The success of neoadjuvant immunotherapy trials like Niagara and those with EV-Pembro means most patients will receive immune therapy before surgery. This fundamentally shifts the clinical landscape, making the question of starting adjuvant immunotherapy less relevant as perioperative treatment becomes the standard.

Sentinel lymph node biopsy was historically inconsistent in CSCC because a positive finding had no approved systemic treatment path. With adjuvant cemiplimab's approval, identifying microscopic nodal disease now directly impacts treatment eligibility, potentially making the procedure a new standard of care for certain high-risk patients.

The INVIGOR-11 trial data should be applied carefully. A positive ctDNA result post-surgery indicates when to *initiate* adjuvant immunotherapy. However, if a patient on neoadjuvant therapy becomes ctDNA-negative, this signals treatment efficacy and is a reason to *continue* the planned course, not a justification for stopping it early.

Following positive Phase III data for adjuvant atezolizumab plus chemotherapy in Stage III MSI-high colon cancer, clinicians are extrapolating this approach to high-risk Stage II patients. For some, they favor using immunotherapy alone, omitting chemotherapy due to its perceived limited additional benefit in the Stage II setting.

Standard cancer surgery often removes lymph nodes—the factories producing immune cells. Administering immunotherapy *before* this destructive process is critical. It arms the immune system while it is still intact and capable of mounting a powerful, targeted response against the tumor.

Dr. Ramalingam describes a nuanced clinical approach based on early NEO ADORA data: using neoadjuvant chemo-osimertinib for N2 positive (Stage 3A) patients, but favoring upfront surgery followed by adjuvant therapy for Stage 2. This shows how specialists apply preliminary findings before they become universal standards.

The failure of the NRG trial (atezolizumab) in limited-stage SCLC suggests a negative interaction between concurrent IO and radiation. The prevailing hypothesis is that radiating the chest destroys immune cells in lymph nodes, eliminating the very T-cells crucial for the immunotherapy's mechanism of action, unlike consolidation IO which has proven effective.

Clinical trial data suggests immunotherapy's timing is crucial in early-stage TNBC. Given with chemotherapy before surgery (neoadjuvant), it improves outcomes. However, when given alone after surgery (adjuvant), the IMPASSION 030 trial showed no benefit and was halted for futility, indicating pre-surgical tumor priming is essential.

Data from KEYNOTE-671 and other trials show that even patients achieving a pathological complete response (PCR) after neoadjuvant chemo-IO have better outcomes with the full perioperative regimen. This challenges the idea of de-escalating adjuvant therapy based on surgical pathology alone.