Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients-A Comparison between Different Immunomodulating Conditions

Abstract

Background: Immunosuppression is strongly associated with an increased risk of developing cutaneous squamous cell carcinoma (cSCC). Studies on solid organ transplant recipients (SOTR) and chronic lymphocytic leukemia (CLL) patients have already demonstrated higher rates of aggressive cSCC tumors in these populations compared to immunocompetent controls. Studies on other immunosuppressed patient groups are scarce. This study was aimed at assessing the effects of different immunomodulating conditions on patients diagnosed with cSCC. We sought to compare the clinical features, treatments, and survival rates among the different study groups, as well as outcomes to those of immunocompetent controls with cSCC.

Methods: A retrospective analysis of 465 cSCC patients, both immunosuppressed (IS) and immunocompetent controls. Etiologies for immunosuppression included SOTR, CLL, chronic kidney disease (CKD), psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematous (SLE).

Results: Compared to the control group, IS patients demonstrated several significant differences. These include higher rates of positive resection margins, higher recurrence rates, and multiple SCC tumors. Patients in the IS group, who were also given immunomodulating agents, demonstrated even lower survival rates. Cox regression analysis demonstrated statistically significant decreased overall survival (OS) rates for IS patients compared to the controls (OR = 1.9, p = 0.031). SOTR patients tend to have multiple cSCC tumors (35%), with the highest number of primary tumors compared to controls (2.54 tumors per patient on average, p < 0.001), but also compared to all other IS groups. The average SCC lesion size in the SOTR group was the smallest, measuring at 13.5 mm, compared to the control group and all other IS groups. Decreased survival rates were seen on Cox regression analysis compared to controls (HR = 2.4, p = 0.001), but also to all other IS groups. CLL patients also had the highest rates of positive margins compared to controls (36% vs. 9%, p < 0.01) and to all other IS groups. They were also most likely to get adjuvant or definitive oncological treatments, either radiotherapy or chemotherapy, compared to controls (36% vs. 15%, p = 0.02) and to other IS groups. Patients in the CKD group demonstrated the highest rates for multiple cSCC (OR = 4.7, p = 0.001) and the worst rates of survival on Cox regression analysis (HR = 3.2, p = 0.001). Both rheumatoid arthritis and psoriasis patients demonstrated the shortest disease-free survival rates (2.9y ± 1.1, 2.3y ± 0.7, respectively), compared to controls (4.1y ± 2.8) and to all other IS groups.

Conclusions: Among cSCC patients, immunosuppression due to SOTR, CLL, CKD, RA, and psoriasis is associated with worse outcomes compared to controls and other IS groups. These patients should be regarded as high-risk for developing aggressive cSCC tumors. This study is the first to assess and compare cSCC outcomes among multiple IS patient groups.

Keywords: CLL; chronic kidney disease; cutaneous SCC; immunosuppression; non-melanoma skin cancer; psoriasis; transplants.

Figure 1

(A) Kaplan-Meier curves representing 5-year overall survival for immunosuppressed patients are in dark red (OR-0.81) and controls are in blue (OR = 0.91). Follow-up is represented in years (p = 0.001). (B) Kaplan-Meier curves representing 5-year overall survival (in years) for the different immunosuppression groups. Solid Organ Transplant Recipients (SOTR) in red; Chronic Lym-phocytic Leukemia (CLL) in bright green; Chronic Kidney Disease (CKD) in dark blue; Rheumatic Arthritis (RA) and Systemic Lupus Erythematosus (SLE) in purple; Psoriasis in green; Controls in blue. (C) Kaplan-Meier curves representing 5-year disease-free survival (in years) for the different immunosuppression groups. Solid Organ Transplant Recipients (SOTR) in red; Chronic Lym-phocytic Leukemia (CLL) in bright green; Chronic Kidney Disease (CKD) in dark blue; Rheumatic Arthritis (RA) and Systemic Lupus Erythematosus (SLE) in purple; Psoriasis in green; Controls in blue.

Figure 1

(A) Kaplan-Meier curves representing 5-year overall survival for immunosuppressed patients are in dark red (OR-0.81) and controls are in blue (OR = 0.91). Follow-up is represented in years (p = 0.001). (B) Kaplan-Meier curves representing 5-year overall survival (in years) for the different immunosuppression groups. Solid Organ Transplant Recipients (SOTR) in red; Chronic Lym-phocytic Leukemia (CLL) in bright green; Chronic Kidney Disease (CKD) in dark blue; Rheumatic Arthritis (RA) and Systemic Lupus Erythematosus (SLE) in purple; Psoriasis in green; Controls in blue. (C) Kaplan-Meier curves representing 5-year disease-free survival (in years) for the different immunosuppression groups. Solid Organ Transplant Recipients (SOTR) in red; Chronic Lym-phocytic Leukemia (CLL) in bright green; Chronic Kidney Disease (CKD) in dark blue; Rheumatic Arthritis (RA) and Systemic Lupus Erythematosus (SLE) in purple; Psoriasis in green; Controls in blue.

Figure 2

Bar-charts for different tumor characteristics (positive margins, adjuvant therapy, multiple primaries, and recurrence rates) for controls (black), SOTR (blue), CLL (polka dots), and CKD (red) patients. Asterisks represent a statistically significant difference (p < 0.05) compared to controls. Error bars represent the average result ± standard deviation. SOTR; Solid Organ Transplant Recipients, CLL; Chronic Lymphocytic Leukemia, CKD; Chronic kidney disease.