Search

Background: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes., Methods: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database., Results: The study included 89 NAST-treated patients and 79 upfront surgery-treated patients. The rate of postoperative complications did not differ between the NAST- and upfront surgery-treated patients (55% vs. 51%; p = 0.643), and steroid treatment for drug toxicity did not influence the complication rate (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.4-3; p = 0.826). No significant differences in postoperative morbidity were observed in terms of seroma (23% vs. 11%; p = 0.570) or lymphedema (36% vs. 51%; p = 0.550). The rate of achieving a textbook outcome was comparable for the two groups (61% vs. 57%; p = 0.641)., Conclusions: The surgical outcomes after lymph node dissections were comparable between the patients who received NAST and those who had upfront surgery, indicating that surgery can be safely performed after NAST with TT or ICI for stage III melanoma., (© 2024. The Author(s).)

Background: Predicting which patients with American Joint Committee on Cancer (AJCC) T1-T2 melanomas will have a positive sentinel lymph node (SLN) is challenging. Melanoma Institute Australia (MIA) developed an internationally validated SLN metastatic risk calculator. This study evaluated the nomogram's impact on T1-T2 melanoma patient management at MIA., Methods: SLN biopsy (SLNB) rates were compared for the pre- and post-nomogram periods of 1 July 2018-30 June 2019 and 1 August 2020-31 July 2021, respectively., Results: Overall, 850 patients were identified (pre-nomogram, 383; post-nomogram, 467). SLNB was performed in 29.0% of patients in the pre-nomogram group and 34.5% in the post-nomogram group (p = 0.091). The overall positivity rate was 16.2% in the pre-nomogram group and 14.9% in the post-nomogram group (p = 0.223). SLNB was performed less frequently in T1a melanoma patients in the pre-nomogram group (1.1%, n = 2/177) than in the post-nomogram group (8.6%, n = 17/198) [p ≤ 0.001]. This increase was particularly for melanomas with a risk score ≥ 5%, with an SLN positivity rate of 11.8% in the post-nomogram group (p = 0.004) compared with zero. For T1b melanomas with a risk score of > 10%, the SLNB rate was 40.0% (8/20) pre-nomogram and 75.0% (12/16) post-nomogram (p = 0.049)., Conclusions: In this specialized center, the SLN risk calculator appears to influence practice for melanomas previously considered low risk for metastasis, with increased use of SLNB for T1a and higher-risk T1b melanomas. Further evaluation is required across broader practice settings. Melanoma management guidelines could be updated to incorporate the availability of nomograms to better select patients for SLNB than previous criteria., (© 2024. The Author(s).)

Purpose: In sentinel node-positive (SN+ve) melanoma patients, active surveillance with regular ultrasound examination of the node field has become standard, rather than completion lymph node dissection (CLND). A proportion of these patients now receive adjuvant systemic therapy and have routine cross-sectional imaging (computed tomography [CT] or positron emission tomography [PET]/CT). The role of concurrent ultrasound (US) surveillance in these patients is unclear. The purpose of our study was to describe the modality of detection of nodal recurrence in SN+ve node fields., Methods: SN+ve melanoma patients who did not undergo CLND treated at a single institution from January 1, 2016 to December 31, 2020 were included., Results: A total of 225 SN+ve patients with a median follow-up of 23 months were included. Of these, 119 (53%) received adjuvant systemic therapy. Eighty (36%) developed a recurrence at any site; 24 (11%) recurred first in the SN+ve field, of which 12 (5%) were confirmed node field recurrence only at 2 months follow-up. The nodal recurrences were first detected by ultrasound in seven (3%), CT in seven (3%), and PET/CT in seven (3%) patients. All nodal recurrences evident on US were also evident on PET/CT and vice versa., Conclusions: The high rate of recurrences outside the node field and the identification of all US-detected nodal recurrences on concurrent cross-sectional imaging modalities suggest that routine concurrent ultrasound surveillance of the node-positive field may be unnecessary for SN+ve melanoma patients having routine cross-sectional imaging., (© 2023. The Author(s).)

