Treatment Of Primary Cutaneous Melanoma Research Articles

The Evolution of the Sentinel Node Biopsy in Melanoma.

The growing repertoire of approved immune-checkpoint inhibitors and targeted therapy has revolutionized the adjuvant treatment of melanoma. While the treatment of primary cutaneous melanoma remains wide local excision (WLE), the management of regional lymph nodes continues to evolve in light of practice-changing clinical trials and dramatically improved adjuvant therapy. With large multicenter studies reporting no benefit in overall survival for completion lymph node dissection (CLND) after a positive sentinel node biopsy (SLNB), controversy remains regarding patient selection and clinical decision-making. This review explores the evolution of the SLNB in cutaneous melanoma in the context of a rapidly changing adjuvant treatment landscape, summarizing the key clinical trials which shaped current practice guidelines.

Clinically Significant Risk Thresholds in the Management of Primary Cutaneous Melanoma: A Survey of Melanoma Experts.

Risk-based thresholds to guide management are undefined in the treatment of primary cutaneous melanoma but are essential to advance the field from traditional stage-based treatment to more individualized care. To estimate treatment risk thresholds, hypothetical clinical melanoma scenarios were developed and a stratified random sample was distributed to expert melanoma clinicians via an anonymous web-based survey. Scenarios provided a defined 5-year risk of recurrence and asked for recommendations regarding clinical follow-up, imaging, and adjuvant therapy. Marginal probability of response across the spectrum of 5-year recurrence risk was estimated. The risk at which 50% of respondents recommended a treatment was defined as the risk threshold. The overall response rate was 56% (89/159). Three separate multivariable models were constructed to estimate the recommendations for clinical follow-up more than twice/year, for surveillance cross-sectional imaging at least once/year, and for adjuvant therapy. A 36% 5-year risk of recurrence was identified as the threshold for recommending clinical follow-up more than twice/year. The thresholds for recommending cross-sectional imaging and adjuvant therapy were 30 and 59%, respectively. Thresholds varied with the age of the hypothetical patient: at younger ages they were constant but increased rapidly at ages 60years and above. To our knowledge, these data provide the first estimates of clinically significant treatment thresholds for patients with cutaneous melanoma based on risk of recurrence. Future refinement and adoption of thresholds would permit assessment of the clinical utility of novel prognostic tools and represents an early step toward individualizing treatment recommendations.

Contemporary management of locoregionally advanced melanoma in Australia and New Zealand and the role of adjuvant systemic therapy.

Australia and New Zealand have the highest incidence and mortality rates for melanoma in the world. Local surgery is still the standard treatment of primary cutaneous melanoma, and it is therefore important that surgeons understand the optimal care pathways for patients with melanoma. Accurate staging is critical to ensure a reliable assessment of prognosis and to guide treatment selection. Sentinel node biopsy (SNB) plays an important role in staging and the provision of reliable prognostic estimates for patients with cutaneous melanoma. Patients with stage III melanoma have a substantial risk of disease recurrence following surgery, leading to poor long-term outcomes. Systemic immunotherapies and targeted therapies, known to be effective for stage IV melanoma, have now also been shown to be effective as adjuvant post-surgical treatments for resected stage III melanoma. These patients should be made aware of this and preferably managed in an integrated multidisciplinary model of care, involving the surgeon, medical oncologists and radiation oncologists. This review considers the impact of a recent update to the American Joint Committee on Cancer (AJCC) staging system, the role of SNB for patients with high-risk primary melanoma and recent advances in adjuvant systemic therapies for high-risk patients.

Guidelines of care for the management of primary cutaneous melanoma

The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is usually curative following early detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.

