Surgical Management Of Melanoma Research Articles

Changes in the Surgical Management of Melanoma and Measures to Implement Change

Cutaneous malignant melanoma has traditionally been a surgically managed disease. Recent clinical trials highlight major shifts in surgical management of this disease, emphasizing a multidisciplinary approach. Clinical trials evaluating the role of completion lymph node dissection (CLND) in the management of sentinel lymph node positive patients and more recent trials evaluating the impact of neoadjuvant immunotherapy on patients presenting with clinically advanced but surgically resectable melanoma are reviewed, as well as ongoing trial evaluating surgical margins. Both DeCOG and MSLT-II trials confirmed that CLND is no longer standard management of the sentinel node positive patient. CLND offers no melanoma-specific survival benefit. Associated surgical morbidity justifies a surveillance and observation approach, combined with adjuvant therapy. Patients presenting with clinically advanced surgically resectable disease are best served by neoadjuvant therapy. This approach demonstrates significantly improved melanoma-specific survival compared to upfront surgery, underscoring the need for rapid adoption by surgeons. Changes in surgical management of melanoma have been dramatic and offer patients improved outcomes though both reduction in the magnitude of surgery, as well as improved disease specific survival for patients with advanced surgically resectable disease.

Surgical procedures in melanoma in 2020: recommended deep and lateral margins, indications for sentinel lymph node biopsy, and complete lymph node dissection.

Introduction Surgery is the main treatment for cutaneous melanoma including the primary melanoma as well as lymph node metastases. The recommended margins have changed over time. Similarly, indications for sentinel lymph node biopsy and complete lymph node dissection are constantly evolving as long as knowledge on the biological behavior of melanomas increases. Evidence acquisition The current guidelines and the most relevant literature was reviewed to provide an update on the existing recommendations for surgical management of melanoma. Evidence synthesis Wide excision margins are evidenced-based but not for all situations. Melanoma in situ requires 0.5-1 cm with increasing evidence for 1 cm particularly those presenting on the head and in the setting of chronic sun damage. Invasive melanomas need 1-2 cm margins, 2 cm for tumors thicker than 2 mm and some large tumors with >1-2 mm thickness and with a lentiginous growth pattern. Lentigo maligna, subungual melanoma, and acral lentiginous melanoma require surgical techniques with complete circumferential peripheral margin assessment. Sentinel lymph node biopsy provides relevant information for melanoma staging. Therefore, it is consistently recommended for melanomas >1-4 mm and highly recommended for melanomas >4 mm, >0.8-1.0 mm or ≤0.8 mm with additional risk factors. Complete lymph node dissection has high morbidity and no impact on survival and is restricted to regional control for clinically detected metastasis. Conclusions Although the trend is to reduce progressively the recommended surgical margins, further evidence is needed to clarify its role in patients' survival. Sentinel lymph node biopsy is important for establishing a prognosis especially upon considering adjuvant therapy; complete lymph node dissection is only relevant for regional disease control.

Internal Pathology Review of Invasive Melanoma: An Academic Institution Experience

BackgroundPrior studies of internal pathology review (IPR) for melanoma have shown that changes in the pathology analysis are common. How these changes impact clinical management of melanoma or how the margin status reports may modify has not been evaluated. Our goal was to determine what changes to staging and surgical management occurred after IPR of newly diagnosed melanomas and to determine how the final surgical pathology report may correlate with the IPR. MethodsA retrospective study was conducted from 2014 to 2016 of newly diagnosed invasive melanomas referred to a single National Comprehensive Cancer Network tertiary care center. ResultsA total of 370 cases met inclusion criteria. The most common feature changed after internal review was mitotic rate, in 155 (41.7%) patients, followed by Breslow depth in 99 (26.9%) patients. Tumor staging was changed in 45 (12.2%) patients. The most common change was a T1a lesion being upgraded to a T1b lesion. These tumor staging changes lead to 38 (10.3%) overall staging differences. A biopsy's deep margin status was changed in 27 (7.3%) patients. Outside hospital reports lacked information about deep margin status in 71 (19.2%) of specimens. Based on the National Comprehensive Cancer Network guidelines, 22 (5.9%) patients had changes in their sentinel lymph node biopsy recommendations and one of these patients had a positive node found on pathology. Of those patients who had changes in the T-stage, 16 (4.3%) of them also had changes in the recommended wide local excision radial margin. ConclusionsIPR of invasive melanoma leads to both changes in staging and the surgical management of melanoma and should remain an important component of care of melanoma patients at a tertiary referral center.

