FORT LAUDERDALE, Fla--Once primary melanoma is excised, choosing among
adjuvant treatment options is a difficult decision, Daniel G. Coit, MD,
of Memorial Sloan-Kettering Cancer Center, said at the National Comprehensive
Cancer Network (NCCN) annual meeting. Dr. Coit presented the network's
preliminary guidelines for melanoma, along with John A. Thompson, MD, of
the University of Washington, Seattle.
Adjuvant treatment and the schedule and intensity of follow-up were
the areas that generated the most discussion among the melanoma guidelines
panel members, Dr. Coit said.
Dr. Thompson noted that "interferon alfa-2b (Intron A) is the first
adjuvant treatment in melanoma that has induced a statistically significant
improvement in relapse-free and overall survival."
In considering guidelines for adjuvant treatment, Dr. Thompson said
that the NCCN panel focused on "patients who can be rendered surgically
free of disease, but who retain a very high risk of relapse in the next
For patients with melanomas less than 4 mm thick, the recommendation
is surgery alone. Patients with melanomas greater than 4 mm thick or anyone
with positive lymph nodes regardless of thickness should be considered
for interferon alfa therapy or a clinical trial, Dr. Thompson said.
For patients who are sentinel node positive, Dr. Thompson said that
the preliminary NCCN recommendation is generally to proceed with lymph
node dissection. "At that point, if no evidence of residual metastatic
disease exists, the clinician may proceed with adjuvant systemic therapy
with interferon," he said.
Dr. Coit called detection of recurrence the cornerstone of the follow-up
of the cancer patient. He emphasized that the NCCN guidelines for follow-up
"are, for the most part, arbitrary, that is, they are points of departure."
Follow-up for Early Melanoma
For early melanoma (stages I and II), the committee adhered to the NCI
consensus guideline, Dr. Coit said, which recommends history and physical
and skin examination every six months for two years, then annually. Optional
follow-up recommendations include chest x-ray, and LDH every 6 to 12 months.
He added that, for more advanced disease, "there really are very little
data to suggest what we should do."
Patients with thicker melanomas and those with node-positive melanomas
recur earlier than those with node-negative or thinner melanomas, he noted.
"In node-positive melanomas, about 80% of all recurrences will be
seen within the first two years, and by five years, well over 95% of all
recurrences will be seen," he said.
Although recurrence is less common in the node-negative and thin melanoma
group, the risk of recurrence is spread out over a much longer period of
time. "Only about 50% of recurrences are seen by two years, and that
curve stretches out to 10 and 20 years," Dr. Coit said.
The NCCN recommends more intensive frequency of follow-up in patients
with positive nodes or thick primary melanomas, with yearly follow-up after
the fifth year, "looking both at the risk of second primary melanoma,
a lifelong event, and the likelihood of a late recurring melanoma,"
Dr. Coit said.
Optional recommendations for follow-up in these patients are chest x-ray
and laboratory studies, including LDH, alkaline-phosphatase, and complete
blood cell count, every 6 to 12 months, and abdominal/pelvic/chest CT scan,
especially if interferon alfa is being considered, he added.
Dr. Coit emphasized that the NCCN guidelines to date are a "work-in-progress"
and will be followed by ongoing review and refinement within the NCCN member
Dr. Coit cautioned that melanoma is primarily a disease of younger people,
and it is crucial that its management in the early phases be determined.
"We're in the midst of a melanoma epidemic," he said, "and
it's becoming a public health problem, ranking second only to adult leukemia
in terms of years of potential life lost."
For patients with in situ melanomas, the NCCN preliminary recommendations
for primary treatment include wide excision with a 0.5 cm margin; for those
with melanomas less than 1 mm thick, a 1 cm margin; and for those with
melanomas measuring between 1 and 4 mm, or greater than 1 mm thick, a wide
excision with a 2 cm margin.
In patients who present with stage III melanoma, wide excision of the
primary melanoma with a regional lymph node dissection is appropriate,
and results in a long-term cure rate of approximately 30% of patients,
Dr. Coit said.
For more advanced regional disease, there are many options, he said.
Those included in the preliminary NCCN practice guidelines are surgical
excision; intradermal injection of nonspecific immunotherapy agents, like
BCG (bacillus Calmette-Guérin), DNCB (dinitrochlor-obenzene), or
interferon-alfa; hyperther-mic perfusion with melphalan (Alkeran); enrollment
in a clinical trial; or systemic therapy.
For patients with systemic metastases not amenable to surgical resection,
Dr. Coit said, the recommended treatment is systemic chemotherapy with
dacarbazine (DTIC), platinum-based combination therapy, or investigational
therapy on a clinical trial.
NCCN Melanoma Guidelines Panel
Alan Houghton, MD
Daniel Coit, MD
William Bloomer, MD
Antonio Buzaid, MD
David Chu, MD
Burton Eisenberg, MD
Joan Guitart, MD
Timothy Johnson, MD
Stanley Miller, MD
Steven Sener, MD
Kenneth Tanabe, MD
John Thompson, MD
Marshall Uriat, MD
Mike Walker, MD