Primary Cutaneous Melanoma

Melanoma presents a significant health burden as its incidence continues to rise in both sexes and remains the most common cause of skin cancer–related death. Risk factors for the development of melanoma include sun exposure, fair complexion, increasing age, previous melanoma, multiple dysplastic nevi, and familial syndromes. Wide local excision is the standard of care for those with early forms of melanoma, with sentinel lymph node biopsy in appropriate populations. Sentinel lymph node status contributes to the discussion as to whether to pursue completion lymphadenectomy. This review outlines surgical treatment of primary cutaneous melanoma, including wide local excision, sentinel lymph node biopsy, and completion lymphadenectomy. This review contains 10 figures, 2 tables and 33 references Key words: biopsy, cutaneous, lymphadenectomy, margin, melanoma, pathology, primary, sentinel node, surgery, treatment

Primary Cutaneous Melanoma

Melanoma presents a significant health burden as its incidence continues to rise in both sexes and remains the most common cause of skin cancer–related death. Risk factors for the development of melanoma include sun exposure, fair complexion, increasing age, previous melanoma, multiple dysplastic nevi, and familial syndromes. Wide local excision is the standard of care for those with early forms of melanoma, with sentinel lymph node biopsy in appropriate populations. Sentinel lymph node status contributes to the discussion as to whether to pursue completion lymphadenectomy. This review outlines surgical treatment of primary cutaneous melanoma, including wide local excision, sentinel lymph node biopsy, and completion lymphadenectomy. This review contains 10 figures, 4 tables and 33 references Key words: biopsy, cutaneous, lymphadenectomy, margin, melanoma, pathology, primary, sentinel node, surgery, treatment

Follow-Up Recommendations after Diagnosis of Primary Cutaneous Melanoma: A Population-Based Study in New South Wales, Australia.

Follow-up practices after diagnosis and treatment of primary cutaneous melanoma vary considerably. We aimed to determine factors associated with recommendations for follow-up setting, frequency, skin surveillance, and concordance with clinical guidelines. The population-based Melanoma Patterns of Care study documented clinicians' recommendations for follow-up for 2148 patients diagnosed with primary cutaneous melanoma over a 12-month period (2006/2007) in New South Wales, Australia. Multivariate log binomial regression models adjusted for patient and lesion characteristics were used to examine factors associated with follow-up practices. Of 2158 melanomas, Breslow thickness was<1mm for 57% and≥1mm for 30%, while in situ melanomas accounted for 13%. Follow-up was recommended for 2063 patients (96%). On multivariate analysis, factors associated with a recommendation for follow-up at a specialist center were Breslow thickness≥1mm [prevalence ratio (PR) 1.05, 95% confidence interval (CI) 1.01-1.09] and initial treatment at a specialist center (PR 1.12, 95% CI 1.08-1.16). Longer follow-up intervals of>3months were more likely to be recommended for females, less likely for people living in rural compared with urban areas, and less likely for thicker (≥1mm) melanomas compared with in situ melanomas. Skin self-examination was encouraged in 84% of consultations and was less likely to be recommended for patients≥70years (PR 0.88, 95% CI 0.84-0.93) and for those with thicker (≥1mm) melanomas (PR 0.92, 95% CI 0.86-0.99). Only 1% of patients were referred for psychological care. Follow-up recommendations were generally consistent with Australian national guidelines for management of melanoma, however some variations could be targeted to improve patient outcomes.

Analysis of patients diagnosed with primary cutaneous melanoma in the last six years in Hospital Erasto Gaertner: epidemiologic profile

Background:Melanoma is one of the conditions with greater increase in incidence worldwide in recent decades. It is a skin cancer with potential high lethality and predominates in Caucasian adults. Treatment of primary cutaneous melanoma is essentially surgical and search for sentinel lymph node can modify the aggressiveness of the treatment. Objective:To analyze the epidemiological profile of patients diagnosed with primary cutaneous melanoma, histopathological features and compare with literature data. Methods:This is a retrospective, observational, single-center, case series study of patients with primary cutaneous melanoma, who underwent surgery between January 2008 and December 2013. The parameters include: Age, sex, clinical stage, date of surgery, tumor location, histological subtype, condition of surgical margins, Breslow thickness, mitotic index, presence of ulceration and metastasis on admission. Results:We included 321 melanoma patients who were treated at Hospital Erasto Gaertner. The population consisted of 58.9% females and 41.1% males with an average age of 52.8 ± 16.3 years. As for the clinical stage, 51.1% were in the initial stage, 24.3% in the clinical stage II (A, B and C), 21.2% in clinical stage III and 3.4% with distant metastases. The most frequent location of the primary melanoma was the trunk, and the histological subtype was superficial spreading pattern. Intermediate and thick melanomas were the most frequent. Study limitations:This is a retrospective study and some information and data could be incomplete or absent. Conclusion:The diagnosis and treatment of melanoma in early stages provides less morbidity and improved survival of patients. Understanding the biological behavior of tumor and knowing the local epidemiology guide health strategies.

