EXPERT ANALYSIS FROM PMO LIVE

SEATTLE (FRONTLINE MEDICAL NEWS)Recent developments in the field of melanoma may help clinicians refine their approach to this disease, according to Dr. Suraj S. Venna, a dermatologist and medical director of the Inova Melanoma and Skin Cancer Center in Fairfax, Va. He discussed several key studies and guideline revisions at a joint meeting of the Global Biomarkers Consortium and World Cutaneous Malignancies Congress.

Sentinel node biopsy for thin melanomas

Guidance regarding staging of and use of sentinel lymph node (SLN) biopsy in cases of thin melanomas, those no more than 1 mm thick, is in flux, and these gray areas pose challenges to management.

In its seventh edition of the TNM Staging System published in 2010, the American Joint Committee on Cancer started incorporating mitotic rate to substage T1 melanomas, according to Dr. Venna. Those having a mitotic rate of at least 1 mitosis/mm2 are now categorized as T1b. Yet, even within this subset, there is a spectrum of 10-year survival according to mitotic rate ( J Clin Oncol. 2011;29:2199-205 ). Also, the association of mitotic rate with regional nodal metastasis is unclear.

Therefore, “T1b is not an automatic recommendation for lymph node biopsy,” he said. Decisions about SLN in patients with such tumors should consider all available clinical and pathologic factors.

The National Comprehensive Cancer Network has also revised its guidelines in this area. In 2011, they advised that SLN could be discussed and considered in stage IA melanomas with various high-risk features and in selected stage IB melanomas based on mitotic rate and thickness.

But in their 2015 update, they gave priority to lesion depth. “What they say is other than Breslow depth, there remains little consensus regarding the significance of ulceration, mitotic rate, or lymphovascular invasion,” Dr. Venna elaborated. Now, SLN biopsy can be considered on a case-by-case basis for stage 1A melanomas that are thicker or have uncertain microstaging, and can be discussed and offered for thicker stage 1B melanomas with ulceration or an elevated mitotic rate.

“At the end of the day, when we are all in our multidisciplinary clinics trying to talk to patients about this, these are nuances that really cause a lot of angst for us and the patient in terms of making decisions,” commented Dr. Venna.

“Acknowledge the prognostic gap in the T1b cohort and that not all T1b melanomas are created equal. We all anticipate that molecular techniques may better identify who among that thin group may benefit from lymph node testing,” Dr. Venna said.

Screening strategies

Population-based screening for melanoma and other skin cancers remains controversial, and this practice is generally limited to areas of the world having high incidence, according to Dr. Venna. Germany was the first country to implement a nationwide program , starting in 2008.

“There is evidence that screening may lead to the prevention of a substantial proportion of melanoma deaths,” he maintained. However, the U.S. National Cancer Institute’s position is that current evidence is inadequate and population-based screening has potential drawbacks such as overdiagnosis.

In the meantime, many opportunities to detect melanoma during routine medical care may be missed, according to Dr. Venna; for example, auscultating a patients’ heart or lungs without pulling up their shirt may miss truncal lesions. “Use every opportunity to screen the patient – that’s opportunistic screening,” he recommended.

He also endorsed listening to patients’ concerns and balancing their requests with judicious removal of lesions, as a large share of melanomas are self-detected. In one study of note, 9 of 166 lesions removed and found to be melanoma were removed only to reassure the patient ( Arch Dermatol. 2005;141:434-8 ).

Barriers to and imperatives for early detection

Data suggest that access to specialist care is problematic for the early detection of melanoma. In a survey of dermatologists, the median wait time for an appointment was 8 days for botulinum toxin type A (Botox) injections, compared with 26 days for evaluation of a suspicious mole ( J Am Acad Dermatol. 2007;57:985-9 ).

“The concern of course is a delay in diagnosis and the fact that the nondermatologists will have an opportunity likely to capture melanoma before we do,” Dr. Venna commented.

Imperatives for early detection include not only better outcomes but also reduced costs, given the hefty price tag of novel targeted therapies being used to treat advanced disease, he noted.

A recent phase III trial found that progression-free survival in advanced melanoma was roughly two to four times longer with the combination of the targeted agents nivolumab (Opdivo) and ipilimumab (Yervoy) than with either agent alone ( ASCO 2015, Abstract LBA1 ). But a discussion touching on costs noted that for the average-weight American, this combination would run about $300,000 annually ( ASCO 2015, Saltz L ).

Risk and protective factors

New data have implicated medications used to treat erectile dysfunction (ED) as a risk factor for melanoma, raising concern given their widespread use, Dr. Venna said.

A cohort study found that melanoma risk was 84% higher with recent use of sildenafil (Viagra) and 92% higher with ever use ( JAMA Intern Med. 2014;174:964-70 ). But the absolute number of excess cases was fairly small.

A case-control study looking at all types of ED drugs found that receipt of a single prescription was associated with a 32% higher risk of melanoma ( JAMA. 2015;313:2449-55 ). Use increased risk of in situ and stage I melanoma, but not more advanced disease. There was no difference between short- and long-acting agents.

“Prospective studies with clearly defined inclusions and exclusions are needed, with dosing in particular,” Dr. Venna summed up. “There appears to be a modest association, but it certainly is not enough to call for widespread discontinuation. In the patients who are on these drugs, it’s good to document [use] until we have more clarity about the biologic effects of this ultimately.”

A study using dietary surveys and having an average follow-up of more than a decade showed that coffee drinkers had a 20% lower risk of melanoma relative to nondrinkers ( J Natl Cancer Inst. 2015 Jan 20;107(2) ). But benefit was significant only among the subset drinking at least 4 cups a day.

“It’s premature to advise coffee intake based on this paper, although it does build upon an earlier Norwegian study from the 1990s which showed a similar trend,” Dr. Venna said. “At the end of the day, these data are intriguing, but obviously there are a lot of side effects of trying to consume 4 cups of coffee a day, so further study is certainly warranted.”

Dr. Venna disclosed that he had no relevant conflicts of interest.

tor@frontlinemedcom.com

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