Welcome to this July twenty twenty-six research review from the Journal of the American Academy of Dermatology. Today we're covering four brief reports with direct relevance to surgical and oncologic dermatology practice: antibiotic timing and immune checkpoint inhibitor survival in Merkel cell carcinoma, a national registry analysis of Mohs surgery in immunosuppressed patients, a cost comparison of superficial radiation therapy versus Mohs surgery, and a survey study linking indoor tanning to earlier melanoma diagnosis. Let's get into it.

Our first article is titled "Antibiotics Prior to Immune Checkpoint Inhibitor Therapy Worsens Survival in Merkel Cell Carcinoma: A TriNetX Retrospective Cohort Study," by Shen, Chen, Kaelber, Nowacki, and Arbesman.

The clinical question here is whether systemic antibiotic exposure prior to initiating immune checkpoint inhibitor therapy affects survival in Merkel cell carcinoma, extending prior observations in melanoma and cutaneous squamous cell carcinoma. This is biologically plausible in Merkel cell carcinoma specifically because these tumors often present as rapidly growing erythematous nodules that are frequently misdiagnosed as infections, creating a real-world risk of unnecessary antibiotic exposure before immunotherapy.

This was a retrospective cohort study using the TriNetX federated health research network, with propensity or balancing score matching applied across three cutaneous malignancies. For Merkel cell carcinoma, one hundred nine antibiotic-exposed patients were matched to one hundred nine controls. For malignant melanoma, three thousand four hundred seventy-four antibiotic-exposed patients were matched to an equal number of controls. For cutaneous squamous cell carcinoma, one thousand one hundred sixty-three antibiotic-exposed patients were matched to controls.

The key findings: in Merkel cell carcinoma, survival was significantly reduced in the antibiotic group within the first four months after immune checkpoint inhibitor initiation, with a hazard ratio of two point one two, a P value of point zero four, and a ninety-five percent confidence interval of one point zero three to four point three five. This difference stabilized by eight and twelve months, meaning the survival curves converged over time. In melanoma, the effect was significant at one month, with a hazard ratio of one point three four, P equals point zero four, ninety-five percent confidence interval one point zero one to one point seven five, again stabilizing by twelve months. In cutaneous squamous cell carcinoma, the effect was more durable, with survival remaining significantly reduced throughout the full twelve months, hazard ratio one point five three, P less than point zero zero one, ninety-five percent confidence interval one point three two to one point seven seven.

The authors interpret this as consistent with a shared mechanism of antibiotic-induced gut dysbiosis impairing antitumor immunity, with the timing of peak risk correlating with known microbiome recovery windows of roughly one to three months post-antibiotic exposure. The takeaway for surgical oncology practice is that antibiotic stewardship matters in the periprocedural and pre-immunotherapy window for patients with ulcerated or infection-mimicking cutaneous tumors, particularly Merkel cell carcinoma, where empiric antibiotics for a "cellulitis-like" presentation should be used judiciously given the downstream implication for checkpoint inhibitor efficacy if that patient proceeds to immunotherapy.

Limitations are important here: this is retrospective, cancer-specific mortality data were not available, only all-cause mortality, some effect windows were not statistically significant especially at later time points, and the Merkel cell cohort, while impressively large for this rare tumor, is still modest in absolute numbers, meaning wide confidence intervals. This is also the first study to examine this question specifically in Merkel cell carcinoma, so replication is warranted.

Our second article, most directly relevant to this audience, is "Immunosuppressed Patients Undergoing Mohs Micrographic Surgery: A Cross-Sectional Analysis of the MohsAIQ National Data Registry," by Ran, Song, and the MohsAIQ Data Release Working Group.

The clinical question is how immunosuppression affects tumor characteristics, surgical complexity, and perioperative management in patients undergoing Mohs surgery, using a large, multi-practice, real-world registry rather than single-center data.

This was a cross-sectional analysis of the MohsAIQ registry, encompassing two hundred sixty-seven thousand five hundred twenty-four Mohs cases performed by one hundred fifty-one surgeons across one hundred twenty practices, the large majority private practice, from 2018 to 2023. Squamous cell carcinomas and basal cell carcinomas in immunosuppressed patients were propensity matched one-to-one to immunocompetent controls, and outcomes were compared using conditional logistic regression across four day-of-surgery metrics: antibiotic prescription, opioid prescription, need for two or more Mohs stages, and flap or graft repair.

