Completion Lymph Node Dissection Group Research Articles

Survival impact of immediate complete lymph node dissection for Chinese acral and cutaneous melanoma with micrometastasis in sentinel nodes: a retrospective study

Sentinel node biopsy (SNB) has become a critical part of standard surgical treatment for melanoma with no clinical metastatic evidence. However, for patients with a positive sentinel node, the MSLT-II and DeCOG-SLT trials have shown that immediate complete lymph node dissection (CLND) does not bring further survival benefits. There is still an argument among the Chinese population dominated by acral subtypes on whether CLND can be omitted. Thus, this study aims to investigate the impact of immediate CLND on relapse-free survival (RFS) in Chinese melanoma patients with a positive sentinel node. Patients with acral or cutaneous melanoma of clinical Stages I–II who received SNB procedure and were detected with nodal micrometastasis were retrospectively collected at Fudan University Cancer Center (FUSCC) from January 2017 to December 2021. The clinicopathologic features and prognostic factors for RFS were analyzed. Out of 381 patients who received SNB in the past 5 years, 130 (34%) cases with SN micrometastasis detected were included in this study. Ninety-nine patients underwent immediate CLND while the other 31 patients received observation alone. Among patients who received CLND, the non-SN(NSN)-positive rate was 22.2%. Most of the clinicopathologic factors were balanced well between the CLND and non-CLND groups. However, more patients in the CLND group were detected with BRAF and NRAS mutation (P = 0.006) and received adjuvant PD-1 monotherapy (P = 0.042) as well. There were slightly fewer N1 patients in the CLND group, although the difference did not reach statistical significance (P = 0.075). The study found no significant difference in RFS between the two groups (P = 0.184). Even for patients with the acral subtype (P = 0.925), primary T4 lesion (P = 0.769), or presence of ulceration (P = 0.249), immediate CLND did not bring more survival benefits. Immediate CLND did not bring further RFS benefit for Chinese melanoma patients with SN micrometastasis in real-world clinical practice, even for patients with acral subtype or more tumor burden such as thick Breslow invasion and ulceration.

Does It Really Pay-Off? Comparison of Lymphadenectomy versus Observational Approach in Skin Melanoma with Positive Sentinel Node Biopsy: Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to answer the question as to whether performing CLND (complete lymph node dissection) is necessary in every case of the melanoma patient after the positive SNB (sentinel node biopsy). To resolve doubts the authors reanalyzed previous articles and systematized the knowledge about the concerning medical problem. The databases such as PubMed, Scopus and Web of Science were screened to find articles that will be helpful to answer the controversial question if performing lymphadenectomy is crucial. The inclusion criteria consisted of randomized clinical trials, comparison of lymphadenectomy versus observation and positive sentinel node biopsy. After which, seven articles were examined. Authors analyzed parameters such as: recurrence, 3-year survival and 5-year survival. There was no relationship between the performance of CLND and melanoma recurrence (OR 1.04; 95% CI: 0.82–1.31; p = 0.75). However, no CLND group had higher 3-year survival (OR 1.22; 95% CI: 1.03–1.44; p = 0.02) and 5-year survival (OR 1.30; 95% CI: 1.19–1.85; p = 0.008). In conclusion, the observational approach to the melanoma patients with positive sentinel node biopsy is associated with comparable or slightly improved 3- and 5-year survival, then in case of routine lymphadenectomy. Although, in each melanoma patient a decision to perform or withhold lymphadenectomy should always be considered individually. Patients with low perioperative risk could be considered for surgical approach. The study was registered in PROSPERO and was assigned with the unique identifying number “CRD42021241272”.

Prevention of Secondary Lymphedema after Complete Lymph Node Dissection in Melanoma Patients: The Role of Preventive Multiple Lymphatic-Venous Anastomosis in Observational Era.

