Complications associated with sentinel lymph node biopsy for melanoma

Background: Sentinel lymph node (SLN) biopsy has become widely accepted as a method of staging the regional lymph nodes for patients with melanoma. Although it is often stated that SLN biopsy is a minimally invasive procedure associated with few complications, a paucity of data exists to specifically determine the morbidity associated with this procedure. This analysis was performed to evaluate the morbidity associated with SLN biopsy compared with completion lymph node dissection (CLND).Methods: Patients were enrolled in the Sunbelt Melanoma Trial, a prospective multi-institutional study of SLN biopsy for melanoma. Patients underwent SLN biopsy and were prospectively followed up for the development of complications associated with this technique. Patients who had evidence of nodal metastasis in the SLN underwent CLND. Complications associated with SLN biopsy alone were compared with those associated with SLN biopsy plus CLND.Results: A total of 2120 patients were evaluated, with a median follow-up of 16 months. Overall, 96 (4.6%) of 2120 patients developed major or minor complications associated with SLN biopsy, whereas 103 (23.2%) of 444 patients experienced complications associated with SLN biopsy plus CLND. There were no deaths associated with either procedure.Conclusions: SLN biopsy alone is associated with significantly less morbidity compared with SLN biopsy plus CLND.W.W.R. and S.L.W. contributed equally to this work.     

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

Background 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.Methods 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.Results 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).Conclusions 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.Preliminary results of this study were presented as an oral presentation during the Melanoma Session on the 59th Annual Cancer Symposium of the Society of Surgical Oncology, San Diego, CA, March 23–25, 2006.     

Observation After a Positive Sentinel Lymph Node Biopsy in Patients with Melanoma

Background

The benefit of completion lymph node dissection (CLND) in melanoma patients with a positive sentinel lymph node (SLN) remains unknown.

Methods

We identified patients with a positive SLN from 1994 to 2012. Patient and tumor characteristics, reasons for not undergoing CLND, patterns of recurrence, and melanoma-specific survival data were analyzed.

Results

Of 4,310 patients undergoing SLN biopsy (SLNB), 495 (11 %) had a positive SLN—167 (34 %) patients underwent nodal observation and 328 (66 %) had immediate CLND. Patients in the no-CLND group were older (66 vs. 56 years; p < 0.001) and more likely to have lower extremity lesions (57 vs. 42 %; p = 0.006). There were no differences in tumor thickness, Clark level of invasion, ulceration, or SLN tumor burden. Median follow-up was 23 and 80 months for the no-CLND and CLND groups, respectively, and median time to recurrence was similar at 9 and 12 months, respectively (p = 0.48). There was no difference in local and in transit recurrence rates between groups (16 %, no CLND, and 18 %, CLND; p = 0.48). Nodal disease as a site of first recurrence occurred in 15 % of patients in the no-CLND group and 6 % of CLND patients (p = 0.002). In contrast, systemic recurrences occurred in 8 % of no-CLND patients compared with 27 % of CLND patients (p < 0.001). While median recurrence-free survival was higher after CLND (34.5 vs. 20.9 months; p = 0.02), melanoma-specific survival was similar (not reached, no CLND vs. 110 months, CLND; p = 0.09).

Conclusions

Immediate CLND after a positive SLNB is associated with fewer initial nodal basin recurrences but similar melanoma-specific survival. These results support ongoing equipoise in the Multicenter Selective Lymphadenectomy Trial II (MSLT-II).     

Age-related disparities in use of completion lymphadenectomy for melanoma sentinel lymph node metastasis

Background

Guidelines recommend that patients with melanoma metastatic to the sentinel lymph node (SLN) undergo a completion lymphadenectomy (CLND) of the affected lymph node basin. We have previously reported on decreased use of SLN biopsy among elderly patients. We hypothesized that elderly patients with SLN metastases would have lower rates of CLND relative to their younger counterparts.

Methods

The Surveillance, Epidemiology, and End Results database was queried for patients who underwent SLN biopsy for intermediate thickness cutaneous melanoma (Breslow thickness 1.01 mm–4.00 mm) from 2004 to 2008 and were found to have SLN metastasis. Patients were categorized according to age by decade. We then used multivariate logistic regression models to predict receipt of CLND. Additional covariates included sex, race/ethnicity, T stage, tumor histology, tumor location, and ulceration. The likelihood of receiving a CLND was reported as OR with 95% CI; significance was set at P ≤ 0.05.

Results

Entry criteria were met by 765 patients. Of these, 548 (71.6%) patients underwent CLND. On multivariate analysis, patients in the age groups 70–79 y old (OR 0.39, CI 0.20–0.78; P = 0.007) and ≥80 y old (OR 0.27, CI 0.12–0.61; P = 0.001) were less likely to undergo CLND than the youngest age group (1–39 y old).

