Neoadjuvant therapy — Treatment given before surgery

In classical cancer management, surgical excision was historically the initial therapeutic manoeuvre, followed optionally by postoperative adjuvant therapy. In contrast, neoadjuvant therapy deliberately positions systemic or regional treatments prior to surgery. This strategy applies to patients presenting with locally advanced, non-metastatic tumours that are technically borderline for complete resection or would require disfiguring, highly extensive operations if addressed immediately.

Administering treatment upfront leverages functional vasculature around unperturbed tumour beds to deliver therapeutic agents effectively. Pathologists subsequently examine the surgically resected specimen to calculate the extent of residual viable tumour tissue. In optimal scenarios, neoadjuvant regimens achieve a 'pathological complete response' (pCR), meaning no viable invasive cancer cells remain detectable under microscopic evaluation, a benchmark frequently correlated with improved long-term survival outcomes.

Neoadjuvant therapy fundamentally influences surgical feasibility and clinical outcomes. By shrinking large tumours, it transforms previously inoperable malignancies into resectable lesions and permits organ-preserving techniques, reducing surgical morbidity and recovery time. Crucially, it treats invisible micrometastases throughout the body early. Observing how the primary tumour shrinks provides real-time biological feedback: if substantial residual cancer remains at surgery, oncologists can pivot to alternative, more aggressive postoperative therapies to prevent future relapse.

Before starting neoadjuvant therapy, complete staging via CT, MRI, or PET scans establishes baseline tumour dimensions. Core needle biopsies provide tissue for histopathological typing and biomarker analysis, including HER2, hormone receptors, or PD-L1 expression. Interval imaging evaluates tumour shrinkage during treatment, and surgical pathology post-resection grades pathological response using scoring systems like the Residual Cancer Burden (RCB).

Neoadjuvant therapy is standard in early-stage HER2-positive and triple-negative breast cancer to downstage tumours for breast-conserving surgery. It is widely employed in locally advanced rectal cancer, muscle-invasive bladder cancer, oesophageal cancer, and non-small cell lung cancer. It is also utilised in soft-tissue sarcomas, head and neck cancers, and locally advanced gastric adenocarcinoma.

Neoadjuvant treatment connects directly to multidisciplinary surgical planning. If a tumour exhibits a pathological complete response, post-surgical adjuvant therapy may be streamlined. Conversely, if viable residual disease persists upon surgical pathology, treatment pathways change: patients may receive secondary adjuvant agents, such as antibody-drug conjugates (e.g., trastuzumab emtansine in breast cancer) or oral fluoropyrimidines, specifically designed to address therapy-resistant disease.