What are the current guidelines for radiation therapy in the treatment of rectal cancer?

Current Guidelines for Radiation Therapy in Rectal Cancer Treatment

Preoperative radiotherapy is the standard of care for locally advanced rectal cancer (stages II-III), as it significantly reduces local recurrence rates and has less toxicity than postoperative radiotherapy. 1, 2

Risk-Stratified Approach to Radiation Therapy

Early Stage Disease

• For very early tumors (cT1-T2), local procedures such as transanal endoscopic microsurgery may be appropriate without radiation 1
• In early favorable cases (cT1-2, some early cT3, N0 with clear circumferential resection margin), surgery alone using total mesorectal excision (TME) technique is appropriate since the risk of local failure is very low 2

Locally Advanced Disease

• For most cT3 tumors without threatened circumferential resection margin (CRM) and some cT4 tumors, preoperative radiotherapy followed by TME is recommended 2
• In the most locally advanced cases (cT3 with positive CRM, cT4 with overgrowth to organs not readily resectable), preoperative radiochemotherapy is strongly recommended 2

Radiation Therapy Regimens

Short-Course Radiotherapy

• 25 Gy delivered in 5 fractions (5 Gy/fraction) over one week followed by immediate surgery (<10 days from first radiation fraction) is a convenient, simple, and low-toxicity treatment option 2
• For very elderly patients (≥80-85 years) or those unfit for chemoradiotherapy, 5×5 Gy with a delay of 8 weeks before surgery can be an option 2

Long-Course Chemoradiotherapy

• 46-50.4 Gy delivered in 1.8-2 Gy fractions with concurrent 5-FU-based chemotherapy 2
• Surgery should be performed 6-8 weeks after completion of chemoradiotherapy 2
• 5-FU can be administered as bolus injections with leucovorin, prolonged continuous infusion (likely better than bolus), or oral capecitabine 2

Preoperative vs. Postoperative Radiation

• Preoperative therapy is strongly preferred over postoperative therapy due to: 2, 1
  • Significant reduction in local recurrence (6% vs 13%)
  • Lower treatment-associated toxicity (27% vs 40%)
  • Potential for tumor downsizing and increased likelihood of sphincter preservation

Special Clinical Scenarios

Local Recurrences

• Patients with recurrence (if radiotherapy was not given initially) should receive preoperative radiotherapy with concomitant chemotherapy 2
• Attempts at radical surgery should take place 6-8 weeks after radiotherapy 2
• For previously irradiated patients, additional radiotherapy using external beam or intraoperative techniques may be considered 2

Metastatic Disease

• For patients with metastatic disease, radiation therapy may be considered as a palliative procedure 2, 3
• In selected cases with oligometastatic disease, treatment may include surgery of resectable liver or lung metastases along with appropriate management of the primary tumor 2

Recent Advances and Considerations

• Total Neoadjuvant Therapy (TNT), which includes neoadjuvant chemotherapy and either short-course radiation or long-course chemoradiotherapy, has emerged as an important treatment approach 1
• Combinations of 5-FU with other cytostatics (oxaliplatin, irinotecan) or targeted biological drugs have shown higher pathologic complete response rates but also increased toxicity 2, 1
• Modern radiation techniques should be used to reduce toxicity to surrounding normal tissues 1, 4

Common Pitfalls and Caveats

• Understaging is common - approximately 22% of patients clinically staged as T3N0 by EUS or MRI are found to have positive lymph nodes after surgery, supporting the use of preoperative chemoRT in these patients 2
• The total duration of perioperative therapy, including chemoRT and chemotherapy, should not exceed 6 months 2
• Postoperative chemoradiotherapy should be considered in patients with positive circumferential margins, perforation in the tumor area, or other high-risk features if preoperative radiotherapy was not given 2