Diagnosis, Evaluation, and Surgical Management of Melanoma

Diagnosis, Evaluation, and Surgical Management of Melanoma

Surgical management of melanoma.

Surgery remains one of the key treatment modalities for melanoma. Wide excision of the primary site with sentinel lymph node biopsy for selected patients has been recognized as the standard surgical approach for patients with early-stage disease. Controversies persist regarding margin width, indications for sentinel lymph node biopsy, and surgical management of regional nodal basins. Additionally, new therapies such as intralesional therapies as well as new systemic therapies are changing the role for surgery in patients with recurrent local-regional as well as metastatic disease. In this chapter, we discuss the current recommendations as well as the topics of debate in the surgical management of melanoma.

Impact of genomics on the surgical management of melanoma.

Although surgery for early-stage melanoma offers the best chance of cure, recent advances in molecular medicine have revolutionized the management of late-stage melanoma, leading to significant improvements in clinical outcomes. Research into the genomic drivers of disease and cancer immunology has not only ushered in a new era of targeted and immune-based therapies for patients with metastatic melanoma, but has also provided new tools for monitoring disease recurrence and selecting therapeutic strategies. These advances present new opportunities and challenges to the surgeon treating patients with melanoma. The literature was reviewed to evaluate diagnostic and therapeutic advances in the management of cutaneous melanoma, and to highlight the impact of these advances on surgical decision-making. Genomic testing is not required in the surgical management of primary melanoma, although it can provide useful information in some situations. Circulating nucleic acids from melanoma cells can be detected in peripheral blood to predict disease recurrence before it manifests clinically, but validation is required before routine clinical application. BRAF mutation testing is the standard of care for all patients with advanced disease to guide therapy, including the planning of surgery in adjuvant and neoadjuvant settings. Surgery remains central for managing primary melanoma, and is an important element of integrated multidisciplinary care in advanced disease, particularly for patients with resectable metastases. The field will undergo further change as clinical trials address the relationships between surgery, radiotherapy and systemic therapy for patients with high-risk, early-stage and advanced melanoma.

Lymph node retrieval rates in melanoma: a quality assessment parameter.

Regional lymph node dissection (rlnd) for melanoma with nodal metastasis is a specialized procedure that is associated with improved disease-specific survival in selected patients. Furthermore, there is evidence that a higher lymph node retrieval rate (lnrr) is associated with improved local control. Currently, no consensus has been reached on the definition of an adequate lnrr. A minimum lnrr has been proposed as a quality assessment parameter that has to be validated. We conducted a retrospective cohort analysis at the Princess Margaret Cancer Centre (University Health Network, Toronto, ON). The lnrrs for all patients who underwent rlnd for malignant cutaneous melanoma during 2000-2010 were recorded. Indications for rlnd were a positive sentinel lymph node biopsy or clinical lymphadenopathy (palpable or radiologically detected). Of the 207 identified rlnds, 146 (70.5%) were subsequent to a positive sentinel lymph node biopsy, and 61 (29.5%) were performed for clinical lymphadenopathy. The median lnrr was 24 nodes (range: 9-47 nodes; 10th percentile: 14 nodes) for axillary rlnd, 12 nodes (range: 5-30 nodes; 10th percentile: 8 nodes) for inguinal rlnd, and 16 nodes (range: 10-21 nodes; 10th percentile: 11 nodes) for ilioinguinal rlnd. The results were similar when comparing patients with positive sentinel lymph nodes and those with clinical lymphadenopathy, and the same surgical techniques were used in both groups. The lnrrs at our institution are similar to rates reported at other tertiary-care melanoma centres. A minimum acceptable lnrr can be considered a quality assessment parameter in the surgical management of melanoma with nodal metastasis.

Surgical Management of Melanoma.

The surgical management of melanoma has undergone considerable changes over the past several decades, as new strategies and treatments have become available. Surgeons play a pivotal role in all aspects of melanoma care: diagnostic, curative, and palliative. There is a high potential for cure in patients with early-stage melanoma and the selection of an appropriate operation is very important for this reason. Staging the nodal basin has become widespread since the adoption of sentinel lymph node biopsy (SLNB) for the management of melanoma. This operation provides the best prognostic information that is currently available for patients with melanoma. The surgeon plays a central role in the palliation of symptoms resulting from nodal disease and metastases, as melanoma has a propensity to spread to almost any site in the body.