Background: The clinical significance of sentinel nodes (SNs) in the triangular intermuscular space (TIS) of patients with melanoma is poorly understood. This study aimed to determine their incidence and positivity rate, and to report their management and patient outcomes., Methods: This was a single-institution retrospective cohort study of patients with unilateral or bilateral TIS SNs on lymphoscintigraphy treated between 1992 and 2017. Recurrence-free survival was analyzed., Results: Lymphoscintigraphy identified TIS SNs in 266 patients. They were bilateral in 17 patients. Of the 2296 patients with a melanoma on the upper back, 259 (11%) had TIS SNs. Procurement of SNs was not attempted in 122 (43%) of the 283 cases and failed in 11 cases (7%). An SN was successfully retrieved from the TIS in 145 patients (53%) and contained metastasis in 18 of 150 TIS SNs. This was the only positive SN in 12 patients (8%), upstaging all of them. Of the 18 patients with a positive SN in the TIS, 9 (50%) underwent completion axillary lymph node dissection, but no additional involved nodes were found in any of these patients. Recurrence in the TIS was observed in six patients (5%), none of whom had their TIS SN surgically pursued previously., Conclusions: Lymphoscintigraphy showed TIS SNs in 11% of patients with melanomas on their upper back. In such cases, retrieval of TIS SNs is required for accurate staging and to minimize the risk of TIS recurrence., (© 2022. Society of Surgical Oncology.)

Background: In-transit metastases (ITMs) affect approximately 4% of patients with cutaneous melanoma. This study sought to identify clinical and pathological characteristics that predict further recurrence and survival following resection of ITMs., Patients and Methods: Patients (n = 573) who underwent surgical resection of their first presentation of ITM following previous surgical treatment of an American Joint Committee on Cancer (AJCC) stage I-II melanoma between 1969 and 2017 were identified from an institutional database. Clinicopathological predictors of patterns of recurrence and survival following ITM resection were sought., Results: The median time of ITM development was 2.4 years after primary melanoma resection. ITMs were most frequently located on the lower limb (51.0%). The most common melanoma subtype associated with ITM development was nodular melanoma (44.1%). After surgical resection of a first ITM, 65.4% of patients experienced recurrent disease. Most recurrences were locoregional (44.7%), with distant metastasis occurring in 23.9% of patients. Lower limb ITMs were more frequently associated with subsequent ITMs [odds ratio (OR) 2.41, p = 0.0002], and the lowest risk of distant metastasis (p < 0.0001) compared with other primary sites. Primary melanomas and ITM on head and neck, as well as the presence of ulceration, were associated with worse survival., Conclusions: Recurrence after surgical resection of a first ITM was common. Patterns of recurrence differed according to anatomical site; further ITM recurrences were more likely for lower limb ITMs, which were also associated with longer distant recurrence-free survival. Distant metastasis was more common for ITM on the head and neck, with worse survival., (© 2022. Crown.)

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance., (© 2022. Society of Surgical Oncology.)

Background: Metastasectomy for selected patients with melanoma was associated with improved survival in the era before effective systemic therapy. Emerging evidence shows that these benefits persist even in this era of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy. This study aimed to evaluate the outcomes of salvage metastasectomy after failure of systemic therapy., Methods: Stage 3 or 4 melanoma patients with extracranial disease progression after at least 4 weeks of systemic treatment between 2009 and 2020 were identified and categorized as resected to no evidence of disease (NED), non-progressive residual disease (NPRD), or progressive residual disease (PRD). Systemic therapy was stratified into BRAF-targeted therapy, immune checkpoint inhibitor immunotherapy, or both. The end points of overall survival (OS), progression-free survival (PFS), and locoregional disease control (LRC) were assessed using Kaplan-Meier curves. Uni- and multivariable Cox regression procedures were used to examine factors associated with OS, PFS and LRC., Results: The study enrolled 190 patients. Among all the patients, the 5-year OS from metastatectomy was 52%, the 3-year PFS was 21%, and the 5-year LRC was 61%. After resection to NED, NPRD, and PRD, the 5-year OS values were 69%, 62% and 8%, respectively. Fewer lines of preoperative therapy, use of preoperative immunotherapy, and resection to NED were predictors of improved OS. After resection to NED, NPRD, and PRD, the 3-year PFS values were 23%, 24% and 10%, and the 5-year LRC values were 61%, 72% and 34%, respectively., Conclusions: Salvage metastasectomy was associated with durable survival and disease control, particularly after resection to NED, preoperative immunotherapy, and fewer lines of preoperative systemic therapy., (© 2021. Society of Surgical Oncology.)