Background and Objectives: Current guidelines have limited the performance of complete lymph node dissection (CLND) for patients with clinically detectable lymphatic metastases. Despite the limitations of this surgical procedure, secondary lymphedema (SL) is an unsolved problem that affects approximately 20% of patients undergoing CLND. Preventive lymphatic–venous micro-anastomoses (PMLVA) has already demonstrated its efficacy in the prevention of SL in melanoma patients with a positive sentinel lymph node biopsy (SLNB), but the efficacy of this procedure is not demonstrated in patients with clinically detectable lymphatic metastases. Materials and Methods: This retrospective cohort study, was performed in two observation periods. Until March 2018, CLND was proposed to all subjects with positive-SLNB andPMLVA was performed in a subgroup of patients with risk factors for SL (Group 1). From April 2018, according to the modification of melanoma guidelines, all patients with detectable metastatic lymph nodes underwent PMLVA during CLND (Group 2). The frequency of lymphedema in subjects undergoing PMLVA was compared with the control group. Results: Database evaluation revealed 172 patients with melanoma of the trunk with follow-up information for at least 6 mounts. Twenty-three patients underwent PMLVA during CLND until March 2018, 29 from April 2018, and 120 subjects underwent CLND without any preventive surgery (control Group). The frequency of SL was significantly lower in both Group 1 (4.3% vs. 24.2%, p = 0.03) and Group 2 (3.5%, p = 0.01). Patients undergoing PMLVA showed a similar recurrence-free periods and overall survival when compared to the control group. Conclusions: PMLVA significantly reduces the frequency of SL both in immediate and delayed CLND. This procedure is safe and does not lead to an increase in length of hospitalization.

Observation policy for sentinel node metastasis of melanoma: Comparative study with completion lymph node dissection in Japanese patients.

Based on the results of international multicenter randomized trials, completion lymph node dissection for patients with sentinel lymph node-positive melanoma is no longer routinely recommended. However, clinicians should take into consideration racial and medical resource differences when applying this evidence to clinical practice in Japan. To evaluate the clinical validity of the observation policy of omitting completion lymph node dissection, we retrospectively surveyed patients with sentinel lymph node-positive melanoma between 2002 and 2020 at Niigata Cancer Center Hospital. A total of 59 patients were categorized into the observation group (n=19) and completion lymph node dissection group (n=40). Newly developed anticancer agents, including targeted therapy and immunotherapy, were more commonly used in the observation group than in the completion lymph node dissection group as either adjuvant therapy (31.6% vs. 5.0%) or post-recurrence therapy (100% vs. 34.8%). The median overall survival in the observation group (not reached) was significantly longer than that in the completion lymph node dissection group (95.0months; p=0.02), which was mainly attributed to the difference in post-recurrence overall survival. There was no significant difference in recurrence-free survival between the two groups (p=0.63). Although the use of new anticancer agents leads to bias, this study demonstrates that observation without prompt completion lymph node dissection provides a favorable overall survival without increasing the risk of recurrence compared with completion lymph node dissection. The observation policy for patients with sentinel lymph node-positive melanoma patients is considered to be clinically valid in real-world medical practice.

Natural history of pain associated with melanoma surgery.

Introduction:After excision of a primary malignant melanoma (MM), treatment of stage IB or higher MM consists of sentinel lymph node biopsy (SLNB). If malignant cells are identified, a complete lymph node dissection (CLND) can be performed.Objective:To determine the natural history of pain and sensory changes after MM surgery.Methods:We prospectively followed 39 patients (29 SLNB-only, 2 CLND-only, and 8 CLND preceded by SLNB) from before inguinal or axillary surgery through 6 months after surgery on measures of pain intensity, sensory symptoms, allodynia, and questionnaires of anxiety, depression, and catastrophizing.Results:No patient had pain preoperatively. Ten days after surgery, 35% had surgical site pain after SLNB-only compared with 90% after CLND (P < 0.003); clinically meaningful pain (Visual Analogue Scale ≥ 30 mm/100 mm) was reported by 3% of patients after SLNB-only compared with 40% after CLND (P < 0.001). At 6 months, all SLNB-only patients were pain-free. By contrast, 4 of 7 in the SLNB + CLND group still had pain (P < 0.002). At 6 months, symptoms of altered sensation or numbness were reported by 32% and 42% of SLNB-only patients, and by 67% and 67% of patients undergoing CLND surgery (both P > 0.05).Conclusion:Acute pain is more common after CLND surgery. Undergoing SLNB followed by more invasive CLND surgery may increase the likelihood of pain at 6 months. Persistent sensory symptoms typical of those associated with nerve injury are more common after CLND. Surgery for MM is a good model for studying the natural history of postsurgical pain and sensory changes.

Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial

Complete lymph node dissection is recommended in patients with positive sentinel lymph node biopsy results. To date, the effect of complete lymph node dissection on prognosis is controversial. In the DeCOG-SLT trial, we assessed whether complete lymph node dissection resulted in increased survival compared with observation. In this multicentre, randomised, phase 3 trial, we enrolled patients with cutaneous melanoma of the torso, arms, or legs from 41 German skin cancer centres. Patients with positive sentinel lymph node biopsy results were eligible. Patients were randomly assigned (1:1) to undergo complete lymph node dissection or observation with permuted blocks of variable size and stratified by primary tumour thickness, ulceration of primary tumour, and intended adjuvant interferon therapy. Treatment assignment was not masked. The primary endpoint was distant metastasis-free survival and analysed by intention to treat. All patients in the intention-to-treat population of the complete lymph node dissection group were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02434107. Follow-up is ongoing, but the trial no longer recruiting patients. Between Jan 1, 2006, and Dec 1, 2014, 5547 patients were screened with sentinel lymph node biopsy and 1269 (23%) patients were positive for micrometastasis. Of these, 483 (39%) agreed to randomisation into the clinical trial; due to difficulties enrolling and a low event rate the trial closed early on Dec 1, 2014. 241 patients were randomly assigned to the observation group and 242 to the complete lymph node dissection group. Ten patients did not meet the inclusion criteria, so 233 patients were analysed in the observation group and 240 patients were analysed in the complete lymph node dissection group, as the intention-to-treat population. 311 (66%) patients (158 in the observation group and 153 in the dissection group) had sentinel lymph node metastases of 1 mm or less. Median follow-up was 35 months (IQR 20-54). Distant metastasis-free survival at 3 years was 77·0% (90% CI 71·9-82·1; 55 events) in the observation group and 74·9% (69·5-80·3; 54 events) in the complete lymph node dissection group. In the complete lymph node dissection group, grade 3 and 4 events occurred in 15 patients (6%) and 19 patients (8%) patients, respectively. Adverse events included lymph oedema (grade 3 in seven patients, grade 4 in 13 patients), lymph fistula (grade 3 in one patient, grade 4 in two patients), seroma (grade 3 in three patients, no grade 4), infection (grade 3 in three patients, no grade 4), and delayed wound healing (grade 3 in one patient, grade 4 in four patients); no serious adverse events were reported. Although we did not achieve the required number of events, leading to the trial being underpowered, our results showed no difference in survival in patients treated with complete lymph node dissection compared with observation only. Consequently, complete lymph node dissection should not be recommended in patients with melanoma with lymph node micrometastases of at least a diameter of 1 mm or smaller. German Cancer Aid.

Impact of Completion Lymph Node Dissection on Patients with Positive Sentinel Lymph Node Biopsy in Melanoma

