Radiation Oncology/Anal canal/Review

Anal Cancer Review

Epidemiology

• U.S. incidence: ~5,200; U.S. death rate ~700 (~13%)
• Risk factors: HPV 16-18 in ~75% cases, immunodeficiency, tobacco
• Clinical presentation: rectal bleeding, 20% asymptomatic
• Work-Up: DRE, inguinal evaluation, pelvic MRI/CT, chest/abdomen CT, PET not validated, GYN exam in women, consider HIV testing
• Anatomy: anal margin to anal verge to dentate line to anorectal sling
• Lymph node drainage: perirectal (N1), inguinal (N2), internal illiac (N2)
  • LN positive ~30% (ACT II)
• 5-year survival
  • Stage I: 69%
  • Stage II: 59%
  • Stage III: 41%
  • Stage IV: 19%

Surgery

• Local excision alone
  • Not considered appropriate for any lesions in anal canal (NCCN v1.2010, ACR 2007)
  • For T1N0 worse outcome (ACR 2007): 5-year local control ~70% (vs 80-90% with RT), 5-year OS ~50% (vs 90-100% with RT)
  • For T1N0 well-differentiated, anal margin (NCCN v1.2010): May be considered
• APR
  • 5-year OS ~50%
  • Toxicity: permanent colostomy
• Surgery vs chemo-RT
  • No randomized trials
  • Swedish cohort data support better outcomes with chemo-RT

Non-surgical approaches

• RT alone
  • Control rate depends on size of primary
  • Tumors <4 cm and cN0 have excellent 10-year local control (85-90%) and overall survival (~80%)
  • Larger tumors have only ~60% local control rate and ~50% overall survival
• Chemo-RT vs RT alone
  • 2 trials (UKCCCR, EORTC), mostly in T3-T4 or N+ patients
  • No difference in overall survival; UKCCCR improved cancer-specific survival. 5-year OS ~55%
  • Local control benefit: 40-50% to 65%
  • Colostomy-free benefit: 40% to 70%
• Chemo-RT: chemo options
  • RTOG 8704 (Flam) +/- Mitomycin
    • Worse colostomy without MMC: 4-year MMC- 22% vs MMC+ 9% (SS)
    • Worse DFS without MMC: 4-year 51% vs 73% (SS); no difference in OS
  • RTOG 9811 (Ajani, update Gunderson) Induction/concurrent 5-FU + cisplatin vs concurrent 5-FU + Mitomycin
    • Worse local control: cisplatin 67% vs Mitomycin 75%; colostomy rate 19% vs 10% (SS)
    • No impact on survial on initial analysis: 5-year OS 70-75%
    • However on update (Gunderson): DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074).
    • Uncreal whether worse outcomes due to induction or due to cisplatin
• Chemo-RT: RT options
  • RTOG 92-08 (Konski) split course to 59.6 Gy
    • Worse colostomy-free survival and DFS
  • RTOG 0529 (Kachnic) IMRT with concurrent 5-FU/mitomycin-C:
    • 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations.