Radar-Guided Localization and Resection for Metastatic Nodal and Soft Tissue Melanoma: A Single-Institution Retrospective Study

Introduction

For isolated locoregional or distant metastatic melanoma such as in-transit disease, recurrent nodal disease, or oligometastatic stage IV disease, surgical resection either before adjuvant therapy or after neoadjuvant therapy is a recommended treatment option. ¹ For clinically detectable resectable nodal disease, current National Comprehensive Cancer Network guidelines recommend complete therapeutic lymph node dissection (TLND), with or without neoadjuvant therapy. ¹ In most cases of clinically detectable nodal metastatic disease, anatomic landmarks are sufficient to guide the lymphadenectomy. However, some metastasectomy procedures require or at least benefit from a guidance method (eg, intraoperative ultrasound or preoperative wire localization), generally due to a nonpalpable tumor.

One procedure that may benefit from the use of a guidance or localization method is targeted index lymph node (ILN) removal after neoadjuvant therapy. Recent studies have shown the potential for ILN removal after neoadjuvant therapy to obviate the need for TLND in some patients.^2,3 In the PRADO trial, patients with stage III nodal disease were treated with 6 weeks of neoadjuvant ipilimumab 1 mg/kg and nivolumab 3 mg/kg followed by ILN removal. Patients found to have a major pathologic response (mPR) to preoperative therapy did not undergo TLND or postoperative adjuvant therapy. This group had better 24-month relapse-free survival and distant-metastasis free survival (93% and 98%, respectively) compared with those who had pathologic partial response and underwent TLND without adjuvant therapy (64% and 64%) as well as those who had pathologic non-response and underwent TLND with adjuvant systemic therapy with or without adjuvant radiotherapy (71% and 76%). The researchers concluded that using ILN response to tailor additional surgical and systemic (adjuvant) treatment is feasible and warrants further study as a personalized approach for melanoma patients who undergo neoadjuvant therapy. ² Compared to either ILN removal or sentinel lymph node (SLN) biopsy, in which only one or a few preoperatively designated and intraoperatively localized nodes are removed, TLND has higher morbidity rates, including higher risk of lymphedema. ⁴ The PRADO trial saw significantly fewer overall surgery-related adverse events (P < .001) as well as a lower incidence of lymphedema (P < .001) in the ILN-only group compared with those who underwent TLND. ² These data support the consideration of ILN removal in lieu of TLND for appropriately selected patients with nodal disease, and thus, there is an unmet need for an effective localization system so that the ILN may be identified weeks or months later, even if preoperative treatment results in marked tumor shrinkage. An ideal system would allow for placement prior to neoadjuvant therapy, not impede any imaging modalities that may be required prior to surgery, and not present risk with prolonged placement – including the possibility that the localized node would never be retrieved due to the development of severe toxicity or disease progression.

For resection of nonpalpable subcutaneous nodules, several guidance methods have been utilized to intraoperatively locate the tumor and facilitate incision placement. Most of the localization approaches used to date for melanoma are similar to those utilized by breast surgeons for nonpalpable breast lesions. Traditionally, wire localization or intraoperative ultrasound have been used for surgical guidance. Wires must be placed on the day of surgery and protrude from the skin, increasing patient discomfort and chance of dislodgement, and intraoperative ultrasound relies on the visibility of the lesion in contrast to the surrounding tissue, in many cases requiring a radiologist or ultrasound technologist to assist the surgeon in the operating room. Newer alternative localization methods use a marker that is placed in advance of surgery and may be located intraoperatively with a handheld probe, with options including radioactive, magnetic, and radar-reflecting markers.

