Clinical UM Guideline

 

Subject: Radioactive Seed Localization of Nonpalpable Breast Lesions
Guideline #:  CG-SURG-58 Publish Date:    12/27/2017
Status: Reviewed Last Review Date:    11/02/2017

Description

This document addresses the use of radioactive seed localization (RSL), which is a technique used to provide localization of nonpalpable breast lesions before breast-conserving surgery. This technique is used as an alternative to wire localization (WL) or radio-guided occult lesion localization.

Clinical Indications

Medically Necessary:

Radioactive seed localization of nonpalpable breast lesions is considered medically necessary as a method to localize a nonpalpable breast lesion in advance of surgical excision.

Radioactive seed localization is considered medically necessary to assist in targeted excision of positive axillary lymph nodes after neoadjuvant therapy.

Not Medically Necessary:

The use of radioactive seed localization is considered not medically necessary when the criteria above have not been met, including but not limited to use as a method to localize palpable breast lesions.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

CPT

 

19281

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; first lesion, including mammographic guidance

19282

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; each additional lesion, including mammographic guidance

19283

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; first lesion, including stereotactic guidance

19284

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; each additional lesion, including stereotactic guidance

19285

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; first lesion, including ultrasound guidance

19286

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; each additional lesion, including ultrasound guidance

19287

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; first lesion, including magnetic resonance guidance

19288

Placement of breast localization device(s) (eg, clip, metallic pellet, wire/needle, radioactive seeds), percutaneous; each additional lesion, including magnetic resonance guidance

 

 

ICD-10 Diagnosis

 

 

All diagnoses

Discussion/General Information

An estimated 246,660 women will have newly diagnosed breast cancer this year and approximately 25% to 35% of identified breast cancers are nonpalpable at detection during mammography or by another method (Lovrics, 2011). Nonpalpable breast lesions may be difficult to locate during follow-up procedures such as surgery. To facilitate identification for later procedures, a variety of localization techniques have been developed, including wire localization, RSL, and radio-guided occult lesion localization. RSL placement is typically done in conjunction with mammography or ultrasonography for confirmation of the seed placement. Locating the I125 seed is done intraoperatively with a handheld gamma scan probe that can distinguish photons from the radioactive seed and the radiation from the radiotracer utilized for sentinel lymph node mapping. The computer-based control probe is able to provide approximate distance information for the surgeon to extract the I125 seed along with the surrounding tissue (Barentsz, 2013; Dauer, 2013). Adverse events include migration of the seed, need for additional localization technique, and inability to retrieve the I125 seed.

The current gold standard technique for localization is wire-guided localization which involves the use of a thin, hooked wire that is inserted into the nonpalpable lesion and the external portion of the wire is secured against the skin surface. Typically, later on the same day of wire placement, the surgeon then utilizes the wire to locate and resect the breast lesion. Challenges with the WL procedure include sequential scheduling of the procedures, dislocation of the wire before or during the surgical procedure, and the entry point of the wire is not always in the surgeon’s line of excision. Therefore, the surgeon still has to estimate the location of the tip of the wire and the breast lesion (Barentsz, 2013; Dauer, 2013; Lovrics, 2011).

RSL utilizes a low-dose, radio-opaque titanium seed containing iodine-125-labelled (I125) which is placed into the center of the nonpalpable breast lesion with imaging guidance (for example, mammography or ultrasound).

Langhans (2017) published the results of a prospective randomized controlled trial (RCT) involving 378 subjects with 390 breast lesions. Subjects were assigned to undergo WL (n=192) or RSL (n=186). The authors reported that there were no significant differences between groups with regard to resection margins (p=0.65), margin status (p=0.62), duration of surgery (p=0.12), weight of the surgical specimen (p=0.54) or pain perception (p=0.28). They concluded that, “RSL offers a major logistic advantage, as localization can be done several days before surgery without any increase in positive resection margins compared with WGL.”

Bloomquist and others (2016) reported the results of an RCT involving 125 subjects randomized to either RSL (n=75) or wires localization (n=55). The authors reported no significant differences between groups with regard to main specimen volume (p = 0.67), volume of the first surgery (p=0.67), or rate of positive margins (p=0.53).

