Squamous Cell Carcinoma: Treatment

SURGICAL

​Shave Removal​

• For clinically well-defined SCCs without adjacent actinic keratoses, most of which were 4.4-11.2mm in diameter, shave biopsy with excisional intent with a 1-2mm margin may be effective.  43% of tumors had negative margins when processed with vertical sections with additional tip processing when treated this way. 5% recurred, 6.4% if you excluded those with <2 yrs follow up.  Recurrence was not predicted by extent of invasion (in situ, superficially invasive, invasive), size, age, or immunosuppression.  Location may predict recurrence, with 87% of recurrence at locations H and M. 36941916​

• It may be reasonable to monitor all SCC that are clinically resolved after biopsy:

Oncologic outcomes for invasive squamous cell carcinoma with a clinically resolved biopsy site managed by watchful waiting: A retrospective cohort study. J Am Acad Dermatol. 2025. PMID: 39706528.

This retrospective study evaluated 148 cases of invasive cutaneous squamous cell carcinoma (cSCC) that appeared clinically resolved after biopsy and were managed by watchful waiting (WW). Over a median follow-up of 35 months, only 2 tumors (1.35%) recurred locally, with no nodal metastasis, distant spread, or disease-specific death. Traditional high-risk factors—including tumor location (e.g., head and neck), positive biopsy margins, and tumor size or stage—did not correlate with recurrence. Immunosuppression and rheumatologic disease were associated with higher recurrence risk in univariate analysis but were not significant in multivariate analysis. These findings suggest WW may be a safe and cost-effective alternative to surgery for carefully selected low-risk cSCC cases with clinically resolved biopsy sites.

IMMUNE-CHECKPOINT INHIBITION (ICI)​

ICI Monotherapy​

Managing large cutaneous squamous cell carcinoma with programmed cell death protein 1 inhibitor monotherapy: Real-world experience at a single center. JAAD Int. 2024. PMID: 38957836.

• ​A retrospective review of 54 patients with cSCC tumors over 3 cm in size treated with either pembrolizumab or cemiplimab.

• 54-58% complete response rate after 4-6 treatments (both pembrolizumab and cepilimumab evaluated accounting for the range).​​

ICI in Transplant Recipients​

• ​​Overall, data is limited regarding the use of ICI in organ transplant recipients treated for skin cancer, and treatment approach and results are mixed. (38985483)

• One study of kidney transplant recipients with cSCC (n=12) were transitioned to an mTOR inhibitor and given a course of prednisone starting day -1 to day +20.  They received cepilimumab. Disease progression occurred in 4 of 11 patients, but there were no cases of transplant rejection. (38985483 ref 2)

• Another study of kidney transplant recipients with cSCC, MCC, or melanoma (n=8) transitioned patients to low dose tacrolimus + 5mg prednisone/day. They received nivolumab. There was disease progression in all patients and 1 graft rejection.  They were switched to ipi/nivo (n=6) and 2 responded, 2 experienced graft rejection. (38985483 ref 3)

• Sample size of these 2 studies is small, and results variable. ​

ADJUVANT RADIATION​

40-GEP as predictor of radiation benefit​

Association of a 40-Gene Expression Profile With Risk of Metastatic Disease Progression of Cutaneous Squamous Cell Carcinoma and Specification of Benefit of Adjuvant Radiation Therapy. Int J Radiat Oncol Biol Phys. 2024. PMID: 38810706.

• Retrospective cohort of SCCs that had 40-GEP performed, underwent definitive excision, and a subset with radiation.  Patients receiving and not receiving ART were matched on clinicopathologic factors.  Adjuvant systemic therapy, however, could not be controlled for, although similar percentages of patients who were class 1 vs class 2B and received ART also received AST (18 vs 20%, resp.)​

• RESULTS: Patients with class 2B results but not patients with class 1 or 2A results who received ART experienced a reduction in the rate of metastatic disease progression.  ​​

FOLLOW-UP

• Over half of SCC recurrences and metastases occur by 1 year, and 95% by 3 years. (38971189, ref 1-3)

  • 55% of poor outcomes (recurrence, metastasis, or death) by year 1, 80% by year 2, 89% by year 3.  This study breaks it down by local recurrence, nodal mets, in transit mets, distant mets, and disease specific death in nice graphs. 38971189  ​

• NCCN guidelines rec 3-12 month skin checks for 2 years, 6-12 for next 3 years, then annually.