Adjuvant therapy for high‐risk cutaneous squamous cell carcinoma: 10‐year review

Abstract

Standard of care for high‐risk cutaneous squamous cell carcinoma (cSCC) is surgical excision of the primary lesion with clear margins when possible, and additional resection of positive margins when feasible. Even with negative margins, certain high‐risk factors warrant consideration of adjuvant therapy. However, which patients might benefit from adjuvant therapy is unclear, and supporting evidence is conflicting and limited to mostly small retrospective cohorts. Here, we review literature from the last decade regarding adjuvant radiation therapy and systemic therapy in high‐risk cSCC, including recent and current trials and the role of immune checkpoint inhibitors. We demonstrate evidence gaps in adjuvant therapy for high‐risk cSCC and the need for prognostic tools, such as gene expression profiling, to guide patient selection. More large‐cohort clinical studies are needed for collecting high‐quality, evidence‐based data for determining which patients with high‐risk cSCC may benefit from adjuvant therapy and which therapy is most appropriate for patient management.

Immunotherapy response in patients with cutaneous squamous cell carcinoma of head and neck with cranial nerve involvement

“…Both are a high-affinity, highly potent human monoclonal antibody (mAb) specific to programmed death receptor-1 (PD-1). 2,4,[12][13][14] Specifically, keynote-629 showed that in patients with unresectable HNcSCC, pembrolizumab monotherapy had a rapid, durable response in first line, as well as in heavily pre-treated patients (second line or later), with a 42.6% overall response rate and PFS of 8.5 months. 3,12,13,20 There are several ongoing studies and other treatment options that are being evaluated including: nivolumab, 2,3,21 cetuximab as neoadjuvant therapy and in combination with other therapies: RT, tyrosin kinase inhibitors (TKIs), and pembrolizumab, 12,13 MEK inhibitors such as trametinib and cobimetinib, in combination with atezolizumab, 3 to name a few.…”

“…For treatment of locally advanced, recurrent or metastatic cSCC that are surgically unresectable or not candidates for curative RT, there are two drugs that are approved: cemiplimab and pembrolizumab. Both are a high‐affinity, highly potent human monoclonal antibody (mAb) specific to programmed death receptor‐1 (PD‐1) 2,4,12–14 . Specifically, keynote‐629 showed that in patients with unresectable HNcSCC, pembrolizumab monotherapy had a rapid, durable response in first line, as well as in heavily pre‐treated patients (second line or later), with a 42.6% overall response rate and PFS of 8.5 months 3,12,13,20 …”

“…The 2 open-label, multicenter studies that led to the approval of cemiplimab are study 1423 and study 1540 (EMPOWER-CSCC 1). 2,4,14,15 Despite the success rates demonstrated with IO, there is a paucity of data specifically in patients with disease present solely within or along CN, and it remains uncertain if the same high response rates or even CR rates can be extrapolated to these patients. Our aim is to describe our experience with IO, with or without RT, in patients with HNcSCC with cranial nerve (CN) perineural invasion.…”

“…Both agents are approved in cSCC that is not amenable to resection or RT. The 2 open‐label, multicenter studies that led to the approval of cemiplimab are study 1423 and study 1540 (EMPOWER‐CSCC 1) 2,4,14,15 …”

The prognostic significance of lymphovascular invasion in cutaneous squamous cell carcinoma

“…[32][33][34][35][36][37][38] Available literature supports ART mostly from retrospective small single-site studies with conflicting findings. [39][40][41][42] Indeed, a systematic review and meta-analysis 43 found no significant difference in the recurrence or disease-specific death rates in high-risk cSCC treated with surgery only compared to the surgery with adjuvant radiotherapy when histologically clear margins are achieved. Our findings agree with this landmark review, with no significant difference in survival in completely excised LVI-positive cases with surgery only compared to incompletely excised LVI-positive cases with adjuvant radiotherapy.…”