Since the advent of effective systemic therapy, quantum changes have occurred in the multidisciplinary management strategies used for patients with American Joint Committee on Cancer stages 3 and 4 melanoma. For high-risk stage 3 patients, neoadjuvant immune checkpoint blockade (ICB) and targeted therapies present a promising novel approach to improving survival outcomes. In particular, patients who respond to ICB have an excellent prognosis, and clinical trials are ongoing to investigate whether those with a pathologic complete response (pCR) or near-pCR in a single node may avoid therapeutic lymph node dissection and adjuvant therapy. Toxicities currently are acceptably low, but when toxic events occur, they can have an enduring impact on a patient's quality of life. To date, nearly all patients evaluated after treatment with neoadjuvant dabrafenib plus trametinib have some clinical and pathologic response. Patients who achieve pCR have improved prognosis, but pCR is not as reliable a predictor of improved outcome as pCR or near-pCR after neoadjuvant ICB. Ongoing studies should ideally be coordinated through the International Neoadjuvant Melanoma Consortium to ensure maximal efficiency at improving outcomes for melanoma patients.

Introduction: Wide surgical excision is the standard treatment for localized primary cutaneous melanomas, with a narrow histologic margin associated with an increased risk of local recurrence. The correlation between surgical and histologic margins is poorly documented in the literature., Methods: An audit was performed to (1) document the shrinkage of formalin-fixed specimens, and (2) use a precisely measured surgical margin in vivo to predict the histologic margin. For patients presenting for wide excision of melanomas and other malignant skin tumors, measured surgical margin, in vivo and ex vivo specimen width, and histologic margins after formalin fixation were recorded. The effects of clinicopathologic characteristics, including age, sex, body mass index (BMI), tumor type, anatomic site, and presence of visible tumor in predicting specimen shrinkage and histologic margin were assessed., Results: In total, 252 specimens were evaluated. When compared with measured width in vivo, the formalin-fixed specimens showed a mean shrinkage of 14% (R 2  = 0.98), regardless of patient age, sex, BMI, or site of the lesion. The measured surgical margin was not a strong predictor of the histologic margin, with a high degree of variability (R 2  = 0.55) not explained by patient factors, tumor subtype, or presence of visible tumor at the time of excision (p > 0.05)., Conclusions: A consistent 14% shrinkage rate of wide excision specimens was found across all patients and excision sites, and we propose a clinically useful 15% correction factor that will account for fixation and shrinkage of cutaneous excision specimens. Excision margins measured by the surgeon were a poor predictor of the histologic margins.

In the original article John F. Thompson was inadvertently omitted as an author. The author list is updated as shown in this correction.

Background: There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma > 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma > 1 mm in BT., Methods: This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma > 1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients' QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation., Results: Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p < 0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p = 0.036). After 12 months' follow-up, no differences were noted in QoL between groups., Discussion: This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.

Background: Sentinel node biopsy (SNB) is commonly performed in contemporary melanoma management, however there is a paucity of long-term quality of life (QoL) estimates required for economic evaluation of this treatment., Methods: A single-center, prospective, cross-sectional study of adults with American Joint Committee on Cancer stage I/II/IIIA melanoma of the limbs, trunk, or neck who had undergone wide excision and SNB, but not complete regional node dissection, was undertaken. Limb volume was measured using perometry, with lymphedema defined as a ≥10% volume increase in the ipsilateral limb compared with the contralateral limb. The Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire measured QoL. Associations between patient and treatment characteristics were assessed using linear regression., Results: Among 694 patients (median time from SNB of 37 months), 14 (2%) had objectively measured lymphedema (i.e. an increase in limb volume of ≥10%). Of 687 stage I/II patients with complete QoL data, the mean weighted QoL was 0.745 (standard deviation 0.04) on a 0-1 scale (i.e. death to full health). In multivariable analysis, weighted QoL was 0.0004 higher for each year of increasing age (p = 0.001); 0.011 lower for females (p = 0.001), 0.018 lower following post-SNB limb trauma (p = 0.002); 0.252 lower for patients who perceived a large increase in limb size (p = 0.015); and 0.027 lower with self-reported difficulty in walking, running, or climbing stairs (p = 0.043)., Conclusions: Our data suggest that very few patients treated at our institution had lymphedema in the long-term following SNB, with weighted QoL strongly associated with perceived rather than actual changes in limb size.

