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.