Physicians differ on the use of sentinel lymph node biopsy for melanoma
Published data receive various interpretations
Editor's note: This is the second installment of a 2-part story on melanoma. Part 1 appeared in the July 1 issue.
Although sentinel lymph node (SLN) biopsy has become the standard of care in the United States for staging of and determining prognosis in patients with intermediate-thickness melanoma and other specified cancers, some physicians question its value in an era of skyrocketing health care costs.
The procedure has been the subject of some debate since an article published in the New England Journal of Medicine in 2006 reported the 5-year results of the Multicenter Selective Lymphadenectomy Trial (MSLT-I). The trial was designed to determine whether the use of SLN biopsy could provide a survival advantage by determining whether melanoma is present in the SLN and then conducting a wider completion lymph node dissection (CLND) if the SLN was positive.
Those results were controversial, because the study found no overall survival advantage for SLN biopsy after 5 years of followup. However, the authors did observe an improvement in diseasefree survival in the biopsy group versus the observation group, making the recommended procedure preferable to observation.
However, not everyone agrees with that interpretation. “It's hard for me to imagine why they said it should be preferred,” says Steven Rosenberg, MD, PhD, chief of surgery at the National Cancer Institute in Bethesda, Maryland. “It does provide prognostic information, but because we don't have any good adjuvant treatments now, in my view there's no good reason to do it.”
An article in the January 2013 issue of the British Medical Journal (BMJ) raised the issue again by questioning why thousands of patients worldwide with melanoma should undergo SLN biopsy despite a “lack of clear evidence that it will improve outcomes.” Among other criticisms of SLN biopsy, the article also raised the issue of postoperative complications, including the risk of lymphedema after both SLN biopsy and CLND. The author also pointed out that “it is generally accepted that only 20% of patients who have SLN biopsy will have positive SLNs, and only 20% of those will have metastatic disease in the nonsentinel nodes,” resulting in 96% of patients undergoing the procedure unnecessarily.
The Case for SLN Biopsy
The lead author of MSLT-I, Donald Morton, MD, who developed the procedure in the early 1990s and is chief of the melanoma program at the John Wayne Cancer Institute in Santa Monica, California, was not available for comment. Vernon Sondak, MD, who trained under Dr. Morton and was one of the early users of the SLN biopsy, was able to speak with CancerScope.
Dr. Sondak, who performs between 4 and 10 SLN biopsies per week, believes strongly in the procedure. He points out that the surgery can be performed at the same time that the primary melanoma is being removed. For many patients, the major difference in adding the SLN biopsy procedure is their having to receive general versus local anesthesia. However, many patients require general anesthesia for the primary excision alone, and there are some surgeons who will perform the SLN biopsy under local anesthesia under certain conditions, he adds.
“The pathologist can see small areas of melanoma that no other form of detection—CT scan, PET scan, and ultrasound— can see,” he says. “The gain in information that the patient receives is potentially quite large.” In particular, the procedure is very reliable in separating patients with a 90% survival rate from those who have a 50% to 60% survival rate, he says. He notes that it is rare for surgeons to not find the SLN, referring to a 2011 meta-analysis of 71 studies, which concluded that the average percentage of SLNs that were successfully mapped was 98.1%.
Furthermore, Dr. Sondak points to a guideline jointly issued by the American Society of Clinical Oncology and the Society of Surgical Oncology that reviewed available evidence and concluded that the procedure should be recommended for patients with intermediate thickness melanoma and should also be considered for patients with thick melanomas and selected “high-risk” thin melanomas. “This highly objective panel came to this conclusion,” he says.
Skin cross section depicting melanoma.
Mark Middleton, PhD, professor of experimental cancer medicine and consultant medical oncologist at the University of Oxford in the United Kingdom, who has performed the procedure for more than a decade, concurs that SLN biopsy is useful. “I believe it allows us to categorize patients' risk of recurrence as accurately as possible, and allows them to make informed decisions about the options for management of their disease,” he says. “It has largely abolished bulky nodal relapses where it is used, and this has historically been a cause of significant morbidity. In our series, published last year, and in work by others, a negative SLN biopsy in patients who have a thick melanoma suggests a much lower risk of recurrence than the current staging system assigns, which is important if considering toxic regimens like interferon or ipilimumab.”
The Case Against SLN Biopsy
Others are not as easily convinced of the merits of SLN biopsy. “Early on, we all hoped there would be a survival benefit but, unfortunately, it's just not working,” says James Grichnik, MD, PhD, director of the melanoma program at the University of Miami Sylvester Comprehensive Cancer Center in Florida. He notes that the procedure, which is fairly expensive, is a good prognostic test but that there may be more economical tests that should be explored, including the tumor proliferation rate, molecular markers on the primary tumor, and circulating cells.
[SLN biopsy] allows us to categorize patients' risk of recurrence as accurately as possible, and allows them to make informed decisions about the options for management of their disease.—Mark Middleton, PhD
“There are common misconceptions about the way lymph nodes work,” Dr. Grichnik says. “We tend to think of them as filters, as if they trap cells as they leave the skin, but tumorigenic stem cells can flow right through the lymph nodes.”
He adds that SLN biopsy is not an exact test; in other words, if a patient's SLNs tests negative, he or she can still die of melanoma. Furthermore, there is good evidence, Dr. Grichnik says, that there are circulating cells fairly early on in these tumors that can slip through the lymph nodes. As a result, CLND may not combat the disease either. “We need to start thinking about other ways of doing staging and do some head-to-head tests,” he says.
Dr. Grichnik believes that SLN biopsy should not be required as a standard of care and that the main focus should be on developing better prognostic tests and therapies. “I believe our ultimate objective is to cure melanoma, and our focus should be on improving overall survival,” he says. “The data and our current concepts of biology explain why SLN biopsy is not helping our patients. I really wanted it to work, but I've moved on.”
“Patients want to live,” Dr. Rosenberg adds. “Once they find out [SLN biopsy] has no impact whatsoever on their survival, most would decide not to undergo a surgical procedure.” Furthermore, he says, physicians play a major role in influencing their patients' attitudes about which tests need to be performed. “In this day and age, when medical costs are completely out of control, it seems to me we shouldn't be doing procedures that have no benefit to the health of the patient,” he says.
The data and our current concepts of biology explain why SLN biopsy is not helping our patients. I really wanted it to work, but I've moved on. —James Grichnik, MD , PhD
Yet even that point is up for debate. “Why would we do any prognostic or staging test if it doesn't improve survival? Survival isn't the only reason we do things,” says Dr. Sondak. “If informed patients believe the information obtained from the SLN biopsy will help them deal with their melanoma, as many patients indeed do, then we believe the benefits justify the associated risks and costs.”
Meanwhile, skeptics and supporters alike await the results of the 10-year follow-up data from the MSLT-I trial, which Dr. Sondak says is currently undergoing peer review, and those of another major trial being led by Dr. Morton. The new study, the Multicenter Selective Lymphadenectomy Trial (MSLT-II), is analyzing the potential benefits of regional lymphadenectomy for melanoma patients with positive SLNs, and is expected to be completed by 2022.