Whether patients with positive SLNB should undergo complete lymph node dissection (CLND) is an important unanswered clinical question. Patients diagnosed with positive SLNB at a melanoma referral center from 1991 to 2013 were studied. Outcomes of patients who underwent CLND were compared with those who did not undergo immediate CLND (observation [OBS] group). There were 471 patients who had positive SLNB; 375 (79.6%) in the CLND group and 96 (20.4%) in the OBS group. The groups were similar except that the CLND group was younger and had more sentinel nodes removed. Five-year nodal recurrence-free survival was significantly better in the CLND group compared with the OBS group (93.1% vs 84.4%; p= 0.005). However, 5-year (66.4% vs 55.2%) and 10-year (59.5% vs 45.0%) distant metastasis-free survival rates were not significantly different (p= 0.061). The CLND group's melanoma-specific survival (MSS) rate was superior to that of the OBS group; 5-year MSS rates were 73.7% vs 65.5% and 10-year MSS rates were 66.8% vs 48.3% (p= 0.015). On multivariate analysis, CLND was associated with improved MSS (hazard ratio= 0.60; 95% CI, 0.40-0.89; p= 0.011) and lower nodal recurrence (hazard ratio= 0.46; 95% CI, 0.24-0.86; p= 0.016). Increased Breslow thickness, older age, ulceration, and trunk melanoma were all associated with worse outcomes. On subgroup analysis, the following factors were associated with better outcomes from CLND: male sex, nonulcerated primary, intermediate thickness, Clark level IV or lower extremity tumors. Treatment of positive SLNB with CLND was associated with improved MSS and nodal recurrence rates. Follow-up beyond 5 years was needed to see a significant difference in MSS rates.

Is there a therapeutic benefit of complete lymph node dissection in melanoma patients with low tumor burden in the sentinel node?

In the case of a positive sentinel lymph node (SLN), melanoma patients are recommended to proceed to complete lymph node dissection (CLND). However, CLND for SLN-positive patients - especially with minimal tumor burden in SLN - is becoming more controversial. We analyzed the clinical course of 305 SLN-positive patients with a mean follow-up of 51.1 months by Kaplan-Meier analyses. Overall, 58/305 (17%) patients did not undergo CLND. These were compared with a matched selection of 58 comparable patients who underwent CLND. Moreover, 106/305 patients with minimal tumor burden in SLN (<0.1 mm diameter of the largest tumor deposit) were analyzed separately. Of these 106 patients, 34 did not undergo CLND, whereas 72/106 patients were treated by CLND. In the matched groups, the CLND group and the non-CLND group did not differ significantly with respect to clinical characteristics, characteristics of the primary melanoma, and histopathological parameters of SLN. There were no differences in recurrence-free survival (P=0.765) and overall survival (P=0.844). The total number of regional lymph node metastases and time to regional lymph node metastases were not significantly higher for non-CLND patients. The subgroup of patients with minimal tumor burden in SLN also did not benefit significantly from CLND. In our analyses from a single German center, we could not find any evidence for a therapeutic survival benefit for CLND after positive SLN. However, future prospective randomized trials should confirm these data.

Complications in the surgical treatment of pediatric melanoma

PurposeThe purpose of this study was to characterize the complications associated with surgical treatment of pediatric melanoma. MethodsWe retrospectively reviewed all pediatric patients who received surgical treatment for melanoma at our institution between 1992 and 2010. We compared complications between three groups: wide local excision only (WLE), WLE and sentinel lymph node biopsy (SLNB), and WLE and completion lymph node dissection (CLND). ResultsOne hundred twenty-five patients were identified: 37 patients received WLE only, 47 received WLE and SLNB, and 41 patients had WLE and CLND. Complication rates differed between the three groups: 19% in WLE, 11% in WLE+SLNB, and 39% in WLE+CLND (P=.006). The risk of complications was significantly lower among patients having WLE+SLNB versus WLE+CLND (OR 0.19, 95% CI 0.06–0.57, P=.0032). Lymphedema was a common complication with a higher incidence in the CLND group compared to the SLNB group (19.5% vs. 2.1%, P=.01). Complications were more frequent in inguinal compared to axillary dissections (52.0% vs. 17.1%, P=.006). ConclusionsIn the surgical treatment of pediatric melanoma, the addition of a completion lymph node dissection significantly increases complication risk. Thus, it is critical to determine which patients truly benefit from this procedure.

