Standard Management of Anal Cancer
Chemoradiation therapy (CRT) is the standard of care for most anal cancers, consisting of external beam radiation therapy with concurrent 5-fluorouracil (5-FU) and mitomycin C (MMC). 1, 2
Treatment Algorithm Based on Disease Stage
- For small (<2 cm), well-differentiated tumors of the anal margin (T1 N0) without sphincter involvement, local excision alone may be appropriate if adequate margins (>5 mm) can be achieved 3, 2
- For all other stages (T2-T4, N+) and anal canal tumors, combined modality chemoradiation is the standard treatment 3, 1, 2
- Primary abdominoperineal resection (APR) is now reserved for patients previously irradiated in the pelvic region or as salvage therapy after failed chemoradiation 3
Standard Chemoradiation Regimen
- Radiation therapy: Minimum dose of 45-50 Gy to the primary tumor and regional lymph nodes 3, 2
- Chemotherapy:
- 5-FU 1000 mg/m² days 1-4 (week 1) and 29-32 (week 5) by continuous 24-hour IV infusion 3
- Mitomycin C 12 mg/m² IV bolus on day 1 (maximum single dose 20 mg) 3
- Capecitabine (825 mg/m²) can be substituted for 5-FU as an oral alternative 2
- Cisplatin (60 mg/m² on days 1 and 29) plus 5-FU is an alternative for patients who cannot tolerate MMC, particularly immunosuppressed patients 2
Important Treatment Considerations
- Avoid treatment breaks during radiation therapy as uninterrupted treatment is radiobiologically most effective 2, 4
- The inguinal lymph nodes should be included in radiation fields for most patients, even without obvious involvement 2
- Neoadjuvant chemotherapy before CRT has not improved outcomes and is not recommended outside clinical trials 3, 2
- Maintenance chemotherapy after completion of CRT has shown no significant benefit 3, 2
Assessment of Treatment Response
- Clinical evaluation should begin at 6-12 weeks after completion of CRT 3, 2
- Response to CRT may be slow - persistent disease may continue to regress up to 26 weeks after treatment initiation 1, 2
- Digital examination at 11,18, and 26 weeks from the start of treatment is recommended 3
- Abdominopelvic CT at week 26 to assess response 3
- Confirm residual or recurrent disease by biopsy (routine biopsies not recommended) 3
Management of Persistent or Recurrent Disease
- Patients with persistent disease should be followed for up to 6 months as long as there is no evidence of progressive disease 2
- Salvage surgery (abdominoperineal resection) is the standard approach for persistent or recurrent disease after adequate follow-up 3, 1, 2
- Salvage surgery can achieve local pelvic control in approximately 60% of cases 1
Evidence Supporting CRT as Standard of Care
- Multiple randomized trials have established CRT as superior to radiation alone, with the UKCCCR trial showing a 46% reduction in the risk of local failure with CRT compared to radiotherapy alone 5
- The RTOG phase III study confirmed the superiority of the combination of MMC and 5-FU over 5-FU alone 3
- CRT achieves similar survival rates to abdominoperineal resection while preserving anal sphincter function 1
- Local control rates of 75% at 5 years can be achieved with chemoradiation regimens 1, 6