identify specific histological features that characterized the association between skip N2 metastasis and adenocarcinoma subtypes and prognosis. “Skip N2 patients have more cases that are acinar adenocarcinoma subtype, well differentiated and located in the right lung than [do] non-skip patients,” they said.
In fact, they found the predictive value of skip N2 was more significant in patients with right-lung disease, with 5-year recurrence-free survival of 36.6% vs. 0% and overall survival of 57.2% vs. 28% in non–right-lung lesions. They also reported that tumor size of 3 cm or smaller in skip N2 was associated with significantly improved survival rates – 43% vs. 6.7% recurrence-free survival and 74.6% vs. 27.6% for overall survival, compared with patients with larger tumors.
The skip N2 lung adenocarcinoma patients had “remarkably lower incidence” of vascular invasion of the lymph nodes, Dr. Chen and his coauthors wrote. Skip N2 patients also had lower, but not statistically significant, rates of pleural invasion. The Fudan University researchers also reported that the incidence of non-skip N2 metastasis was “significantly high” in patients with papillary-predominant subtype.
“Considering our results, skip N2 should not be recognized as [a] predictor for better survival in all lung adenocarcinoma cases, but in [a] more specific group of patients,” Dr. Chen and his coauthors said.
A multivariate analysis confirmed the predictive significance of skip N2 for recurrence-free survival, but not so much for overall survival. Single N2 metastasis was also an independent predictor for better recurrence-free and overall survival, Dr. Chen and his colleagues said.
The study received funding from the Key Construction Program of the National “985” Project , Ministry of Science and Technology of China; the National Natural Science Foundation of China; the Science and Technology Commission of Shanghai Municipality; and Shanghai Hospital Development Center.
The authors had no disclosures.