The Impact of Primary Melanoma Thickness and Microscopic Tumor Burden in Sentinel Lymph Nodes on Melanoma Patient Survival

The primary objectives of this work are to (1) quantitate tumor burden in sentinel lymph nodes (SLNs), and (2) assess the independent contributions of SLN tumor burden and primary melanoma thickness (PMT) with respect to progression-free survival (PFS) and overall survival (OS). Sixty-three patients (41 male and 22 female) with one or more positive SLNs were available for review in this study, with median follow-up of 6.8 years. PMT was measured and SLN metastases were assessed for size, as maximum metastasis size (MMS) in mm, by hematoxylin and eosin (H&E) and immunohistochemistry (S100 and HMB45). PFS and OS were calculated from time of SLN resection until melanoma recurrence or death. Univariate and multivariate analyses and trend test were performed. Kaplan-Meier estimates of PFS and OS differed significantly by MMS (log-rank P = 0.031 for PFS and P = 0.016 for OS) and PMT (log-rank P = 0.036 for PFS and P < 0.001 for OS). After adjusting for age and gender, the hazard ratio (HR) associated with MMS was 1.09 per mm increase (P = 0.05) for PFS, and 6.30 (P = 0.014) and 5.41 (P = 0.048) for OS in patients, respectively, with MMS of 0.6-5.5 mm and MMS ≥5.5 mm compared with those with MMS <0.6 mm. When patients were stratified by their tumor characteristics of PMT, the risk for disease progression and worse OS was substantially higher for the group with PMT ≥ 4.5 mm (HR = 13.10 and P = 0.022 for PFS; HR = 17.26 and P < 0.001 for OS) relative to the baseline group with PMT <1.6 mm. All patients had completion lymph node dissection (CLND) except for four patients. Patients with positive CLND (14, 22.2%) showed significant worse PFS (P = 0.002) and OS (P = 0.0003) than the negative CLND group (45, 71.4%). PMT and MMS were independently prognostic of PFS and OS in melanoma patients. Patients with negative CLND had significantly better PFS and OS than those with positive CLND.

Why Does No One Want to Perform Lymph Node Dissection Anymore?

In this issue of Annals of Surgical Oncology, Kingham et al. from Memorial Sloan-Kettering Cancer Center present their single-institution retrospective experience of melanoma patients who did not undergo completion lymph node dissection (CLND) for a tumor-positive sentinel lymph node (SLN). Of 313 patients who had a tumorpositive SLN, 271 underwent CLND and 42 did not. Of the 42 patients who did not undergo CLND, 5 did not do so because they were found to have stage IV disease on further workup, leaving 37 patients who should reasonably have considered CLND. The nodal recurrence rates were no different in the no-CLND group (7%) versus the CLND group (6%). Because the disease-free and disease-specific survival rates were similar between the groups, the authors question the value of CLND. We must recognize the limitations of this study. It is a small, retrospective review from a single institution. The groups are not well balanced in terms of clinicopathologic factors. Patients in the no-CLND group versus the CLND group were older (median age, 70 vs. 56 years, P .01), more often had lower-extremity melanomas (40% vs. 13%, P .01), and had a trend toward thicker (3.5 vs. 2.8 mm, P .06), more often ulcerated (62 vs. 44%, P = .09) melanomas. Why did the patients not undergo CLND in this study? In 33% of cases, it seems that the surgeon essentially talked the patient out of having a CLND. Although patient refusal was cited as the most common reason for failure to perform CLND (45%), it is likely that the surgeon’s opinion strongly influenced the patients’ decisions in these cases as well. The patients who chose to forego CLND did not do so for random reasons; selection bias is a major drawback of this study. In my experience, most patients choose CLND if recommended by their surgeon. So what does this study really tell us? I believe it tells us that the experienced melanoma surgeons at Memorial Sloan-Kettering Cancer Center were very good at selecting patients who were unlikely to have nodal recurrence and/or were very likely to develop distant metastatic disease, and thus were unlikely to benefit from CLND. It does not tell us that CLND is of no value. The authors cite population studies that indicate that only 50–69% of melanoma patients in the United States who have a tumor-positive SLN undergo CLND. So why are surgeons so reluctant to perform CLND these days? To address this question, we must consider the reasons for performing CLND. There are two goals: regional disease control and cure. The patients who undergo CLND for a tumor-positive SLN fall into three camps: (1) those who do not need CLND because they do not have, and never will have, additional nodal disease; (2) those who will not benefit from CLND because they are going to die of distant metastatic disease or because their disease will recur in the regional nodes, despite the best possible lymph node dissection; and (3) those who have nonsentinel node metastases for whom CLND will prevent regional nodal recurrence and, in some cases, result in cure. The third camp undoubtedly represents the smallest group. The article by Kingham et al. implies that the third camp does Society of Surgical Oncology 2009