Key findings: immunosuppressed patients accounted for two point six percent of all cases, with the highest representation in academic and physician-owned practices, at nine point one percent and nine point nine percent respectively. The leading causes of immunosuppression were solid organ transplantation at thirty-two point eight percent, iatrogenic immunosuppression at thirty-two point six percent, and hematologic malignancy at nineteen point two percent.

In the matched squamous cell carcinoma cohort, immunosuppressed patients were more likely to receive day-of-surgery antibiotics, forty-two point two percent versus thirty-three percent, odds ratio one point five, ninety-five percent confidence interval one point three six to one point six four. They were also more likely to require two or more Mohs stages, thirty-six point one percent versus thirty-one point two percent, odds ratio one point two six, confidence interval one point one four to one point three eight. There was no significant difference in opioid prescriptions or flap and graft repair rates for squamous cell carcinoma.

In the matched basal cell carcinoma cohort, immunosuppressed patients again had higher antibiotic use, thirty-five point nine percent versus twenty-eight point six percent, odds ratio one point three nine, confidence interval one point two five to one point five six; more frequent need for two or more stages, forty-four point nine percent versus forty-one point seven percent, odds ratio one point one four, confidence interval one point zero three to one point two seven; and a higher rate of complex flap or graft repairs, twenty-seven point one percent versus twenty-three point two percent, odds ratio one point two three, confidence interval one point zero nine to one point four. Opioid prescription rates did not differ.

The practical takeaway for Mohs surgeons: immunosuppressed patients, particularly those with basal cell carcinoma, should be counseled preoperatively about a higher likelihood of requiring additional stages and more complex reconstruction, and practices should anticipate higher perioperative antibiotic use in this population, though this study does not establish whether that antibiotic use was prophylactic, therapeutic, or driven by clinical judgment versus protocol. Limitations include the cross-sectional, registry-based design, which cannot establish causality; residual confounding despite matching, since standardized mean differences for some baseline variables such as previously treated tumor status remained elevated; and the predominantly private-practice case mix, which may limit generalizability to academic settings where immunosuppressed patients are proportionally more common and potentially more complex.

Our third article is "The Costs of Superficial Radiation Therapy Are Greater Than Mohs Micrographic Surgery for the Treatment of Nonmelanoma Skin Cancer: Analysis from the CMS Provider and Service Data Set," by Light, Freeman, McEvoy, Lim, Council, J. Michalski, and B. Michalski.

The clinical question is a direct cost comparison between image-guided superficial radiation therapy and Mohs micrographic surgery for nonmelanoma skin cancer, using national Medicare billing data, given the increasing utilization of superficial radiation and claims of favorable cost-effectiveness from its proponents.

The study design queried the Medicare public-use data set from 2018 to 2022, examining billing claims for superficial radiation therapy, CPT code seventy-seven four zero one, along with simple, intermediate, and complex radiation simulation codes and the ultrasonic guidance code G six zero zero one, all as rendered by dermatologists.

Key findings: the number of dermatologists performing superficial radiation therapy increased by thirty-seven point five percent from 2018 to 2022, while the number using image guidance increased by twelve hundred fifty percent, an extraordinarily disproportionate rise. Simple radiation simulations increased in frequency by one hundred twenty-three percent over the same period, and by 2022, simple simulations were billed in ninety percent of superficial radiation therapy sessions, up from fifty-one percent in 2018; when intermediate and complex simulations are included, simulations were billed in ninety-five percent of sessions.

On direct cost comparison, in 2022, image-guided superficial radiation therapy at twelve, twenty, and twenty-five fractions cost two hundred seventeen percent, four hundred twenty-eight percent, and five hundred fifty-nine percent more, respectively, than a typical Mohs case involving two stages with complex closure. When compared against Mohs cases requiring flap reconstruction, image-guided superficial radiation therapy still cost one hundred sixty-seven percent, three hundred forty-five percent, and four hundred fifty-seven percent more at those same fraction numbers. In dollar terms, twenty-five fractions of image-guided superficial radiation therapy totaled ten thousand five hundred nine dollars, compared with one thousand five hundred ninety-four dollars for Mohs surgery of the head and neck with one additional stage and complex repair, or one thousand eight hundred eighty-eight dollars for Mohs involving the eyelid, nose, ear, or lip region with flap reconstruction.