Background: Inconsistent data suggests extranodal spread (ENS) is an adverse prognostic factor in Stage III melanoma patients but it remains contentious. By rigorously matching cohorts, this study sought to clarify associations with recurrence and survival., Methods: Melanoma patients with lymph node metastases (AJCC Stage III), with or without ENS, sub-classified on the basis of known (MKP) or unknown primary (MUP), were identified from a single institution prospective database. Of 725 ENS patients identified, 567 were able to be precisely matched 1:1 with a non-ENS cohort. Clinicopathologic factors were analyzed for associations with outcome., Results: There were 481 MKP and 86 MUP patients in each cohort. ENS, compared to non-ENS, was an independent predictor of worse melanoma specific survival (MSS) (HR = 1.71, 95% CI = 1.39-2.11, P < 0.0001) with median MSS 56.4 versus 175.2 months, P < 0.001; worse disease free survival (DFS) (HR = 1.16, 95%CI = 1.00-1.34, P = 0.044) with median DFS 15.6 versus 21.5 months, P = 0.009; and worse post-recurrence survival (PRS) (HR = 1.66, 95%CI = 1.37-2.02, P < 0.0001) with median PRS 20.1 versus 51.1 months, P < 0.001. ENS was also associated with reduced time to distant recurrence (Distant Disease Free Survival [DDFS]) (HR = 2.00, 95% CI = 1.24-3.24, P = 0.0047), however median time to distant recurrence not reached within the study time period., Conclusions: ENS represents a significant independent predictor of worse MSS, DFS, PRS and DDFS in Stage III melanoma patients. ENS should be considered in the stratification of patients in adjuvant therapy trials.

Objective: This study was designed to determine the minimum safe pathologic excision margin for primary cutaneous melanomas 1.01-2.00-mm thick (T2) and to identify prognostic factors that influence survival in these patients., Background: Several studies have shown previously that "narrow" clinical excision margins (1-2 cm in vivo) are as safe as "wide" excision margins (4-5 cm) for management of primary T2 melanomas. However, pathologic margins are likely to be a better predictor of recurrence than clinical margins., Methods: Clinicopathologic and follow-up data for 2131 T2 melanoma patients treated at Melanoma Institute Australia between January 1992 and May 2012 were analyzed., Results: Of the 2131 patients, those who had a pathologic excision margin of <8 mm (equivalent to 1 cm in vivo) had poorer prognosis in terms of disease-free survival compared with the 8-16-mm group (equivalent to 1-2 cm in vivo; P = 0.044). When comparing 8-mm with 16-mm pathologic margins, no differences were observed in any of the survival outcomes. Only the deep margin proved to be an independent predictor of local and in-transit recurrence-free survival (P = 0.003) in all excision margin categories. Pathologic excision margins <8 mm were associated with worse regional node recurrence-free survival and distant recurrence-free survival compared with margins ≥8 mm (P = 0.049 and P = 0.045; respectively). However, these results failed to translate into a statistically significant difference in melanoma-specific survival., Conclusions: The results of this study suggest that if a peripheral/radial pathologic excision margin for a T2 primary cutaneous melanoma is <8 mm consideration should be given to performing a wider excision.

Background: At presentation, most primary cutaneous melanomas are "thin" (Breslow thickness ≤1 mm, designated T1 in the American Joint Committee on Cancer staging system) and local recurrence (LR) is rare. Most current management guidelines recommend 1 cm surgical excision margins for T1 melanomas, but evidence to support this recommendation is sparse. We sought to identify clinical and pathologic factors associated with LR in patients with T1 melanomas that might guide primary tumor management., Methods: From a large, prospectively collected, single-institution database, patients with primary cutaneous melanomas ≤1 mm thick diagnosed between 1970 and 2011 who developed LR were identified and matched with controls. Clinical and pathologic parameters were analyzed for their association with LR., Results: From 11,290 primary melanomas ≤1 mm thick, 176 (1.56 %) cases with LR were identified and 176 controls (without LR) were selected. LR occurred after a median time of 37 months (range 3-306 months) and was associated with narrower excision margins (hazard ratio = 0.95, 95 % confidence interval 0.92-0.98, p = 0.001), desmoplastic, acral, and lentigo maligna melanoma subtypes (p = 0.008), and melanomas composed predominantly of spindle cells (p = 0.005). However, Breslow thickness, Clark level, ulceration, mitotic rate, regression, and lymphovascular invasion were not., Conclusions: LR was associated with <8 mm histologic excision margins (corresponding to <1 cm margins in vivo) and desmoplastic, acral, and lentigo maligna melanoma subtypes. This study provides evidence that a ≥1 cm clinical excision margin for thin (T1) primary melanomas reduces the risk of LR.

