NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study.

BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

Is sentinel lymph node biopsy needed for lentigo maligna melanoma?

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases. METHODS: We performed a retrospective review of the National Cancer Database (2012-2020) and the Surveillance, Epidemiology, and End Results (2010-2019) database for patients with cutaneous nonmetastatic LMM with Breslow thickness >1.0 mm. Multivariable logistic regression identified factors associated with SLNB performance and sentinel lymph node (SLN) positivity. Univariable and multivariable analyses assessed overall survival (OS) and melanoma-specific survival (MSS) based on SLNB performance and SLN status. RESULTS: Compared to other melanoma subtypes, LMM had lower rates of SLNB (66.6% vs. 80.0%-84.0%) and SLN positivity (11.3% vs. 18.6%-34.2%). Compared to patients who did not undergo SLNB, SLN status was significantly associated with improved OS in patients with SLN positive (HR = 0.64 [0.55-0.76]) and SLN negative (HR = 0.68 [0.49-0.94]), and worse MSS only in patients with positive SLN (HR = 3.93, p < 0.05). CONCLUSION: The improved OS associated with SLNB likely implies surgical selection bias. Analysis of MSS confirms appropriate patient selection and suggests important prognostic value associated with SLN status. These results support continued SLNB for LMM patients according to standard guidelines.

The effect of surgical timing in nonmetastatic melanoma.

BACKGROUND AND OBJECTIVES: There is no consensus guidelines on the best timing to perform Sentinel lymph node biopsy (SLNB) in high-risk melanoma patients. We aimed to understand the impact of surgical timing on nodal upstaging in patients with cutaneous melanoma. METHODS: We queried the National Cancer Database from 2004 to 2018 for patients with T2-T4, N0, M0 melanomas, who underwent melanoma excision and nodal surgery. We included patients who underwent surgery within 2-19 weeks postdiagnosis. We aimed to determine the association of surgical delay (weeks) with nodal positivity. RESULTS: A total of 53 355 patients were included, of whom 20.9% had positive lymph nodes. Patients underwent surgery at a median of 5 (4-7) weeks after diagnosis. The rate of positive nodes increased with increased weeks to surgery (line of best-fit slope = 0.38). Multivariable regression analysis identified an association between time to surgery and nodal positivity (2.4% increased risk per week, p < 0.05). Our analysis showed significantly increased likelihood of nodal positivity beginning 9 weeks after diagnosis (odds ratio [OR] = 1.3, p < 0.05). Furthermore, patients with T2-3 tumors had a significant increase in nodal positivity with increased time to surgery (OR = 1.03 per week, p < 0.001). However, no significant trend in nodal positivity was identified for patients with T4 melanomas (OR = 1.01 per week, p = 0.596). CONCLUSION: Surgery within 9 weeks of melanoma diagnosis was not associated with increased likelihood of nodal positivity. These data can guide clinical conversations regarding the importance of surgical timing for melanoma.

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

A Clinical Decision Tool to Calculate Pretest Probability of Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

BACKGROUND: Although sentinel lymph node biopsy (SLNB) status is a strong prognostic indicator for cutaneous melanoma, unnecessary SLNBs have substantial cost and morbidity burden. OBJECTIVE: This study was designed to develop, validate, and present a personalized, clinical, decision-making tool using nationally representative data with clinically actionable probability thresholds (Expected Lymphatic Metastasis Outcome [ELMO]). METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2017 and the National Cancer Database (NCDB) from 2004 to 2015 were used to develop and internally validate a logistic ridge regression predictive model for SLNB positivity. External validation was done with 1568 patients at a large tertiary referral center. RESULTS: The development cohort included 134,809 patients, and the internal validation cohort included 38,518 patients. ELMO (AUC 0.85) resulted in a 29.54% SLNB reduction rate and greater sensitivity in predicting SLNB status for T1b, T2a, and T2b tumors than previous models. In external validation, ELMO had an accuracy of 0.7586 and AUC of 0.7218. Limitations of this study are potential miscoding, unaccounted confounders, and effect modification. CONCLUSIONS: ELMO ( https://melanoma-sentinel.herokuapp.com/ ) has been developed and validated (internally and externally) by using the largest publicly available dataset of melanoma patients and was found to have high accuracy compared with other published models and gene expression tests. Individualized risk estimates for SLNB positivity are critical in facilitating thorough decision-making for healthcare providers and patients with melanoma.

Predictors of sentinel lymph node metastasis in very thin invasive melanomas.

