What is adjuvant chemotherapy?

What is Adjuvant Chemotherapy?

Adjuvant chemotherapy is systemic chemotherapy given after primary curative treatment (typically surgery) to eliminate microscopic residual disease and reduce the risk of cancer recurrence, thereby improving survival. 1, 2

Core Definition and Purpose

• Adjuvant chemotherapy targets occult micrometastases that remain after surgical removal of the primary tumor, even when no visible disease is present 1, 3
• The treatment is administered after complete surgical resection with curative intent, distinguishing it from neoadjuvant chemotherapy (given before surgery) or palliative chemotherapy (given for advanced disease) 1, 4
• The goal is to reduce recurrence risk and improve overall survival, not to treat visible disease 2, 5

Biological Rationale

• Chemotherapy is most effective against minimal tumor burdens - microscopic disease is far more chemosensitive than macroscopic tumors 3, 6
• Treatment that is only partially effective against visible disease can be highly curative when directed at microscopic residual cancer cells 3
• Patients at highest risk for recurrence paradoxically may benefit less because they likely have larger subclinical tumor burdens that may have already crossed from curable to incurable thresholds 6

Clinical Application Across Cancer Types

When Adjuvant Chemotherapy is Standard of Care:

• Stage III colon cancer: Mandatory for all patients following complete resection, with FOLFOX or XELOX for 6 months providing approximately 15% absolute survival benefit 2
• Node-positive breast cancer: Standard treatment with regimens like TAC (docetaxel, doxorubicin, cyclophosphamide) showing improved outcomes 1, 7
• High-risk stage II colon cancer: Recommended for T4 tumors and may be considered when multiple high-risk features are present 2, 8
• Stage II/IIIA/IIIB gastric cancer after D2 gastrectomy: S-1 monotherapy for 12 months demonstrated significant survival benefit in Japanese populations 1

When Adjuvant Chemotherapy is Controversial or Not Recommended:

• Low-risk stage II colon cancer: NOT routinely recommended as harms outweigh benefits in unselected populations 2, 8
• Bladder cancer: Evidence is weaker than for neoadjuvant therapy, though may delay recurrences in high-risk patients (≥pT3 or node-positive disease) 1
• MSI-high/dMMR stage II colon cancer: Should NOT receive fluoropyrimidine-based chemotherapy routinely 2, 8
• Soft tissue sarcomas: Not standard treatment despite some meta-analyses suggesting limited benefit, due to conflicting study results 1

Key Distinctions from Other Treatment Approaches

Adjuvant vs. Neoadjuvant Chemotherapy:

• Neoadjuvant chemotherapy is given BEFORE surgery to downsize tumors, increase resectability, and treat micrometastases earlier 4
• Neoadjuvant therapy has stronger evidence in bladder cancer than adjuvant therapy, with meta-analyses showing 5% absolute 5-year survival improvement 1, 4
• Neoadjuvant therapy ensures higher treatment compliance - patients are more likely to complete chemotherapy before surgery than after 4

Adjuvant vs. Palliative Chemotherapy:

• Adjuvant therapy is given when no detectable disease remains after surgery 2
• Palliative chemotherapy treats visible metastatic or advanced disease to control symptoms and prolong survival, not to cure 1

Treatment Duration and Timing

• Most curative adjuvant programs require 3-6 months of intensive treatment, not the protracted 1-2 year regimens previously used 6
• Start within 8 weeks of surgery, ideally as soon as the patient has recovered from surgical complications 2, 8
• Dose intensity and early use of non-cross-resistant agents are more important than chronic administration of suboptimal doses 6

Common Pitfalls to Avoid

• Do not withhold adjuvant chemotherapy based on age alone - elderly patients tolerate regimens like capecitabine well, and younger low-risk patients should not receive chemotherapy solely because of age 2, 8
• Do not substitute carboplatin for cisplatin in perioperative bladder cancer - no survival benefit has been demonstrated 1, 4
• Do not offer adjuvant chemotherapy to all stage II colon cancer patients - risk stratification is critical, and treatment should be reserved for high-risk features 2, 8
• Do not assume adjuvant chemotherapy is always beneficial - in receptor-positive breast cancer subgroups, the benefit may be smaller or unclear compared to receptor-negative disease 7

Evidence Quality Considerations

• The strongest evidence exists for stage III colon cancer and node-positive breast cancer, where multiple randomized trials and meta-analyses demonstrate survival benefits 1, 2
• Evidence is weaker or conflicting for stage II colon cancer, bladder cancer, and soft tissue sarcomas, requiring individualized risk-benefit discussions 1, 8
• Subset analyses must be interpreted cautiously - the most secure finding is always the overall study result, not post-hoc subgroup analyses 7