Quality of Life After Axillary or Groin Sentinel Lymph Node Biopsy, With or Without Completion Lymph Node Dissection, in Patients With Cutaneous Melanoma

BackgroundThe aim of this study was to asses quality of life (QoL) after axillary or inguinal sentinel lymph node biopsy (SLNB) with or without completion lymph node dissection (CLND) in patients with cutaneous melanoma by comparing patients to a norm group of the general population and by comparing QoL between four patient groups depending on surgical procedure and location, i.e., patients receiving an axillary or groin SLNB, or an axillary or groin CLND.MethodsBetween 1995 and 2003, a total of 242 axillary and inguinal SLNBs were performed. Of the 127 patients eligible for the study, 116 patients participated (91%). QoL was measured by the 30-item European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the McGill Pain Questionnaire and the Groningen Activity Restriction Scale.ResultsMedian age at diagnosis was 50 (range, 18–77) years; median Breslow thickness 2.0 (range, 1–13) mm; median follow-up 56 (range, 4–94) months. SLNB only was performed in 89 patients (77%): 48 in the groin and 41 in the axilla. CLND was performed in 27 patients (23%): 13 in the axilla and 14 in the groin. More postoperative complications (13 vs. 5; P < 0.001) and lymphedema (10 vs. 8; P < 0.001) occurred in the CLND group than in the SLNB group. The total group of patients reported better physical (P < 0.001), role (P < 0.001), emotional (P < 0.001), and social functioning (P = 0.049), global QoL (P < 0.001), and less fatigue (P < 0.001) and pain (P < 0.001) than a German norm group. Analysis of variance revealed significant differences in role functioning (P = 0.02) and tendencies toward physical problems (P = 0.051) and fatigue (P = 0.051) between the four groups. Post hoc Bonferroni tests showed that the axillary CLND group had more problems than the axillary and inguinal SLNB groups. Kruskal-Wallis tests showed that the axillary CLND group reported most pain.ConclusionsQoL in melanoma survivors after axillary or inguinal SLNB with or without CLND was better than that in a norm group. Patients who underwent CLND in the axilla after SLNB reported most problems.

Prediction of Nonsentinel Lymph Node Metastasis in Malignant Melanoma

Sentinel lymph node biopsy (SLNB) is the standard at many institutions caring for melanoma patients. Patients with positive SLNB results are currently offered completion lymph node dissection (CLND) of the affected lymph node basin. This procedure entails considerable morbidity and is often applied to patients with shortened life expectancies. Because 80% of CLNDs yield no additional positive nodes and there is no proof that CLND leads to survival improvement, criteria are needed to limit this procedure to those most likely to harbor nonsentinel lymph node (SLN) metastases. A retrospective review of 349 cases of melanoma from January 1999 to April 2007 that underwent sentinel lymph node biopsy at a single institution was done. Statistical analysis was used to compare two subgroups of patients: a positive CLND group and a negative CLND group. These two groups were compared with regards to multiple variables related to patient demographics, primary tumor characteristics, and SLN tumor burden. Age and total size of SLN tumor deposit were the factors with the strongest correlation with CLND positivity. By applying a risk score model that uses the cutoff values of age 55 y and SLN tumor deposit of 5 mm, it is possible to predict CLND positivity in SLN-positive melanoma patients. The likelihood of CLND positivity in SLN-positive melanoma patients can be predicted from two criteria readily available: size of SLN tumor deposit and patient age.