BACKGROUND: Melanomas < 0.8 mm in Breslow depth have less than a 5% risk for nodal positivity. Nonetheless, nodal positivity is prognostic for this group. Early identification of nodal positivity may improve the outcomes for these patients. OBJECTIVES: To determine the degree to which ulceration and other high-risk features predict sentinel lymph node (SLN) positivity for very thin melanomas. METHODS: The National Cancer Database was reviewed from 2012 to 2018 for patients with melanoma with Breslow thickness < 0.8 mm. Data were analysed from 7 July 2022 through to 25 February 2023. Patients were excluded if data regarding their ulceration status or SLN biopsy (SLNB) performance were unknown. We analysed patient, tumour and health system factors for their effect on SLN positivity. Data were analysed using χ2 tests and logistic regressions. Overall survival (OS) was compared by Kaplan-Meier analyses. RESULTS: Positive nodal metastases were seen in 876 (5.0%) patients who underwent SLNB (17 692). Factors significantly associated with nodal positivity on multivariable analysis include lymphovascular invasion [odds ratio (OR) 4.5, P < 0.001], ulceration (OR 2.6, P < 0.001), mitoses (OR 2.1, P < 0.001) and nodular subtype (OR 2.1, P < 0.001). Five-year OS was 75% and 92% for patients with positive and negative SLN, respectively. CONCLUSIONS: Nodal positivity has prognostic significance for very thin melanomas. In our cohort, the rate of nodal positivity was 5% overall in these patients who underwent SLNB. Specific tumour factors (e.g. lymphovascular invasion, ulceration, mitoses, nodular subtype) were associated with higher rates of SLN metastases and should be used to guide clinicians in choosing which patients will benefit from SLNB.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

The impact of the COVID-19 pandemic in 2020 on the diagnosis, treatment, and outcomes of invasive cutaneous melanoma: A retrospective national cohort study.

BACKGROUND: Prior multiinstitutional studies demonstrate that patients diagnosed with melanoma during the Coronavirus Disease 2019 (COVID-19) pandemic presented with more advanced melanomas. OBJECTIVES: To further characterize patients diagnosed with melanoma during the COVID-19 pandemic. METHODS: Retrospective population-based cohort study of the Surveillance, Epidemiology, and End-Results (SEER) registry of patients diagnosed with cutaneous melanoma from 2018-2020. RESULTS: Patients diagnosed with melanoma in 2020 were more likely to have increased Breslow depth, more ulceration, nodular tumors, and more advanced stage at diagnosis despite less treatment delays. Patients tended to be from wealthier, more urban areas. Primary surgical treatment was more likely to be with Mohs surgery. Diagnosis in the year 2020 was not correlated with overall or disease specific survival. LIMITATIONS: This is a retrospective cohort review and limited by short follow-up times, which could affect survival outcomes. There was a 15.5% drop in melanoma diagnosis in 2020 compared to prior years, which could relate to delayed presentation. CONCLUSIONS AND RELEVANCE: Patients diagnosed with melanoma in 2020 tended to have thicker, more ulcerated, and more advanced tumors, but this was not associated with survival. Further studies are needed to characterize outcomes for patients diagnosed with melanoma during the COVID-19 pandemic.

Asian American and Pacific Islander patients with melanoma have increased odds of treatment delays: A cross-sectional study.

BACKGROUND: Asian American and Pacific Islander (AAPI) melanoma patients have higher mortality than non-Hispanic White (NHW) patients. Treatment delays may contribute, but whether AAPI patients have longer time from diagnosis to definitive surgery (TTDS) is unknown. OBJECTIVES: Investigate TTDS differences between AAPI and NHW melanoma patients. METHODS: Retrospective review of AAPI and NHW melanoma patients in the National Cancer Database (NCD) (2004-2020). The association of race with TTDS was evaluated by multivariable logistic regression, controlling for sociodemographic characteristics. RESULTS: Of 354,943 AAPI and NHW melanoma patients identified, 1155 (0.33%) were AAPI. AAPI patients had longer TTDS for stage I, II, and III melanoma (P < .05 for all). Adjusting for sociodemographic factors, AAPI patients had 1.5 times the odds of a TTDS between 61 and 90 days and twice the odds of a TTDS >90 days. Racial differences in TTDS persisted in Medicare and private insurance types. Uninsured AAPI patients had the longest TTDS (mean, 53.26 days), while those with private insurance had the shortest TTDS (mean, 34.92 days; P < .001 for both). LIMITATION: AAPI patients comprised 0.33% of the sample. CONCLUSIONS: AAPI melanoma patients have increased odds of treatment delays. Associated socioeconomic differences should inform efforts to reduce disparities in treatment and survival.

Incidence and Survival Outcomes of Dermatofibrosarcoma Protuberans From 2000 to 2020: A Population-Based Retrospective Cohort Analysis.

