In bowel cancer, enlarged lymph nodes can be a good prognostic feature

At the Champalimaud Colorectal Cancer Conference, last February, Gina Brown, from the Imperial College London, questioned the validity of the current staging strategy for colon cancer. Indeed, research shows that lymph nodes are not the main culprit in colon cancer spread, and can actually be a sign that the patient’s immune system is fighting back. 

A widespread system for determining the stage of bowel cancer from magnetic resonance imaging (MRI) and computed tomography (CT), with critical implications for treatment and outcome, is so-called TNM (Tumour, Node, Metastasis). T describes the depth of the tumour, N whether the cancer has spread to the lymph nodes, and M whether it has spread to other parts of the body.

In the past few years, gastrointestinal imaging specialist Gina Brown, from the Imperial College London, has “advanced methods to identify previously unseen and poorly understood pathways of spread of colorectal cancer in vivo”, according to her website. She has characterised tumour deposits and venous invasion on imaging and shown that they are more significant for cancer outcomes than lymph nodes. “The chief pathway of cancer spread is not via the lymph nodes, but via the venous system”, Brown said during her talk.

It has been shown that more than 90 percent of colorectal cancer patients who develop liver metastases (some of who might also have had “positive” lymph nodes for cancer) have signs of tumours in their vascular system, either within the veins or within nodules associated with the venous system. “This is the pathway of spread – from tumor to vein to nodules – and if we keep being content to call them lymph nodes, we are not giving the correct prognostic information to patients about their risk of recurrence ”, emphasised Brown.

She went even further by saying that lymph nodes can actually be a good prognostic feature for colorectal cancer, because their enlargement indicates a strong immune response from the patient. “Our understanding of the immune processes that fight cancer are only beginning to come to light”, she said.

José Azevedo – colorectal surgeon at the Champalimaud Foundation’s Digestive Unit and one of the Conference’s organisers – expands on this. “We're now starting to realise that, from the evidence we had, perhaps the differences we were seeing in lymph nodes were due to the fact that some of these supposed lymph nodes were actually tumour deposits with vascular invasion, precisely those responsible for the worst prognosis”, he says.

But in order to improve the accuracy of staging, nodules have to be distinguished from lymph nodes.

Brown explained that identifying patients with vascular invasion and a vascular pathway of spread on MRI is easy, because blood vessels are anatomically obvious on the images – and that when the nodules grow along blood vessels, they are tumor deposits and not lymph nodes. 

“If we take the trouble to look carefully at these nodules and see whether they're aligned with a vein or separate from it, we start to see that not everything round is a lymph node”, she pointed out. 

Brown advocates for a different staging system, called TDV (Tumour, Deposit, Venous). When the depth of tumour growth into the vessels is more than five millimeters, this means venous invasion, which carries a poor prognosis. “Look out for tumour extension into the blood vessels and resist the temptation to measure lymph nodes”, she exhorted the audience. “It is the absence of nodules that gives patients a survival advantage, as well as a better outcome in terms of recurrence.”

The inaccuracy of the TNM system has also been shown for breast cancer. “When you look at the clones of breast cancer cells inside lymph nodes”, Brown said, “you see that the cancer has bypassed the lymphatic system. The clones in the lymph nodes are not the same as those that eventually become metastases”. 

The lack of a good staging is a problem in colon cancer, would later comment Tsuyoshi Konichi, a colorectal surgeon currently working at MD Anderson Cancer Centre, and also a speaker at the Conference. “Gina nicely addressed how we should change the current diagnostic system”, he said. A very enlarged lymph node, which might conventionally be considered positive, often ends up being a negative node. On the other hand, small tumours, small deposits with some heterogeneity and irregularity, are actually cancerous deposits that may pass as positive lymph nodes.

Joep Knol, also a speaker and a Belgian specialised in colorectal surgery at the ZOL hospital in Genk, agreed. “I think we need to pay much more attention to tumour deposits than we do. Tumour deposits are prognostically worse than lymph nodes.”

Text by Ana Gerschenfeld, Health & Science Writer of the Champalimaud Foundation.