Essential Components of Melanoma Histopathological Reporting: The Surgical Oncologist's Perspective.

Histopathological reporting plays a critical role in guiding the surgical oncologist's management plan in treatment of primary cutaneous melanoma. The International Collaboration on Cancer Reporting (ICCR) espouses various components of structured histopathological reporting as “essential” or “recommended.” From a surgical oncologist's perspective, we discuss the clinical relevance of each essential component, as well as prognostic and treatment implications with regard to treatment planning.

177 Surveillance adherence of patients after treatment of primary cutaneous melanoma

177 Surveillance adherence of patients after treatment of primary cutaneous melanoma

Guidelines of the Brazilian Dermatology Society for diagnosis, treatment and follow up of primary cutaneous melanoma--Part I.

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute to diagnosis and treatment of primary cutaneous melanoma? What margins should be used to treat lentigo maligna melanoma and melanoma in situ?

Effect of biopsy type on outcomes in the treatment of primary cutaneous melanoma

BackgroundSurgical excision remains the primary and only potentially curative treatment for melanoma. Although current guidelines recommend excisional biopsy as the technique of choice for evaluating lesions suspected of being primary melanomas, other biopsy types are commonly used. We sought to determine the impact of biopsy type (excisional, shave, or punch) on outcomes in melanoma. MethodsA prospectively collected, institutional review board–approved database of primary clinically node–negative melanomas (stages cT1–4N0) was reviewed to determine the impact of biopsy type on T-staging accuracy, wide local excision (WLE) area (cm2), sentinel lymph node biopsy (SLNB) identification rates and results, tumor recurrence, and patient survival. ResultsSeven hundred nine patients were diagnosed by punch biopsy (23%), shave biopsy (34%), and excisional biopsy (43%). Shave biopsy results showed significantly more positive deep margins (P < .001). Both shave and punch biopsy results showed more positive peripheral margins (P < .001) and a higher risk of finding residual tumor (with resulting tumor upstaging) in the WLE (P < .001), compared with excisional biopsy. Punch biopsy resulted in a larger mean WLE area compared with shave and excisional biopsies (P = .030), and this result was sustained on multivariate analysis. SLNB accuracy was 98.5% and was not affected by biopsy type. Similarly, biopsy type did not confer survival advantage or impact tumor recurrence; the finding of residual tumor in the WLE impacted survival on univariate but not multivariate analysis. ConclusionsBoth shave and punch biopsies demonstrated a significant risk of finding residual tumor in the WLE, with pathologic upstaging of the WLE. Punch biopsy also led to a larger mean WLE area compared with other biopsy types. However, biopsy type did not impact SLNB accuracy or results, tumor recurrence, or disease-specific survival (DSS). Punch and shave biopsies, when used appropriately, should not be discouraged for the diagnosis of melanoma.

Guidelines of care for the management of primary cutaneous melanoma

The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.

Shave Biopsy Is a Safe and Accurate Method for the Initial Evaluation of Melanoma

