neoadjuvant therapy

**Definition and contrast** - Neoadjuvant therapy is given before the primary definitive treatment (usually surgery). Adjuvant therapy is given after surgery to eliminate residual or micrometastatic disease. Induction therapy is initial therapy that is often followed by definitive chemoradiation, for example in head and neck cancer. Palliative therapy aims to relieve symptoms or prolong life when cure is not possible.

**Rationale and advantages** - Downstages the tumor, which can convert borderline or unresectable disease to resectable disease. - Allows organ preservation or less extensive surgery, such as breast-conserving surgery instead of mastectomy, or sphincter preservation in rectal cancer. - Treats micrometastatic disease early. - Gives in vivo assessment of chemosensitivity. Response guides further therapy, for example adding capecitabine in residual-disease TNBC or T-DM1 in residual-disease HER2+ breast cancer. - Pathologic complete response (pCR), meaning no residual invasive tumor, correlates with better survival, especially in TNBC and HER2+ breast cancer.

**Disadvantages and risks** - Disease may progress on therapy and lose its window for resection. - Overtreatment is possible if staging is inaccurate. - Treatment toxicity can delay surgery or increase perioperative complications. - Treatment can distort the pathologic staging that surgery would otherwise provide.

**Classic examples (high-yield)** - **Rectal cancer (locally advanced, T3-4 or node-positive):** Neoadjuvant chemoradiation (5-FU or capecitabine plus radiation), or total neoadjuvant therapy (TNT), is followed by total mesorectal excision. It reduces local recurrence and can allow sphincter preservation. - **Breast cancer:** Used for locally advanced or inflammatory disease, and for TNBC and HER2+ disease. Regimens include anthracycline and taxane, plus trastuzumab and pertuzumab for HER2+ disease, and pembrolizumab for high-risk TNBC. Endocrine therapy can be used in selected ER+ patients. - **Esophageal and gastroesophageal junction cancer:** CROSS regimen (carboplatin, paclitaxel, and radiation) or perioperative FLOT for gastric and GEJ cancer. - **Pancreatic cancer:** Used for borderline resectable disease, typically with FOLFIRINOX. - **Bladder cancer (muscle-invasive):** Cisplatin-based chemotherapy (for example, gemcitabine-cisplatin or ddMVAC) before radical cystectomy improves survival. - **Osteosarcoma:** Neoadjuvant chemotherapy (MAP: methotrexate, doxorubicin, cisplatin) is given before limb-salvage surgery. Histologic response (>90% necrosis) is prognostic. - **Others:** Anal cancer (Nigro protocol, which is definitive chemoradiation), locally advanced cervical cancer, non-small cell lung cancer (neoadjuvant nivolumab plus chemotherapy), and melanoma (neoadjuvant immunotherapy in stage III disease).

**Board-relevant pearls** - Adverse effects to know: doxorubicin causes cardiotoxicity (dilated cardiomyopathy), cisplatin causes nephrotoxicity, ototoxicity, and neuropathy, trastuzumab causes cardiotoxicity, and taxanes cause neuropathy. Check an echocardiogram before anthracycline or trastuzumab therapy. - If a question stem describes chemo or radiation given before surgery to shrink a tumor, the answer is neoadjuvant. If chemo is given after resection to reduce recurrence risk, such as in node-positive colon cancer (FOLFOX) after colectomy, the answer is adjuvant. - Neoadjuvant therapy is not the same as palliative therapy. It is given with curative intent. - Response is measured by RECIST criteria (imaging) and, after surgery, by pathologic response (pCR).