‘The Nodes Always Know’! Free

The recent article ‘Multiparametric evaluation of mediastinal lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers’ by Wang et al. [1] proposes 3 radiologic parameters plus patient age, and CEA levels to predict which clinical stage T0-T1c non-small-cell lung cancer patients (T0-1NSCLC) had positive hilar and/or mediastinal lymph node (MLN) metastases. The study retrospectively forecasts the 72 (13.9%) T0-1NSCLC patients of the 517 study group who had positive hilar and/or MLN. Although tumour characteristics such as solid component size, tumour SUV max and ratio of consolidation/tumour (CTR) may predict positive lymph nodes, only the pathologic evaluation of hilar and MLN for micro-metastases is the final word. To paraphrase, only the histologic examination of T0-1NSCLC lymph nodes seals the deal on pathologic staging or ‘The Nodes Always Know’!

In a 2017 publication, Bille et al. [2] noted that 9% T1-T2 lung cancers had occult pN2 disease and that 16% pN2 had MLN outside the lobe-specific lymph node drainage pattern. Pari, et al. [3], showed 6.8% and 13.3% positive MLN for ≤1.0 and 1.1–2.0-cm diameter lung cancers respectively. The definitive final histology ie, micropapillary adenocarcinoma, mucinous adenocarcinoma or lepidic predominant adenocarcinoma is important in the MLN prediction models, and this information is not available until several days later—when lymph node biopsy is no longer possible.

The 79 pure ground-glass nodules (GGN) in this study and the 39 partly solid or 6 pure solid lesions with less than a 10-mm diameter had no positive lymph nodes harvested. This argues for foregoing mediastinal dissection in patients with these specific characteristics. However, 164 patients is a relatively small population and long-term survival, or incidence of recurrent disease is not available on these patients. Remember that 8.3% of this study’s partially solid lesions had positive lymph nodes, with the partially solid designations not being determined until the final pathology was interpreted several days after the operation concluded.

The American College of Surgeons Commission on Cancer [4] recommends 1 hilar and 3 mediastinal lymph nodes (10 total nodes) be biopsied during curative lung resection. The European Society of Thoracic Surgeon’s [5] guidelines call for at least 3 hilar nodes and 3 mediastinal stations in which the sub-carinal station is always included as their minimum lung cancer lymph node dissection. If we use predictive models to eliminate mediastinal lymph node dissection, a certain percentage of patients will likely have their occult mediastinal lymph node metastases missed.

A recent Veterans Administration Hospital study [6] shows that only 25.8–34.7% of lung cancer resections had 1 hilar and 3 mediastinal lymph node stations biopsied. If the Wang publication [1] is frequently cited, an even lower percentage of thoracic surgeons may perform the recommended lymph node sampling.

Although 28 of 72 (38.9%) lymph node-positive patients had only N1-positive nodes, positive hilar nodes result in a pathologic upstage, and the recommendation for a follow-up CT changes to adjuvant therapy. Additionally, 89.3% of the patients had lobectomy in the study, meaning that N1 nodes were harvested. If the study patients having segmentectomy/wedge resection did not have N1 nodes harvested, the patients with positive N1 nodes may actually be underreported in this study.

With the addition of better chemotherapeutic, marker based and immunotherapeutic options, the importance of positive hilar/MLN in directing who qualifies for adjuvant therapy seems even more important.

The ability to predict with certainty lymph node status would be invaluable as patients could avoid minimally invasive (still painful) Video Assisted Thoracic Surgery (VATS) and robotic procedures, which harvest MLN. If MLN dissection was only a confirmative exercise, then other less invasive ablation techniques such as SBRT [7], microwave or cryotherapy might offer comparative outcomes for selected subsets NSCLC.

The 19 patients with skip lesions (hilar nodes negative, but positive MLN involvement) were usually accompanied by pleural invasion and positive EGFR marker (13/19). Should the T0-1NSCLC patients with pleural involvement on preoperative CT scan be another indicator for MLN dissection. The authors have not championed this recommendation but perhaps it should be added as one of the predictive parameters. Certainly, patients having visceral pleural involvement (with or without positive MLN) would be a cohort more likely to receive adjuvant therapy.

The advent of sampling plasma RNA and DNA for cancer may drastically alter our treatment strategies. However, not all cancers have positive plasma tests nor do all patients with metastatic disease, positive MNL or recurrence have any predictable correlation with plasma RNA or DNA positivity. When that day dawns then the requirements for MLN dissection may change.

Until postoperative studies demonstrate that specific T0-T1NSCLC never has positive MLN or is always positive, I would advocate MLN sampling on all patients undergoing curative lung cancer resection. At the present time, ‘The Nodes Still Know’!

REFERENCES