Radar-guided localization (RGL) employs the use of a small percutaneously placed radar-reflecting clip that is located intraoperatively using a handheld detection probe, which emits micro-impulse radar and employs infrared light technology to activate and localize the reflector. ⁵ Visual and audible cues indicate the distance from the probe to the reflector. The reflector is non-radioactive and wire-free, about the size of a medium titanium surgical clip, and its relatively inert nature and lack of imaging artifact allows it to be placed well in advance of surgery, even in advance of neoadjuvant therapy. The SCOUT® system (Merit Medical, Jordan, UT), previously called SAVI Scout, is a RGL system with United States Food and Drug Administration 510(k) clearance as a Class II-regulated device for placement in soft tissue lesions for greater than 30 days to mark a site intended for surgical removal. The use of radar guidance with the SCOUT® system has been well-studied for use in breast surgery, where it has been shown to have lower re-resection rates ⁶ and similar rates of margin positivity as wire localization.^7,8 RGL has also been used in resection of soft tissue sarcoma and thoracoscopically for lung nodules;^9,10 however, published use of RGL for melanoma is limited to one case in which RGL was used to localize a subcutaneous in-transit metastasis in a stage IIIC melanoma patient. ¹¹ Our study represents the largest institutional series describing the efficacy of RGL for melanoma metastasectomy.

Methods

After receiving an exempt determination from the Institutional Review Board (IRB #00000971), a retrospective study was performed that included patients age 16 and older with American Joint Committee on Cancer (AJCC) stage III or IV melanoma who underwent a RGL melanoma metastasectomy between December 2020 and June 2023 at our cancer center. Patients meeting these criteria were selected consecutively, eliminating potential bias. Procedures were performed by surgical oncologists in the Department of Cutaneous Oncology. Patients deemed appropriate for RGL melanoma metastasectomy had radar reflectors placed prior to surgery in either a lymph node or other stage III or stage IV soft tissue site of metastasis. The reporting of this study conforms to STROBE guidelines. ¹²

Our facility uses the SCOUT® system by Merit Medical (Jordan, UT). Reflectors are placed days to months ahead of surgery. In some cases with high suspicion of disease likely to require neoadjuvant therapy, reflectors are placed at the time of percutaneous needle biopsy. Reflector placement is performed by interventional or diagnostic radiology under local anesthesia. Using ultrasound guidance, the radiologist advances a 16-gauge needle preloaded with the radar reflector into the tumor and deploys the reflector (Figure 1A). Placement in the tumor is confirmed with at least one of the following: ultrasound imaging (Figure 1B), signal retrieval from the reflector, and/or radiography. Intraoperatively, the reflector is located using a handheld probe that emits radar signals and reflector-activating infrared light, and the system gives both auditory and visual cues to indicate distance between the probe and reflector, guiding the surgeon to the tumor (Figure 1C). The presence of the reflector in the excised tissue is confirmed using intraoperative specimen radiography (Figure 1D). All excised tissue is sent to in-house pathologists for histologic analysis.OPEN IN VIEWER

Data was collected retrospectively from patient charts and included demographics, primary melanoma characteristics, treatments prior to and after the RGL procedure, timing and characteristics of the RGL procedure, surgical pathology results, and recurrence and disease status at last follow-up. The surgical pathology report was used to assess margin status and presence of viable melanoma pathological response after neoadjuvant therapy. All patient data have been de-identified.

Staging is reported according to the AJCC eighth Edition guidelines. ¹³ Clear margins were defined as no microscopic disease present at the margins of the surgical specimen containing the reflector-marked nodule. For those who underwent neoadjuvant treatment, pathologic complete response (pCR) was defined as no viable tumor in the specimen, pathologic partial response (pPR) was defined as ≤50% viable tumor, and pathologic non-response (pNR) was defined as >50% viable tumor. Radiologic progression was defined as >25% enlargement of metastatic foci on imaging or development of new lesions.

Results

Over the course of this study, there were 25 cases in which 24 patients had radar reflectors placed in metastatic sites at our facility (one patient underwent a second RGL metastasectomy for a regional recurrence). All reflectors were placed successfully by radiology as confirmed on ultrasound, and there were no complications attributable to reflector insertion. Eight reflectors were placed on the same day as the initial needle biopsy of the metastasis due to high clinical or radiological suspicion of disease. Two cases were excluded from analysis; one patient elected to forego additional treatment after reflector placement, and another patient had their TLND performed at a different facility. Reflector placement and retrieval status, and resultant number of cases included for each portion of the analysis, are outlined in Figure 2.OPEN IN VIEWER

Case Characteristics

Characteristics of each RGL case can be found in Table 1. All patients were white, and patients ranged in age from 16-84 years. At the time of their RGL metastasectomy, patients had either AJCC stage III (20; 87%) or IV disease (3; 13%), with stage IIIC being the most common at 39% of cases. The stage IV patients had evidence of only oligometastatic disease at the time of reflector placement. Four patients had not had a prior melanoma surgery.

