Not Waiting to Progress; How the COVID-19 Pandemic Nudged Neoadjuvant Therapy for Stage III Locally Advanced Melanoma Patients.

Background: Early-phase neoadjuvant trials have demonstrated promising results in the utility of upfront immunotherapy in locally advanced stage III melanoma and unresected nodal disease. Secondary to these results and the COVID-19 pandemic, this patient population, traditionally managed through surgical resection and adjuvant immunotherapy, received a novel treatment strategy of neoadjuvant therapy (NAT). Methods: Patients with node-positive disease, who faced surgical delays secondary to COVID-19, were treated with NAT, followed by surgery. Demographic, tumour, treatment and response data were collected through a retrospective chart review. Biopsy specimens were analysed prior to the initiation of NAT, and therapy response was analysed following surgical resection. NAT tolerability was recorded. Results: Six patients were included in this case series; four were treated with nivolumab alone, one with ipilimumab and nivolumab and one with dabrafenib and trametinib. Twenty-two incidents of adverse events were reported, with the majority (90.9%) being classified as grade one or two. All patients underwent surgical resection: three out of six patients following two NAT cycles, two following three cycles and one following six cycles. Surgically resected samples were histopathologically evaluated for the presence of disease. Five out of six patients (83%) had ≤1 positive lymph node. One patient showed extracapsular extension. Four patients demonstrated complete pathological response; two had persisting viable tumour cells. Conclusions: In this case series, we outlined how in response to surgical delays secondary to the COVID-19 pandemic, NAT was successfully applied to achieve promising treatment response in patients with locally advanced stage III melanoma.

Mitigating Breast-Cancer-Related Lymphedema-A Calgary Program for Immediate Lymphatic Reconstruction (ILR).

With increasing breast cancer survival rates, one of our contemporary challenges is to improve the quality of life of survivors. Lymphedema affects quality of life on physical, psychological, social and economic levels; however, prevention of lymphedema lags behind the progress seen in other areas of survivorship such as breast reconstruction and fertility preservation. Immediate lymphatic reconstruction (ILR) is a proactive approach to try to prevent lymphedema. We describe in this article essential aspects of the elaboration of an ILR program. The Calgary experience is reviewed with specific focus on team building, technique, operating room logistics and patient follow-up, all viewed through research and education lenses.

Higher Rate of Lymphedema with Inguinal versus Axillary Complete Lymph Node Dissection for Melanoma: A Potential Target for Immediate Lymphatic Reconstruction?

BACKGROUND: The present study was conducted to define the lymphedema rate at our institution in patients undergoing axillary (ALND) or inguinal (ILND) lymph node dissection (LND) for melanoma. It aimed to examine risk factors predisposing patients to a higher rate of lymphedema, highlighting which patients could be targeted for immediate lymphatic reconstruction (ILR). METHODS: A retrospective chart review was conducted between October 2015 and July 2020 to identify patients who had undergone ALND or ILND for melanoma. The main outcome measures were rates of transient and permanent lymphedema. Univariate and multivariate analyses were performed to assess the relationship between lymphedema rate and factors related to patient characteristics, surgical procedure, pathology findings, and adjuvant treatment. RESULTS: Between October 2015 and July 2020, 66 patients underwent LND for melanoma: 34 patients underwent ALND and 32 patients underwent ILND. At a median follow-up of 29 months, 85.3% (n = 29) of patients having had an ALND did not experience lymphedema, versus 50.0% (n = 16) of ILND (p = 0.0019). The rates of permanent lymphedema for patients having undergone ALND and ILND were 11.8% (n = 4) and 37.5% (n = 12) respectively (p = 0.016, NS). The rate of transient lymphedema was 2.9% (n = 1) for ALND and 12.5% (n = 4) for ILND (p = 0.13, NS). On univariate analysis, the location of LND and wound infection were found to be significant factors for lymphedema. On multivariate analysis, only the location of LND remained a significant predictor, with the inguinal location predisposing to lymphedema. CONCLUSION: This study highlights the high rate of lymphedema following ILND for melanoma and is a potential target for future patients to be considered for ILR.

Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration.

BACKGROUND: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population. METHODS: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada. Univariable and multivariable logistic regression analyses were performed to identify predictors of SLNB positivity. RESULTS: Overall, 676 patients were analyzed. Most patients had one or more high-risk features: Breslow thickness 0.8-1 mm in 78.1% of patients, ulceration in 8.3%, mitotic rate > 1/mm2 in 42.5%, Clark's level ≥ 4 in 34.3%, lymphovascular invasion in 1.4%, nodular histology in 2.9%, and absence of tumor-infiltrating lymphocytes in 14.4%. Fifty-three patients (7.8%) had a positive SLNB. Breslow thickness and mitotic rate independently predicted SLNB positivity. The odds of positive SLNB increased by 50% for each 0.1 mm increase in thickness past 0.7 mm (95% confidence interval [CI] 1.05-2.13) and by 22% for each mitosis per mm2 (95% CI 1.06-1.41). Patients who had one excised node (vs. two or more) were three times less likely to have a positive SLNB (3.6% vs. 9.6%; odds ratio 2.9 [1.3-7.7]). CONCLUSIONS: Our international multi-institutional data confirm that Breslow thickness and mitotic rate independently predict SLNB positivity in patients with T1 melanoma. Even within this highly selected population, the number needed to diagnose is 13:1 (7.8%), indicating that more work is required to identify additional predictors of sentinel node positivity.

Canadian Melanoma Conference Recommendations on High-Risk Melanoma Surveillance: A Report from the 14th Annual Canadian Melanoma Conference; Banff, Alberta; 20-22 February 2020.

Introduction: There are a lack of established guidelines for the surveillance of high-risk cutaneous melanoma patients following initial therapy. We describe a novel approach to the development of a national expert recommendation statement on high-risk melanoma surveillance (HRS). Methods: A consensus-based, live, online voting process was undertaken at the 13th and 14th annual Canadian Melanoma Conferences (CMC) to collect expert opinions relating to "who, what, where, and when" HRS should be conducted. Initial opinions were gathered via audience participation software and used as the basis for a second iterative questionnaire distributed online to attendees from the 13th CMC and to identified melanoma specialists from across Canada. A third questionnaire was disseminated in a similar fashion to conduct a final vote on HRS that could be implemented. Results: The majority of respondents from the first two iterative surveys agreed on stages IIB to IV as high risk. Surveillance should be conducted by an appropriate specialist, irrespective of association to a cancer centre. Frequency and modality of surveillance favoured biannual visits and Positron Emission Tomography Computed Tomography (PET/CT) with brain magnetic resonance imaging (MRI) among the systemic imaging modalities available. No consensus was initially reached regarding the frequency of systemic imaging and ultrasound of nodal basins (US). The third iterative survey resolved major areas of disagreement. A 5-year surveillance schedule was voted on with 92% of conference members in agreement. Conclusion: This final recommendation was established following 92% overall agreement among the 2020 CMC attendees.

A population-based assessment of melanoma: Does treatment in a regional cancer center make a difference?

BACKGROUND: Regionalization of care to specialized centers has improved outcomes for several cancer types. We sought to determine if treatment in a regional cancer center (RCC) impacts guideline adherence and outcomes for patients with melanoma. METHODS: In Alberta, Canada, 561 patients with stage I-IIIC primary melanoma were diagnosed between January 2009 and December 2010. The electronic health record was used to capture demographic and pathologic data. Provincial guidelines for sentinel lymph node biopsy (SLNB) and wide local excision (WLE) are based on recommendations of several pre-existing guidelines including the National Comprehensive Cancer Network. RESULTS: 148 of 561 patients were identified as having been treated at a RCC. Median follow-up was 45 months. Patients treated at the RCC presented with higher stage melanomas. The RCC was more likely to follow guideline recommendations for performing SLNB (81.3% vs. 55.4%, P < 0.0001) but not for the extent of WLE (76.6% vs. 84.1%, P = 0.054). Overall survival was impacted by tumor thickness (HR 1.14, P < 0.0001), ulceration (HR 5.58, P < 0.0001), and mitoses (HR 0.59, P = 0.05). CONCLUSIONS: The RCC more closely followed guidelines for SLNB but not for WLE. Despite patients treated at the RCC presenting with a more advanced stage, overall survival and disease-free survival appear to not be affected by treatment center.