Cutaneous Melanoma and Sentinel Lymph Node Biopsy

To the Editors: As authors of a similar article,1 we read with great interest the report by Koskivuo et al.,2 in the December issue of the Annals of Surgical Oncology. We enthusiastically support the basic rationale for this paper and the two researched patient groups, which have been correctly balanced for most of the important prognostic factors, such as Breslow thickness, ulceration status, and tumor site. However, some other methodological and other points may not have been entirely correctly addressed. In the previous study from our center,1 we compared two patient groups that consisted of node-positive patients. One group underwent wide local excision (WLE) and developed a regional lymph node metastasis for which we performed a therapeutic lymph node dissection (TLND). The other group had a positive sentinel node (SN) and underwent a completion lymph node dissection (CLND). Recently we have updated our follow-up information; the median follow-up time is now 5 8 months for the TLND group and 5 1 months for the SN+CLND group. When survival rates were calculated from the diagnosis date of the primary tumor, there seemed to be a trend towards a 14% survival benefit for the CLND group (P = 0.065). However, when patients with minimal SN tumor burden (according to the Rotterdam criteria <0.1 mm in maximum diameter3,4) were excluded, because their prognosis is identical to SN-negative patients, this survival benefit disappeared (P = 0.333). Treatment (WLE followed by TLND versus SN followed by CLND) was not an independent prognostic factor for survival.1 The initial paper from our institute1 was already scrutinized for its lack of follow-up balance between the two groups (the WLE-only group versus the SN-staged group), which is now 58 (+2) versus 51 (+14) months. The present study2 has an even greater misbalance in follow-up: a median of 7 4 months for the WLE versus 16 for SN group. It stands to reason to expect that the SN group will develop more recurrences and deaths. Even though the WLE group has a significantly longer follow-up, there seems to be a critical misbalance in nodal disease between the two groups. There were 72 nodal recurrences in the WLE group (11.7%) versus 50 positive SNs (16.4%). This is even without the nodal relapses (n = 5; 1.6%) in the SN group.2 This suggests that not all positive sentinel nodes will develop into palpable nodal disease. The authors state that improved regional disease control is an obvious therapeutic advantage of SN staging and immediate CLND. This statement can only be made in the context of a comparison of nodal recurrence rates after SN+CLND versus those after TLND. This comparison has not been made in the present study. Instead the authors compare the 1.6% nodal recurrences after SN+CLND with the 11.7% of patients that undergo a TLND after WLE only. This is obviously an incorrect comparison since the lymph node dissection in one group has already been performed and therefore this comparison does not make sense. Another important observation in light of another recent publication from Sheri et al.5 in the October edition of this same journal, but also in light of a study from our institute, is the rate and survival of patients in the Starz I tumor burden (<0.3 mm) category.6 The rate of Starz I patients was 9/49 (18%), which is virtually identical to the results from our institute.3, 4 More importantly was the observation of a 100% overall survival rate from this group, which is again a confirmation of the excellent survival of patients with minimal SN tumor burden from other series and recently from a multicenter experience presented at ECCO 14 in Barcelona in September 2007.3 Finally, we agree with the authors with regard to the fact that SN staging is necessary to provide the optimal treatment to melanoma patients. In the absence of effective chemo- or immunotherapy, such treatments need to be identified by the conduct of randomized controlled trials for which SN status is a crucial stratification. SN staging will have increasing competition however from ultrasound-guided fine-needle aspiration cytology (FNAC), which may be able to replace the current SN staging in most patients based on a trial in 400 patients as reported in the Presidential Session of the last ECCO meeting.7

