Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Keratinocyte carcinomas (KCs) are the most diagnosed cancers worldwide and are commonly excised via complete margin assessment (CMA) or excision with sectional assessment (SA). National Comprehensive Cancer Network guidelines encourage CMA for KC with high-risk features. OBJECTIVE: To systematically compare recurrence outcomes for CMA vs SA in high-risk KC based on National Comprehensive Cancer Network guidelines criteria. MATERIALS AND METHODS: EMBASE and MEDLINE were searched for articles reporting recurrences of high-risk KC undergoing excision using CMA or SA. High-risk KCs were defined as recurrent, having perineural invasion (PNI), or basal cell carcinomas (BCC) with aggressive histology. Chi-squared tests and risk ratios evaluated differences between CMA and SA groups, and a random-effects meta-analysis was performed. RESULTS: Twenty-eight studies met inclusion criteria. Pooled percentages of locoregional recurrences were significantly lower with CMA vs SA for all KCs (3.9% [95% CI: 2.9-4.9] vs 13.5% [7.7, 19.2, p = .001]), cutaneous squamous cell carcinoma with PNI (9.8% [5.4-14.1] vs 32.0% [25.0-39.0], p < .001), and recurrent BCC (4.4% [2.9-5.9] vs 11.9% [8.0-15.8], p < .001). CONCLUSION: For high-risk KCs, recurrence risk was over 3-times greater with SA compared with CMA. Expanded access to CMA for high-risk KC is likely to reduce recurrence risk and improve clinical outcomes.

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis.

BACKGROUND: To provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of response (DOR) and impact on quality of life (QoL). METHODS: Patients received cemiplimab 3 mg/kg every 2 weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally advanced CSCC, n=78) or cemiplimab 350 mg every 3 weeks (group 3, mCSCC, n=56). Primary endpoint was objective response rate (ORR) per independent central review (ICR). QoL was repeatedly measured at day 1 of each treatment cycle (groups 1 and 2: 8 weeks; group 3: 9 weeks). RESULTS: Median duration of follow-up was 15.7 months. Overall, ORR per ICR was 46.1% (95% CI: 38.9% to 53.4%). Complete response (CR) rates were 20.3%, 12.8%, and 16.1% for groups 1, 2, and 3, respectively. Median time to CR was 11.2 months. Among patients with partial response or CR, the estimated proportion of patients with ongoing response at 12 months from the first objective response was 87.8% (95% CI: 78.5% to 93.3%), with median DOR not reached. Kaplan-Meier estimated probability of overall survival (OS) was 73.3% (95% CI: 66.1% to 79.2%) at 24 months, with median OS not reached. Global Health Status (GHS)/QoL improvements were observed as early as cycle 2 and were significantly improved and durable until last assessment. Kaplan-Meier estimate of median time to first clinically meaningful improvement for pain was 2.1 (95% CI: 2.0 to 3.7) months and was significantly improved in responders versus non-responders (p<0.0001). CONCLUSIONS: This is the largest (n=193) clinical dataset for a programmed cell death-1 inhibitor against advanced CSCC, confirming the sustained substantial clinical activity of cemiplimab in these patients, including new findings of improved CR rates over time, increasing DOR, and durable pain control and GHS/QoL improvement. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02760498), https://clinicaltrialsgov/ct2/show/NCT02760498.

Total Margin-Controlled Excision is Superior to Standard Excision for Keratinocyte Carcinoma on the Nose: A Veterans Affairs Nested Cohort Study.

BACKGROUND: Keratinocyte carcinoma (KC), including basal and squamous cell carcinoma, is the most common human malignancy. Limited real-world data have compared surgical outcome or cost between total margin-controlled excision (TMCE) and standard excision (SE), the two most common treatments for invasive KC. We compared reconstruction, margin status, and cost between TMCE and SE for KC on the nose at a Veterans Affairs (VA) healthcare system. METHODS: Randomly selected primary KCs on the nose ≤3 cm that were confined to soft tissue, without nerve or lymphovascular invasion, and treated with SE or TMCE between 2000 and 2010, were assessed. Utilization of flap or graft reconstruction and margin status following all surgical attempts were recorded. Costs were based on Current Procedural Terminology codes standardized to 2019 Medicare payments. RESULTS: Overall, 148 cases were included in each treatment group. Baseline characteristics were similar between groups, although SE tumor median diameter was 1 mm larger. SE was associated with increased utilization of flap or graft reconstruction (odds ratio 2.05, 95% confidence interval 1.16-3.59, p = 0.01). Positive margins were present in 24% of SEs initially and remained positive after the final recorded excision in 9% of cases. No positive final margins were noted in TMCE cases. SE cost per tumor was significantly higher than TMCE ($429.03 ± 143.55; p = 0.003). CONCLUSIONS: Surgical management of KC with SE is associated with increased reconstruction complexity, a significant risk of positive margins, and higher cost compared with TMCE. The 23% risk of positive margins supports National Comprehensive Cancer Network guidelines for the treatment of high-risk KC with TMCE, unless delayed reconstruction is employed.

