Frederick C. Morgan

The positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management

Background: There is limited evidence on the utility of radiologic imaging for prognostic staging of cutaneous squamous cell carcinoma (CSCC). Objective: Review utilization of radiologic imaging of high‐stage CSCCs to evaluate whether imaging impacted management and outcomes. Methods: Tumors classified as Brigham and Womens Hospital (BWH) tumor (T) stage T2B or T3 over a 13‐year period were reviewed to identify whether imaging was performed and whether results affected treatment. Disease‐related outcomes (DRO: local recurrence, nodal metastasis, death from disease) were compared between patients by type of imaging used. Results: 108 high‐stage CSCCs in 98 patients were included. Imaging (mostly computed tomography, 79%) was utilized in 45 (46%) patients and management was altered in 16 (33%) patients who underwent imaging. Patients that received no imaging were at higher risk of developing nodal metastases (nonimaging, 30%; imaging, 13%; P = .041) and any DRO (nonimaging, 42%; imaging, 20%; P = .028) compared to the imaging group. Imaging was associated with a lower risk for DRO (subhazard ratio, 0.5; 95% CI 0.2‐0.9; P = .046) adjusted for BWH T stage, sex, and location. Limitations: Single institution retrospective design and changes in technology overtime. Conclusions: Radiologic imaging of high‐stage CSCC may influence management and appears to positively impact outcomes. Further prospective studies are needed to establish which patients benefit from imaging.

Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data

Importance Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) has been associated with an increased risk of poor outcomes. Patients with PNI may present with clinical symptoms and/or radiologic evidence of PNI (clinical PNI [CPNI]), yet most patients are asymptomatic and PNI is often found on histologic examination (incidental PNI [IPNI]). Evidence-based estimates of the risks of disease-related outcomes comparing IPNI and CPNI are limited in the dermatology literature. Objectives To review and synthesize outcomes data for patients with CSCC and CPNI or IPNI. Data Sources A systematic review was conducted in MEDLINE and EMBASE for English-language articles published since inception to November 11, 2016. Study Selection All studies that reported a disease-related outcome (local recurrence, nodal metastasis, distant metastasis, or disease-specific death) of CSCCs with CPNI and IPNI were included. Data Extraction and Synthesis Articles were screened for eligibility, and any possible discrepancies in this screening were resolved. Data extracted included study characteristics, tumor characteristics, treatments performed, and disease-related outcomes. Overall risks of disease-related outcomes were generated by pooling patients from eligible studies. &khgr;2 Statistics and Fisher exact tests were used to evaluate differences in disease-related outcomes. Main Outcomes and Measures Risks of disease-related outcomes and 5-year recurrence-free, disease-specific, and overall survival. Results A total of 12 studies containing 241 patients with CPNI and 381 patients with IPNI were included in the systematic review and analysis. The overall risks of local recurrence and disease-specific death were significantly higher in patients with CSCC and CPNI compared with those with CSCC and IPNI (local recurrence, 37% vs 17%; P < .001; disease-specific death, 27% vs 6%; P < .001). The risks of nodal metastasis and distant metastasis did not differ significantly by PNI classification. Patients with CSCC and CPNI had poorer mean 5-year recurrence-free survival and disease-specific survival compared with patients with IPNI (recurrence-free survival, 61% vs 76%; P = .009; disease-specific survival, 70% vs 88%; P = .002). Conclusions and Relevance Patients with CSCC and CPNI are at an increased risk of local recurrence and disease-specific death compared with patients with CSCC and IPNI and have a 30% risk of death. Patients with PNI may benefit from increased long-term surveillance. Further studies are needed to establish standardized guidelines on follow-up and dermatologic surveillance in this high-risk patient population.

