• Melanoma-specific survival [ Designated as safety issue: No ]
  

• Disease-free survival [ Designated as safety issue: No ]
  
• Time to recurrence (the first recurrence, any type) [ Designated as safety issue: No ]
  
• Time to regional lymph node recurrence [ Designated as safety issue: No ]
  
• Time to distant recurrence [ Designated as safety issue: No ]
  
• Time to recurrence in the regional lymph node basin [ Designated as safety issue: No ]
  
• Time to death from all causes [ Designated as safety issue: No ]
  
• Tumor burden in sentinel node, in terms of tumor area, tumor diameter, and interdigitating dendritic cells [ Designated as safety issue: No ]
  
• DNA/RNA markers in primary tumor, lymph node, and serum [ Designated as safety issue: No ]
  
• Genetic markers [ Designated as safety issue: No ]
  
• Serum tumor markers (e.g., TA90-IC, MIA, S-100) [ Designated as safety issue: No ]
  
• Quality of life assessed at baseline, at 4 and 12 months, and then annually for up to 10 years [ Designated as safety issue: No ]
  
• Surgery-related morbidity [ Designated as safety issue: No ]
  
• Adverse events [ Designated as safety issue: Yes ]
  
• Abnormal laboratory tests [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the melanoma-specific survival of patients with localized cutaneous melanoma and sentinel node (SN) metastasis who undergo complete lymph node dissection (CLND) vs observation with serial nodal ultrasound after intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL).

Secondary

• Compare disease-free survival of these patients.
• Compare the frequency of same-basin recurrence after LM/SL in patients who do not undergo CLND with the frequency of nonsentinel node (NSN) metastasis detectable using histopathology specimens from patients who undergo CLND.
• Determine, prospectively, the prognostic accuracy of molecular staging by reverse transcriptase-polymerase chain reaction of the SN.
• Determine if new histopathologic techniques applied to SNs predict the presence of metastasis in the NSN and the likelihood of recurrence and death from melanoma.
• Determine if indices of the endogenous immune response to melanoma-associated antigens can predict regional or distant subclinical metastasis of melanoma before and after LM/SL.
• Assess patient blood samples before and after surgery for molecular markers (e.g., DNA, RNA, and proteomic markers [serum protein]) of melanoma.
• Assess patient blood samples before and after surgery for molecular tumor markers (e.g., MIA, S-100, TA90-IC) and evaluate their prognostic significance.
• Assess primary tumors of patients for DNA markers and evaluate the capacity of these markers to predict disease outcome.
• Retrospectively assess lymph nodes after CLND for evaluation of histopathologically inapparent occult metastases by molecular analysis.
• Compare the quality of life of these patients.

OUTLINE: This is a prospective, randomized, multicenter study. Patients are stratified according to sentinel node status (positive by hematoxylin and eosin [H&E] staining or immunohistochemistry [IHC] vs negative by H&E or IHC but positive by reverse transcriptase-polymerase chain reaction [RT-PCR]), Breslow thickness (> 3.5 mm vs ≤ 3.5 mm), and participating center (MSLT center vs non-MSLT center). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo complete lymph node dissection (CLND) of the axillary, inguinal, popliteal, neck, or ectopic (if appropriate) lymph nodes.
• Arm II: Patients undergo observation comprising nodal ultrasound of the dissected nodal basin every 4 months for 2 years and then every 6 months for 3 years. Patients with nodes suspicious for recurrence undergo confirmatory biopsy of the nodal basin. If the nodal basin is tumor-positive, patients undergo CLND.

Quality of life is assessed at baseline, at 4 and 12 months, and then annually for up to 10 years.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 4,200 patients will be accrued for the screening phase of this study. A total of 1,925 patients will be accrued for the randomized phase of the study.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary localized cutaneous melanoma involving the head, neck, trunk, extremity, scalp, palm, sole, or subungual skin tissues

  • No primary melanoma of the eye, ear, mucous membranes, or internal viscera
  • Has undergone diagnostic biopsy of the primary melanoma within the past 120 days

• Tumor-positive sentinel node (SN)*, as determined by either of the following methods:

  • Hematoxylin and eosin (H&E) staining or immunohistochemistry using S-100, MART-1, and HMB-45

  • Reverse transcriptase-polymerase chain reaction (RT-PCR) allowed provided the primary melanoma meets 1 of the following criteria:

    • Breslow thickness ≥ 1.20 mm and Clark level III
    • Clark level IV or V, regardless of Breslow thickness
    • Ulceration, regardless of Breslow thickness or Clark level NOTE: *Patients with tumor-negative SNs will be followed annually

• Has undergone lymphatic mapping (LM) followed by sentinel lymphadenectomy (SL) and wide local excision (WLE) (prior to randomization)**

  • Able to localize 1-2 SN drainage basins by preoperative lymphoscintigraphy
  • Must have clear margins after undergoing WLE NOTE: **Patients may enter study prior to undergoing LM, SL, and WLE but must undergo these procedures prior to randomization
• No prior or concurrent (i.e., secondary primary) invasive melanoma
• No physical, clinical, radiographic, or pathologic evidence of satellite, in-transit, regional, or distant metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 10 years from the time of diagnosis (not considering the melanoma in question)
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other solid tumor or hematologic malignancy within the past 5 years except for squamous cell or basal cell carcinoma T1 skin lesions or cervical cancer
• No allergy to vital blue dye or any radiocolloid
• No organic brain syndrome or significant impairment of basal cognitive function
• No psychiatric disorder that would preclude study participation or be exacerbated by therapy (e.g., severe depression)
• No primary or secondary immune deficiencies or known significant autoimmune disease

PRIOR CONCURRENT THERAPY:

• No prior complete lymph node dissection (CLND) or SL that may have altered the lymphatic drainage pattern from the primary cutaneous melanoma to a potential lymph node basin
• No prior organ transplantation
• More than 6 months since prior and no concurrent oral or parenteral immunosuppressive agents (except for topical or inhaled steroids)
• No prior skin grafts or tissue transfers or flaps that have the potential to alter the lymphatic drainage pattern from the primary tumor to a lymph node basin
• No concurrent melanoma-related operative procedures not corresponding to criteria described in the protocol

• No concurrent participation in another experimental protocol that might confound trial analysis

  • Participation in adjuvant therapy protocols after disease recurrence allowed
• No concurrent alternative therapies that might confound trial analysis