Nonsurgical options increasing for skin cancers

Surgery was once a primary option for treating nearly all skin cancers, but advancing technology is expanding treatment options. New laser applications, biologics, and other modalities are giving dermatologists more effective nonsurgical treatments of skin cancers in a growing range of patients.

Thuzar M. Shin, MD, PhD: “Melanomas with higher risk for subclinical spread may benefit from surgical techniques with more exhaustive histologic assessment of margins.”

Those improvements were examined March 6 during “Cutaneous Oncology” (S065).

Early data suggests many basal cell carcinomas (BCC) can be treated successfully by laser. Laser treatment produces little or no scarring, requires no anesthesia, leaves patients with minimal post-operative discomfort compared to surgery, and reduces treatment time.

“Clinicians must precisely control thermal damage to avoid unintentionally burning non-targeted tissue,” cautioned Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital and associate professor of dermatology at Harvard Medical School. “Selective thermal damage to an absorbing target is achieved with appropriate laser parameters to produce minimal damage to surrounding tissues.”

Key parameters include wavelength, fluence, and pulse duration. The goal is to ablate the target faster than the time required for heat conduction to the surrounding tissue.

BCC microvessels are significantly larger and more fragile than normal vasculature, Dr. Avram said. That makes it possible to tailor the pulse duration to selectively target the BCC microvasculature, inducing tumor regression while sparing the surrounding tissue.

The ideal wavelength has yet to be determined. Pulsed-dye laser is well absorbed by oxyhemoglobin but does not penetrate deeply. The 1064 nm Nd:YAG penetrates deeper and can target arterial vessels. High-fluence 1064-nm shows good promise, as does sequential 595 nm/1064 nm therapy.

Laser treatment is not standard of care, Dr. Avram noted, but could be if larger studies with longer follow-up support early results.

Radiation and biologics are another nonsurgical alternative for many skin cancers. A recent meta-analysis shows good results for imiquimod in melanoma, said Anna Bar, MD, assistant professor of dermatology at Oregon Health and Science University in Portland. About 78 percent of patients had clinical clearance and 77 percent had histologic clearance. Only 1.8 percent progressed to metastatic melanoma.

A similar review found that six to seven applications of imiquimod per week had nine times greater odds for histologic clearance versus one to four applications per week. More than 60 applications over 12 weeks had an eight times greater chance for histologic clearance compared to fewer than 60 applications.

Radiation therapy is another option, with clearance rates up to 100 percent. A recent systematic review showed recurrence rates from zero to 31 percent for melanoma.

Vismodegib, a hedgehog pathway inhibitor, can also be effective. The agent has been approved by the Food and Drug Administration to treat basal cell carcinoma.

Surgical excision remains the primary treatment for melanoma under the latest National Comprehensive Cancer Network guidelines, said Thuzar M. Shin, MD, PhD, assistant professor of dermatology at Perelman School of Medicine at the University of Pennsylvania. However, surgery is not perfect.

“Melanomas with higher risk for subclinical spread may benefit from surgical techniques with more exhaustive histologic assessment of margins prior to reconstruction,” Dr. Shin said.

Adjuvant therapy is promising.

Ipilimumab showed a median five-year recurrence-free survival of 40.8 percent versus 30 percent for placebo for patients with advanced melanoma in a recent study. Adverse events are a limiting factor. In the study’s ipilimumab arm, 54.1 percent of patients had grade 3 or 4 adverse events versus 26.2 percent for placebo. Immune-related adverse events hit 41.6 percent for ipilimumab versus 2.7 percent of placebo patients.

Single-agent anti-PD-1 regimens have response rates of 30-40 percent and durable responses of two to three years in early-stage trials, Dr. Shin noted. However, the lack of randomized head-to-head trials comparing different targeted immunotherapies leaves uncertainty about which drug or combination is the optimal first-line therapy. Data on ipilimumab, pembrolizumab, and nivolumab are still being collected.

Systemic agents are also emerging as risk factors for new skin cancers. Five-year prospective cohort data showed a six-fold higher incidence of non-melanoma skin cancer (NMSC), mostly squamous cell carcinoma (SCC), in psoriasis patients treated with cyclosporine, noted John Koo, MD, professor of dermatology at the University of California, San Francisco.

Non-melanoma skin cancer risk is further increased with more than two years of consecutive exposure to cyclosporine or prior treatment with methotrexate or other immunosuppressives.

Anti-TNF agents also increase the risk of NMSC. A recent longitudinal cohort study found that patients with psoriasis treated with a variety of anti-TNF agents showed a 42 percent increased risk for NMSC, mostly SCC. The study had a mean follow-up of 5.86 years.

“At least with anti-TNF biologics, there is confirming data from the real world, versus clinical trials, showing increased risk of NMSC in psoriasis patients,” said Mio Nakamura, MD, psoriasis and clinical research fellow at the UCSF Psoriasis and Skin Treatment Center.

The increased skin cancer risk may have more to do with the disease than the treatment. A prospective cohort study showed increased risk for NMSC in patients with psoriasis compared to rheumatoid arthritis treated with anti-TNF agents. Phototherapy, systemic immunosuppressives, and chronic skin inflammation may also play roles in the increased risk of NMCS in patients with psoriasis.

“Psoriasis patients should have regularly scheduled full-body skin checks, especially patients with a history of treatment with photodynamic therapy or other immunosuppressive agents,” Dr. Nakamura said. “There is a low threshold to biopsy any suspicious lesions.”

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