Is radiotherapy (Radiation Therapy) effective as a locotherapy for Cholangiocarcinoma?

Radiotherapy as Locotherapy for Cholangiocarcinoma

Radiotherapy is NOT recommended as monotherapy for cholangiocarcinoma, but can be effective as part of combined modality treatment with chemotherapy in specific clinical scenarios, particularly for unresectable disease or as adjuvant therapy in high-risk patients. 1

Evidence Against Radiotherapy Alone

• There is currently no evidence supporting the use of radiotherapy alone for intrahepatic cholangiocarcinoma. 1
• Radiotherapy has only been studied and shown benefit when used in conjunction with systemic chemotherapy, not as standalone locotherapy. 1
• External beam radiotherapy alone has no proven survival benefit in advanced cholangiocarcinoma and carries significant toxicity. 2

When Radiotherapy Can Be Effective (Combined Modality)

Adjuvant Setting After Resection

• Postoperative adjuvant chemoradiation may reduce local recurrence and improve overall survival, particularly in high-risk patients (those with regional lymph node metastasis or positive margins). 1
• Several retrospective reports suggest survival benefit with adjuvant chemoradiotherapy in both gallbladder and biliary duct cancer. 1
• Fluorouracil-based chemoradiotherapy has been the traditional approach, though gemcitabine with or without oxaliplatin has shown feasibility. 1

Definitive Treatment for Unresectable Disease

• For unresectable, localized intrahepatic cholangiocarcinoma, combined modality therapy (chemotherapy plus radiation) significantly improves overall survival compared to chemotherapy alone. 3
• A National Cancer Database analysis of 1,636 patients showed 2-year overall survival of 26% with combined modality therapy versus 20% with chemotherapy alone (p<0.05). 3
• Definitive chemoradiation along with biliary stenting in the nonoperative setting may confer a small survival benefit for ductal cholangiocarcinoma. 1

Specific Radiation Techniques with Better Outcomes

Stereotactic Body Radiotherapy (SBRT):

• Can be considered for peripheral lesions of intrahepatic cholangiocarcinoma when surgery is not possible. 1
• SBRT following chemotherapy has shown promising early local control and is well tolerated. 1
• Selected unresectable cases may be considered for SBRT with neoadjuvant and/or concurrent chemotherapy. 4

Hypofractionated Radiotherapy:

• Can be considered for more centrally located disease (typically 15 fractions). 1

Proton Beam Therapy:

• Can be considered for peripheral lesions, though data are limited. 1

Alternative Locotherapies with Stronger Evidence

When surgery is not feasible, other locoregional therapies have stronger evidence than radiotherapy alone:

For Small Tumors (<3-5 cm)

• Radiofrequency ablation (RFA) or microwave ablation provides good local tumor control for lesions ≤5 cm located away from segmental bile ducts, liver surface, and major vessels. 1
• Meta-analysis shows median overall survival of 33-38.5 months for small to intermediate intrahepatic cholangiocarcinoma treated with ablation. 1
• 1-, 3-, and 5-year overall survival rates after RFA are 82%, 47%, and 24% respectively. 5

For Larger or More Advanced Disease

• Transarterial chemoembolization (TACE) is supported for more advanced intrahepatic cholangiocarcinoma, with median survival of 9.1-30 months. 1, 2
• Transarterial radioembolization (TARE) shows benefit for unresectable disease, particularly after failed first-line chemotherapy, with disease control rates of 81.8%. 1, 2

Clinical Algorithm for Treatment Selection

For Potentially Resectable Disease:

1. Surgery remains the only curative option and should be pursued when feasible. 1
2. If high-risk features present after resection (positive nodes, close/positive margins), consider adjuvant chemoradiation. 1

For Unresectable Localized Disease:

1. If tumor <5 cm and peripherally located: Consider RFA/microwave ablation. 1
2. If tumor >5 cm or centrally located: Consider SBRT (peripheral) or hypofractionated RT (central) combined with chemotherapy. 1
3. For more diffuse intrahepatic disease: Consider TACE or TARE. 1
4. Never use radiotherapy alone—always combine with systemic chemotherapy (gemcitabine plus cisplatin standard). 1

For Advanced/Metastatic Disease:

1. Systemic chemotherapy (gemcitabine plus cisplatin) is standard of care. 1
2. Radiotherapy may be added for symptomatic liver disease or as part of combined modality approach in selected patients. 1

Critical Pitfalls to Avoid

• Do not use external beam radiotherapy as monotherapy for cholangiocarcinoma—it has no proven survival benefit and significant toxicity. 1, 2
• Do not delay systemic chemotherapy in favor of radiation alone for unresectable disease. 2, 6
• Recognize that approximately 75% of inoperable patients in the United States do not receive radiation as part of combined modality therapy, potentially missing a survival benefit. 3
• Most deaths from cholangiocarcinoma are attributable to local disease progression rather than distant metastases, supporting the rationale for locoregional approaches, but these should be combined with systemic therapy. 7