The use of multiple RLS seeds was reported in a moderate sized retrospective case series study published by Al-Hilli and others in 2015. This study involved 461 subjects with suspected or confirmed breast cancer who received multiple I125 seeds for bracketing of lesions, presence of multiple lesions in the same breast, or for replacement of a failed prior seed localization attempt. Removal of the targeted lesion was successful in all cases. In total, 28% of subjects had close or positive margins resulting in a second procedure, and 34% of subjects with bracketing procedures underwent re-excision of positive margins or culminated in a mastectomy. The authors stated that the use of multiple radioactive seeds for localizing multiple lesions in the same breast or bracketing lesions is feasible and safe.

A randomized controlled trial performed at three participating centers enrolled 333 women who had planned for localization and breast conserving surgery for confirmed invasive or ductal carcinoma in situ (DCIS) (Lovrics, 2011). The WL group included 153 randomized participants and the RSL group had 152 participants, all who were treated between 2004 and 2010. There was no significant difference in the rates of positive margins between the groups (10.5% RSL vs. 11.8% WL; p=0.99). The mean excised tumor size was similar for both groups. The RSL group had a significantly shorter operative time of 19.4 minutes compared to the WL group’s 22.2 minutes (p<0.001). The satisfaction survey for radiologists and the participants did not show any significant differences. However, the surgeons had a satisfaction rating that favored RSL (p=0.008). Seed migration was reported in one RSL case and the wire migrated in two cases. In one case, the wire fell out during surgery. The surgeons were able to remove 100% of the index lesions successfully.

Gray and colleagues (2001) reported results from a randomized trial of 106 women with nonpalpable breast lesions treated between 1999 and 2001. Data was missing for 5 participants, leaving 97 evaluable cases, with 51 in the RSL cohort and 46 in the WL cohort. No significant difference in the mean volume of excised tissue was reported. However, there was a significant difference in the excised margins being pathologically involved in less specimens from the RSL group compared to the WL group (26% vs. 57%; p=0.96). There was no significant difference in the mean times to localization and excision of the masses.

In 2014, Diego reported the results of a retrospective, nonrandomized study involving 324 excisional breast biopsies, 196 using wire localization and 128 involving RSL. The authors reported no significant differences between groups with regard to operating room time (p=0.9), upstage rate (p=0.5), or target lesion retrieval rate (p=0.5). Specimen volume was significantly greater in the wire group vs. the RSL group (p=0.001). The authors concluded that RSL is comparable to WL for excisional breast biopsy of high-risk lesions. The lower specimen volume in the RSL group may translate into improved cosmetic outcomes without sacrificing the diagnostic accuracy.

Murphy (2013) reported the results of a retrospective nonrandomized study comparing RSL and WL. The study involved 431 RSL and 256 WL cases. Most seeds (90%) were placed before the day of surgery. Positive margins were present in 7.7% of RSL versus 5.5% of WL patients, and 16.9% of RSL versus 19.9% of WL had close margins (p=0.38). The median operative time was longer for lumpectomy and sentinel lymph node biopsy (SLNB) in the RSL group (55 vs. 48 min, p<0.0001). No significant difference in the volume of tissue excised between groups was reported. The authors noted that in the first 6 months of RSL, operative scheduling was simplified, while rates of positive and close margins were similar to those seen after many years of experience with WL.

Donker and colleagues (2013) reported the results of a study comparing radio-guided occult lesion localization (ROLL) with technetium-99 m colloid to RSL. This retrospective nonrandomized or blinded study involved 154 subjects being treated with neoadjuvant systemic treatment who underwent breast-conserving surgery with the ROLL (n=83) or RSL (n=71). The authors reported no significant differences between groups with regard to median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7% vs. 8%). They concluded that ROLL and RSL demonstrated comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Furthermore, they noted that because RSL does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling.

The largest RCT available, by Dauer (2013), involved the use of RSL in 1127 subjects. They reported that the median length of time from RSL implant to surgical excision was 2 days. They also reported on that the median I125 activity at time of implant was 3.1 MBq (1.9 to 4.6). The median dose rate from individuals with a single seed was 9.5 µSv h-1 and 0.5 µSv h-1 at contact and 1 m, respectively. The maximum contact dose rate was 187 µSv h-1 from a superficially-placed seed. They concluded that RSL performed greater than 1 day before surgery is a viable alternative to WL, allowing flexibility in scheduling, minimizing day of surgery procedures, and improving workflow in breast imaging and surgery.

