Genetic profiling is valuable in both diagnosis and prognosis of skin cancer. Hedgehog inhibitors and (superficial radiation therapy) SRT are strong contenders for treating nonmelanoma skin cancer. Advances in targeted therapies and biologics are part of the new wave of melanoma treatments.
Dr. RigelSkin cancer overall, including melanoma, is one of the few cancers for which rates are still rising.
Early diagnosis is critical.
“If you catch melanoma early and treat it early, the patient should be in pretty good shape,” says Darrell Rigel, M.D., a clinical professor of dermatology at New York University. “However, once melanoma spreads, there is still basically no effective treatment at this point.”
One of the technologies to diagnose skin cancer is confocal microscopy, whereby without doing a biopsy “you can look down several millimeters into the skin,” Dr. Rigel tells Dermatology Times, in a post-presentation on skin cancer at February’s 2017 South Beach Symposium in Miami Beach, Fla.
Ultrasound is also being revisited. Plus, some studies of electrical impedance suggest that the resistance seen in cancer cells “is different than the electrical resistance that you see in benign cells,” Dr. Rigel says.
Adhesive tape stripping is also part of the diagnostic mix.
“You basically place a piece of clear tape on the suspicious lesions,” Dr. Rigel says. “When the tape is removed, some of the RNA from the lesion remains on the tape. Looking at the pattern of the RNA, you can assess whether the patient has a diagnosis of skin cancer.”
But the hottest trend in melanoma is probably incorporating genetic profiling for tumors, both benign and malignant, to access both diagnosis and prognosis.
MyPath (Myriad Genetics Inc.) is a genetic test that was recently released to profile 23 genes.
“The degree of expression of these genes helps to differentiate whether the lesion is melanoma or benign,” Dr. Rigel says.
Dr. Rigel notes that use of the myPath test is increasing because it allows pathologists to make a more definite diagnosis of melanoma in equivocal lesions.
“Prognosis is important, too, for managing these cases,” Dr. Rigel says.
DecisionDx (Castle Biosciences Inc.) is a 31-gene expression profile test to determine prognosis.
“Like myPath, the degree of expression of each of these genes can be assessed to gauge whether the patient is at high risk or low risk for metastatic disease,” Dr. Rigel says. “As a result, you can follow these patients appropriately and adjust your management accordingly.”
Class I is low risk for metastatic disease, while Class II is high risk.
“Why this is important is that about three-fourths of diagnosed invasive melanomas are less than 1 mm in thickness, which is the government’s definition of early detection,” Dr. Rigel says.
Thin lesions have the best prognosis, if detected early, according to Dr. Rigel. “But because of the overwhelming number of people diagnosed with thin lesions, more people die from thin lesions than thicker lesions,” he says.
Similarly, because so many more people have a negative sentinel lymph node biopsy (SLNB) than positive result, more people with negative SLNBs die from their melanomas than those with a positive SLNB.
“We are just starting to scratch the surface with these gene expression profiles for a variety of conditions,” Dr. Rigel says. “Gene profiling has already been shown to be highly successful in detecting tumors in breast cancer and colon cancer, even in ocular melanoma.”
Moreover, these diagnostic approaches are being used to evaluate squamous cell carcinoma to determine who is at the highest risk for metastatic disease.
“I believe that within the next few years, these new genetic diagnostic and prognostic approaches are going to become standard of care as we integrate the information from them to make management decisions for our skin cancer patients,” Dr. Rigel says.
Next: Treatments, old and new
On the treatment front, for nonmelanoma skin cancer, clinicians are returning to superficial radiation therapy (SRT). “The advantages of SRT are that it is basically painless and you achieve a reasonably good cosmetic result in areas where surgery might leave a defect,” Dr. Rigel says.
The disadvantage of SRT, however, is that radiation scars worsen over time, “so you would minimize this approach with a young person,” Dr. Rigel says. “In most cases, treatment is reserved to those at least 60 years old. The scar will not be as impactful as for a younger person.”
Hedgehog inhibitors for basal cell carcinomas also show promise. “These are drugs that attack a gene that is abnormal in 90% of basal cells,” Dr. Rigel says.
Patients with tumors that are too large for surgery can first be given hedgehog inhibitors to shrink the tumor beforehand.
“Although there are a lot of side effects with these drugs, they are a viable option for advanced tumors that are challenging to manage,” Dr. Rigel says.
Targeted therapy is one of the greatest advances in melanoma because “each melanoma tends to have its own genetic profile and genetic mutation,” Dr. Rigel says.
For instance, the BRAF mutation is present in about 60% of melanomas.
“There are BRAF inhibitor drugs that attack tumors that have this mutation,” Dr. Rigel says.
Similarly, nivolumab and pembrolizumab are two drugs in a new class of biologics that blocks programmed cell death protein 1 (PD-1).
“What is particularly exciting about this class of drugs is that after three years of use, the mortality curves appear to flatten, suggesting that we may be approaching a ‘cure’ for those surviving this therapy,” Dr. Rigel says.
Disclosures: Dr. Rigel reports that he is a consultant and an investigator for Castle Biosciences Inc. and a board member of Sensus.