Treatment approaches in immunosuppressed patients with advanced cutaneous squamous cell carcinoma

Abstract

Immunosuppression, both iatrogenic and disease-related, is associated with a greatly increased incidence of cutaneous SCC (cSCC) and with aggressive cSCC and worse disease outcomes. Consequently, rapid access to skin cancer services and prudent surgical choices, such as circumferential margin assessment, is essential when treating advanced cSCC in an immunosuppressed patient. For high-risk cancers and control of cSCC multiplicity, additional strategies should be actively considered within the multidisciplinary clinical care team. These include minimization or revision of immunosuppressive medications, systemic chemoprevention (including retinoids, nicotinamide, capecitabine) and adjuvant therapies such as radiotherapy. Unfortunately, there is a relative paucity of good evidence for many of these treatments in the immunosuppressed. Systemic treatments for metastatic cSCC are often contraindicated in organ transplant recipients, notably checkpoint inhibitor immunotherapy. There are also toxicity concerns with some conventional chemotherapies and EGFR inhibitors. Until recently, clinical trials have largely excluded immunosuppressed individuals. Development of more effective treatment for advanced cSCC in this high-risk group and prospective clinical trials are now research priorities.

<p>microRNA-26a Directly Targeting MMP14 and MMP16 Inhibits the Cancer Cell Proliferation, Migration and Invasion in Cutaneous Squamous Cell Carcinoma</p>

“…23 Studies show that the onset age of CSCC tends to be younger, which seriously threatens people's health and quality of life. 24 Due to the existence of chemotherapy resistance, the treatment of CSCC has great limitations. 25 In recent years, with the introduction of the concept of precision medicine, molecular targeted therapy for a variety of diseases has become a hot topic.…”

Benchmarking Survival Outcomes Following Surgical Management of pT3 and pT4 Cutaneous Squamous Cell Carcinoma of the Head and Neck

“…This was an unexpected finding as the association between immunosuppression and worse disease outcomes has been documented in several previous studies including those from our institution, but this was likely due to the low number of patients who were immunosuppressed in our cohort. 7,14,15 Molecular or genetic markers may offer greater accuracy in identifying aggressiveness of disease compared with morphological characteristics (this is beyond the scope of this article, but is an active area of research at our institution). 16 Comparison with Emerging Therapies Surgery and PORT is current standard of care for advanced cSCC, with concurrent chemoradiotherapy being routine for some institutions in cases where there is extranodal extension in regional metastasis.…”

Oh, the Mutations You’ll Acquire! A Systematic Overview of Cutaneous Squamous Cell Carcinoma

“…TSKs demonstrate strong upregulation of genes related to cell motility and extracellular matrix remodeling. Spatial gene-expression analysis identified proximity of TSKs with stromal cells (cancer- Prophylactic retinoids (vitamin A derivatives) [24] and capecitabine (inhibitor of DNA repair) are currently prescribed off-label for AK and cSCC in transplant patients. Metaanalyses suggest some efficacy but also serious adverse reactions.…”

“…Prevention and treatment of cSCC in immunocompromised patients represents a critical and growing clinical problem. Prophylactic retinoids (vitamin A derivatives) [ 24 ] and capecitabine (inhibitor of DNA repair) are currently prescribed off-label for AK and cSCC in transplant patients. Metaanalyses suggest some efficacy but also serious adverse reactions.…”

“…However, tumor placement, advancement, and patient health can prohibit surgical intervention [ 26 ]. Therefore, adjuvant radiotherapy is recommended for immunosuppression, incomplete excision, metastasis, perineural invasion, and recurrence [ 24 , 27 ]. Local recurrence, lymph node metastasis, and distant metastases occur in 3–14%, 3.7–16%, and 5% of patients respectively [ 28 – 30 ].…”