The authors note that claims of lower recurrence rates with image-guided superficial radiation therapy come from studies limited by short follow-up, weak comparator groups, and heterogeneous populations. They also raise a technical concern that high-frequency ultrasound cannot reliably determine tumor depth below one millimeter at frequencies under thirty megahertz, calling into question the precision rationale used to justify image guidance. Notably, a new 2026 Medicare local coverage determination will reduce reimbursement by disallowing repeated simulations with each treatment fraction and by deeming high-frequency ultrasound not medically necessary, and the American College of Mohs Surgery and American Society for Radiation Oncology have jointly supported restricting daily ultrasound guidance and daily simulation billing.

The takeaway for practice: from a health-system cost perspective, image-guided superficial radiation therapy is substantially more expensive than Mohs surgery for nonmelanoma skin cancer, and this cost differential should inform discussions with patients and referring physicians, while acknowledging that superficial radiation therapy may still have a role for patients who are poor surgical candidates due to morbidity, advanced age, or informed refusal of surgery. Limitations include that this analysis captures only the specified CPT codes and does not account for facility fees or other indirect costs, does not incorporate the Multiple Procedure Payment Reduction rule, and does not address patient-reported experience or long-term recurrence outcomes.

Our fourth article is "Younger Age at Melanoma Diagnosis: A Survey Study of Indoor Tanning Use," by Mahoney, Wu, Li, Guo, Burbidge, Batuyong, Poleman, Ernst, and Cheng.

The clinical question is whether age at first indoor tanning exposure and cumulative dose intensity are associated with age at melanoma diagnosis and specific tumor characteristics, building on the group's prior work showing indoor tanning users are diagnosed over a decade earlier.

This was a survey-based study of patients with cutaneous melanoma accrued at the Tom Baker Cancer Centre in Calgary between December 2013 and March 2021, excluding ocular, mucosal, and acral lentiginous subtypes. A twenty-four item risk assessment survey was administered at consultation. Among eight hundred fifty-four patients, with a median age of sixty-two years, ranging from nineteen to ninety-seven, and forty-four point five percent women, the large majority were fair-skinned, ninety-three percent Fitzpatrick type one or two. Of eight hundred twenty-nine evaluable patients, two hundred seventy-six, or thirty-three point three percent, reported indoor tanning use.

Key findings: indoor tanning users were diagnosed at a significantly younger median age than nonusers, fifty-two years versus sixty-three years, P less than point zero zero one. After adjusting for gender, skin type, hair color, eye color, sun exposure, and family history, indoor tanning use was associated with diagnosis nine point six years earlier, P less than point zero zero one. This held consistently across sex, skin type, and family history subgroups.

The dose-response relationship was striking: early users, defined as first exposure before age twenty-five, were diagnosed seventeen years earlier than later users, forty-one years versus fifty-eight years, P less than point zero zero one. Heavy users, defined as the top quartile of total dose, trended toward earlier diagnosis compared with lighter users, forty-eight versus fifty-three years, though this did not reach statistical significance, P equals point zero eight.

Tumor characteristics also differed: indoor tanning users more often developed melanoma on intermittently sun-exposed skin, sixty-one percent versus fifty percent, P equals point zero one one, and were more likely to harbor BRAF V600E mutations, twenty-two percent versus eighteen percent, P equals point zero zero one. Other histopathologic features did not differ significantly between groups.

The authors argue that the temporal gradient, meaning earlier first exposure correlating with a larger shift in age at diagnosis, supports a causal relationship rather than simple confounding, reinforcing indoor tanning as a modifiable risk factor and supporting policy restricting youth access to tanning beds. For dermatologic oncology practice, this reinforces counseling relevance: a history of early indoor tanning initiation before age twenty-five should raise the index of suspicion for earlier-onset melanoma and may correlate with BRAF-mutant tumor biology, which carries implications for systemic therapy selection.

Limitations include the retrospective design, missing molecular data in a subset of cases, referral bias inherent to a tertiary cancer center population, and potential residual confounding by cumulative sun exposure despite statistical adjustment. Recall bias in a survey capturing tanning behavior years or decades prior is also an inherent limitation of this design.

That concludes this month's review. Across these four reports, several threads are relevant to surgical and oncologic dermatology: the immunologic consequences of antibiotic timing before checkpoint inhibitor therapy in Merkel cell carcinoma, the added surgical complexity and antibiotic use seen in immunosuppressed Mohs patients within a large national registry, the substantial cost disadvantage of image-guided superficial radiation therapy relative to Mohs surgery, and the continued evidence linking early indoor tanning exposure to younger age at melanoma diagnosis and BRAF-mutant biology. Thank you for listening, and we'll see you next month.