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Table 1.

Characteristics of Melanoma Metastasectomy Cases Performed With Radar-Guided Localization.

Case	AJCC Stage at RGL	Sex	Age at RGL	RGL Reflector Placement Site	Metastasectomy Procedure	Neoadjuvant Therapy	Reflector Placed Before Neoadjuvant Initiated?	Days from Reflector Placement to Metastasectomy	Reflector Retrieved?	RGL Margin Status	Response to Neoadjuvant	Adjuvant Therapy	Progression or Recurrence Sites Post-RGL (if any)	Months from RGL to First Progression or Recurrence	Time to Follow-Up (Months)	Disease Status at Last Follow-Up
1	III	M	79	Axillary LN	ILNR	ICI	No	50	Yes	Clear	pNR	ICI	None	N/A	4	NED
2	IIIB	F	83	STN	STNR	None	N/A	9	Yes	Clear	N/A	ICI	R	9	27	AWD
3	IIIB	F	84	STN	STNR	None	N/A	2	Yes	Clear	N/A	ICI	R	13	17	AWD
4	IIIB	F	84	Axillary LN	ILNR	ICI	Yes	223	Yes	NVT a	pCR	ICI	None	N/A	16	NED
5	IIIB	M	65	Axillary LN	ILNR	ICI	Yes	128	Yes	NVT a	pCR	None	None	N/A	19	NED
6	IIIB	M	50	Inguinal LN	ILNR	ICI	Yes	282	Yes	NVT a	pCR	None	D	1	3	DoD
7	IIIB	F	48	Inguinal LN	ILNR	ICI, BRAF inhibitor	Yes	190	Yes	NVT a	pCR	None	R	2	4	AWD
8	IIIB	F	53	Cervical LN	ILNR	ICI	Yes	134	Yes	NVT a	pCR	None	None	N/A	0	NED
9	IIIC	F	66	STN	STNR	None	N/A	23	Yes	Clear	N/A	ICI	R	8	16	AWD
10	IIIC	F	46	Axillary LN	TLND	None	N/A	14	Yes	Clear	N/A	BRAF inhibitor	L, R, D	9	26	AWD
11	IIIC	F	58	STN	STNR	None	N/A	20	Yes	Clear	N/A	ICI	L, D	5	30	AWD
12	IIIC	M	44	Back LN	ILNR	None	N/A	3	Yes	Clear	N/A	ICI, XRT	None	N/A	12	NED
13	IIIC	F	66	Inguinal LN	ILNR	ICI	Yes	137	Yes	Clear	pPR	ICI (planned)	None	N/A	3	NED
14	IIIC	M	59	Axillary LN	ILNR	ICI	Yes	163	Yes	Clear	pNR	None	R, D	3	13	DoD
15	IIIC	F	72	Axillary LN	ILNR	ICI	Yes	77	Yes	NVT a	pCR	None	None	N/A	8	NED
16	IIIC	M	16	Inguinal LN	ILNR	ICI	Yes	98	Yes	NVT a	pCR	None	None	N/A	0	NED
17	IIIC	F	61	Cervical LN	ILNR	None	N/A	71	No	N/A c	N/A	None	None	N/A	5 c	NED c
18	IIID	M	76	Inguinal LN	ILNR	None	N/A	9	Yes	NVT b	N/A	None	R	4	22	NED
19	IIID	F	35	Axillary LN	TLND	ICI	Yes	96	Yes	NVT a	pCR	None	None	N/A	17	NED
20	IIID	F	67	STN	STNR	None	N/A	11	Yes	N/A d	N/A	XRT d	None	N/A	1 d	AWD d
21	IV	F	22	STN	STNR	None	N/A	23	Yes	Clear	N/A	None	D	0	7	DoD
22	IV	F	59	STN	STNR	BRAF inhibitor	No	10	Yes	NVT a	pCR	None	D	2	9	AWD
23	IV	M	77	STN	STNR	ICI	No	7	Yes	NVT a	pCR	None	None	N/A	1	NED

Abbreviations: AJCC: American Joint Committee on Cancer; ICI: immune checkpoint inhibitor; AWD: alive with disease; ILNR: index lymph node removal; D: distant; M: male; DoD: dead of disease; L: local; F: female; LN: lymph node; NED: no evidence of disease; R: regional; NVT: no viable tumor; STN: soft tissue nodule; pCR: pathologic complete response; STNR: soft tissue nodule removal; pNR: pathologic non-response; TLND: therapeutic lymph node dissection; pPR: pathologic partial response; XRT: radiation therapy.