Surgical Management of Melanoma and Other Skin Cancers

The prevalence of malignant skin cancers has increased significantly over the past several years. Approximately 1.2 million cases of non-melanoma skin cancer are diagnosed per year. More alarming, up to 80,000 cases of melanoma are diagnosed per year, an incidence that has been steadily increasing, with a lifetime risk of 1 in 50 for the development of melanoma. The disturbing increase in the incidence of both non-melanoma skin cancer and melanoma can largely be attributed to the social attitude toward sun exposure. The clinical assessment and management of skin lesions can be challenging. This review describes the assessment process, including thorough history and examination; the need for possible biopsy; and excision criteria. Specific types of skin cancer are distinguished and include basal cell carcinoma; squamous cell carcinoma; and melanoma; and for each type the incidence; epidemiology; histologic subtypes; diagnosis; and both surgical and non-surgical treatments are provided. Stages I-IV of melanoma are detailed, with prognostic factors described. Surgical treatment for stages I and II include description of the margins of excision and sentinel lymph node biopsy. The surgical treatment of Stage III melanoma further includes therapeutic lymph node dissection and isolated limb perfusion. Adjuvant therapies are also presented and include radiotherapy and chemotherapy. The additional treatment of metastasectomy for Stage IV melanoma is described. For both Stage III and IV melanoma, the study of vaccines to host immune cells is reported. For Stage IV melanoma, the text also describes immunotherapy treatment. Operative procedures specific to superficial and deep groin dissections are outlined. This review contains 9 figures, 3 tables, and 96 references.

Increasing the Efficacy of SLNB in Cases of Malignant Melanoma Located in Close Proximity to the Lymphatic Basin

Background. Being predictive of the entire nodal bed, sentinel lymph node biopsy (SLNB) is invaluable in the surgical management of melanoma. Although the concept is simple, sentinel lymph node (SLN) identification and removal can be technically challenging. Methods. A total of 102 consecutive patients have undergone SLNB in the Division of Plastic and Reconstructive Surgery of Soroka University Medical Center from 2009 to 2012. Patients have undergone SLNB using a radioactive tracer and blue stain in order to identify the SLN. Although SLNB usually precedes the wide excision of melanoma, primary lesions in close proximity (<10 cm) to the lymph basin require wide excision before beginning the SLN quest. Results. All pathology reports confirmed the excision of lymph nodes. Conclusions. When treating MM in close proximity to the lymph basin, changing the sequence of the SLNB procedure seems to increase the efficacy of the method.

Surgical Management of Melanoma

Historically, the surgical management for melanoma was ossified for nearly 50 years with the standard of care being wide local excisions with 5-cm margins. Several clinical studies have now brought to light new data that have enabled academic groups such as the American Joint Committee on Cancer and the National Comprehensive Cancer Network to update surgical guidelines reliant on evidence with long-term follow-up. In addition, basic research at the bench has dispelled the myth that all melanomas are genetically identical and behave in a homogeneous way on the basis of the Breslow depth of the original tumor. It is now known that although all melanomas arise from the melanocyte, melanoma encompasses a variety of cancers that are genetically distinct with variable predicted outcomes often associated with the anatomic location of the tumor. This article cites the evidence on which the current surgical guidelines are based and it addresses some of the ongoing controversies regarding the surgical management of the various types of melanoma.

Disparities in the management of melanoma in elderly patients: An analysis of patients from the National Cancer Database.

8522 Background: Disparities in the surgical management of melanoma in elderly patients has been reported, but the magnitude and distribution of these disparities is ill-defined. Methods: Using the...