Purpose: To analyze a large, single-institution database to further understanding of melanoma in-transit metastases (ITM) with regard to incidence, prognosis, and the role of lymphadenectomy., Methods: A total of 11,614 patients with single primary cutaneous melanomas were treated at Melanoma Institute Australia between January 1994 and December 2009. Of these, 505 developed ITM. Clinicopathologic characteristics, sentinel node (SN) status, patterns of disease progression, and outcomes were analyzed., Results: In the 505 patients with ITM, the median primary tumor thickness was 2.95 mm, and 39.4 % were ulcerated. The ITM rates for patients with primary melanomas <1 or ≥1 mm in size and in those who underwent sentinel node biopsy were 0.4, 7.8, and 7.2 %, respectively. The ITM rates for SN-positive and SN-negative patients were 21.6 and 4.7 %, respectively. The median time from primary diagnosis to the development of ITM was 17.9 months. After ITM diagnosis, the median survival time was 19.9 months, 5-year survival was 32.8 %, and 10-year survival was 27.5 %. After ITM diagnosis, primary tumor site (head/neck, trunk) and ulceration were predictors of poorer survival. Five-year survival from the time of ITM ranged from 47.9 % for nonulcerated limb primary lesions to only 13.6 % for ulcerated trunk primary lesions. Elective lymph node dissection in clinically node-negative patients with ITM did not significantly alter overall survival., Conclusions: This large study demonstrates that the diagnosis of melanoma ITM carries serious adverse prognostic implications and will assist in improving the accuracy of staging and prognostic estimates as well as treatment in these patients.

Background: Primary cutaneous head and neck melanomas (HNM) are reported to be associated with a higher incidence of brain metastasis than trunk and limb melanomas (TLM). In this study, the incidence of brain metastases in patients with HNM and risk factors for the development of brain metastases were analyzed., Methods: From a large, prospectively-collected database, 1,687 HNM patients and 8,793 TLM patients who presented with American Joint Committee on Cancer (AJCC) stage I and II disease were identified. Survival was assessed using the Kaplan-Meier method and multivariate Cox regression analysis. Independent risk factors were determined by binary logistic regression analysis., Results: The incidence of brain metastases 5 years after diagnosis of HNM was 6.7 % compared with 4.7 % for brain metastases from TLM (p = 0.003). Patients with scalp melanomas were most likely to develop brain metastases (12.7 %). Independent risk factors for brain metastasis in patients with HNM were Breslow thickness, ulceration, and scalp location., Conclusion: Patients with primary scalp melanomas had a much higher incidence of brain metastasis than patients with melanomas on other head and neck sites, who in turn had a higher incidence than patients with melanomas on sites elsewhere on the body. More intensive monitoring of patients with scalp melanomas, who are at particularly high risk of brain metastasis, might lead to earlier discovery of metastatic disease in the brain, offering the prospect of earlier intervention and better outcomes.

Background: Several reports in the literature suggest a difference in outcome between melanoma patients with macroscopic (clinically palpable) nodal disease from an unknown primary (MUP) and a known primary (MKP). The purpose of this study was to compare the outcomes for MUP and MKP patients after therapeutic lymph node dissection (TLND) for macroscopic nodal disease., Methods: From a large, prospective, single-institution database, the details of melanoma patients who first presented with macroscopic nodal disease and underwent TLND between 1971 and 2010 were extracted and analyzed., Results: There were 287 MUP patients and 264 MKP patients who fulfilled the study selection criteria. MUP patients had better disease-free, distant metastasis-free, and melanoma-specific survival after their TLND than MKP patients (all p < 0.001). Extranodal melanoma extension, >3 positive lymph nodes, and administration of adjuvant radiotherapy were all independent predictors of reduced disease-free and melanoma-specific survival (all p < 0.05). MUP patients also had a better prognosis than MKP patients whose primary melanoma had regression (p = 0.001)., Conclusions: The occurrence and improved outcome of MUP patients may be due to immune-induced total regression of the primary tumor and better immunologic prevention or control of distant metastatic disease. Alternatively, in some MUP patients, melanoma may not be metastatic but may originate de novo from nevus cells in lymph nodes, with the more favorable prognosis attributable to their primary nodal origin and complete surgical resection.