BACKGROUND: Recent changes in the incidence and survival of dermatofibrosarcoma protuberans (DFSP) have not been described. OBJECTIVE: To characterize the incidence and survival of DFSP. MATERIALS AND METHODS: A retrospective cohort study of patients with DFSP from 2000 to 2020 in the Surveillance, Epidemiology, and End Results database was performed. Cox and Fine-Gray regression models were used to assess overall and DFSP-specific survival. RESULTS: The incidence of DFSP has not changed from 2000 to 2020 with 4.6 cases/million person-years, with higher rates in dark-skinned and middle-age individuals. Factors associated with overall mortality in DFSP patients include advanced age ( p < .0001), male sex (hazard ratio [HR] 1.8, p < .0001), larger tumors (HR 1.002 per millimeter, p < .001), lower household income (HR 1.8, p = .0002), and lower extremity location (HR 1.7, p = .008). Mohs surgery is associated with improved overall survival (HR 0.4, p = .02). Large tumor size (6.0+ cm, HR 6.7, p = .01) and advanced age (age 80+ years, HR 21.3, p = .003) were associated with worse DFSP-specific mortality. CONCLUSION: Dermatofibrosarcoma protuberans incidence has remained constant from 2000 to 2020. Increasing age and tumor size, decreased income, male sex, and lower extremity location are associated with worsened survival. Mohs surgery is associated with improved overall survival. Increased age and tumor size are associated with worsened DFSP-specific mortality.

Development of a core outcome set for basal cell carcinoma.

BACKGROUND: There is variation in the outcomes reported in clinical studies of basal cell carcinoma. This can prevent effective meta-analyses from answering important clinical questions. OBJECTIVE: To identify a recommended minimum set of core outcomes for basal cell carcinoma clinical trials. METHODS: Patient and professional Delphi process to cull a long list, culminating in a consensus meeting. To be provisionally accepted, outcomes needed to be deemed important (score, 7-9, with 9 being the maximum) by 70% of each stakeholder group. RESULTS: Two hundred thirty-five candidate outcomes identified via a systematic literature review and survey of key stakeholders were reduced to 74 that were rated by 100 health care professionals and patients in 2 Delphi rounds. Twenty-seven outcomes were provisionally accepted. The final core set of 5 agreed-upon outcomes after the consensus meeting included complete response; persistent or serious adverse events; recurrence-free survival; quality of life; and patient satisfaction, including cosmetic outcome. LIMITATIONS: English-speaking patients and professionals rated outcomes extracted from English language studies. CONCLUSION: A core outcome set for basal cell carcinoma has been developed. The use of relevant measures may improve the utility of clinical research and the quality of therapeutic guidance available to clinicians.

Surgical Techniques Following Free Cartilage Grafting.

BACKGROUND: Reconstruction of surgical defects with free cartilage grafts poses unique challenges. OBJECTIVES: To characterize surgical techniques following free cartilage grafting. MATERIALS AND METHODS: A literature review was performed using the Embase, PubMed Medline, Cochrane Library, ClinicalTrials.gov , and Web of Science databases from inception to May 21, 2021. Studies describing free cartilage grafts harvested from the ear or nose under local anesthesia, specifically for reconstruction of facial surgical defects, were selected for inclusion. Only surgical defects resulting from tumor resection were included. RESULTS: In total, 34 studies involving 713 patients with 723 surgical defects met inclusion criteria. The mean age of patients was 63.3 ± 10.4 years. Free cartilage grafts were most commonly harvested from the ear (93.1%). The most common recipient site was the nose (90.3%), followed by the lower eyelid (6.7%) and ear (3.0%). CONCLUSION: Free cartilage grafts are an effective reconstructive option for patients with deep or cartilaginous defects that have compromised structural support on the nose, ear, or eyelid.

NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022.

The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.

Sentinel lymph node biopsy guideline concordance in melanoma: Analysis of the National Cancer Database.

BACKGROUND AND OBJECTIVES: This study investigated the impact of treating facility type on guideline-concordant sentinel lymph node biopsy (SLNB) management in T1a* (defined as a Breslow depth <0.76 mm without ulceration or mitoses) and T2/T3 melanoma. METHODS: This was a retrospective cohort study utilizing the National Cancer Database from 2012 to 2016. RESULTS: Our cohort included 109,432 patients. For T1a* melanomas, 85% of patients received guideline-concordant SLNB management at community and academic facilities versus 75% of patients at integrated network facilities (p < .001). Over 83% of patients with T2/T3 melanoma treated at an academic facility received guideline-concordant SLNB management versus 77% treated at a community facility (p < .001). Adjusting for demographic and clinical factors, integrated (adjusted odds ratio, aOR = 0.54), and comprehensive community (aOR = 0.74) facilities were less likely to provide guideline-concordant SLNB management in patients with T1a* melanoma compared to academic facilities. Community facilities (aOR = 0.72) were less likely to provide guideline-concordant SLNB management in patients with T2/T3 melanoma compared to academic facilities. CONCLUSION: Academic facilities provide the highest rate of guideline-concordant sentinel lymph node management. Comparatively, community programs may underutilize SLNB in T2/T3 disease, while integrated and comprehensive community facilities may over-utilize SLNB in T1a* disease.