Variation in the Depth of Excision of Melanoma: A Survey of US Physicians

To assess current practices and recommendations of US physicians regarding depth of excision for melanomas of varying histologic thicknesses. A 2-page, 13-question survey of depth of excision practices for the treatment of melanoma was developed and distributed. Both private and academic settings. A total of 1184 US physicians (1000 dermatologists and 184 melanoma specialists) were sent the survey. The 184 melanoma specialists included dermatologists, oncologists, and surgeons working in pigmented lesion clinics. Depth of excision practices reported for melanomas of varying histologic thicknesses and comparison of treating physician groups. Results were tabulated, and descriptive frequencies were used to describe demographics and survey responses. The final study analysis included 498 completed surveys. The overall response rate was 45% (498 of 1097 [1184 total respondents - 87 ineligibles]). The response rate for the specialists was 63% (115 of 183 [184 total respondents - 1 ineligible]), and for nonspecialist dermatologists it was 43% (383 of 892 [1000 total respondents - 108 ineligibles]). Specialists were more likely to practice in an urban setting than were nonspecialist dermatologists (78% vs 46%) (P < .001). Fifty-eight percent of nonspecialist dermatologists reported more than 400 patient visits per month compared with only 16% of specialists (P < .001). While specialists reported fewer patient visits per month, 51% reported diagnosing over 20 invasive melanomas in the previous year compared with 11% of nonspecialist dermatologists. There was no significant difference in excision depth reported among the specialties for melanoma in situ (P = .15). For invasive melanoma, significant differences were observed among treating groups, with the greatest incongruence reported for thin invasive melanoma (<0.50 mm, P = .02; 0.50-0.75 mm, P < .001; and 0.76-1.00 mm, P < .001). Specialist nondermatologists consistently reported excising more deeply than specialist dermatologists and nonspecialist dermatologists. More specialist nondermatologists report excising to the fascia for thin invasive melanoma than do both specialist and nonspecialist dermatologists. For thicker melanomas (>1.00 mm), differences in excision depths among treating physician groups decreased: most physicians in each group reported excising to the fascia. There is considerable variation among physician groups with regard to depth of excision practices for the treatment of melanoma. Given the current lack of clinical data available, studies assessing depth of excision and patient outcomes are needed to better define our surgical management of melanoma.

Surgical Management of Melanoma in Situ on Chronically Sun-Damaged Skin

Lentigo maligna (LM) commonly presents as a slow-growing pigmented macular lesion in chronically sun-damaged skin and may progress to invasive melanoma. Many regard it as a subtype of melanoma in situ (MIS), and surgical excision remains the preferred treatment, but standard 5-mm surgical margins recommended for typical MIS are often insufficient for LM due to its indistinct borders both clinically and histologically. A search of the literature was conducted to review specialized surgical techniques for the treatment of LM, focusing on methods that employ total peripheral margin assessment prior to definitive closure, using either frozen or permanent histologic sections. Many investigators have reported surgical modalities utilizing permanent sections for margin control, including variations of the "square" procedure and "perimeter" technique. Recurrence rates are low with these methods, but only short-term data have been reported. Similarly, several studies have demonstrated the efficacy of Mohs micrographic surgery (MMS) for treatment of MIS, with recurrence rates generally less than 1% over 3 to 5 years of follow-up. Many investigators have had success with immunohistochemical stains to identify melanocytes on frozen sections, aiding margin assessment in MMS. Compared to standard excision, methods that employ surgical margin control offer superior cure rates for LM and should be utilized when available. Total peripheral margin assessment using staged excisions and permanent sections is a simple and effective alternative to MMS for institutions that lack the resources for intraoperative frozen section analysis.

Surgical Therapy of Cutaneous Melanoma

For most solid tumors therapy has evolved from surgery alone to a multidisciplinary approach. Malignant melanoma remains an exception, with surgery maintaining the principal role not only for treatment of the primary lesion but also staging and the management of advanced disease. The surgical management of melanoma has evolved over the years, resulting in a substantial decrease in the morbidity associated with treatment without a compromise in outcome. This article will review the changes that have occurred leading to the current surgical approach to melanoma, the evidence behind these recommendations, and new questions that need to be addressed.

Current surgical management of melanoma

The surgical management of melanoma has changed dramatically over the last few decades. Through the development and conduction of well-designed, prospective, randomized trials, we have been able to refine the way that we surgically manage patients with melanoma. Indeed, many important issues have been addressed through such trials: the proper surgical margins for the primary melanoma, utility of the elective lymph node dissection and the role for selective lymphadenectomy, to name a few. This review will also discuss what we have learned from past clinical trials and address several issues with regards to where we are going in the future.

