Roxanne Nelson

May 31, 2015

CHICAGO, IL — Optimal management of the neck in early oral cancers has been a matter of debate, but the results of a large randomized phase 3 trial have now settled the question, say the authors.

"Elective neck dissection [END] should be the standard of care for early node negative squamous cell cancers," said lead study author Anil D'Cruz, MBBS, professor and chief, Department of Head and Neck Surgery, Tata Memorial Centre, Mumbai, India.

An interim analysis of the first 500 patients showed that END improved overall survival by 12.5% in absolute numbers compared with therapeutic neck dissection (TND). END also reduced the relative risk for death by 36% and of recurrence by 55%.

Dr D'Cruz presented the results of his study during the plenary session here at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting.

The study has also been published in the New England Journal of Medicine to coincide with the ASCO presentation.

"This study provides long-awaited answers to a question doctors worldwide have struggled with," commented ASCO expert Jyoti D. Patel, MD. "We never want to do more surgery than we have to, but for patients with early oral cancer, we now know that more extensive surgery prolongs lives."

We now know that more extensive surgery prolongs lives. Dr Jyoti D. Patel

But another expert questioned the generalizability of the results.

Hisham Mehanna, MD, from the University of Birmingham, United Kingdom, who acted as discussant of the study, said at this time, END should be standard of care — but for cancers of a certain depth.

Two Schools of Thought

To date, there have not been any strong clinical practice recommendations advocating neck dissection for early oral cancers, and thus there has been a wide range of variability in practice. Dr D'Cruz noted that the treatment of early oral cancer has been a matter of considerable debate among physicians — one that has spanned 5 decades.

The management of early oral cancers is primarily surgical, and there are two schools of thought: the "watch and wait" approach, which has TND as a progressive option as needed, and END.

According to Dr D'Cruz, TND has never shown a conclusive survival advantage, and patients must undergo an additional surgical procedure, which increases the risk for morbidities.

END, however, has been associated with better control and survival and involves only one surgical procedure.

Improved Overall and Disease-Free Survival

The primary end point of the study was overall survival, and the secondary end point was disease-free survival.

The trial, which was conducted at Tata Memorial Centre between 2004 and 2014, randomly assigned 596 patients with lateralized stage T1 or T2 oral squamous cell carcinomas to END or TND. An interim intent-to-treat analysis of 500 patients (255 TND, 245 END) with a minimum follow-up of 9 months was performed as mandated by the center's Data and Safety Monitoring Committee.

In this group, there were 427 tongue, 68 buccal mucosa, and 5 floor-of-mouth tumors; about half (n = 221) were TI, and 279 were T2.

There were 81 recurrences and 50 deaths in the elective surgery group, and 146 recurrences and 79 deaths in the therapeutic surgery group.

At 3 years, END resulted in an overall survival rate of 80% compared with 67.5% for TND (hazard ratio for death, 0.64 in the elective surgery group; P = .01).

At that time, the END group also had a higher rate of disease-free survival compared with the TND group (69.5% vs 45.9%; P < .001).

The rates of adverse events were 6.6% in the END group vs 3.6% for those in the TND group.

"For every eight patients who undergo [END], one death is prevented," said Dr D'Cruz, "And for every four patients who undergo the procedure, one recurrence is prevented."

Important...but Not Ready to Change Standard

This is an important study because it was a large randomized trial, and one that would have been difficult to conduct in the United States, commented Lori J. Wirth, MD, medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston.

"In the US, neck dissection is done in early-stage oral cancer, but the decision to do it is based on the depth of the cancer," she told Medscape Medical News. "So it is part of the standard of care for those cases, and we have seen that it can improve survival, but its importance appears to be greater than we may have previously thought."

However, although the data are important, Dr Mehanna does not believe END should be standard of care for everyone.

"END should be used for early oral cancer with tumors that have a depth of more than 3 mm," he said during his discussion. "There is inadequate evidence currently about ultrasound surveillance, and while we await further results, sentinel node biopsy can be used."

Sentinel node biopsy can help avoid neck dissection in about 70% to 75% of cases, Dr Mehanna explained, but acknowledged that it can be logistically difficult, resource-intensive, and may not be useful in resource-poor settings.

"In the future, biomarkers can hopefully be used to help determine the presence of occult metastasis," he added.

"This was an ambitious study with difficult randomization and has helped resolve one of the important controversies," Dr Mehanna concluded. "The study has potential to resolve even more of them."

The study was funded by the Department of Atomic Energy, Clinical Trial Center. Dr. D'Cruz, disclosed that he is with the Speakers' Bureau with Merck Serono and received research funding (institutional) from GlaxoSmithKline

American Society of Clinical Oncology (ASCO) 2015 Annual Meeting: Presented May 30, 2015. Abstract LBA 9002.


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