^aNo viable tumor due to complete response to neoadjuvant therapy.

^bNo viable tumor due to inconclusive biopsy pathology.

^cReflector unable to be located intraoperatively; no incision was made. Excluded from margin status and follow-up analysis.

^dReflector migrated and did not contain tumor upon excision; tumor was not excised. Patient received alternative treatment with XRT. Excluded from margin status and follow-up analysis.

The 23 metastasectomy cases consisted of 8 soft tissue nodule removals (35%), 13 targeted ILN removals (57%), and 2 TLNDs (9%). In 13 of 23 cases (57%), patients received neoadjuvant therapy leading up to metastasectomy, which consisted of immune checkpoint inhibitors (ICIs) alone (11; 85%), BRAF inhibitors alone (1; 8%), or ICIs followed by BRAF inhibitors (1; 8%). In 10 of the 13 neoadjuvant cases (77%), the reflector was placed in the index node or nodule ahead of neoadjuvant initiation. Three reflectors were placed after neoadjuvant initiation due to patient scheduling/transportation challenges (1) and placement deemed necessary after tumor shrinkage to aid in identifying the tumor at surgery (2). The median time from reflector placement to metastasectomy was 13 days for those who did not receive neoadjuvant therapy (range 2-71 days) and 128 days in those who received neoadjuvant therapy (range 7-282 days).

Discussion

In selecting a surgical guidance method, important factors to consider include timing of placement in relation to surgery, whether neoadjuvant therapy will be used, imaging needs, depth of the tumor, and intraoperative considerations such as instrumentation needs and availability of support for ultrasound interpretation. Traditional wire localization maintains the advantages of low cost and deep marking capability. However, wires must be placed the morning of surgery and have significant risk for dislodgment. ¹⁴ Other markers including radioactive, magnetic, and radar reflectors, in comparison, are placed ahead of surgery, which has the advantage of decoupling radiology and surgery schedules^8,15 but the disadvantage if not placed on the day of biopsy of requiring an additional trip to the office for patients, some of whom live several hours away. Use of wires in the axilla has additional considerations, including proximity to sensitive structures and risk of dislodgement with arm movement. ¹⁴ With careful attention to prevent dislodgement, situations for which wire localization may be well-suited for use in melanoma include patients who have deep tumors or who do not benefit from having a marker placed in advance.

Publications on the use of localization techniques in melanoma are limited and are focused on wire localization,^16-19 with few reports on use of the magnetic seed,^3,20 radioactive seed, ²¹ and RGL. ¹¹ In the context of breast surgery, RGL has been shown to have similar or better efficacy than alternatives including low migration rates.^6,8,22 Two major advantages of RGL over alternative markers are its inert nature and lack of radiologic artifact, allowing it to remain in vivo indefinitely and not interfere with imaging or require polymer surgical instruments. While the radioactive seed and the magnetic seed may also be placed ahead of surgery, radioactive seeds present a regulatory burden in the operating room and should not remain in the body for more than 5-7 days due to radiation exposure, making placement ahead of neoadjuvant therapy impractical. ¹⁴ Magnetic seeds pose minimal safety risks and may be placed far in advance of surgery, but drawbacks include interference with magnetic resonance imaging (MRI) and preclusion of the use of metal surgical instruments for operating, at least while the magnetic detection probe is in use. ³ Intraoperative ultrasound has the advantage of not requiring placement of a marker, and a network meta-analysis found ultrasound guidance to have the decreased margin positivity rates (odds ratio .19, 95% confidence interval .11-.60) compared to localization techniques for breast cancer, including wire localization and radioactive seed localization; there was insufficient data on magnetic seeds and radar guidance. ²³ However, drawbacks include reliance on the visibility of the lesion in contrast to the surrounding tissue and requirement of enhanced training or a radiologist or ultrasound technologist to assist the surgeon in the operating room. Ultrasound guidance may also be beneficial as contingency to have in rare cases that a pre-operatively placed marker is unable to be located with its probe.