Shave biopsy of cutaneous lesions is simple, efficient, and commonly used clinically. However, this technique has been criticized for its potential to hamper accurate diagnosis and microstaging of melanoma, thereby complicating treatment decision-making. We retrospectively analyzed a consecutive series of patients referred to the University of Florida Shands Cancer Center or to the Moffitt Cancer Center for treatment of primary cutaneous melanoma, initially diagnosed on shave biopsy to have Breslow depth < 2 mm, to determine the accuracy of shave biopsy in T-staging and the potential impact on definitive surgical treatment and outcomes. Six hundred patients undergoing shave biopsy were diagnosed with melanoma from extremity (42%), trunk (37%), and head or neck (21%). Mean (± SEM) Breslow thickness was 0.73 ± 0.02 mm; 6.2% of lesions were ulcerated. At the time of wide excision, residual melanoma was found in 133 (22%), resulting in T-stage upstaging for 18 patients (3%). Recommendations for additional wide excision or sentinel lymph node biopsy changed in 12 of 600 (2%) and 8 of 600 patients (1.3%), respectively. Locoregional recurrence occurred in 10 (1.7%) patients and distant recurrence in 4 (0.7%) patients. These data challenge the surgical dogma that full-thickness excisional biopsy of suspicious cutaneous lesions is the only method that can lead to accurate diagnosis. Data obtained on shave biopsy of melanoma are reliable and accurate in the overwhelming majority of cases (97%). The use of shave biopsy does not complicate or compromise management of the overwhelming majority of patients with malignant melanoma.

Therapie und Nachsorge des kutanen Melanoms

Surgical treatment of primary cutaneous melanoma has significantly changed in the last decades. Tumors are excised with lateral margins of 1-2 cm depending on the depth of tumor infiltration, and reconstructive procedures for defect closure are rarely necessary. Elective lymph node dissection has been replaced by the sentinel lymph node procedure and radical lymph node dissection is restricted to patients with positive lymph nodes. Follow-up of melanoma has been adapted to the individual risk profile of the patient. In early stage melanoma only clinical follow-up examinations are warranted. Ultrasound investigations of the regional lymph nodes is recommended for patients with locally advanced melanoma and with lymph nodes metastases. CT-scans, MRI and PET/CT are recommended only for stage III patients and it has to be taken into account that these evaluations may have only limited value regarding the prognosis of the patients. In stage IV melanoma, the follow-up scheme should be adapted to the individual needs of the patient.

Cutaneous head and neck melanoma treated with Mohs micrographic surgery

Previous studies show that Mohs micrographic surgery is a viable treatment option for cutaneous melanoma. The head and neck region represents an anatomic location of historically high recurrence/metastasis rates and poor survival rates. Our purpose was to determine the safety and efficacy of Mohs micrographic surgery for the treatment of primary cutaneous melanoma of the head and neck. A consecutive sample of 625 patients referred for treatment of primary cutaneous melanoma of the head and neck comprised the study group. Mean follow-up for the group was 58.0 months. All melanomas were excised using Mohs micrographic surgery and surgical margin examination was performed using frozen section tissue in all cases. After stratification using updated American Joint Commission for Cancer (AJCC) Breslow thickness criteria, the Kaplan-Meier method was used to calculate 5-year local recurrence rates, metastasis rates, and disease specific survival rates. Tumors were then re-stratified by earlier Breslow thickness criteria for comparison to historical controls for local recurrence rates, metastasis rates, and disease-specific survival rates. Recommendations for predetermined excision margins were proposed and were based on the surgical margin widths that achieved complete melanoma removal in 97% of the cases in this study. Mohs micrographic surgery for the treatment of head and neck melanoma achieved five-year local recurrence rates, metastasis rates, and disease specific survival rates comparable to or better than historical controls after Breslow thickness stratification. The size of the surgical margin required for complete excision was significantly related to tumor thickness but not tumor size or specific location. Mohs micrographic surgery is an effective treatment modality for primary cutaneous melanoma, and may contribute to favorable outcomes especially on the head and neck where extensive sub-clinical spread is relatively common.

Surgical margins for resection of primary cutaneous melanoma

The increasing prevalence of melanoma in the United States is alarming. The limited efficacy of adjuvant therapies in successfully treating regional or distant disease underscores the importance of surgical treatment of primary cutaneous melanoma. The historic paradigm of wide margin excision (5 cm) with or with lymphadenectomy has been proven in multiple clinical trials to show no benefit of improved patient survival. Conservative margin resection of melanoma is a procedure of low morbidity that offers statistically identical outcomes and spares the patient excessive surgical efforts. Mohs micrographic surgery may have a role in the management of melanomas in anatomic sites where standard margins may prove difficult to achieve.