Tumor primary site as a prognostic factor for Merkel cell carcinoma disease-specific death.

BACKGROUND: Merkel cell carcinoma (MCC) primary site has not been fully investigated as a potential prognostic factor. OBJECTIVE: To determine the incidence by tumor primary site of death due to MCC. METHODS: We undertook a retrospective analysis of the Survival, Epidemiology, and End Results database. MCC patients treated between 1973 and 2016 were grouped by tumor primary site and a competing risks analysis was performed to test the impact of primary site on disease-specific death. Cumulative incidence of Merkel cell carcinoma-specific mortality (CMMI) at 5 years was estimated for each primary site. RESULTS: Of 9407 MCC patients identified, 6305 (67.0%) had localized disease, 2397 (25.5%) had regional metastasis, and 705 (7.5%) had distant metastasis. Tumor primary site was predictive of CMMI and varied by stage at diagnosis. Tumors involving the scalp/neck carried the highest CMMI among localized MCC (26.0%). Tumors involving the lip had the highest CMMI among MCC with regional metastasis (56.7%) and distant metastasis (82.1%). LIMITATIONS: Tumor size data were missing for a large proportion of patients, precluding stratification by stage according to current American Joint Committee on Cancer guidelines. CONCLUSIONS: Probability of MCC disease-specific death varies by primary site. The primary site of the tumor may be useful as a prognostic indicator for MCC.

Systematic review and meta-analysis of local recurrence rates of head and neck cutaneous melanomas after wide local excision, Mohs micrographic surgery, or staged excision.

BACKGROUND: Prospective trials have not compared the local recurrence rates of different excision techniques for cutaneous melanomas on the head and neck. OBJECTIVE: To determine local recurrence rates of cutaneous head and neck melanoma after wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision. METHODS: A systematic review of PubMed, EMBASE, and Web of Science identified all English case series, cohort studies, and randomized controlled trials that reported local recurrence rates after surgery for cutaneous head and neck melanoma. A meta-analysis utilizing a random effects model calculated weighted local recurrence rates and confidence intervals (CI) for each surgical technique and for subgroups of MMS and staged excision. RESULTS: Among 100 manuscripts with 13,998 head and neck cutaneous melanomas, 51.0% (7138) of melanomas were treated by WLE, 34.5% (4826) by MMS, and 14.5% (2034) by staged excision. Local recurrence rates were lowest for MMS (0.61%; 95% CI, 0.1%-1.4%), followed by staged excision (1.8%; 95% CI, 1.0%-2.9%) and WLE (7.8%; 95% CI, 6.4%-9.3%). LIMITATIONS: Definitions of local recurrence varied. Surgical techniques included varying proportions of invasive melanomas. Studies had heterogeneity. CONCLUSION: Systematic review and meta-analysis show lower local recurrence rates for cutaneous head and neck melanoma after treatment with MMS or staged excision compared to WLE.

Evidence-based clinical practice guideline: Reconstruction after skin cancer resection.

A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.

Systematic Review of Technical Variations for Mohs Micrographic Surgery for Melanoma.

BACKGROUND: Mohs micrographic surgery (MMS) for cutaneous melanoma is becoming more prevalent, but surgical technique varies. OBJECTIVE: To define variations in published techniques for MMS for melanoma. METHODS AND MATERIALS: A systematic review was performed of PubMed, EMBASE, and Scopus databases to identify all articles describing surgical techniques for MMS for melanoma. Technical details were recorded for the preoperative, intraoperative, and postoperative phases of MMS. RESULTS: Twenty-four articles were included. Mohs surgeons vary in how they assess clinical margins, how wide a margin they excise on the first MMS layer, and how they process tissue to determine tumor stage and margin clearance during MMS for melanoma. CONCLUSION: Mohs micrographic surgery for melanoma is performed with varied surgical techniques. To establish best practices, additional research is necessary to determine how different techniques affect outcomes.

Evidence-Based Clinical Practice Guideline: Reconstruction after Skin Cancer Resection.

SUMMARY: A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.