Avoiding Skin Grafts: The Keystone Flap in Cutaneous Defects.

The Keystone Design Perforator Island Flap is a fasciocutaneous perforator flap resembling two end-to-end VY flaps. We used a modification of the original design to avoid extending the incision into an elliptical pattern, and maintained a trailing skin bridge whilst incising fascia in a tunneling fashion. Thirty patients underwent 32 flaps mainly on the lower leg to close defects that would traditionally require skin grafting. All flaps survived completely, with minor complications in four patients. All but five patients were allowed unrestricted ambulation after surgery. The modified design is straightforward to learn, has reliable perfusion, and provides a simpler recovery for patients. CLINICAL QUESTIONS/LEVEL OF EVIDENCE: Therapeutic, IV.

Kikuchi-Fujimoto lymphadenitis imitating metastatic melanoma on positron emission tomography: a case report.

BACKGROUND: Accurate staging is critical for decision-making for the treatment of malignant conditions. Fluoro-deoxy-glucose positron emission tomography-computed tomography (FDG PET-CT) is a highly sensitive imaging modality for the assessment of distant metastases; however false positive results are possible due to its lower specificity with detection of other hypermetabolic pathologies. CASE PRESENTATION: A patient with high-risk thigh melanoma was staged with FDG PET-CT. Four ipsilateral inguinal nodes (three superficial, one deep) demonstrated intense hypermetabolic activity. Metastatic melanoma was confirmed in the largest superficial inguinal node with ultrasound-guided fine needle aspiration. Histopathology demonstrated metastatic melanoma in one superficial node and histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease in five deep inguinal nodes. CONCLUSION: This case illustrates a false positive FDG PET-CT due to coincidental, synchronous melanoma and Kikuchi-Fujimoto disease in the same draining lymph node basin.

Isolated limb infusion: Efficacy, toxicity and an evolution in the management of in-transit melanoma.

BACKGROUND: Isolated limb infusion (ILI) delivers low-flow chemotherapy via percutaneous catheters to treat melanoma in-transit metastases. OBJECTIVE: To describe the experience of two regional referral centres with ILI. METHODS: A retrospective review of patients who underwent ILI between 2002 and 2012 was performed. Outcomes were measured using the WHO criteria for response, the Wieberdink toxicity score and long-term limb function using the Toronto Extremity Salvage Score (TESS). RESULTS: Fifty-two patients (mean age 66 years [range 27 to 90 years], female sex 65%, and lower [treated] limb in 86%) with 54 ILIs were reviewed. Wieberdink toxicity score was ≥3 in 21 (39%) procedures. Median follow-up was 18 months (range one to 117 months). Initial complete response (CR) was 29%, partial response 27%, stable disease 18% and progressive disease 27%. Predictors of better initial response were low disease burden and previous treatment. One or more treatments after ILI were common (65%). At 12 months, 19% of ILI patients had died from melanoma but 44% of surviving patients experienced limb CR. At 24 months, 57% of surviving patients experienced limb CR. The quality of life in the surviving, contactable patients according to the Toronto Extremity Salvage Score was 89%. CONCLUSION: Even if ILI does not result in CR for melanoma intransit metastases. it may slow disease progression as a single therapy, but more frequently in combination with other modalities.