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

BACKGROUND: Though the National Comprehensive Cancer Network recommends consideration of localized adjuvant radiation after clear-margin surgery for cutaneous squamous cell carcinoma (cSCC) with large-caliber (≥0.1-mm) nerve invasion (LCNI) and other high-risk features, only a single small study has compared surgery plus adjuvant radiation therapy (S+ART) to surgical monotherapy (SM) for cSCC. OBJECTIVE: Compare S+ART to SM for primary cSCCs with LCNI and other risk factors. METHODS: Matched retrospective cohort study of primary cSCCs (matched on sex, age, immune status, type of surgery, diameter, differentiation, depth, and LCNI) treated with S+ART versus SM. A subgroup analysis of cSCCs with LCNI was performed. RESULTS: In total, 62 cSCCs were included in matched analysis (31 S+ART and 31 SM) and 33 cSCCs in the LCNI analysis (16 S+ART and 17 SM). There were no significant differences in local recurrence, metastasis, or death from disease in either analysis. Risk of local recurrence was low (8%, 7/89), with 3 of the local recurrences being effectively treated upon recurrence. LIMITATIONS: Single academic center and nonrandomized design. CONCLUSION: Adjuvant radiation did not improve outcomes compared with SM due to a low baseline risk of recurrence, although adjuvant radiation for named nerve invasion and LCNI of ≥3 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.

Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors.

While the majority of cutaneous squamous cell carcinomas (cSCCs) can be treated surgically, the additional work-up and treatments indicated for high-risk cSCC remain undefined. In recent years, improvements in tumor staging systems have allowed for the more accurate stratification of tumors into high- and low-risk categories. This insight, along with the publication of cSCC guidelines, brings us closer to the development of a consensus approach. The second article in this continuing medical education series addresses in question and answer format the most common questions related to advanced and high-stage cSCCs, with a simplified flowchart. The questions include the following: 1) Does my patient have high-risk cSCC?; 2) What is the next step for patients with cSCC and palpable lymphadenopathy?; 3) In patients with no clinically evident lymphadenopathy, who are candidates for lymph node staging?; 4) What forms of radiologic imaging can help detect subclinical lymph node metastases?; 5) What is the role of sentinel lymph node biopsy in cSCC?; 6) Which patients with cSCC need adjuvant radiation therapy?; 7) Is adjuvant chemotherapy an option for patients with high-stage cSCC after surgery?; 8) Are targeted and immunologic therapies an option for advanced cSCC?; 9) How often should I follow up with my patient after he/she has been diagnosed with a high-risk cSCC?; 10) What are the options for chemoprophylaxis in a patient with an increased risk of cSCC?; and 11) What chemopreventive measures can be started in coordination with medical oncology or transplant physicians?

Impact of National Comprehensive Cancer Network Guidelines on Case Selection and Outcomes for Sentinel Lymph Node Biopsy in Thin Melanoma.

BACKGROUND: In 2010, the National Comprehensive Cancer Network (NCCN) recommended sentinel lymph node biopsy (SLNB) for thin melanomas ≤1 mm with mitotic rate (MR) ≥1. In 2016, the criteria were changed to Breslow depth >0.75 mm and MR ≥1. OBJECTIVE: To compare the impact of 2010 and 2016 NCCN guidelines on SLNB case selection and thin melanoma outcomes. MATERIALS AND METHODS: Ten-year retrospective cohort of primary thin melanomas at an academic hospital was retroactively stratified for SLNB eligibility using the 2010 and 2016 NCCN guidelines. Nodal recurrence-free survival (NRFS) and disease-free survival (DFS) were compared. RESULTS: Eight hundred two patients with 859 tumors and median follow-up of 79 months were included. Eleven percent fewer tumors qualified for SLNB under 2016 versus 2010 NCCN guidelines (19% vs 8%, p < .001). The 2016-qualifying cases also had lower 10-year NRFS (70.7% vs 95.2%, p < .001) and DFS (64.7% vs 91.4%, p < .001). Among 2016-qualifying cases, those that received SLNB had improved NRFS (85.6% vs 35.3%, p = .001) and DFS (80.2% vs 30.5%, p < .001) as compared to those that did not receive SLNB. CONCLUSION: The 2016 NCCN guidelines reduced the number of thin melanomas qualifying for SLNB and more accurately selected cases with higher risks of nodal recurrence and death.