Excision margins in the treatment of primary cutaneous melanoma: a systematic review of randomized controlled trials comparing narrow vs wide excision.

The optimal excision margin for primary cutaneous melanoma remains controversial, although several clinical studies have suggested that wide local excision is unnecessary. Wide excision margins do not improve survival in patients with melanoma. To describe the published evidence and determine the effectiveness of wide surgical margins compared with narrow surgical margins. Systematic review of randomized controlled trials that compared narrow margins with wide excision margins for cutaneous melanoma. Randomized controlled trials available by March 2001. The included trials comprised 2406 participants. Surgical excision of melanoma using narrow excision margins compared with excision using wide excision margins. Effect of width of excision margin on melanoma recurrences, disease-free survival, and overall survival. We identified and analyzed 4 randomized controlled trials. All 4 trials failed to demonstrate statistically significant differences in overall survival and disease-free survival when comparing wide vs narrow excision. Peto pooled odds ratio for overall survival was 0.79 (95% confidence interval, 0.61-1.04) and for disease-free survival was 0.89 (95% confidence interval, 0.69-1.13), indicating a statistically nonsignificant improvement with wide excision. Not one of the included studies showed any statistically significant difference between the 2 groups treated with narrow or wide excision margins with regard to recurrences and survival. However, current evidence is not sufficient to address the optimal surgical margins for all melanomas, and further research is required.

Treatment of primary cutaneous melanoma.

ITH A LACK OF SCIENTIFIC data, standard of care for treatment of patients with melanoma at the beginning of the 20th century called for extensive mutilating surgery and/or local amputation of involved body areas. In the mid1900s, aggressive lymph node dissections were popular in an attempt to control metastatic disease despite the lack of scientific data that such procedures did, indeed, affect the survival of patients with melanoma. The treatment of melanoma has changed significantly in the intervening years, and can now be guided by data regarding clinical outcomes. The purpose of this review is to present clinicians with an evidence-based summary of the current literature regarding therapy for primary cutaneous melanoma. Surgical Margins

The vertical dimension in the surgical treatment of cutaneous malignant melanoma – how deep is deep?

The surgical treatment of primary cutaneous malignant melanoma has been an issue of debate throughout the past decades. It is generally accepted that the excised tumor-free surgical margins around the lesion should be proportional to the lesion thickness. However, the issue of adequate thickness of tumor-free margins to be resected in the depth of the lesion has not been addressed as yet. In order to assess the influence of thickness of the tumor-free margins resected under malignant melanoma on patients outcome, we have reviewed 48 patients treated for primary cutaneous malignant melanoma in the Rabin Medical Center in the years 1987–1988. Biopsy specimens and clinical charts were evaluated, the tumor-free margin in depth of the excision was measured and compared with clinical outcome. The study population comprised 21 men and 27 women with an average age of 60.2±15.2 years. Most of the primary melanomas were of intermediate thickness with a mean Breslow thickness of 1.6 mm. During a median follow-up time of 112.8 months, ten (21%) patients developed relapse of their malignancy and 13 patients (27.08%) died. In univariate analysis, the thickness of the tumor-free margin excised under the melanoma was one of seven clinical and pathological variables that showed significant predictive value for patient survival. The 10-year survival rate in patients with tumor-free margins thinner than 3 mm was 50%, compared with 82% in patients with thicker tumor-free margins (P=0.01). In multivariate analysis, these margins remained an independent significant prognostic factor, as were four other variables. Evidence indicating a tendency for local and distant melanoma recurrence in thin excisions with small margin/tumor thickness ratio was detected. The recurrence rate in the group with margin/tumor thickness ratio smaller than 1 was nearly five times higher than the rate in patients with higher ratios (66% vs 14%, P=0.003). In univariate and multivariate analysis of 10 years survival, this ratio also proved to be an independent prognostic factor. In this study we have shown that the tumor-free margins resected under the lesion play an important role in the comprehensive surgical treatment of primary cutaneous melanoma and in determining the clinical outcome of the patients.