PAPER Is Completion Lymphadenectomy After a Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma Always Necessary? Nahel Elias, MD; Kenneth K. Tanabe, MD; Arthur J. Sober, MD; Michele A. Gadd, MD; Martin C. Mihm, MD; Barrett Goodspeed, MS; A. Benedict Cosimi, MD Hypothesis: Completion lymph node dissection (CLND) Results: In 28 patients, all SLNs were found to con- has usually been recommended after metastatic disease is tain metastatic melanoma. Seven (25%) of these identified in the sentinel lymph node (SLN) biopsy to eradi- patients had additional metastases identified in the cate further metastases in nonsentinel nodes. We hypoth- CLND specimen. In 52 patients, 1 or more SLNs did esized that patients with negative lymph nodes included not contain metastatic melanoma. Five (10%) of these in the initial SLN specimen have low risk of metastases in patients had additional metastases in the CLND speci- the residual draining basin and may not require CLND. men (P=.02). Design: Chart review. Conclusions: Although no evidence of metastatic mela- noma was found on CLND in most patients in whom Setting: University-affiliated tertiary care referral center. negative nodes had been removed with positive SLNs at the initial biopsy, 10% of these patients did have further Patients: Between January 1, 1997, and May 31, 2003, metastases. This subgroup of patients (positive SLNs and 506 consecutive patients underwent SLN biopsy for stag- negative nodes in the SLN biopsy specimen) is at signifi- ing of primary cutaneous melanoma. cantly lower risk for further metastasis, but CLND can- not be safely omitted even for these patients. Intervention: The SLN biopsy identified 87 patients (17.2%) with metastatic melanoma, of whom 80 under- went CLND. Arch Surg. 2004;139:400-405 HE INCIDENCE OF MELA- survival of these patients by approxi- noma in the United States mately 40%, independent of, and super- has been increasing more seding, any primary tumor characteris- rapidly than that of any other tics.2 Thus, it was incorporated into the cancer during the past few new American Joint Committee on Can- decades. The lifetime risk of developing cer staging system for cutaneous mela- T 3 melanoma in 1960 was 1 in 600 individu- noma. The logical goal, therefore, has been als; it is currently approximately 1 in 70 in- to develop therapeutic strategies that dividuals; and it is projected to be 1 in 50 would remove involved lymph nodes early individuals by 2010.1 It is the most deadly in the course of the disease. Until re- form of skin cancer and currently the eighth cently, one such approach included elec- most common cancer in the United States. tive lymph node dissection (ELND) for pa- Moreover, melanoma affects young per- tients with high-risk primary lesions. sons who are in the most productive years Despite the theoretical benefits of this pro- of their lives; accordingly, it constitutes a cedure, prospective trials have failed to major public health problem. confirm a survival advantage for the pa- Primary treatment of cutaneous mela- tients randomized to ELND4-6 except for noma has always included wide local ex- perhaps selected subgroups.7 Obviously, From the Departments of cision, but the assessment and manage- this results from the inclusion, in the Surgery (Drs Elias, Tanabe, ment of regional nodes has remained ELND group, of all high-risk patients, most Gadd, and Cosimi), Dermatology (Dr Sober), and controversial. Clearly, regional lymph node of whom do not have positive nodes and Pathology (Dr Mihm and metastasis in patients with primary cuta- therefore could not have benefited from Mr Goodspeed), Massachusetts neous melanoma is the most important regional node dissection. General Hospital and Harvard prognostic factor for tumor recurrence and The introduction and validation of Medical School, Boston. survival. Its presence decreases the 5-year sentinel lymph node (SLN) mapping and (REPRINTED) ARCH SURG/ VOL 139, APR 2004 WWW.ARCHSURG.COM 400 ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 biopsy during the past decade now permits identifica- tion of a subgroup of patients with metastatic disease with minimal morbidity. This technique has gained wide ac- ceptance since the first report by Morton and colleagues in 1992,8 in particular since SLN results in significantly less morbidity than ELND and also identifies unsus- pected draining nodal basins with the aid of lymphos- cintigraphy. Completion lymph node dissection (CLND) is rec- ommended for the approximately 20% of patients with metastatic disease identified in sentinel nodes,9,10 based on the apparent benefit provided to this subgroup com- pared with delayed lymph node dissection at the time that clinical metastases are identified.6 As a result, SLN bi- opsy has evolved as the accepted regional nodes staging method, ELND has become a concept of historical in- terest, and approximately 80% of patients