Conclusions

Elderly patients with SLN metastasis are less likely to receive CLND than their younger counterparts. A multi-center randomized clinical trial evaluating the potential survival benefit of CLND is ongoing. Further research to assess reasons why the elderly are less likely to receive CLND are needed.     

Histological Features of Melanoma Sentinel Lymph Node Metastases Associated with Status of the Completion Lymphadenectomy and Rate of Subsequent Relapse

Background The current recommendation for patients with cutaneous melanoma and a positive sentinel lymph node (SLN) biopsy is a completion lymph node dissection (CLND). This study sought to define a population of SLN-positive patients, based on their histological pattern of SLN metastases, who may not require CLND. Methods All patients with SLN-positive cutaneous melanoma who underwent CLND between March 1999 and December 2004 at a single academic institution were enrolled. Metastatic deposits in the SLN were categorized by their histological zone of involvement (subcapsular, parenchymal and/or sinusoidal). Logistic regression was used to examine the effect of SLN zone, size of nodal metastases, and other histological factors on CLND positivity. Kaplan-Meier and Cox models were used to study disease recurrence. Results A total of 127 patients were included, and 15.8% had positive non-sentinel nodes. In adjusted analyses, the size of the largest tumor deposit in the SLN was the only factor associated with CLND status. No patients with a tumor deposit ≤0.20 mm had a positive CLND. Although a specific zone of tumor involvement was not predictive of CLND status, involvement of all three zones was independently associated with increased recurrence. Size of the largest tumor deposit was also associated with recurrence, with no recurrences in patients with nodal deposits ≤0.20 mm. Conclusion Histologic features of tumor metastases in positive SLN may be useful in defining a population of patients who may be spared CLND and a group at high risk of recurrence.     

Microscopic Satellitosis in Patients with Primary Cutaneous Melanoma: Implications for Nodal Basin Staging

Background  Microscopic satellitosis in melanoma is uncommon. The role of regional basin staging/therapy in patients with this high-risk feature has not been well defined. Methods  Patients presenting from 1996 to 2005 with clinically localized melanoma containing microscopic satellitosis were identified from a prospective, single-institution database. Multiple factors were analyzed to determine their predictive value for recurrence. The management of the draining nodal basin was evaluated to determine its impact on recurrence and survival. Results  Thirty-eight patients presented to our institution during this time period with clinically localized melanoma containing microscopic satellitosis. The 5-year overall and disease-free survivals in these patients were 34% and 18%, respectively. Sixty-eight percent had pathologically involved regional nodal metastases. With median follow-up of 21 months, 68% recurred, with a median time to recurrence of 9 months. Lymphovascular invasion (LVI) (p = 0.01), tumor regression (p = 0.04), and positive regional lymph nodes (p = 0.02) were associated with an increased risk of recurrence. Of the 31 patients who underwent sentinel lymph node (SLN) biopsy, 22 had metastasis in the SLN (71%). Fifteen of these patients underwent completion lymphadenectomy (CLND) and seven were observed. There was no difference in disease-free survival (DFS), disease-specific survival (DSS), or overall survival (OS) between these groups (p = 0.42). Conclusions  Pathological lymph node metastases were more prevalent (68%) than in any group previously defined. Regional nodal status predicted recurrence but not nodal recurrence. In SLN-positive patients, CLND did not improve DFS, DSS, or OS, although the number of patients was small. Further studies are needed to determine the utility of regional nodal staging/therapy in these high-risk patients.     

Axillary recurrence is low in patients with breast cancer who do not undergo completion axillary lymph node dissection for micrometastases in sentinel lymph nodes

Completion axillary lymph node dissection (CLND) is presently the standard of care after a positive sentinel lymph node biopsy (SLNB). We hypothesize that the incidence of axillary recurrence in patients who do not undergo CLND for micrometastases is low, and CLND is not necessary for locoregional control. We performed a retrospective chart review of patients with invasive breast carcinoma and micrometastases detected on SLNB. The Memorial Sloan Kettering Nomogram (MSKN) predicting the likelihood of nonsentinel lymph node (NSN) metastases was compared with the incidence of positive NSN. There were 61 patients identified with a mean follow-up of 70 months. The average tumor size was 2 cm. The median number of positive SLNs was one. Twenty-eight (46%) patients had a CLND; of these, 20 patients had one positive NSN (2 of 28 [7%]) and the mean MSKN score was 12 per cent. There were 33 (54%) patients who had SLNB alone, and their mean MSKN score was 13 per cent. Axillary recurrence in this group was 1.6 per cent. We conclude the incidence of axillary recurrence in patients with micrometastases detected by SLN biopsy who do not undergo CLND is low. The use of a predictive nomogram to estimate likelihood of metastatic disease to NSN may overestimate the actual incidence of positive NSN in patients with micrometastases.     

