Time to rethink the role of lymph nodes in cancer, lecturer says

Daniel G. Coit, MD, FACS

While surgical oncologists have become the acknowledged experts in removing regional lymph nodes, most contemporary clinical trial data do not support the practice for improving survival.

“There have been a legion of prospective, randomized clinical trials comparing the removal of more lymph nodes with the removal of fewer lymph nodes. With few, if any, exceptions, none of these trials has shown any survival advantage associated with removing more lymph nodes,” said Daniel G. Coit, MD, FACS, Immediate past-president of the Society of Surgical Oncology, a surgical oncologist at Memorial Sloan Kettering Cancer Center, and professor of surgery at Weill Cornell Medical College, New York, NY.

“When I entered the world of surgical oncology, I believed what I was taught, that the complete and elegantly beautiful removal of all regional lymph nodes was the Holy Grail of cancer surgery,” he said. “Remarkably consistent data from multiple rigorous prospective randomized trials have taught me otherwise. Surgery for cancer is much more complicated than simply perfecting the technique of removing regional lymph nodes.”

The challenge for surgical oncologists is distinguishing between patients likely to benefit from extended node removal and those who will not, said Dr. Coit, who will present Wednesday’s Commission on Cancer Oncology Lecture, The Evolving Enigma of Regional Lymph Nodes in Surgical Oncology.

The two current hypotheses regarding the function of regional lymph nodes are that they either act as governors of cancer progression, in which case removal should affect outcome; or that they are simply indicators of outcome, in which case the status of the regional nodes has prognostic value, but removal of more than those needed for that prognostic information is unlikely to impact outcome. The reality is likely to be much more complex, Dr. Coit said.

“Many surgeons, especially classically trained surgical oncologists, are reluctant to accept the conclusion that we should not be taking out so many lymph nodes in every patient,” he said. “Yet there have been some very informative clinical trials recently saying that removing lymph nodes makes no difference clinically. The way forward may be to look at the indicators of nodotrophism. Once we recognize which cancers are more likely to migrate to and remain in the nodes, and which ones couldn’t care less about lymph nodes, we will be able to focus our efforts to better clinical effect.”

True nodotrophism is a new and unproven hypothesis, Dr. Coit noted. It’s also a more tenable hypothesis in light of current data than older suggestions that lymph nodes act either as filters that catch and concentrate tumor cells or as indicators of tumor aggressiveness.

“We need to explore the molecular signatures, the genetic drivers of tumors that remain confined to the regional lymph nodes and those that did not,” Dr. Coit said. “We are entering an extraordinary new era in the management of cancer patients, one in which we are developing new molecular tools to interrogate both the tumor and the host in an effort to more appropriately tailor treatment for maximal benefit and minimal morbidity.”

The Commission on Cancer Oncology Lecture is sponsored by the Commission on Cancer. It was established in 1988 to explore major developments in oncology and to focus on the surgeon’s role in caring for cancer patients.