Indications for SLN Biopsyin Melanoma and Breast Cancer

Patients with melanoma most likely to benefit from SLNB have an intermediate thickness (1.0–4.0mm) lesion.⁷ The incidence of nodal metastases ranges from 6% for patients with a 1.0mm melanoma to 35% in patients with a 4.0mm melanoma.12 For patients with melanoma <1.0mm, other indications for SLNB include Clark IV depth, presence of tumor regression, and presence of ulceration.¹⁵ Some relative indications may include younger age, a high number of mitoses, male gender, and axial location.¹⁶ Patients with thick melanoma (>4.0mm) have a high incidence of systemic disease and should undergo a proper extent of disease evaluation. For patients without distant metastases or clinically positive nodes, SLNB should still be offered as it provides valuable staging and prognostic information.¹⁷

For patients with breast cancer, SLN mapping and biopsy is indicated for T1 and T2 lesions (<5cm), provided that there are no clinically palpable nodes.³ The incidence of finding a positive SLN is 30–35% for patients with earlystage breast cancer.^3,9–11 The incidence of finding a positive SLN in patients with ductal carcinoma in situ (DCIS) is so small that SLN mapping is not recommended for patients undergoing lumpectomy.³ However, SLNB is acceptable for patients with DCIS when total mastectomy is to be performed, mainly because SLNB is impossible after all breast tissue is removed, and if invasive cancer is found in the specimen, the patient would be committed to axillary lymph node dissection (ALND).

Clinical Trials Involving SLN Mapping for Melanoma

Four major prospective, randomized clinical trials are evaluating lymphatic mapping and SLNB for melanoma. The first two are the Multicenter Selective Lymphadenectomy Trial-I (MSLT-I) and the MSLT-II. The MSLT-I randomized patients with intermediate thickness melanoma to receive wide-excision and observation or wide-excision plus SLNB. If the SLNB revealed a positive node, patients then had a completion lymph node dissection (CLND). The goal of this study was to determine if early detection and management of regional nodes would improve survival.Patients who had wide-excision alone had a therapeutic lymph node dissection (TLND) only if clinical nodal recurrence was detected during the observation period. Results from the MSLT-I were recently presented at the 2005 American Society of Clinical Oncology (ASCO) meeting and demonstrated no difference in five-year overall survival between the two groups.¹⁸ However, 18% of patients treated by wide-excision alone had regional nodal recurrence, indicating that SLNB followed by CLND provides excellent locoregional nodal control. The goal of the MSLT-II is to determine if SLNB alone is adequate therapy for patients with a positive SLN, or if patients should proceed to CLND.The MSLT-II enrolls patients with intermediate thickness melanoma to wide excision with an SLNB, and then randomizes patients with a positive SLN to either observation or CLND. Results from the MSLT-II are not yet available.

The hypothesis of the Florida Melanoma Trial (FMT) is that patients with a positive SLN who undergo CLND have no disease-free survival or overall survival advantage when compared to patients who have an SLNB alone, provided that all patients are also treated post-operatively with adjuvant interferon alpha-2b (IFN α−2b).This trial further stratifies patients based on the method of detection of metastases in the SLN, as determined by H&E, IHC, and by quantitative polymerase chain reaction (PCR).

The Sunbelt Melanoma Trial (SBMT) has a complex study design, with a total of seven arms in the randomization process. All patients with melanoma >1.0mm had SLN mapping and biopsy, with histologic analysis for micrometastases determined by H&E and IHC.All patients with a histologically positive SLN had CLND, and then patients were further randomized to either observation or adjuvant IFN α-2b. This part of the trial will determine the role of adjuvant IFN α-2b in patients with minimal nodal disease. Patients who had a histologically negative SLN then had further molecular analysis of the node by PCR. Patients with a PCR negative node will be observed, but those with a PCR positive node were randomized to observation, CLND, or CLND with IFN α-2b.This part of the trial will determine the value of molecular staging by PCR, and will determine the optimal treatment for patients upstaged by PCR.