HISTORIQUE: La perfusion d'un membre isolé (PMI) libère une chimiothérapie à faible dose par des sondes percutanées afin de traiter les métastases en transit des mélanomes. OBJECTIF: Décrire l'expérience de deux centres régionaux spécialisés à l'égard de la PMI. MÉTHODOLOGIE: Les chercheurs ont réalisé une analyse rétrospective des patients qui ont subi une PMI entre 2002 et 2012. Ils ont mesuré les résultats à l'aide des critères de réponse de l'OMS, du score de toxicité de Wieberdink et de la fonction des membres à long terme selon le score de sauvetage des membres de Toronto (TESS). RÉSULTATS: Les chercheurs ont analysé le cas de 52 patients (âge moyen de 66 ans [plage de 27 à 90 ans], 65 % de femmes et jambe [traitée] dans 86 % des cas) ayant eu 54 PMI. Dans 21 (39 %) des interventions, le score de toxicité de Wieberdink s'élevait à 3 ou plus. Le suivi médian était de 18 mois (plage de un à 117 mois). La réponse complète (RC) initiale était de 29 %, la réponse partielle de 27 %, la stabilisation de 18 % et l'évolution de 27 %. Un faible fardeau de la maladie et un traitement antérieur étaient les prédicteurs d'une meilleure réponse initiale. Il était courant d'administrer au moins un traitement après la PMI (65 %). Au bout de 12 mois, 19 % des patients étaient décédés à cause du mélanome, mais 44 % des survivants présentaient une RC du membre. Au bout de 24 mois, 57 % des survivants présentaient une RC du membre. La qualité de vie des survivants non perdus au suivi s'établissait à 89 % d'après le TESS. CONCLUSION: Même si la PMI ne suscite pas une RC des métastases en transit des mélanomes, elle peut ralentir l'évolution de la maladie seule, mais surtout en association avec d'autres modalités.

Final trial report of sentinel-node biopsy versus nodal observation in melanoma.

BACKGROUND: Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. METHODS: We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (± SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3 ± 1.8% vs. 64.7 ± 2.3%; hazard ratio for recurrence or metastasis, 0.76; P=0.01), and those with thick melanomas, defined as >3.50 mm (50.7 ± 4.0% vs. 40.5 ± 4.7%; hazard ratio, 0.70; P=0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1 ± 4.8% among those with metastasis versus 85.1 ± 1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0 ± 7.0% and 64.6 ± 4.9% (hazard ratio, 1.75; P=0.03). Biopsy-based management improved the 10-year rate of distant disease-free survival (hazard ratio for distant metastasis, 0.62; P=0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P=0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted. CONCLUSIONS: Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease-free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. (Funded by the National Cancer Institute, National Institutes of Health, and the Australia and New Zealand Melanoma Trials Group; ClinicalTrials.gov number, NCT00275496.).

Intra-lesional interleukin-2 therapy for in transit melanoma.

Intra-lesional interleukin-2 (IL-2) is effective in treating in transit melanoma metastases. Results from multiple studies were examined to evaluate the efficacy of IL-2 for in transit disease. In the published literature, complete response ranged from 0% to 69% per patient, and 41% to 96% per lesion, with excellent tolerability. Combining the results of six studies show complete response in 50% of patients and 78% of lesions. Intra-lesional IL-2 should be considered early in the course of treatment for in transit disease, ahead of other, more toxic therapies.

Comparison of outcomes for malignant melanoma of the face treated using Mohs micrographic surgery and wide local excision.

BACKGROUND: Mohs micrographic surgery (MMS) is an accepted treatment for nonmelanoma skin cancer and has an evolving role in melanoma. OBJECTIVE: To review oncologic outcomes of MMS and wide local excision (WLE) treatments for facial melanoma. METHODS AND MATERIALS: A retrospective review of patients with invasive melanoma of the face between 1997 and 2007 identified from the Alberta Cancer Registry (Canada) was performed. Outcome measures were local recurrence (recurrence <2 cm from excision scar), distant recurrence (regional or systemic), and disease-specific survival. RESULTS: One hundred fifty-one patients were available for analysis (60 MMS, 91 WLE). Median follow-up time was 48 months. The groups differed in tumor location and mitotic rate. Overall, there was no significant difference in 5-year local recurrence (7.9% WLE vs 6.2% MMS, p = .58), regional or systemic recurrence (18.8% vs 8.8%, p = 0.37) or disease-specific survival (82.8% vs 92.4%, p = .59). Breslow thickness was the only consistent predictor of local recurrence or other recurrence and disease-specific survival on multivariate analysis. Subset analysis of tumors with Breslow thickness less than 2 mm did not reveal any difference in outcomes. CONCLUSION: Mohs micrographic surgery has oncologic outcomes of local recurrence, distant recurrence and overall survival similar to those of WLE for invasive facial melanoma.

