Expert Insights and Clinical Decision-Making: Neoadjuvant and Perioperative Strategies in Early-Stage NSCLC

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Identifying Candidates for Neoadjuvant ICI Therapy and Postsurgery Adjuvant Therapy Considerations

Neoadjuvant ICI Therapy: Identification of Candidates

Neoadjuvant immunotherapy, specifically immune checkpoint inhibitors (ICI), is a treatment approach administered prior to surgery to enhance the body’s immune response to cancer. It is increasingly being explored for various cancer types, including non-small cell lung cancer (NSCLC), melanoma, and other solid tumors. Medical professionals consider several factors when identifying patients who should receive neoadjuvant ICI before surgery:

Cancer Type and Stage:

• Neoadjuvant ICI therapy is typically considered for patients with locally advanced, resectable tumors, especially those with high-risk features, such as NSCLC (stage III) or certain types of melanoma.
• In NSCLC, stage II and III cancers are common candidates for ICI therapy, as they may benefit from the systemic immune activation before resection.

Tumor Characteristics:

• PD-L1 Expression: PD-L1 expression is a key biomarker guiding ICI therapy. Patients with high PD-L1 expression on tumor cells are more likely to respond to ICI therapy. PD-L1 testing is often used to assess the suitability of ICI for neoadjuvant therapy.
• Tumor Mutational Burden (TMB): Higher TMB is associated with a greater likelihood of benefiting from ICI therapy. High TMB may enhance the immune system’s recognition of tumor cells, improving the response to immunotherapy.
• Microsatellite Instability (MSI): MSI-high tumors, often found in cancers like colorectal cancer, are another group where neoadjuvant ICI therapy has demonstrated promise.

Overall Health and Performance Status:

• Patients with an ECOG performance status of 0 or 1 are more likely to tolerate ICI therapy and have a better chance of responding favorably to treatment.
• Age, comorbidities, and other factors like autoimmune disease can influence the decision to administer neoadjuvant ICI therapy. Those with significant autoimmune disorders may be at higher risk for adverse reactions to ICIs.

Molecular and Genetic Factors:

• BRCA mutations and other specific molecular alterations may also guide the decision for ICI use in certain cancers, particularly in those with a high likelihood of genetic instability or response to immunotherapy.

Adjuvant Therapy Considerations Post Surgery

Post surgery, the decision to use additional adjuvant therapy, including chemotherapy, radiation, or ICI, depends on several key factors:

• Pathologic Response to Neoadjuvant Therapy:
  • If the patient has received neoadjuvant ICI therapy, the pathologic response to that therapy is a critical factor in determining the need for further adjuvant therapy. If the tumor significantly regresses (ie, a pathological complete response), the patient may have a lower risk of recurrence and might not require additional adjuvant therapy.
  • Conversely, incomplete responses may prompt the use of additional adjuvant ICI or chemotherapy to reduce the risk of recurrence.
• Lymph Node Involvement:
  • Presence of lymph node metastasis after surgery is a key indicator of the need for adjuvant therapy. If lymph nodes are involved, it signifies a higher risk of recurrence, often necessitating adjuvant chemotherapy or immunotherapy.
• Tumor Stage Post Resection:
  • Postsurgical staging (eg, based on the pathological assessment) is essential in determining whether further therapy is needed. Patients with stage II/III cancers who have residual disease may benefit from adjuvant ICI or chemotherapy to prevent recurrence.
• Molecular and Genetic Markers:
  • Patients with high TMB or MSI-high tumors may benefit from additional adjuvant ICI therapy, even after surgery, to improve long-term outcomes and reduce the risk of recurrence.
  • PD-L1 Expression: High PD-L1 expression may also be used as a biomarker for selecting patients who could benefit from adjuvant ICI therapy post surgery.
• Risk of Recurrence:
  • Adjuvant therapy is more likely to be recommended for patients who have a high risk of recurrence based on factors like tumor grade, margins of resection, and the presence of microscopic residual disease.
• Immune and Clinical Factors:
  • The patient’s immune system profile and potential for immune-mediated adverse effects must be taken into account. Immunotherapy may not be suitable for patients with significant autoimmune diseases or other contraindications to immune modulation.
• Other Adjuvant Options:
  • Adjuvant chemotherapy remains the standard of care in some settings, especially for cancers like NSCLC, where the patient has not shown a complete response to neoadjuvant therapy. Radiation therapy may be used in select cases, depending on the tumor’s location and aggressiveness.

Conclusion: The decision to administer neoadjuvant ICI therapy is largely influenced by cancer type, tumor biomarkers (such as PD-L1 expression and TMB), and the patient’s general health. Post surgery, the need for additional adjuvant therapy is guided by the pathologic response to neoadjuvant therapy, tumor stage, lymph node involvement, and molecular markers. Ongoing clinical trials and personalized approaches based on genetic and immune profiling will continue to refine these decision-making processes, helping to optimize outcomes for patients undergoing cancer treatment.