An ecological study of skin biopsies and skin cancer treatment procedures in the United States Medicare population, 2000 to 2015

Background: Analyses of skin cancer procedures adjusted for population changes are needed. Objective: To describe trends in skin cancer–related biopsies and procedures in Medicare beneficiaries. Methods: An ecological study of Medicare claims for skin biopsies and skin cancer procedures in 2000 to 2015. Results: Biopsies increased 142%, and skin cancer procedures increased 56%. Mohs micrographic surgery (MMS) utilization increased on the head/neck, hands/feet, and genitalia (increasing from 11% to 27% of all treatment procedures) but was low on the trunk/extremities (increasing from 1% to 4%). Adjusted for increased Medicare enrollment (+36%) between 2000 and 2015, the number of biopsies and MMS procedures performed per 1000 beneficiaries increased (from 56 to 99 and from 5 to 15, respectively), whereas the number of excisions and destructions changed minimally (from 18 to 16 and from 19 to 18, respectively). Growth in biopsies and MMS procedures slowed between each time period studied: 4.3 additional biopsies per year and 0.9 additional MMS procedures per year per 1000 beneficiaries between 2000 and 2007, 2.2 and 0.5 more between 2008 and 2011, and 0.5 and 0.3 more between 2012 and 2015, respectively. Limitations: Medicare claims–level data do not provide patient‐level or nonsurgical treatment information. Conclusions: The increased number of skin cancer procedures performed was largely the result of Medicare population growth over time. MMS utilization increased primarily on high‐ and medium‐risk and functionally and cosmetically significant locations where tissue sparing and maximizing cure are critical.

Association of Nodal Metastasis and Mortality With Vermilion vs Cutaneous Lip Location in Cutaneous Squamous Cell Carcinoma of the Lip

Importance Although the lip is considered a high-risk location in cutaneous squamous cell carcinoma (cSCC), it has not been established whether this risk stems from vermilion or cutaneous locations or both. Objective To compare differences in risks of recurrence, metastasis, and death from cSCCs on the vermilion vs cutaneous lip. Design, Setting, and Participants Retrospective cohort study of 303 patients with 310 primary cSCCs of the lip (138 cutaneous, 172 vermilion) diagnosed between 2000 and 2015 at 2 academic tertiary care centers in Boston, Massachusetts. Main Outcomes and Measures Development of local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death. Results Of the 303 study participants with 310 SCCs of the lip, 153 (50.5%) were men, and 150 (49.5%) were women; median age at diagnosis, 68 years (range, 27-93 years). Outcomes were as follows for vermilion vs cutaneous locations: local recurrence, 6.4% (11 of 172) vs 2.9% (4 of 138); nodal metastasis, 7.6% (13 of 172) vs 1.5% (2 of 138); distant metastasis, 0.6% (1 of 172) vs 0.7% (1 of 138); disease-specific death, 3.5% (6 of 172) vs 2.9% (4 of 138); and all-cause death, 26.7% (46 of 172) vs 29.0% (40 of 138). The difference was statistically significant for nodal metastasis (P = .01). In multivariable analysis, nodal metastasis was associated with vermilion lip location (subhazard ratio, 5.0; 95% CI, 1.1-23.8) and invasion beyond fat (fascia or beyond for vermilion lip) (subhazard ratio, 4.4; 95% CI, 1.3-14.9). Conclusions and Relevance The risk of nodal metastasis is 5-fold greater for cSCCs on the vermilion lip compared with those on the cutaneous lip. Squamous cell carcinomas of the cutaneous lip have a nodal metastasis risk similar to cSCCs in general (1.5%). Thus, vermilion involvement appears responsible for the increased risk associated with cSCC of lip. Vermilion involvement may merit radiologic nodal staging and inclusion in future tumor staging, since it was independently associated with higher-risk cSCC of the lip region.

An evaluation of high-stage cutaneous squamous cell carcinoma outcomes by gender

Data from the World Health Organization indicate that global overall age-adjusted cancer incidence and mortality rates are 1.2- and 1.5-fold higher in men as compared to women, respectively.1 Non-melanoma skin cancer (NMSC) is the most common cancer among white populations, yet the prognostic significance of gender remains unclear.2 A possible relationship may exist given that in melanoma, women have a lower mortality risk as compared to men.3,4 This article is protected by copyright. All rights reserved.

Dermatologists are the primary treating physicians of skin cancer in the United States Medicare population

REFERENCES 1. Ingram JR, Piguet V. Phenotypic heterogeneity in hidradenitis suppurativa (acne inversa): classification is an essential step toward personalized therapy. J Invest Dermatol. 2013;133: 1453-1456. 2. Canoui-Poitrine F, Le Thuaut A, Revuz JE, et al. Identification of three hidradenitis suppurativa phenotypes: latent class analysis of a cross-sectional study. J Invest Dermatol. 2013;133:1506-1511. 3. Kottner J, Audige L, Brorson S, et al. Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were proposed. J Clin Epidemiol. 2011;64:96-106. 4. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159-174. 5. van der Zee HH, Jemec GB. New insights into the diagnosis of hidradenitis suppurativa: clinical presentations and phenotypes. J Am Acad Dermatol. 2015;73:S23-S26.

