What are the indications for neoadjuvant chemotherapy in cancer treatment?

Indications for Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy is indicated for locally advanced cancers requiring tumor downstaging to achieve operability or breast-conserving surgery, and for any patient who would otherwise receive adjuvant chemotherapy, as it provides equivalent survival with the added benefit of early response assessment and improved surgical options. 1, 2

Primary Indications by Cancer Type

Breast Cancer

• Locally advanced breast cancer (stage II-III) requiring tumor downstaging to enable breast-conserving surgery or achieve operability 1, 3
• Any breast cancer patient who would receive adjuvant chemotherapy can be offered neoadjuvant therapy as an equivalent option 1, 4
• HER2-positive stage II-III disease should receive neoadjuvant chemotherapy with dual HER2 blockade (trastuzumab and pertuzumab) plus taxanes 1
• Triple-negative breast cancer benefits from neoadjuvant chemotherapy with higher pathologic complete response rates, particularly when platinum compounds are added for BRCA1/2 mutation carriers 3
• Large operable tumors (>2 cm) where breast-conserving surgery is not initially feasible or would result in suboptimal cosmetic outcomes 1, 3
• Tumors with aggressive features including low/absent hormone receptor status, high-grade histology, non-lobular invasive histology, high Ki67 proliferation index, and luminal B subtype 1

Gastric and Gastroesophageal Junction Cancer

• Locally advanced gastric cancer (cT3-4aN+M0, stage cIII) should receive neoadjuvant chemotherapy with FOLFOX, SOX, or FLOT regimens 5
• Oesophageal adenocarcinoma should receive FLOT as standard perioperative chemotherapy (4 preoperative cycles) 6
• Serosal infiltrating tumors, bulky metastatic nodes, or Borrmann type 4 cancers to increase R0 resectability rates 5
• Gastric cancer T≥3 and/or with metastatic nodes on preoperative workup 5

Cervical Cancer

• Locally advanced cervical cancer (stages IB2 to IIB) may benefit from neoadjuvant chemotherapy followed by radical surgery, though this remains investigational pending EORTC 55994 trial results 5
• Neoadjuvant chemoradiotherapy for EGJ carcinoma (cT3-4aN+M0) with 45-50.4 Gy concurrent with fluoropyrimidine, platinum, or taxanes 5

Lung Cancer

• Stage II-IIIA non-small cell lung cancer after radical resection, though adjuvant chemotherapy has stronger evidence than neoadjuvant approaches 5
• Neoadjuvant chemotherapy in lung cancer remains experimental with limited randomized trial data 5

Rectal Cancer

• Locally advanced rectal cancer benefits from neoadjuvant chemoradiotherapy to reduce tumor size, increase resection rates, and improve anus retention 7
• Middle and low rectal cancers benefit more than high rectal cancers 7

Bladder Cancer

• Muscle-invasive bladder cancer should receive neoadjuvant cisplatin-based chemotherapy before cystectomy, as this has stronger evidence than adjuvant approaches 5

Treatment Selection Algorithm

Step 1: Assess Surgical Feasibility

• If breast-conserving surgery is not feasible or would result in poor cosmesis → neoadjuvant therapy is preferred 1
• If breast-conserving surgery is feasible with acceptable cosmesis → neoadjuvant therapy is optional but can still be offered 1
• If tumor is locally advanced or inflammatory → neoadjuvant therapy is mandatory 1, 3

Step 2: Evaluate Tumor Biology

• HER2-positive disease → neoadjuvant chemotherapy with dual HER2 blockade mandatory 1
• Triple-negative disease → neoadjuvant chemotherapy with consideration of platinum agents 3
• Hormone receptor-positive/HER2-negative with aggressive features → neoadjuvant chemotherapy 1
• Hormone receptor-positive without aggressive features → consider neoadjuvant endocrine therapy (≥6 months) only if chemotherapy contraindicated 3

Step 3: Patient Assessment

• Perform comprehensive geriatric assessment for elderly patients to categorize as "fit" versus "frail" 3
• Evaluate comorbidities, functional status, cardiac function (LVEF), and renal function (creatinine clearance) 3
• Fit elderly patients should receive identical treatments to younger counterparts with full drug doses 3
• Frail elderly patients may require less aggressive regimens 3

Standard Chemotherapy Regimens

Breast Cancer

• Anthracycline and taxane-based regimens (sequential or combination) are the backbone 1
• At least 6 cycles over 4-6 months should be planned and delivered preoperatively 1
• Do not use concomitant anthracycline and trastuzumab outside clinical trials due to cardiac toxicity 1

Gastric/Gastroesophageal Cancer

• FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel): 4 preoperative cycles every 2 weeks 6
• FOLFOX, SOX, or PF as alternatives 5
• Where FLOT unavailable: cisplatin and fluorouracil (2 three-weekly cycles) 6

Bladder Cancer

• Minimum 3 cycles of cisplatin-based combination (ddMVAC, gemcitabine plus cisplatin, or CMV) 5
• Do not substitute carboplatin for cisplatin in perioperative setting—no survival benefit demonstrated 5

Critical Timing Considerations

• Surgery should occur 2-4 weeks after completion of neoadjuvant chemotherapy 1
• Do not delay neoadjuvant therapy initiation beyond 2-4 weeks after diagnosis and staging completion 1
• All planned chemotherapy should be delivered preoperatively without dividing into preoperative and postoperative periods, regardless of response magnitude 3
• Neoadjuvant endocrine therapy duration: at least 6 months or until maximum response achieved 1

Pre-Treatment Requirements

• Core biopsy mandatory before starting neoadjuvant therapy to confirm invasive cancer and obtain predictive markers (histological subtype, tumor grading, ER/PR status, HER2 status) 1
• Referral to breast surgeon and radiation oncologist before initiating neoadjuvant therapy 1
• Multidisciplinary team discussion for all locally advanced cases to determine individualized treatment plans 5

Common Pitfalls to Avoid

• Do not assume neoadjuvant therapy is only for locally advanced disease—it is appropriate for any patient who would receive adjuvant chemotherapy 1, 3
• Do not withhold appropriate neoadjuvant chemotherapy based solely on chronological age—elderly patients derive similar survival benefits though face increased toxicity risk 3
• Do not use neoadjuvant endocrine therapy in patients who are candidates for chemotherapy unless specific contraindications exist 3
• Do not proceed with surgery if complete clinical response achieved—patients with resectable disease should still undergo surgery even after complete response 6
• Do not use carboplatin instead of cisplatin in perioperative bladder cancer treatment 5

Survival and Outcome Data

• Meta-analyses demonstrate no difference in survival or overall disease progression between neoadjuvant and adjuvant therapy 1, 2
• Patients achieving pathologic complete response have significantly improved long-term outcomes 1, 8
• 5-year survival probability is 0.74 in those with complete response versus 0.36 with partial response in breast cancer 8
• Independent predictors of better survival: complete histopathological response, complete clinical response to chemotherapy, and completion of 5-6 cycles versus 4 or less 8