with high- risk primary lesions are spared the morbidity associated with ELND. The SLN is identified by intraoperative lymphoscin- tigraphy with the use of a handheld gamma counter and by direct visualization of blue-stained tissue (Figure 1) in the draining lymphatic basin after intradermal injec- 99m tion of a radioactive tracer (technetium Tc 99m [ Tc] Figure 1. Intraoperative photograph of a sentinel lymph node and the sulfur colloid) and isosulfan blue around the primary mela- afferent lymphatic. Note the isosulfan blue staining of the sentinel node and noma biopsy site. The use of the blue dye in combination the afferent lymphatic. with the radioactive colloid has been demonstrated to lead to optimal detection and identification of the SLNs.11-18 Since only 15% to 20% of patients with a positive consecutive patients treated between January 1, 1997, and May 31, 2003. None of the patients had clinical evidence of meta- SLN biopsy specimen are found to have further meta- 19 static melanoma at the time of their lymphatic mapping as as- static disease in the CLND specimen, many authors have sessed by clinical history and physical examination findings. sought to identify prognostic factors that predict the re- All of these patients underwent SLN biopsy with the plan to sidual nodal basin disease status after SLN biopsy be- perform CLND if SLN metastases were identified; none of these fore CLND and, thereby, limit CLND to patients with patients underwent an initial ELND. probable further metastases. Previous multi-insti- Of these patients, we identified and further evaluated the tution20 and single-institution21 studies have concluded subgroup that had histologically positive SLNs. The pathologi- that primary tumor features, such as thickness or ulcer- cal characteristics of the primary melanoma, the number of nodes ation, cannot reliably identify patient subpopulations with recovered during SLN biopsy, the number of nodes with evi- minimal risk of metastatic disease in the nonsentinel dence of metastatic melanoma, the number of patients who un- 22 derwent CLND after SLN biopsy, and the pathology reports of nodes. More recently, Reeves et al used a more com- the CLND specimens were reviewed. plex scoring system that combines primary tumor ulcer- ation and size of SLN metastases. They concluded that SLN MAPPING TECHNIQUE patients with a score of 0 are unlikely to have nonsenti- nel node metastases or to benefit from CLND. Since only The technique of SLN mapping was previously reported in de- 21 patients were included in this group, however, this tail by Gadd et al.23 In brief, approximately 3 hours before the 99m recommendation requires validation in larger studies. operation, Tc sulfur colloid (CIS-US Inc, Bedford, Mass) was We have questioned whether the finding of histo- injected into the dermis surrounding the site of the primary logically negative lymph nodes together with histologi- melanoma or biopsy scar. The total dose was typically divided into 4 equal parts. Planar gamma images were obtained 5 to cally positive SLNs in the biopsy specimen accurately pre- 60 minutes after injection to define the location of the SLNs. dicts the absence of further metastasis in the remaining In the operating room, most patients then received an injec- nodes in the sampled basin, and consequently elimi- tion of 0.5 to 1.5 mL of 1% isosulfan blue vital dye (Lymp- nates the necessity for CLND. hazurin; Zenith Parenterals, Rosemont, Ill) into the dermis cir- cumferentially around the biopsy scar or melanoma. A handheld METHODS gamma detector (Care Wise Medical Products, Morgan Hill, Ca- lif, or Neoprobe Corp, Dublin, Ohio) was used intraopera- tively to precisely identify the location of the SLNs. Sentinel PATIENTS lymph nodes were defined as those that were stained with Lym- We reviewed the records of the Department of Pathology da- phazurin dye and/or concentrated 99mTc sulfur colloid. Accept- tabase and the Department of Surgery case log at the Massa- able basin counts after SLN excision were defined as less than chusetts General Hospital, Boston, to identify all patients who 10% of the counts of the most radioactive lymph node. In all underwent intraoperative lymphatic mapping for cutaneous patients, the entire SLN was immediately placed into isotonic melanoma with a primary tumor thickness of greater than 1 sodium chloride solution. The primary melanoma site was widely mm or invasive to Clark level IV or greater. This identified 506 reexcised during the same operation in most patients. (REPRINTED) ARCH SURG/ VOL 139, APR 2004 WWW.ARCHSURG.COM 401 ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 Table 1. Patient, Tumor, and SLN Characteristics of Patients With a Positive SLN Characteristic Negative CLND Positive CLND No CLND Patients No. 68 12 7 Sex, No. M/F 37/31 6/6 6/1 Age, mean ± SD, y 46.29 ± 15.31 50.16 ± 17.54 46.57 ± 14.18 Primary tumor site, No.