In terms of implementation, the technical aspect of the RGL probe and system is intuitive for surgeons, as it is utilized similarly to gamma probes for SLN biopsies. The detector probe may be reused, and reflectors themselves are inexpensive, disposable, inert, nonpalpable, and not bothersome to the patient after placement. ¹⁴ When there is high suspicion of metastasis, the reflector may be placed at the time of biopsy and patients may benefit from fewer trips to the office and fewer procedures. Other studies have shown high patient and physician satisfaction with RGL in comparison with other localization methods.^24-26 Though only anecdotal in our case, our surgeons report high satisfaction and ease of use of the technology.

As with all new technology, there are some limitations to use, and RGL is no exception. Rare but potential RGL complications include migration of the reflector and inability to detect the reflector secondary to either migration, deactivation, or depth exceeding the probe’s signal strength. Previous authors have reported when using RGL is deactivation by electrocautery.^9,24 Lack of retrieval is also reported, but if the reflector is not removed, fortunately there are no known concerns with the reflectors remaining in the body indefinitely. With regard to deactivation, other authors have reported that by the time electrocautery was close enough to the reflector to deactivate it, the reflector had already served its purpose by guiding them to the tumor, and targeted removal could continue.^9,24 In our case of inability to locate the reflector, it is unknown why the reflector deactivated, as no incision had been made, and it therefore could not have been deactivated by electrocautery. Cox et al. suggested that halogen lights (which emit in the infrared spectrum) may interfere with the detection of the reflector, but this may be mitigated with shielding, dimming, or redirecting the light, and many facilities now use LED lights which do not emit infrared radiation. ²⁴ Migration of RGL reflectors is rare but does occur, and in one of our cases the reflector migrated from the tumor for unknown reason. An additional disadvantage of RGL is that depth restraints for attaining signal (6 cm) make it less suitable for deeper tumors. ²⁴ The only known potential contraindication for SCOUT reflector placement is nickel allergy, as the SCOUT reflector contains a nickel alloy, nitinol. ²⁷

The ability and safety of RGL to be placed well in advance of surgery are of increasing significance in light of the PRADO trial, which showed excellent outcomes for patients who were complete responders to neoadjuvant therapy and received ILN removal. ² As more evidence arises supporting surgical de-escalation and fewer indications for TLND, identifying individual tumor-bearing nodes will become of high significance, and localization technologies such as RGL will play an increasingly important role in melanoma surgery. Additionally, with the growing evidence for improved outcomes with neoadjuvant therapy, ²⁸ RGL has utility in marking tumors prior to neoadjuvant therapy, preserving the exact location of the specific node following response before resection.

Limitations of this study include small sample size, retrospective nature, single institution, and lack of a control group leading to low external validity. A prospective controlled study could shed more light on the effectiveness of RGL on achieving clear margins and keeping tumors marked without migration during the course of neoadjuvant treatment in melanoma patients. However, the success of RGL in breast surgery combined with the data presented in this manuscript lead us to conclude that RGL is a safe, effective, and efficient technique to localize and then resect metastatic melanoma lesions at any time, including after neoadjuvant treatment.

Conclusion

In our experience, RGL is a safe and effective surgical guidance method for melanoma metastasectomy with very few cases of surgical challenges. An important advantage of the technology is the inert nature of the reflector, allowing it to remain in the body indefinitely. This feature lends RGL to use in marking tumors ahead of neoadjuvant treatment, which in the case of response to treatment, keeps the shrinking tumor marked and localizable for eventual resection. As ILN removals rise in the wake of the PRADO trial, RGL may be applied to aid surgeons in removing only the index node(s). Additional advantages of RGL include decoupling of placement and surgery scheduling, ability to be placed at biopsy, infrequent reflector migration, lack of interference with MRI, and patient comfort. This study supports that RGL may be successfully used for melanoma metastasectomy, as it has been for several years in breast surgery.