In 2011, McGhan reported on a case series study involving 1000 RSL breast procedures that were performed in 978 subjects. The authors reported that a total of 1148 seeds were deployed using image guidance, with 76% placed greater than or equal to 1 day prior to surgery; most procedures (86%) utilized one seed. A negative margin was achieved at the first operation in 97% of subjects with invasive carcinoma and 97% of subjects with ductal carcinoma in situ (DCIS). An additional 9% of subjects with invasive carcinoma and 19% with DCIS had close (≤ 2 mm) margins, and underwent re-excision. Adverse events included 3 seeds (0.3%) not deployed correctly on first attempt and 30 seeds (2.6%) displaced from the breast specimen during excision of the targeted lesion. All seeds were successfully retrieved, with no radiation safety concerns. Local recurrence rates were 0.9% for invasive breast cancer and 3% for DCIS after mean follow-up of 33 months. They reported that there was no evidence of a learning curve.

Several other smaller case series studies have also reported similar results (Da Silva, 2017; Gobardhan, 2013; Hughes, 2008; Sung, 2013; Theunissen, 2017; van Riet, 2010).

The available evidence indicates that RSL, WL, and radio-guided localization of nonpalpable breast lesions are at least as likely to produce equivalent therapeutic results when used to localize a nonpalpable breast lesion in advance of surgical excision.

The use of RSL has been proposed for use in assisting the targeting of positive axillary lymph nodes after neoadjuvant therapy prior to excision. Diego and others (2016) published a retrospective review of 30 subjects with biopsy-proven lymph nodes who had RSL placement prior to excision following neoadjuvant chemotherapy. The authors noted that all radioactive seeds were successfully retrieved and 29 of 30 nodes were successfully localized with RSL. Nineteen subjects had no residual axillary disease; 11 had persistent disease. All subjects who remained node positive had disease in the biopsied nodes. The authors concluded that RSL combined with sentinel lymph node biopsy is a promising approach for axillary staging after neoadjuvant chemotherapy in individuals whose disease becomes cN0, and that the status of the lymph node after neoadjuvant chemotherapy predicted nodal status, suggesting that localization of the lymph node may be more accurate than SLNB alone for staging the axilla in the cN0 patient after neoadjuvant chemotherapy.

Another study by Caudle and others (2016) described the use of RSL in 208 subjects with biopsy confirmed lymph node breast cancer metastases who were treated with neoadjuvant chemotherapy. All subjects had I125 seeds placed in the biopsied nodes under ultrasound guidance 1-5 days prior to surgery. This study evaluated the role of targeted axillary dissection in patients with breast cancer after neoadjuvant chemotherapy vs. removal of all axillary lymph nodes. While no data is provided regarding the impact of RSL in this population, its use as a preferred method of localization over the use of wire localization should be noted.

References

Peer Reviewed Publications:

  1. Ahmed M, Douek M. Radioactive seed localisation (RSL) in the treatment of non-palpable breast cancers: systematic review and meta-analysis. Breast. 2013; 22(4):383-388.
  2. Al-Hilli Z, Glazebrook KN, McLaughlin SA, et al. Utilization of multiple I-125 radioactive seeds in the same breast is safe and feasible: a multi-institutional experience. Ann Surg Oncol. 2015; 22(10):3350-3355.
  3. Barentsz MW, van den Bosch MA, Veldhuis WB, et al. Radioactive seed localization for non-palpable breast cancer. Br J Surg. 2013; 100(5):582-588.
  4. Bloomquist EV, Ajkay N, Patil S, et al. A randomized prospective comparison of patient-assessed satisfaction and clinical outcomes with radioactive seed localization versus wire localization. Breast J. 2016; 22(2):151-157.
  5. Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016; 34(10):1072-1078.
  6. Da Silva M, Porembka J, Mokdad AA, et al. Bracketed radioactive seed localization vs bracketed wire-localization in breast surgery. Breast J. 2017 Jul 14. [Epub ahead of print]
  7. Dauer LT, Thornton C, Miodownik D, et al. Radioactive seed localization with 125I for nonpalpable lesions prior to breast lumpectomy and/or excisional biopsy: methodology, safety, and experience of initial year. Health Phys. 2013; 105(4):356-365.
  8. Diego EJ, McAuliffe PF, Soran A, et al. Axillary staging after neoadjuvant chemotherapy for breast cancer: a pilot study combining sentinel lymph node biopsy with radioactive seed localization of pre-treatment positive axillary lymph nodes. Ann Surg Oncol. 2016; 23(5):1549-1553.
  9. Diego EJ, Soran A, McGuire KP, et al. Localizing high-risk lesions for excisional breast biopsy: a comparison between radioactive seed localization and wire localization. Ann Surg Oncol. 2014; 21(10):3268-3272.
  10. Donker M, Drukker CA, Valdés Olmos RA, et al. Guiding breast-conserving surgery in patients after neoadjuvant systemic therapy for breast cancer: a comparison of radioactive seed localization with the ROLL technique. Ann Surg Oncol. 2013; 20(8):2569-2575.
  11. Hughes JH, Mason MC, Gray RJ, et al. A multi-site validation trial of radioactive seed localization as an alternative to wire localization. Breast J. 2008; 14(2):153-157.
  12. Gobardhan PD, de Wall LL, van der Laan L, et al. The role of radioactive iodine-125 seed localization in breast-conserving therapy following neoadjuvant chemotherapy. Ann Oncol. 2013; 24(3):668-673.
  13. Gray RJ, Salud C, Nguyen K, et al. Randomized prospective evaluation of a novel technique for biopsy or lumpectomy of nonpalpable breast lesions: radioactive seed versus wire localization. Ann Surg Oncol. 2001; 8(9):711-715.
  14. Langhans L, Tvedskov TF, Klausen TL, et al. Radioactive seed localization or wire-guided localization of nonpalpable invasive and in situ breast cancer: a randomized, multicenter, open-label trial. Ann Surg. 2017; 266(1):29-35.
  15. Lovrics PJ, Goldsmith CH, Hodgson N, et al. A multicentered, randomized, controlled trial comparing radioguided seed localization to standard wire localization for nonpalpable, invasive and in situ breast carcinomas. Ann Surg Oncol. 2011; 18(12):3407-3414.
  16. McGhan LJ, McKeever SC, Pockaj BA, et al. Radioactive seed localization for nonpalpable breast lesions: review of 1,000 consecutive procedures at a single institution. Ann Surg Oncol. 2011; 18(11):3096-3101.
  17. Murphy JO, Moo TA, King TA, et al. Radioactive seed localization compared to wire localization in breast-conserving surgery: initial 6-month experience. Ann Surg Oncol. 2013; 20(13):4121-4127.
  18. Pouw B, de Wit-van der Veen LJ, Stokkel MP, et al. Heading toward radioactive seed localization in non-palpable breast cancer surgery? A meta-analysis. J Surg Oncol. 2015; 111(2):185-191.
  19. Sung JS, King V, Thornton CM, et al. Safety and efficacy of radioactive seed localization with I-125 prior to lumpectomy and/or excisional biopsy. Eur J Radiol. 2013; 82(9):1453-1457.
  20. Theunissen CI, Rust EA, Edens MA, et al. Radioactive seed localization is the preferred technique in nonpalpable breast cancer compared with wire-guided localization and radioguided occult lesion localization. Nucl Med Commun. 2017; 38(5):396-401.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Radiology. ACR Practice Parameter for the imaging management of DCIS and invasive breast cancer. 2014. Available at: http://www.acr.org/Quality-Safety/Standards-Guidelines/Practice-Guidelines-by-Modality/Breast-Imaging. Accessed on September 1, 2017.
  2. NCCN Guidelines for Detection, Prevention, & Risk Reduction (NCCN Guidelines©) 2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on August 29, 2016.
    • Breast Cancer Screening and Diagnosis (V1.2017). Revised June 2, 2017.
  3. United States Food and Drug Administration. Approval letter for BrachySciences Radioactive Seed Localization Needle with AnchorSeed®. K111979. October 18, 2011. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf11/K111979.pdf. Accessed on September 1, 2017.
  4. United States Food and Drug Administration. Approval letter for Best® Localization Needle with I-125 Seed. K122704. January 9, 2013. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf12/k122704.pdf. Accessed on September 1, 2017.
Index

AnchorSeed®
Best® Localization Needle

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Revised

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review.

Revised

11/01/2017

Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale and Reference sections 

Revised

11/03/2016

MPTAC review.

Revised

11/02/2016

Hematology/Oncology Subcommittee review. Added MN statement for when RSL is used to assist in targeted axillary excision of positive lymph nodes after neoadjuvant therapy. Updated Rationale and Reference sections 

New

08/04/2016

MPTAC review. Initial document development.