A comparison of skin cancer screening and treatment costs at a Massachusetts cancer center, 2008 versus 2013

Background Temporal analyses of skin cancer costs are needed to examine how expenditure differences between diagnoses are changing. Objective To tabulate the costs of skin cancer–related care (SCRC), including both screening and treatment, at an academic cancer center at 2 time points. Methods Cost data (insurance and patient payments) at an academic cancer center from 2008 and 2013 were queried for International Classification of Diseases, Ninth Revision, codes pertaining to skin cancer. Screening costs were separated from treatment costs through associated Current Procedural Terminology codes. Results The total annual cost of SCRC increased by 64%, the number of patients receiving SCRC increased by 45%, and the mean cost per patient treated increased by 13%. Screening accounted for 17% and 16% of total annual costs in 2008 and 2013, respectively. The mean cost per patient with melanoma increased by 84%, which was the largest increase among skin cancer diagnoses. In 2013, the few patients with melanoma who were treated with ipilimumab (n = 48 [4% of patients with melanoma]) accounted for 42% of melanoma treatment costs and 20% of SCRC costs. Limitations Prescription costs were unavailable. Conclusions Melanoma costs have increased as a result of the introduction of ipilimumab. Ongoing studies are needed to monitor the cost‐effectiveness of SCRC at a national level.

Comparison of Tumor Classifications for Cutaneous Squamous Cell Carcinoma of the Head and Neck in the 7th vs 8th Edition of the AJCC Cancer Staging Manual

Importance Previous studies have shown that the AJCC Cancer Staging Manual, 7th edition (AJCC 7), tumor classification for cutaneous squamous cell carcinoma (CSCC) failed to accurately stratify disease-related outcomes. The recently released 8th edition (AJCC 8) features a revised tumor classification for only head and neck CSCC (HNCSCC). Objective To compare AJCC 7 and AJCC 8 tumor classifications for HNCSCC and to validate AJCC 8. Design, Setting, and Participants This was a 10-year retrospective cohort study (2000-2009) at an academic tertiary care center reviewing 680 primary HNCSCC tumors in 459 patients. Main Outcomes and Measures Primary HNCSCC tumors were reviewed for disease-related outcomes (DROs): local recurrence (LR), nodal metastasis (NM), and disease-specific death (DSD). Tumors were stratified by AJCC 7 and AJCC 8 tumor classification. Distinctiveness (outcome differences between categories), homogeneity (outcome similarity within categories), and monotonicity (outcome worsening with increasing categories) were assessed for both classifications. Results Most of the 459 patients were white (451 [98.3%]) and male (312 [68.0%]). AJCC 8 high tumor categories (T3/T4) accounted for 121 (17.8%) of total cases but 50 of 71 DROs (70.4%) (22 of 34 of LRs [64.7%], 17 of 24 NMs [70.8%], and 11 of 13 of DSDs [84.6%]). This was a significant improvement over AJCC 7, where only 12 of 71 DROs (16.9%) (4 of 34 LRs [11.8%], 3 of 24 NMs [12.5%], and 5 of 13 DSDs [38.5%]) occurred in T3/T4 categories. However, AJCC 8 T2 and T3 were indistinct, with overlapping 95% CIs for 10-year cumulative incidences of LR, NM, and DSD. The 10-year cumulative incidence of DROs in the 119 AJCC 8 T3 cases were 19.7% (95% CI, 13.0%-29.7%) for LR, 14.1% (95% CI, 9.7%-20.7%) for NM, and 9.3% (95% CI, 6.8%-14.0% for DSD). Conclusions and Relevance AJCC 8 demonstrates superior homogeneity and monotonicity compared with AJCC 7. It now may be possible for AJCC 8 HNCSCC T2, T3, and T4 cases to be recorded and tracked by tumor registries because they represented a 23.1% subset in this study, which includes nearly all poor outcomes (85.9%). Further work is needed to validate AJCC 8 with population-level data and to compare AJCC 8 performance against alternative tumor classifications.