Immunosuppression Risk Factor for Poor cSCC Outcomes

PHOENIX — Immunosuppression is an independent risk factor for poorer outcomes in patients with cutaneous squamous cell carcinoma (cSCC), according to new research that was presented at the American College of Mohs Surgery (ACMS) 2024 Annual Meeting.

Even though immunosuppression is strongly associated with an increased risk for cSCC, studies to date have generally not shown it to be an independent risk factor for metastasis and disease-specific death (DSD), after accounting for primary tumor stage.

“Solid organ transplant puts patients at risk for developing cutaneous squamous cell carcinoma, and it’s more likely to have aggressive features,” said study author Jason Klein, MD, PhD, a dermatology resident at University of Texas Southwestern Medical Center, Dallas. “But it’s still not known if immunosuppression is an independent risk factor.”

Other groups “have tried to tackle this, but they have all primarily been single-institution data,” he noted, adding that “results so far have been tipping the scale towards immunosuppression not being an independent risk factor” for worse outcomes.

Immunosuppressed individuals face a greater risk for cSCC than the general population and often present with more aggressive, multifocal disease. However, Klein explained that a previous retrospective study comprising a cohort of approximately 7600 tumors from two centers reported that immunosuppression was not an independent risk factor for both tumor metastasis and cancer-specific death after adjusting for tumor characteristics.

Tipped the Scale

Therefore, the goal of the current study was to repeat this analysis but in a much larger retrospective cohort. Klein and his colleagues pooled cSCC data from 12 dermatology centers (11 academic and one private) that were located in the United States, Spain, and Brazil. The cohort included 4392 patients (3769 immunocompetent patients and 623 immunosuppressed patients) with 19,237 tumors (15,191 immunocompetent and 4046 immunosuppressed). Study endpoints included local recurrence, metastasis (nodal, satellite/in-transit, and distant), DSD, and “major poor outcomes” (defined as metastasis and DSD combined).

About 30% of the immunosuppressed patients were organ transplant recipients (OTR) and 10% had chronic lymphocytic leukemia (CLL). Half of the immunocompetent patients (50.3%) underwent Mohs surgery as the primary treatment, as did 58.2% of the immunosuppressed patients.

On multivariable analysis, significant predictors of “major poor outcomes” included immunosuppression (subdistribution hazard ratio [SHR], 1.3; P = .04), Brigham and Women’s Hospital tumor stage (SHR 6.7 for T2a, 18.1 for T2b, and 37.2 for T3; P < .001 for all), location on the head/neck (SHR, 2.1; P < .001), and adjuvant radiation (SHR, 1.6; P < .001).

But when metastasis and DSD were evaluated separately, immunosuppression was only predictive of DSD (SHR, 1.7; P = .008) but not metastasis (SHR, 1.2; P = .21). Klein explained that they also conducted a separate subanalysis limited to OTR and patients with CLL, which demonstrated that immunosuppression was no longer a significant predictor of “major poor outcomes” (SHR, 0.9; P = .66 for OTR; SHR, 1.4; P = .25 for CLL).

“Organ transplant status and CLL were not independent risk factors for major poor outcomes,” he said. “But in summary, we may be tipping the scale to immunosuppression being a risk factor.”

Approached by Medscape Medical News for an independent comment, Naissan O. Wesley, MD, director of Mohs surgery, Skin Care and Laser Physicians of Beverly Hills, Los Angeles, California, stated that “this larger scale study presented at this meeting was important to further confirm what we see in everyday practice that immunosuppression may lead to poorer outcomes in patients with cutaneous squamous cell carcinoma.”

Also weighing in on the data, Jesse M. Lewin, MD, chief of Mohs micrographic and dermatologic surgery, at the Icahn School of Medicine at Mount Sinai, New York City, noted that the treatment of cSCC in high-risk patients has been challenging because of the historical lack of data and large studies to guide management.

“The authors provide a large cohort to help stratify which patients are most at risk for poor outcomes, which can inform our decision to refer for neoadjuvant or adjuvant treatment and multi-disciplinary management,” he said. “This is the first step in being able to optimize cure in these patients.”

The study was independently supported. Klein, Lewin, and Wesley reported no relevant financial relationships.

Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape Medical News.

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