Invasive melanoma of the face: Management, outcomes, and the role of sentinel lymph node biopsy in 260 patients at a single institution.

BACKGROUND AND OBJECTIVES: The face is a common site of melanoma occurrence. The purpose of this study was to examine the management and outcomes of patients with invasive melanoma of the face. METHODS: Patients with invasive melanoma of the face managed at our institution from 1997 to 2008 were retrospectively reviewed. Details of sentinel lymph node biopsy (SNB), disease recurrence, and deaths were recorded. RESULTS: Two hundred sixty patients were reviewed (mean age 68, mean tumor thickness 0.87 mm). Of 100 patients eligible for SNB (tumor thickness ≥ 1 mm, Clark level ≥ IV, or ulceration) this was performed in only 29 (29%), and those who underwent SNB were younger than those who did not (mean age 59 vs. 79 years, P < 0.0001). SNB was successful in 28 (97%), and no complications occurred. SNB was positive in 3 (11%). After mean follow-up of 30 months, nodal recurrence occurred in 9 (3.5%) and distant recurrence in 20 (7.7%). There were 60 deaths (overall mortality 23%); attributed to melanoma in only 16 cases (disease specific mortality 6.2%). CONCLUSIONS: Facial melanoma is associated with low rates of regional recurrence despite underutilization of SNB. Older patients are less likely to undergo SNB. Due to the advanced age of patients with facial melanoma, most deaths occurring are from unrelated causes.

Population-based review of the outcomes following hepatic resection in a Canadian health region.

BACKGROUND: Higher hospital and surgeon volumes have been associated with improved outcomes following hepatic resection; however, there appear to be additional factors that also play a role. The objective of our study was to examine the outcomes following hepatic resection over the past 13 years in a large urban Canadian health region. METHODS: We used administrative procedure codes to identify all patients from 1991/92 to 2003/04 who underwent a hepatic resection in the Calgary health region, which has a referral base of about 1.5 million people. The primary outcome was operative mortality, defined as death before discharge. RESULTS: There were 424 hepatic resections performed in the stated time period. Annual volume was stable until 2000, when it increased substantially. This corresponded to the formation of a multidisciplinary group that provided care to these patients. There were 25 deaths over the study period for a mean mortality of 5.9%. The mean length of stay in hospital was 14.6 (median 10) days. Over time, however, mortality steadily decreased. This corresponded to a concomitant increase in the volume of hepatic resections performed. CONCLUSION: Over the past 13 years, the number of hepatic resections performed has increased; there has been a corresponding improvement in mortality rates. The improved rates are likely the result of multiple factors.

False negative sentinel lymph node biopsies in melanoma may result from deficiencies in nuclear medicine, surgery, or pathology.