Background: Melanoma patients with lymph node (LN) metastases have variable survival after lymphadenectomy. This study investigates whether lymphadenectomy at different times in the course of disease progression influences disease-free survival (DFS; time from primary diagnosis to first recurrence after lymphadenectomy), post recurrence survival (PRS; time from first recurrence after lymphadenectomy to death), and overall survival (OS; time from diagnosis to death)., Methods: Between 1992 and 2010, a total of 1,704 patients underwent lymphadenectomy; 502 underwent immediate completion lymphadenectomy (ICL) after positive sentinel node biopsy (SNB), 214 had delayed completion lymphadenectomy (DCL) for regional recurrence after positive SNB with no ICL or after an earlier false-negative SNB, 709 had no SNB and later required delayed therapeutic lymphadenectomy (DTL) for clinically evident metastasis, and 279 had immediate therapeutic lymphadenectomy (ITL) for clinically positive LNs at primary melanoma diagnosis., Results: Median DFS for ICL, DCL, DTL, and ITL was 68, 48, 82, and 16 months, respectively (p < 0.001). Median PRS for ICL, DCL, DTL, and ITL was 14, 8, 9, and 9 months, respectively (p < 0.001). Median OS for ICL was not reached whilst for DCL, DTL, and ITL it was 71, 101, and 29 months, respectively (p < 0.001). Extranodal spread and tumor, node, metastasis classification system N stage were the only significant prognostic factors for OS within each group. ICL patients had significantly improved DFS (p = 0.005) and OS (p = 0.012) beyond 5 years compared to DTL patients., Conclusions: Variable outcomes after lymphadenectomy were observed with different timing of surgery and LN tumor burden. ICL patients had the best outcome.

Purpose: A worldwide web-based survey was conducted among melanoma surgeons to investigate opinions about completion lymph node dissection (CLND) in patients with positive sentinel nodes (SN)., Methods: A questionnaire was designed following input from a group of melanoma surgeons. Cognitive interviews and pilot testing were performed. Surgeons identified through a systematic-review of the SN and CLND literature were invited by email., Results: Of 337 surgeons, 193 (57.2 %) from 25 countries responded (January-July 2011). Most respondents work in melanoma (30.1 %) and surgical oncology (44.6 %) units. In patients with a positive SN, 169 (91.8 %) recommend CLND; the strength of the recommendation is mostly influenced by patient comorbidities (64.7 %) and SN tumor burden (59.2 %). Seventy-one responders enroll patients in the second Multicenter Selective-Lymphadenectomy Trial (MSLT-2), and 64 of them (76 %) suggest entering the trial to majority of patients. In cases requiring neck CLND, level 1-5 dissection is recommended by 35 % of responders, whereas 62 % base the extent of dissection on primary site and lymphatic mapping patterns. Only inguinal dissection or ilioinguinal dissection is performed by 36 and 30 % of surgeons, respectively. The remaining 34 % select either procedure according to number of positive SNs, node of Cloquet status, and lymphatic drainage patterns. Most surgeons (81 %) perform full axillary dissections in positive SN cases., Conclusions: The majority of melanoma surgeons recommend CLND in SN-positive patients. Surgeons participating in the MSLT-2 suggest entering the trial to the majority of patients. More evidence is needed to standardize the extent of neck and groin CLND surgeries.

