Cutaneous squamous cell carcinoma staging may influence management in users: A survey study.

PURPOSE: This study aims to determine whether there is consensus regarding staging and management of cutaneous squamous cell carcinoma (CSCC) across the various specialties that manage this disease. MATERIALS AND METHODS: A survey regarding CSCC high-risk features, staging, and management was created and emailed to cutaneous oncology experts including dermatology, head and neck surgery/surgical oncology, radiation oncology, and medical oncology. RESULTS: One hundred fifty-six (46%) of 357 invited physicians completed the survey. Depth of invasion (92%), perineural invasion (99%), histologic differentiation (85%), and patient immunosuppression (90%) achieved consensus (\u3e80%) as high-risk features of CSCC. Dermatologists were more likely to also choose clinical tumor diameter (79% vs. 54%) and histology (99% vs. 66%) as a high-risk feature. Dermatologists were also more likely to utilize the Brigham and Women\u27s Hospital (BWH) staging system alone or in conjunction with American Joint Committee on Cancer (AJCC) (71%), whereas other cancer specialists (OCS) tend to use only AJCC (71%). Respondents considered AJCC T3 and higher (90%) and BWH T2b and higher (100%) to be high risk and when they consider radiologic imaging, sentinel lymph node biopsy, post-operative radiation therapy, and increased follow-up. Notably, a large number of respondents do not use staging systems or tumor stage to determine treatment options beyond surgery in high-risk CSCC. CONCLUSION: This survey study highlights areas of consensus and differences regarding the definition of high-risk features of CSCC, staging approaches, and management patterns between dermatologists and OCS. High-risk CSCC is defined as, but not limited to, BWH T2b and higher and AJCC T3 and higher, and these thresholds can be used to identify cases for which treatment beyond surgery may be considered. Dermatologists are more likely to utilize BWH staging, likely because BWH validation studies showing advantages over AJCC were published in dermatology journals and discussed at dermatology meetings. Additional data are necessary to develop a comprehensive risk-based management approach for CSCC

Evaluation of the utility of localized adjuvant radiation for node-negative primary cutaneous squamous cell carcinoma with clear histologic margins

Background Though NCCN recommends consideration of localized adjuvant radiation following clear-margin surgery for cutaneous squamous cell carcinoma (CSCC) with large caliber (≥0.1mm) nerve invasion (LCNI) and other high-risk features, only a single small study has compared surgery plus adjuvant radiation (S+ART) to surgical monotherapy (SM) for CSCC. Objectives Compare surgery plus adjuvant radiation (S+ART) to surgical monotherapy (SM) for primary CSCCs with LCNI and other risk factors. Methods Matched retrospective cohort study of primary CSCCs (matched on gender, age, immune status, type of surgery, diameter, differentiation, depth and LCNI) treated with S+ART versus SM. Subgroup analysis of CSCCs with LCNI was performed. Results 62 CSCCs were included in matched analysis (S + ART: 31, SM: 31) and 33 in LCNI analysis (S+ART: 16, SM: 17). There was no significant difference in local recurrence (LR), metastasis, or death from disease in either analysis. Risk of LR was low (7, 8%) with 3 of the LRs being effectively treated upon recurrence. Limitations Single academic center, non-randomized design. Conclusion Adjuvant radiation did not improve outcomes compared to SM due to a low baseline risk of recurrence; although ART for named nerve invasion and LCNI of 3 or more nerves has been shown to improve outcomes in a prior study. Randomized studies are needed to define the subset of CSCC for whom adjuvant radiation has utility

Validation of a 40-Gene Expression Profile Test to Predict Metastatic Risk in Localized High-Risk Cutaneous Squamous Cell Carcinoma

Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value (PPV) for identifying patients who will experience metastasis. Objective: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management. Methods: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n=586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n=202) and validated in a separate, non-overlaping, independent cohort (n=324). Results: A prognostic, 40-gene expression profile (40-GEP) test was developed and validated, stratifying high-risk cSCC patients into classes based on metastasis risk: Class 1 (low-risk), Class 2A (high-risk), and Class 2B (highest-risk). For the validation cohort, 3-year metastasis-free survival (MFS) rates were 91.4%, 80.6%, and 44.0%, respectively. A PPV of 60% was achieved for the highest-risk group (Class 2B), an improvement over staging systems; while negative predictive value, sensitivity, and specificity were comparable to staging systems. Limitations: Potential understaging of cases could affect metastasis rate accuracy.Conclusion: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC

PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma

BACKGROUNDNo systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.METHODSWe report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.RESULTSIn the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.CONCLUSIONSAmong patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors

Detection of Subclinical Disease with Baseline and Surveillance Imaging in High-Risk Cutaneous Squamous Cell Carcinomas

BACKGROUND: There are limited studies on imaging for management of high-risk cutaneous squamous cell carcinoma (HRCSSC). OBJECTIVE: To evaluate the impact of baseline (i.e. at diagnosis) and surveillance (i.e. subsequent time points following diagnosis) imaging on management of HRCSCCs. METHODS: All primary CSSCs treated at Brigham and Women\u27s Hospital (BWH) Mohs Surgery Clinic and Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic from 1/1/2017-6/1/2019 were reviewed to identify tumors that underwent baseline or surveillance imaging. Tumors that underwent imaging were reviewed to determine the impact of imaging on management and ability of imaging to identify subclinical disease. RESULTS: Eighty-three patients underwent imaging for 87 primary HRCSCCs, of which 48 (58%) underwent surveillance imaging. 146 (59%) abnormal results were obtained from 248 imaging studies. Management was altered by 42 (24%) studies. Imaging detected subclinical disease in 21% of cases studied. A majority (56%) of detections were not seen initially but rather during surveillance imaging in the 2 years post treatment. LIMITATIONS: Single institution retrospective design. CONCLUSIONS: Imaging identifies subclinical disease in HRSCC. Prospective studies are needed to determine best practices for screening and surveillance in HRCSCC

Cutaneous squamous cell carcinoma tumor accrual rates in immunosuppressed patients with autoimmune and inflammatory conditions; a retrospective cohort study

BACKGROUND: Immunosuppression is a known risk factor for the development of cutaneous squamous cell carcinoma (CSCC), especially in solid organ transplant recipients and chronic lymphocytic leukemia. However, this risk is less well defined in autoimmune and inflammatory conditions.OBJECTIVE: Assess the impact that disease-type, duration of immunosuppression, and systemic medications have on CSCC accrual rates, defined as the number of CSCCs a patient develops per year, in autoimmune and inflammatory conditions.METHODS: Retrospective review of 94 immunosuppressed (rheumatoid arthritis (RA): 31[33.0%], inflammatory bowel disease (IBD): 17[18.1%], psoriasis (PsO): 11[11.7%], autoimmune other (AO): 24[25.5%], inflammatory other (IO): 21[22.3%]) and 188 immunocompetent controls to identify all primary, invasive CSCCs diagnosed from 2010 to 2020.RESULTS: Immunosuppressed patients had higher CSCC accrual rates than immunocompetent controls (0.44±0.36): total cohort (0.82±0.95, p&lt;0.01), RA (0.88±1.10, p&lt;0.01), IBD (0.94±0.88, p&lt;0.01), PsO (1.06±1.58, p&lt;0.01), AO (0.72±0.56, p&lt;0.01), and IO (0.72±0.61, p&lt;0.01). There was an association between increased tumor accrual rates and exposure to systemic medications including, immunomodulators, TNF-inhibitors, non-TNF inhibitor biologics, and corticosteroids, but not with number of systemic medication class exposures or duration of immunosuppression.LIMITATIONS: Retrospective, single-center study CONCLUSION: Patients with autoimmune and inflammatory conditions accrue CSCCs at higher rates than immunocompetent patients.</p