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Elective neck dissection in early oral cancer: debate resolved

A debate over whether to remove lymph nodes from the neck during surgical treatment of early oral cancer has gone on for decades. Now findings from a randomized control trial reported last June at the American Society of Clinical Oncology’s (ASCO) annual meeting, in Chicago may finally put that controversy to rest.

After just over 3 years of follow-up, 80% of 245 patients who had the nodes removed during surgical treatment of the primary tumor were still alive, compared with 67.5% of 255 patients randomized to a watch-and-wait policy who had the nodes removed only when metastases were suspected. “The elective node dissection (e.g., removal) prevented one death in every eight patients and one recurrence in every four patients who received it,” said Anil D’Cruz, M.D., chief of the department of head and neck surgery at the Tata Memorial Centre in Mumbai, India, and the study’s principal investigator. “[From] those results, I believe elective neck dissection should be the standard of care for all patients with early-stage, node-negative oral cancer.”

Appearing most often on the tongue, or on skin membranes in the cheek, oral cancer results mainly from tobacco and alcohol abuse. It’s especially common among men in South Asian countries such as India, where betel nut chewing adds to the risk. Infection with the human papillomavirus 16 (HPV-16) virus is also a risk factor, especially among younger, nonsmoking women. The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program predicts that 47,000 people will be diagnosed with oral cancer in the United States in 2015. Since it rarely produces pain or other detectable symptoms before it metastasizes to the lymph nodes, and then typically to the lungs, oral cancer is usually diagnosed at late stages when 5-year survival rates rarely exceed 50%. By contrast, 5-year survival rates in early-stage oral cancers treated successfully with surgery can exceed 90%, but early detection of the primary tumor depends on access to health care. In India, where health care access is poor, only 10%–15% of oral cancer patients are diagnosed with early-stage disease, compared with about 25% in the United States.

Identifying occult nodal metastases in the neck can be challenging. According to Robert Ferris, M.D, Ph.D., a professor at the University of Pittsburgh Cancer Institute, these small malignancies are difficult to feel manually during a physical exam, and they don’t readily show up on positron emission tomography scans or on magnetic resonance imaging. Clinicians must therefore choose between two options: elective dissection, meaning that the nodes are removed during surgery for assessment by a pathologist, or watch and wait, whereby the nodes are checked at various intervals for evidence of cancer and then removed later if needed.

Choice Between Two Options

The argument in favor of watch and wait—especially for those with primary tumors smaller than 4 mm—is that nodal dissection carries a risk of long-term shoulder pain. (That’s because the surgical field sometimes crosses a nerve that interfaces with the shoulder muscles.) Only one in five patients with early oral cancer have occult metastases in the nodes, and according to Ferris, elective dissection would expose those who don’t to potential shoulder pain without any clinical benefit. But if the nodes turn out to be cancerous, he added, patients can be treated with a potentially life-saving regimen of radiation and possibly chemotherapy.

“The impact of finding these cancerous nodes is critically important,” Ferris said. “Only through the elective procedure can we segregate those who have metastases from those who don’t, and so the dissection can very strongly confer prognostic information.”

Earlier studies dating back to the mid-1960s lacked the statistical power needed to resolve this debate over the two alternatives. The studies generated divergent results, and so practice standards varied around the world, with proponents of watch and wait insisting that neck nodes could be removed later without compromising survival.

Answers From a Definitive Trial

To produce a definitive answer, D’Cruz launched his study in 2004. A total of 596 patients with T1 or T2 squamous cell oral carcinoma were randomized to either elective dissection or watch and wait. All patients had surgery to remove the primary tumor and adjuvant radiotherapy when indicated. After a median follow-up of 39 months, recurrences in the watch-and-wait arm numbered 146, compared with 81 in the elective dissection arm. Elective dissection also improved survival by a statistically significant 12.5% and reduced risk of death by 36%.

“I think it’s a very good study,” said Hisham Mehanna, Ph.D., chair of head and neck surgery at the University of Birmingham in the United Kingdom, and a discussant at D’Cruz’s ASCO presentation. “It’s well powered, well conducted, and the findings are conclusive.”

Ferris agreed. “The real benefit is that it provides level 1 evidence for what was already standard of care in the United States,” he said. “We’re now required to have level 1 evidence, so this is important. It validates the clinical benefits of elective dissection, and suggests that the procedure is also cost effective.”

The study didn’t address how many neck nodes to remove. However, a different presentation at ASCO showed that the best survival outcomes are obtained by removing 18 nodes or more. Vasu Divi, M.D., an assistant professor at Stanford School of Medicine in Stanford, Calif., and colleagues, reviewed data from 572 patients treated in two clinical trials—RTOG 9501 and 0234—with a median follow-up of 8 years. They concluded that dissecting fewer then 18 nodes results in statistically worse overall survival rates in both HPV-16–positive and HPV-16–negative patients. That finding was consistent with evidence from an April 2014 study in the Annals of Surgical Oncology. Led by Ardalan Ebrahimi, M.D., from the Royal Prince Alfred Hospital in Sydney, Australia, that study also confirmed that no fewer than 18 nodes should be removed during elective dissection in patients with oral squamous cell carcinoma.

Insights From Ultrasound?

According to Mehanna, ultrasound imaging might detect occult nodal metastases in the neck and preclude the need for an elective dissection. To investigate that possibility, D’Cruz’s study also randomized patients after surgery to ultrasound-guided surveillance or to standard surveillance based on clinical exam. Those data have yet to be reported, “and until they are, we should continue with the elective procedure,” Mehanna said.

D’Cruz concurred. “Our [unreported] analyses so far show that whether you follow patients with ultrasound, or with clinical exam and ultrasound combined, you still have a survival detriment with watchful waiting.” He added, “We will have better figures to address this issue, but as of now the elective procedure should be the standard of care. We may find a small subset of patients that can be adequately followed on ultrasound, but we can’t jump to any conclusions yet.”

A version of this blog post first appeared in Journal of the National Cancer Institute.

Featured image credit: RGB-ray by Lasse Rintakumpu. CC BY 2.0 via Flickr.

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