Background: There is little literature describing quality assurance (QA) validation of an individual surgeon's ability to perform sentinel node biopsy (SNB) in melanoma patients. This study aims to evaluate incomplete SNB rates and SNB positivity rates as potential QA parameters., Methods: An institutional database identified 2,874 patients with primary melanoma who had SNB performed when there was lymphoscintigraphy drainage to a single lymphatic field. Lymphoscintigraphy data were obtained from another database. Lymphoscintigraphy utilized small-particle colloid, allowing visualization of channels entering sentinel nodes on early dynamic scanning. Incomplete SNB was defined as retrieval of fewer sentinel nodes than identified on lymphoscintigraphy., Results: The overall rate of incomplete SNB was 17.7 % (including axilla 7.8 %, neck 23.3 %, and groin 28.8 %). Individual surgeons varied significantly in their proportion of SNBs performed in each region (p < 0.001). The surgeons' overall incomplete SNB rate varied significantly (p < 0.001). The surgeons' incomplete SNB rate in the axilla ranged 3-16 % (p < 0.001), median 6 %; groin 21-41 % (p = 0.002), median 26 %; and neck 19-43 % (p = 0.374), median 22 %. The respective axillary, groin, and neck SNB positivity rate for incomplete SNB patients were 10, 23, and 18 % compared to "complete" SNB patients 14, 19, and 14 %. There were no significant differences between surgeons' SNB positivity rates., Conclusions: Incomplete SNB rates vary between surgeons in each region. SNB positivity rates do not vary commensurate with the incomplete SNB rates. The ranges described could be used as QA parameters, however because none of these experienced surgeons are outliers, the robustness of these parameters remains unproven.

Background: Approximately 3-5% of patients with thin (≤ 1 mm) cutaneous melanomas develop distant metastases. We sought to identify clinical and pathologic factors associated with distant metastasis and survival in a large number of patients with thin melanoma treated at a single institution., Methods: We identified patients with a single invasive melanoma ≤ 1 mm in thickness diagnosed between January 1983 and December 2003 who developed distant metastasis (cases), and matched patients with no recorded recurrence during follow-up (control subjects). Cases and control subjects were matched for age, sex, and year of primary melanoma diagnosis. Associations of clinical and pathologic parameters with distant metastasis-free survival and melanoma-specific survival were analyzed., Results: A total of 178 cases and 178 control subjects were identified. Factors associated with development of distant metastasis were: increasing Breslow thickness (P < 0.001), increasing Clark level of invasion (P < 0.001), increasing mitotic rate (P = 0.001), ulceration (P = 0.025), and American Joint Committee on Cancer T subcategory (P < 0.001). Multivariable models including Breslow thickness (but not Clark level) showed that factors independently associated with poorer distant metastasis-free survival were increasing age [hazard ratio (HR) 1.01, 95% confidence interval (CI) 1.00-1.02]; increasing Breslow thickness (HR 3.21, 95% CI 1.73-5.94, and HR 3.77, 95% CI 2.11-6.74 for 0.51-0.75 mm and 0.76-1.00 mm, respectively, compared with 0.01-0.50 mm); ulceration (HR 1.87, 95% CI 1.14-3.06) and mitotic rate (HR 1.13, 95% CI 1.05-1.21). Similar associations with melanoma-specific survival were found., Conclusions: Clinical and pathologic predictors of distant metastasis and survival identified in this large study of patients with thin primary cutaneous melanomas will enable more accurate stratification of risk of distant metastasis and poor survival in such patients, and will assist in formulating clinical management and follow-up regimens based on the level of risk.

Background: In melanoma patients, we define incomplete sentinel node biopsy (I-SNB) as when fewer lymph nodes are removed during sentinel node biopsy (SNB) than identified on preoperative lymphoscintigraphy (LS). This study quantifies the frequency of I-SNB and evaluates any correlation with patient outcomes., Methods: Evaluation of a prospective database of consecutive patients having LS and negative SNB from 1996 to 2006. Additional LS information was obtained from a nuclear medicine database. All statistical analyses were performed using the IBM SPSS Statistic 19.0 software package., Results: I-SNB occurred in 20% of the cohort (n = 2007). For axillary (n = 895), groin (n = 569), and neck/axial patients (n = 334) I-SNB occurred in 12%, 26%, and 28% of cases, respectively (P < .001). On univariate analysis, there was a significant association between I-SNB and worse disease-free survival (DFS), P = .007 and trend toward worse melanoma-specific survival (MSS), P = .056. I-SNB was not associated with worse regional recurrence-free survival (RRFS), P = .144. There was no relationship between I-SNB and worse DFS, RRFS, or MSS on multivariate analysis. Sentinel node region (axilla better than groin and neck/axial) had a significant association with RRFS (P = .039) on univariate analysis and DFS on univariate (P = .009) and multivariate analysis. Significantly worse outcomes for MSS, DFS, and RRFS were seen with male gender, increasing age, high mitotic count, ulceration, and increasing Breslow thickness., Conclusion: This study demonstrates no statistically significant relationship between I-SNB and patient outcomes when adjusting for known prognostic factors. These data do not exclude the possibility that I-SNB may have a weak association with worse outcomes.

