Precursor Immunotherapy to Prevent Squamous Cell Carcinoma

A brief course of treatment with calcipotriol plus 5-fluorouracil (5-FU) applied to the face and scalp is associated with induction of T cell immunity and tissue-resident memory (Trm) cell formation against actinic keratoses, according to a recent study published in JCI Insight. This combination also reduces the risk of squamous cell carcinoma (SCC) manifestation within 3 years of treatment, the researchers found.

“This study solidifies the combination of calcipotriol and 5-flouorouracil as a great option,” said dermatologist Jerry D. Brewer, MD, MS, a professor of dermatology at the Mayo Clinic in Rochester, Minnesota, in an exclusive interview with Cancer Network.

Rosenberg et al found that calcipotriol with 5-FU–induced Trm cell formation in the skin at the level of the face and scalp was associated with significantly higher erythema scores vs control (P < .01).

More patients in the test cohort were SCC-free over ≥ 1,500 days of follow-up (P = .0765), with significantly fewer developing SCC on the treated face and scalp within 3 years (2 of 30 [7%] vs 11 of 40 [28%] in the control group [hazard ratio, 0.215; 95% CI, 0.048–0.972]; P = .032). Thus, significantly more epidermal Trm cells persisted in the calcipotriol with 5-FU–treated face and scalp skin vs control (P = .0028). No significant difference in basal cell carcinoma (BCC) incidence was observed between the treatment groups.

A 4-day course of topical calcipotriol plus 5-FU combination was compared with Vaseline plus 5-FU (control) in the current blinded prospective cohort study involving participants in a randomized double-blind clinical trial focusing on treatment of actinic keratosis. Frequencies of SCC and BCC were determined at 1, 2, and 3 years after the trial ended. Furthermore, tissues were evaluated for calcipotriol plus 5-FU–induced T cell skin immunity.

Previous research has shown that a 4-week course of topical 5-FU monotherapy for actinic keratosis field treatment decreases SCC risk on the face and ears at 1 year post-treatment; this effect, however, was gone at 2 years. The results of the current study suggest that calcipotriol plus 5-FU treatment is effective in thwarting SCC development on the face and scalp within 3 years after treatment.

This chemopreventive effect is linked to the induction of a long-lasting T cell immunity in the skin. Thus, the researchers suggest that their findings hold broad implications by establishing a novel concept: that an immunotherapeutic agent that is effective in eliminating precancerous lesions can possibly offer long-term cancer prevention.

Lack of protection vs BCC manifestation on the face and scalp after treatment with calcipotriol plus 5-FU could be secondary to the immune-based mechanism of this combination therapy. The 4-day course of calcipotriol plus 5-FU immunotherapy targets actinic keratoses, which carry a mutational burden and an antigenic composition akin to SCC. Lack of protection vs BCC, a distinct cancer from SCC, makes sense in light of the likely antigen-specific Trm cell response induced by calcipotriol plus 5-FU.

“Field treatment in patients with significant actinic damage can be so impactful and potentially improve the quality of life of patients with a high skin cancer tumor burden,” reflected Brewer. “This study solidifies the combination of calcipotriol and 5-flouorouracil as a great option.”