Approximately 70% to 80% percent of patients who undergo elective neck dissection (END) for early-stage oral cavity cancer do not have cancer in their lymph nodes. This statistic begs the question: Is there a better way to detect the 20% to 30% of patients who do have cancer?
Explore This IssueJuly 2021
That’s what researchers hope to answer with clinical trial NRG-HN006, Randomized Phase II/III Trial of Sentinel Lymph Node Biopsy versus Elective Neck Dissection for Early-Stage Oral Cavity Cancer.
The answer may hinge, in part, on the definition of “better.”
Unlike many trials, HN006 will consider the patient perspective. “We’re considering quality of life and morbidity,” said Stephen Lai, MD, PhD, professor of head and neck surgery at The University of Texas MD Anderson Cancer Center in Houston and the primary investigator for NRG-HN006. The current standard of care—elective neck dissection (END) for nearly all patients with early-stage oral cavity cancer—can result in significant shoulder impairment for many patients. That’s why NRG-HN006 will assess patient-reported neck and shoulder function, scarring, and length of hospital stay in addition to disease-free and overall survival.
Current Practices in the Management of Early-Stage Oral Cancer
For nearly 40 years, debate regarding the management of patients with early-stage, node-negative oral cancer centered around END or “watchful waiting” followed by neck dissection if cancer spread to the neck. As studies have found that 20% to 30% of patients with early-stage oral cancer will develop lymphatic metastases (J Clin Oncol. 2010;28:1395–1400), which are associated with decreased survival, American surgeons have largely tended toward END.
However, evidence for the utility of sentinel lymph node biopsy (SLNB) has been growing. A prospective multi-institutional trial published in 2010 found that SLNB correctly predicted a pathologically negative neck in 95% of patients (J Clin Oncol. 2010;28:1395-1400). The study included 140 patients with stage T1 and T2, N0 invasive oral cancers; for T1 lesions, 100% of metastases were correctly identified.
By 2014, SLNB was included as a management option in the National Comprehensive Cancer Network (NCCN) Guidelines for cancer of the oral cavity. “The guidelines said you could do either elective neck dissection or sentinel lymph node biopsy; they didn’t say one is preferred, but either is an option,” said John D. Cramer, MD, assistant professor in the department of otolaryngology–head and neck surgery at Wayne State University School of Medicine in Detroit.
By 2019, after several single-arm prospective studies demonstrated the accuracy of SLNB and showed that the procedure was associated with positive cancer outcomes, SLNB was “pretty widely adopted in Europe,” Dr. Cramer said. Currently, SLNB is the preferred option for the management of early-stage oral cancer in Amsterdam, The Netherlands, and other parts of Europe. “I’ve had physicians there tell me, ‘Based upon our experience with sentinel lymph node biopsy for early-stage oral cavity cancer, we actually think it’s unethical to randomize patients in a trial for an elective neck dissection,’” Dr. Lai said. In other parts of Europe, he said, debate rages. “In the UK right now, there is a group of surgeons who are saying, ‘We should only do elective neck dissection. We shouldn’t even consider sentinel lymph node biopsies,’” Dr. Lai said.
In the United States, SLNB for early-stage oral cancer remains rare. Dr. Cramer and his colleagues conducted a retrospective cohort study of patients with stage I to II oral cavity squamous cell carcinoma who underwent staging of the neck between 2012 and 2015, and found that just 240 of 8,328 patients, or 2.9%, underwent SLNB (Laryngoscope. 2019;129:162-169). The study noted that although SLNB is associated with a reduced hospital stay and equivalent overall survival compared to END, “SLNB remains rarely used in the United States.”
Dr. Cramer said the slow uptake of SLNB in the U.S. (and in other parts of the world) may be due to the fact that, to date, there hasn’t been strong evidence to favor either SLNB or END. Additionally, physicians view SLNB as a “de-escalation of treatment,” he said. “The tendency in cancer treatment is often to do more. Any time that we do something that’s perceived as ‘less,’ people are hesitant.”
Logistical and economic factors may also be inhibiting the use of SLNB. Some hospitals require the surgeon to perform the nuclear medicine injection to map the lymph drainage, which may necessitate a trip to the nuclear medicine department and tack on additional time to the case. “And sentinel node biopsy pays less than an elective neck dissection,” Dr. Cramer said.
Patients helped fuel momentum for SLNB in the management of breast cancer, but to date, no such advocacy has been noted in oral cancer. “It’s a rare cancer that has worse overall survival than breast cancer, so there are fewer people around five or 10 years later to speak about their experiences,” Dr. Cramer said.