What is the treatment approach for a patient with a Level 3 (third tier) lymph node involvement?

From the Guidelines

The treatment approach for a patient with Level 3 lymph node involvement should prioritize neoadjuvant systemic therapies, such as pembrolizumab monotherapy, to improve clinical outcomes and reduce the risk of recurrence. According to the most recent guidelines, neoadjuvant therapy is generally preferred over the previous standard approach of therapeutic lymph node dissection (TLND) followed by adjuvant systemic treatment 1. The NCCN Guidelines Insights highlight the importance of neoadjuvant systemic therapies, including immune checkpoint inhibitors and targeted therapy, in the treatment of resectable stage III melanoma 1.

Key considerations in the treatment approach include:

• The use of neoadjuvant pembrolizumab monotherapy, which has been shown to improve clinical outcomes and reduce the risk of recurrence 1
• The potential benefits of neoadjuvant therapy, including an earlier start of systemic therapy and elimination of unnecessary surgery 1
• The importance of a multidisciplinary tumor board to coordinate care and ensure close follow-up with physical examinations and imaging 1

In terms of specific treatment options, the NCCN Guidelines recommend the following:

• Neoadjuvant pembrolizumab monotherapy as a preferred regimen for resectable stage III melanoma 1
• Other recommended regimens, including "flip dose" nivolumab and ipilimumab, as well as dabrafenib/trametinib and talimogene laherparepvec (T-VEC) in certain circumstances 1
• Adjuvant radiation therapy and concurrent chemotherapy may also be considered for patients with high-risk features, such as extracapsular extension or positive margins 1

Overall, the treatment approach for a patient with Level 3 lymph node involvement should prioritize neoadjuvant systemic therapies and a multidisciplinary approach to care, with the goal of improving clinical outcomes and reducing the risk of recurrence.

From the FDA Drug Label

The efficacy of KEYTRUDA was investigated in KEYNOTE-054 (NCT02362594), a multicenter, randomized (1:1), double-blind, placebo-controlled trial in patients with completely resected Stage IIIA (>1 mm lymph node metastasis), IIIB, or IIIC melanoma Patients were randomized to KEYTRUDA 200 mg intravenously every three weeks or placebo for up to one year until disease recurrence or unacceptable toxicity. Randomization was stratified by American Joint Committee on Cancer 7th edition (AJCC) stage (IIIA vs. IIIB vs. IIIC 1-3 positive lymph nodes vs IIIC ≥4 positive lymph nodes)

The treatment approach for a patient with a Level 3 (third tier) lymph node involvement is to receive KEYTRUDA 200 mg intravenously every three weeks or placebo for up to one year until disease recurrence or unacceptable toxicity, as investigated in the KEYNOTE-054 trial 2.

• Key points:
  • KEYTRUDA is used for the adjuvant treatment of patients with completely resected Stage III melanoma
  • The trial demonstrated a statistically significant improvement in RFS (Recurrence-Free Survival) and DMFS (Distant Metastasis-Free Survival) for patients randomized to the KEYTRUDA arm compared with placebo
  • Patients with Level 3 lymph node involvement may be eligible for this treatment approach, depending on their specific clinical characteristics and medical history.
• Important considerations:
  • Patients should be closely monitored for adverse reactions and laboratory abnormalities while receiving KEYTRUDA
  • The treatment approach should be individualized based on the patient's specific needs and clinical characteristics. 2

From the Research

Treatment Approach for Level 3 Lymph Node Involvement

The treatment approach for a patient with Level 3 lymph node involvement typically involves a combination of therapies, including surgery, radiation therapy, and chemotherapy.

• The goal of treatment is to control the cancer, reduce symptoms, and improve quality of life.
• According to the study 3, postoperative radiotherapy plus cisplatin can be an effective treatment for high-risk head and neck squamous cell carcinoma patients with lymph node involvement.
• Another study 4 suggests that concurrent selective lymph node radiotherapy and S-1 plus cisplatin can be a effective treatment approach for esophageal squamous cell carcinoma patients.

Radiation Therapy and Chemotherapy

Radiation therapy and chemotherapy are commonly used to treat lymph node involvement.

• The study 5 found that superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) can be effective for metastatic lymph nodes in head and neck squamous cell carcinoma.
• The study 6 showed that preoperative concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil and elective lymph node irradiation can be a feasible treatment approach for clinical stage II/III esophageal squamous cell carcinoma.
• The study 7 found that postoperative radiation therapy with or without concurrent chemotherapy can be effective for node-positive thoracic esophageal squamous cell carcinoma.

Toxicity and Efficacy

The toxicity and efficacy of treatment approaches can vary.

• The study 3 reported that postoperative radiotherapy plus cisplatin can result in severe mucositis and hematologic toxicity.
• The study 4 found that concurrent selective lymph node radiotherapy and S-1 plus cisplatin can result in grade 3 or 4 toxicities, including leukopenia, neutropenia, and thrombocytopenia.
• The study 7 reported that postoperative chemotherapy plus radiation therapy can result in more severe early toxic reactions compared to radiation therapy alone.