OBJECTIVE: To investigate a cohort of melanoma patients with false negative (FN) sentinel node (SN) biopsies (SNBs) to identify the reasons for the FN result. SUMMARY OF BACKGROUND DATA: SNB is a highly efficient staging method in melanoma patients. However, with long-term follow-up FN SNB results of up to 25% have been reported. METHODS: Seventy-four SNs from 33 patients found to have had an FN SNB were analyzed by reviewing the lymphoscintigraphy, surgical data, and histopathology, and by assessing nodal tissue using multimarker real-time quantitative reverse transcription (qRT) polymerase chain reaction, and antimony concentration measurements (as a marker of "true" SN status) using inductively coupled plasma mass spectroscopy. RESULTS: Nine SNs (12%) from 9 patients (27%) had evidence of melanoma on histopathologic review. Twelve SNs (16%) from 10 patients (30%) were qRT(+). Four of these 12 SNs were positive on histopathology review and 8 were negative. Four patients (12%) were upstaged by qRT. Sixteen patients had their SNB histology, lymphoscintigraphy, and surgical data reviewed. Identifiable causes of the FN SNBs were not found after review of all modalities in 4 patients. SNs from all 4 patients had antimony levels indicative of an SN. Of the SNs evaluable by qRT, 1 was qRT(+) and 7 SNs from 2 patients were qRT(-). CONCLUSIONS: An FN SN can occur because of deficiencies in nuclear medicine, surgery, or pathology. qRT can detect "occult" metastatic melanoma in SNs that have been identified as negative by histopathology.

A sentinel node biopsy does not increase the incidence of in-transit metastasis in patients with primary cutaneous melanoma.

BACKGROUND: It has been suggested that performing a sentinel node biopsy (SNB) in patients with cutaneous melanoma increases the incidence of in-transit metastasis (ITM). METHODS: ITM rates for 2018 patients with primary melanomas > or =1.0 mm thick treated at a single institution between 1991 and 2000 according to 3 protocols were compared: wide local excision (WLE) only (n = 1035), WLE plus SNB (n = 754), and WLE plus elective lymph node dissection (n = 229). RESULTS: The incidence of ITM for the three protocols was 4.9%, 3.6%, and 5.7%, respectively (not significant), and as a first site of recurrent disease the incidence was 2.5%, 2.4%, and 4.4%, respectively (not significant). The subset of patients who were node positive after SNB and after elective lymph node dissection also had similar ITM rates (10.8% and 7.1%, respectively; P = .11). On multivariate analysis, primary tumor thickness and patient age predicted ITM as a first recurrence, but type of treatment did not. Patients who underwent WLE only and who had a subsequent therapeutic lymph node dissection (n = 149) had an ITM rate of 24.2%, compared with 10.8% in patients with a tumor-positive sentinel node treated with immediate dissection (n = 102; P = .03). CONCLUSIONS: Performing an SNB in patients with melanoma treated by WLE does not increase the incidence of ITM.

Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy.

BACKGROUND: A negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB. METHODS: Survival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined. RESULTS: The median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them. CONCLUSIONS: This large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.

Histopathologic excision margin affects local recurrence rate: analysis of 2681 patients with melanomas < or =2 mm thick.

OBJECTIVE: Prospective trials have shown that 1-cm and 2-cm margins are safe for melanomas <1 mm thick and > or =1 mm thick, respectively. It is unknown whether narrower margins increase the risk of LR or mortality. SUMMARY BACKGROUND DATA: To determine the relationship between histopathologic excision margin, local recurrence (LR) and survival for patients with melanomas < or =2 mm thick. METHODS: Data were extracted from the Sydney Melanoma Unit database for all patients with cutaneous melanoma < or =2 mm thick, diagnosed up to 1996. Patients with positive excision margins or follow-up <12 months were excluded, leaving 2681 for analysis. Outcome measures were LR (recurrence <5 cm from the excision scar), in-transit recurrence, and disease-specific survival. Factors predicting LR and overall survival were tested with Cox proportional hazards analysis. RESULTS: Median follow-up was 83.8 months. LR was identified in 55 patients (median time to recurrence, 37 months). At 120 months, the actuarial LR rate was 2.9%. Five-year survival after LR was 52.8%. In multivariate analysis, only margin of excision and tumor thickness were predictive of LR (both P = 0.003). When all patients with a margin <0.8 cm in fixed tissue (corresponding to a margin of <1 cm in vivo) were excluded from analysis, margin was no longer significant in predicting LR. Thickness, ulceration, and site were predictive of survival, but margin was not (P = 0.49). CONCLUSIONS: Histopathologic margin affects the risk of LR. However, if the in vivo margin is > or =1 cm, it no longer predicts risk of LR. Patient survival is not affected by margin.