Preoperative lactate dehydrogenase (LDH) serum level has impact on survival of melanoma patients after therapeutic lymph node dissection (TLND) but not on patients after completion lymph node dissection (CLND)

8568 Background: The aim of the study was to evaluate the additional prognostic value of preoperative LDH serum level on overall survival (OS) of AJCC stage III cutaneous melanoma patients. Methods: The preoperative LDH serum level was available in 402 consecutive melanoma patients, who underwent radical LND (196 CLND after positive sentinel node biopsy and 206 TLND for clinically/cytologically detected regional lymph node metastases) between 1994 and 2004. Median follow-up time was 36 months (range: 6–110 months). Results: LDH serum level was increased before LND in 92 patients (22.9%) in the entire group of stage III melanoma patients [56 patients (27%) in TLND group and in 36 patients (18.4%) in CLND group (p=0.03)]. There were significant differences for OS (calculated from the date of LND) between patients with normal and high preoperative LDH level in the entire group of patients: median OS time was 51.2 months (95% CI: 34.8–91.9) and 27.9 months (95% CI: 18.2-); 5-year OS rate was 45.2% and 37.5%, respectively (p=0.0079 in univariate analysis and p=0.02 in multivariate analysis). However, to these differences mainly contributed the patients from TLND group: for patients with normal and high preoperative LDH level median OS time was 36.6 months (95% CI: 24.9–57.6) and 15.1 months (95% CI: 12.4- 27.9); 5-year OS rate was 40.0% and 20.3%, respectively (p=0.0013 in univariate analysis and p=0.01 in multivariate analysis). We did not observe any differences between patients with normal and high preoperative LDH level in CLND group: median OS time was 60.0 months (95% CI: 39.8-) and 65 months (95% CI: 45.6-); 5-year OS rate was 51% and 58%, respectively (p=0.703 in univariate analysis). Conclusions: Pre-LND increased LDH serum level has additional negative impact on OS of melanoma patients with palpable nodal metastases after TLND. [Table: see text]

Survival Analysis and Clinicopathological Factors Associated With False-Negative Sentinel Lymph Node Biopsy Findings in Patients with Cutaneous Melanoma

We analyzed the outcomes and factors associated with false-negative (FN) results of sentinel lymph node (SLN) biopsy findings in patients with cutaneous melanoma. SLN biopsy failure rate was defined as nodal recurrence in the biopsied regional basin without previous local or in-transit recurrence. Between April 1997 and December 2004, a total of 1207 patients with cutaneous melanoma with a median Breslow thickness of 2.4 mm underwent SLN biopsy by preoperative and intraoperative lymphoscintigraphy combined with dye injection. In 228 cases, we found positive SLNs; of these, 220 underwent completion lymph node dissection (CLND). Median follow-up was 3 years. The SLN biopsy failure rate was 5.8% (57 of 979 SLN negative). Median time to occurrence of FN relapse after SLN biopsy was 16 months (range, 3-74 months). The FN SLN biopsy results correlated with primary tumor thickness >4 mm (P = .0012), primary tumor ulceration (P = .0002), primary tumor level of invasion Clark stage IV/V (P = .0005), and nodular melanoma histological type (P = .0375). Five-year overall survival, calculated from the date of primary tumor excision, in the FN group was 53.7%, which was not statistically significantly worse than the CLND group (56.8%; P = .9). The FN group was characterized by a higher ratio of two or more metastatic nodes and extracapsular involvement of lymph nodes after LND compared with the CLND group (P < .0001 and P < .0001, respectively). Additional detailed pathological review of FN SLN revealed metastatic disease in 14 patients, which decreased the SLN biopsy failure rate to 4.4% (43 of 979). Survival of patients with FN results of SLN biopsy does not differ statistically significantly from that of patients undergoing CLND, although it is slightly lower. The SLN biopsy failure rate is approximately 5.0% in long-term follow-up and is associated mainly with the same factors that indicate a poor prognosis in primary melanoma.