Is completion lymphadenectomy after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary?

HYPOTHESIS: Completion lymph node dissection (CLND) has usually been recommended after metastatic disease is identified in the sentinel lymph node (SLN) biopsy to eradicate further metastases in nonsentinel nodes. We hypothesized that patients with negative lymph nodes included in the initial SLN specimen have low risk of metastases in the residual draining basin and may not require CLND. DESIGN: Chart review. SETTING: University-affiliated tertiary care referral center. PATIENTS: Between January 1, 1997, and May 31, 2003, 506 consecutive patients underwent SLN biopsy for staging of primary cutaneous melanoma. INTERVENTION: The SLN biopsy identified 87 patients (17.2%) with metastatic melanoma, of whom 80 underwent CLND. RESULTS: In 28 patients, all SLNs were found to contain metastatic melanoma. Seven (25%) of these patients had additional metastases identified in the CLND specimen. In 52 patients, 1 or more SLNs did not contain metastatic melanoma. Five (10%) of these patients had additional metastases in the CLND specimen (P =.02). CONCLUSIONS: Although no evidence of metastatic melanoma was found on CLND in most patients in whom negative nodes had been removed with positive SLNs at the initial biopsy, 10% of these patients did have further metastases. This subgroup of patients (positive SLNs and negative nodes in the SLN biopsy specimen) is at significantly lower risk for further metastasis, but CLND cannot be safely omitted even for these patients.     

Higher rates of regional disease but improved outcomes in pediatric versus adult melanoma

BackgroundMalignant melanoma is rare in the pediatric population and management is largely extrapolated from adult guidelines. Adult data have shown that immediate completion lymph node dissection (CLND) does not improve overall survival in selected patients with clinically node negative, sentinel lymph node-positive disease. Current nodal management in children is unknown.MethodsThe National Cancer Database (NCDB) was queried for patients with melanoma from 2012-2017 and patients categorized as pediatric (≤18 years, n=962) or adult (n=327,987). Factors associated with CLND in children with positive SLNB were evaluated in multivariable analysis. Kaplan-Meier survival analysis was performed.ResultsCompared to adults, children present with thicker primary tumors (T3 or T4 26.5% vs 15.5%, p<0.001), resulting in higher rates of nodal assessment with SLN biopsy or LND (60.2% vs 36.6%, p<0.001) and higher rates of regional nodal disease (35.1% vs 23.4%, p<0.001). Children underwent higher rates of CLND after SLN biopsy (10.4% vs 4.1%) and upfront lymph node dissection (15.2% vs 8.7%). A decreased rate of CLND was noted in 2017 compared to 2012 (odds ratio (OR) 0.16 (p=0.005). CLND was performed more often on multivariable analysis for older pediatric age (>12 years, OR=1.6, p=0.037) and lower extremity primary (OR=0.29, p<0.001). Children with regional nodal disease have improved 3-year overall survival compared to adults (96.5% vs 71.0%, p<0.001).ConclusionsChildren with melanoma have higher rates of nodal disease but better survival than adults. As in adults, there has been a recent increase in close nodal observation rather than CLND for patients with positive SLN. Further study of nodal surveillance for pediatric patients is warranted.     

Results of Sentinel Lymph Node Biopsy in Patients With Thin Melanoma

Background Sentinel lymph node (SLN) biopsy has been shown to be a highly accurate method of staging nodal basins in melanoma patients. Although this technique is widely accepted in patients with intermediate-thickness tumors, it is unclear what the indications are for thin (≤1 mm) melanoma. Methods From May 1991 to October 2004, 223 patients with thin melanoma underwent SLN biopsy at Memorial Sloan-Kettering Cancer Center. Most patients with thin melanoma were selected for the procedure because of high-risk clinicopathologic features. Results Nodal metastases were found in eight patients (3.6%) who underwent SLN biopsy. All positive SLNs were found in patients with ≥.75 mm-thick and Clark level IV melanoma (8 of 114; 7%). Age, sex, tumor location, thickness, Clark level, ulceration, regression, tumor-infiltrating lymphocytes, mitotic rate, and number of mapped nodal basins were not predictive of positive SLNs (χ²; P = not significant). With a median follow-up of 25 months, there have been no recurrences or deaths in patients with melanoma <.75 mm. Six patients have had regional and/or systemic recurrences (2.7%), only one of whom had a positive SLN. Three patients have died of melanoma; all had negative SLNs. Conclusions Nodal metastasis in thin melanoma is uncommon, especially in patients with <.75 mm and Clark level II or III melanoma. In our experience, no single clinicopathologic factor was predictive of nodal metastases. The prognostic implications of positive SLNs in thin melanoma remain undefined.