Definitions and Rationales for Neoadjuvant, Adjuvant, and Perioperative Chemoimmunotherapy
Neoadjuvant chemoimmunotherapy is systemic treatment given before surgery, adjuvant therapy is given after surgery, and perioperative therapy combines both pre- and post-operative treatment—each with distinct strategic advantages that should guide your selection based on tumor stage, nodal status, and surgical feasibility.
Neoadjuvant Chemoimmunotherapy
Definition: Systemic treatment administered before definitive surgical resection 1.
Key Rationales:
Improves surgical options by downstaging tumors, converting inoperable cases to operable ones, and enabling breast-conserving surgery when mastectomy would otherwise be required 1, 2
Provides early prognostic information through pathological response assessment—patients achieving pathological complete response (pCR) demonstrate superior survival outcomes regardless of subsequent treatment 3
Activates anti-tumor immunity in situ by expanding tumor-specific T-cell clones while the tumor is still present, potentially addressing occult micrometastatic disease more effectively 4
Reduces mortality with comparable efficacy to adjuvant therapy—meta-analyses show no survival difference between neoadjuvant and adjuvant approaches, making it a standard alternative 1
Clinical Application: Offer neoadjuvant therapy to all patients who would otherwise be candidates for adjuvant chemotherapy, particularly when breast-conserving surgery is not feasible or cosmetically suboptimal, or when tumors express markers of good chemotherapy response (hormone receptor-negative, high-grade, high Ki67) 1.
Adjuvant Chemoimmunotherapy
Definition: Systemic treatment administered after complete surgical resection 3.
Key Rationales:
Eliminates micrometastatic disease that may remain after surgery despite complete resection
Avoids preoperative attrition to surgery—15-24% of patients receiving neoadjuvant therapy never reach the operating room due to disease progression (5-8%) or evolving surgical ineligibility 4
Preserves the surgical window for potentially curable patients who might lose resectability with upfront systemic therapy 4
Remains essential when preoperative staging is inadequate—current limitations in invasive lymph node staging mean adjuvant immunotherapy remains an important strategy 3
Clinical Application: Consider adjuvant-only approaches for selected stage II N0 disease where upfront surgery is feasible, or when the risk of preoperative disease progression outweighs potential benefits of tumor downstaging 5.
Perioperative Chemoimmunotherapy
Definition: Combined strategy delivering systemic treatment both before (neoadjuvant) and after (adjuvant) surgical resection 6, 7, 3.
Key Rationales:
Maximizes pathological response rates while providing sustained immune activation postoperatively
Improves event-free survival and overall survival compared to chemotherapy alone in stage II-IIIA NSCLC 7, 3
Addresses both local tumor burden and systemic micrometastases through dual-phase treatment
Allows treatment adaptation based on surgical pathology findings, though optimal strategies for post-surgical treatment modification remain under investigation 6
Clinical Application: Perioperative approaches are particularly appropriate for resectable stage III and N-positive disease where both tumor downstaging and sustained systemic control are priorities 5.
Critical Decision Algorithm
For Stage II N0 Disease:
- Consider upfront surgery followed by adjuvant therapy if tumor is clearly resectable and patient has favorable prognostic features
- Choose neoadjuvant/perioperative if breast-conserving surgery is not feasible or tumor biology suggests high chemotherapy responsiveness 1, 5
For Stage II-III N+ Disease:
- Prioritize neoadjuvant or perioperative chemoimmunotherapy as the new standard after multidisciplinary board discussion 5
- Ensure pathological mediastinal staging and molecular testing before initiating therapy 5
For Locally Advanced Disease:
- Neoadjuvant therapy is standard of care to improve resectability 1
Common Pitfalls and Caveats
Preoperative Attrition Risk: Approximately 1 in 5 patients receiving neoadjuvant therapy may lose their surgical window—this represents a clinically meaningful tradeoff requiring careful patient selection and shared decision-making 4.
No Direct Comparison Exists: No phase 3 trial has directly compared neoadjuvant/perioperative strategies against the traditional upfront surgery plus adjuvant therapy approach—the PROSPECT-LUNG trial (NCT06632327) is now addressing this gap 4.
PD-L1 Status: PD-L1-negative tumors are not excluded from immunotherapy benefit, though the magnitude of benefit is lower—do not withhold treatment based solely on PD-L1 negativity 5.
Current Evidence Limitations: No data currently favor perioperative over neoadjuvant strategy in efficacy, or vice versa—regimen choice should consider trial eligibility criteria, local drug approvals, and individual patient factors 5.
Biomarker Development Needed: Identifying patients at risk for primary resistance who would be better served by immediate surgery remains a high-priority research area 4, 5.