Background: Regional lymph node dissection (RLND) is currently the most effective therapy for metastatic melanoma in groin lymph nodes. With thorough surgery, RLND lymph node (LN) retrieval numbers have a predictable distribution. Whether patients have inguinal or ilioinguinal dissection varies between institutions. This study was designed to provide LN retrieval parameters for inguinal and ilioinguinal LN dissections, and secondarily, to analyze known predictors for survival outcomes, including LN ratio, i.e., involved/total number LN removed., Methods: A prospective database was used to identify 189 patients who had 200 groin dissections between July 2002 and February 2008 to derive parameters of LN retrieval. A subgroup of 177 patients who had one RLND was assessed for predictors of survival outcome., Results: Inguinal dissection had median LN retrieval of 11 (interquartile range, 10-14); 8 LN or more were retrieved in 90% of cases, and 38% of cases had 10 LN or less. Ilioinguinal dissection had median LN retrieval of 21.5 (interquartile range, 17-25); 14 LN or more were retrieved in 90% of cases, and 0 cases had 10 LN or less. The strongest predictors of survival on multivariate analysis were LN ratio, macroscopic LN disease, and ulceration of the primary melanoma. Overall 39% of ilioinguinal dissections had positive pelvic LNs, but only 9.3% of those completed after positive sentinel node biopsy., Conclusions: Thorough groin RLNDs have a predictable LN yield. LN ratio is the strongest predictor of outcome. Because pelvic LNs are frequently positive ilioinguinal dissection should be considered for all patients, especially those with macroscopic metastases to groin LNs.

Background: A modified procedure for ilio-inguinal regional lymph node dissection (I-I RLND) involving 2 small skin incisions was evaluated with the aim of assessing surgical and oncological noninferiority compared with the traditional single, longitudinal incision I-I RLND., Materials and Methods: A total of 20 melanoma patients with positive groin lymph nodes who had traditional I-I RLND were compared with 20 patients who had a minimal access I-I RLND using 2 small surgical access incisions of 3-6 cm in length--one sited below and one above the inguinal ligament. Clinical, staging features, number of lymph nodes retrieved, length of hospital stay, time drains remained in situ, morbidity (wound infections, dehiscence, hematoma, seroma, and lymphedema), and disease free survival were compared., Results: Patients in the groups were comparable with the exception that the minimal access I-I RLND group had a higher rate of AJCC stage N3 disease (60% vs 20%; P = .03) and more cases with extranodal spread (45% vs 15%; P = .041). After a median follow-up of 5 months (range 1-8) for the minimal access group and median 13 months (range 1-30) for the standard group there were no differences in disease-free survival (P = .13). Retrieved lymph node counts were similar (P = .34) including for the inguinal and pelvic components of the operations separately. No significant differences in wound complications or rates of early lymphedema were observed., Conclusions: At early follow-up, minimal access I-I RLND is feasible and noninferior to single longitudinal incision I-I RLND in regard to surgical morbidity and oncological outcome. Further evaluation is progressing.

Background: During the last 4 years, the keystone-design fasciocutaneous island flap has become the principal form of reconstruction in our unit for primary melanoma defects of the leg distal to the knee where primary closure is not possible., Methods: Data describing the primary tumor, surgical management, and outcome were collected prospectively for consecutive keystone flap cases. The study's primary end points were complication rates and length of hospital stay., Results: A total of 176 patients with new primary melanomas of the lower limb were treated over 4 years. The average Breslow thickness was 1.33 mm (range, in situ to 9.0 mm), and the average width of the defect was 3 cm. The reconstructions comprised 106 standard, 65 modified, and 5 double-opposing keystone type flaps performed from the knee to the dorsum of the foot. Complications that required further therapeutic intervention were seen in eight patients (4.6%), with only one partial flap necrosis (.6%) and one total flap loss (.6%). In this series, modification of the flap design significantly decreased the complication rate (Fisher's exact test, P = .033). There was no increase in complications in the distal third of the leg. The procedure was performed in day-only surgery setting in almost a quarter of patients., Conclusion: We present the largest series of flap reconstructions for melanoma of the leg. The keystone flap is extremely reliable, affords excellent cosmesis, and is technically straightforward to perform. At the Sydney Melanoma Unit, reconstruction after primary melanoma excision on the leg has been transformed so that skin grafts are now rarely performed.