The treatment of melanoma with an emphasis on immunotherapeutic strategies

Melanoma continues to be one of the most difficult to treat of all solid tumors. Many new advances have been made in the surgical management of melanoma, including new guidelines for margins of excision, as well as sentinel node biopsy for the diagnosis of lymph node micrometastases. The search continues for an effective adjuvant melanoma treatment that can prevent local and distant recurrences. Melanoma is one of the most immunogenic of all tumors, and several clinical trials testing the immunotherapy of melanoma have been conducted, including trials in interferon, interleukin-2, and melanoma vaccines. Here we discuss many of the recent clinical trials in the surgical management of melanoma, in addition to the advances that have been made in the field of immunotherapy. A new second-generation melanoma vaccine, DC-MelVac (patent # 11221/5), has recently been granted FDA approval for Phase I clinical trials and will be introduced in this review.

Current concepts in the management of patients with melanoma.

Melanoma is a significant health problem. Despite public education and free cancer screenings, the incidence and mortality of melanoma continues to rise; however, many currently diagnosed melanomas are thin lesions, suggesting that education and awareness is having an impact. In addition, there are still subsets of patients who need increased surveillance in order to increase their survival. Although large congenital nevi may be precursors of melanoma, small and medium congenital nevi have an insignificant risk for melanoma development. Large congenital nevi, which are axial in location, appear to be more likely to develop melanoma and are associated with melanocytosis and melanoma of the CNS, both of which portend a poor prognosis. Recently, the recommended margins of excision have become more conservative so that many of the surgical defects can be closed primarily. Lymphoscintigraphy and sentinel node biopsy have replaced elective node dissections, thus decreasing the morbidity associated with the surgical management of melanoma. Although controversy still exists as to whether or not sentinel lymph node biopsy alters a patient's prognosis, it has been shown to be a powerful prognostic indicator. Although most melanomas are managed by routine surgical excision, other modalities are sometimes employed. For example, cryosurgery or radiation therapy may be indicated in the frail, elderly individual with a large facial lentigo maligna. Mohs surgery is the treatment of choice for head and neck melanomas and those located in areas where maximum preservation of tissue is required and for desmoplastic and acral lentiginous melanomas. Much more work remains in the area of adjuvant therapy, chemotherapy, and immunotherapy. Dacarbazine remains the drug of choice in disseminated melanoma, but remissions are usually short lived. Interleukin and biochemotherapy has yielded good results but the percentage benefiting is small. Although high dose interferon increases disease-free and overall survival in some patients, it remains a controversial drug which is not easily tolerated. In the new staging system for melanoma, ulceration is second only to Breslow's thickness. In transit (satellite) lesions have also been included in this new system. The new system also recognizes that patients with only microscopic metastatic nodal disease fare better than patients with clinically enlarged metastatic nodes and that it is the number of nodes involved with metastases, not their size, that determines the patient's prognosis. Except for lesions <1mm thick, the Clark's level of invasion has been de-emphasized.

MALIGNANT MELANOMA

The incidence of malignant melanoma is increasing at a rate greater than any other cancer occurring in humans. In this era of managed care, patients with a suspicious pigmented lesion may first present to their primary care physician for evaluation. Therefore it is mandatory that the primary care physician be capable of distinguishing between benign and malignant pigmented lesions, know how to evaluate such patients, and know when to refer patients with suspicious or malignant pigmented lesions. Surgical removal remains the mainstay of treatment for patients with melanoma. Thus, to increase the cure rate for melanoma, both the public and nondermatologists need to be educated regarding the prevention and early detection of melanoma. Only in this way can the diagnosis of melanoma be made early before deep invasion has occurred and the patient placed at risk for systemic spread. In recent years, the surgical management of melanoma has become more conservative and rational. Limb amputation, arbitrary 5-cm margins of excision, and elective lymph node dissections are no longer performed. The recommended margins of excision are now based on objective pathologic and clinical data and are more conservative, and the sentinel node biopsy is now used to determine which high-risk patients should undergo a formal lymph node dissection. Although encouraging results are being seen with immunotherapy protocols, to date the only adjunctive therapy shown to increase survival in patients at high risk for systemic spread is alpha-interferon. With this drug, the improved survival is modest at best; it is expensive and a minority of patients can tolerate it in the doses recommended. Although response rates of 20% are seen with chemotherapy in patients with disseminated disease, these responses are short-lived, and there is no associated increased survival. Except for lentigo maligna, radiation therapy, even when its delivery is modified, still is useful only as an adjunct to surgery or for palliation.

The John Wayne Clinical Research Lecture. Surgical management of melanoma: results of prospective randomized trials.

The John Wayne Clinical Research Lecture. Surgical management of melanoma: results of prospective randomized trials.