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Anal Cancer


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Power point presentation talking in short about diagnosis and treatment guidelines of anal cancer.

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Anal Cancer

  1. 1. By Osama Elzaafarany, MD Assistant lecturer of clinical oncology Medical Research Institute, Alexandria University Jan 2015
  2. 2. Estimated new cases and deaths from anal, anal canal, and ano-rectal cancer in the United States in 2014: • New cases: 7,210. • Deaths: 950. Anal cancer is an uncommon malignancy and accounts for only a small percentage (2%) of all GIT cancers. Peak incidence in 70th decade, but highly variable
  3. 3.  Human papilloma virus (HPV-16, 18 & 31)  Female gender (many series of data)  HIV positive patients.  Sexual promiscuity- particularly receptive anal intercourse  Cigarette smoking
  4. 4. Anal canal extends from the anorectal ring (dentate line) to the anal verge(3-4 cm). Regions:- Intraanal lesions: Cannot be visualized or only slightly visualized with gentle traction on the buttocks Perianal lesions: Completely visible; within a 5-cm radius of anal opening with gentle traction Skin lesions: Outside of the 5-cm radius
  5. 5.  Distal anal canal drains to inguinal nodes, femoral and hence ext iliac  Proximal tumours drain to mesorectal, then inf mesenteric, to para-aortic  Lymph node involvement at diagnosis is observed in 30%–40% of cases while systemic spread is uncommon with distant extra-pelvic metastases recorded in 5%–8% at onset.
  6. 6.  Anal cancer may arise from a precursor dysplastic lesion(AIN) or “anal squamous intra-epithelial lesions”.  progression from AIN 3 to invasive malignancy in immuno- competent patients is rare, but appears to be more likely in immuno- suppressed patients, and is influenced by HIV seropositivity, low CD4 count and serotype of HPV infection.  HPV-associated tumours usually retain wild-type P53, and this explains why patients with HPV-associated tumours respond well to concurrent chemoradiotherapy.  Data on the interaction with wild-type P53 in cigarette smokers, as in head and neck cancer, are lacking.  HPV-related vaginal and cervical intra-epithelial and malignant squamous lesions should be screened for in younger women.
  7. 7.  Squamous cell carcinoma:  Cloacogenic carcinoma.  Transitional cell carcinoma,  Basaloid carcinoma.  Keratinizing carcinoma.  Adenocarcinoma.  Small cell carcinoma.  Undifferentiated ca. The World Health Organization (3rd & 4th edition) classification of malignant epithelial tumors of the anal canal includes :-
  8. 8.  Tumours of the anal margin are generally well differentiated and often occur in men, in contrast to canal tumours which are normally poorly differentiated and more common in women.  Some authors report that a basaloid histological subtype has a higher risk of developing metastatic disease.  The biology and prognosis of keratinising and non- keratinising tumours of the anal canal also appear to be similar.  Verrucous carcinomas: are a variant and are sometimes described as giant condylomas or Buschke–Lowenstein tumours, which may have a better prognosis than SCC, for whom some consider surgery the best option.
  9. 9. • Abdomino-perineal resection was previously thought to be required for all but small anal cancers occurring below the dentate line with about 70% of patients surviving 5 or more years, but such surgery is no longer the treatment of choice. • However, smaller lesions (<2 cm in diameter), involving the anal margin and not poorly differentiated may be treated by primary surgery in the form of a local excision provided adequate margins (>5 mm) can be obtained without compromising sphincter function. • Radiation therapy alone may lead to a 5 year survival rate in excess of 70%, but high doses (≥60 Gy) may yield necrosis or fibrosis.
  10. 10. Chemotherapy with fluorouracil (5FU) and cisplatin concurrent with lower dose radiation therapy as utilized in the RTOG8314 trial has a 5 ys survival rate in excess of 70% with low levels of acute and chronic morbidity, and few patients require surgery for dermal or sphincter toxic effects. The optimal dose of radiation with concurrent chemotherapy to optimize local control and minimize sphincter toxic effects has been studied in the RTOG9208 trial, for example, and appears to be in the 45 - 60 Gy range
  11. 11. The Anal Cancer Trial (ACT1) from the United Kingdom Coordinating Committee on Cancer Research:  Demonstrated the superiority of chemoradiation with 5-FU and mitomycin C (MMC) over radiation alone with regard to local failure and deaths from anal cancer.  Longterm follow up of this study has revealed 25.3 fewer patients with locoregional relapse and 12.5 fewer anal cancer deaths per 100 patients treated with chemoradiation compared with 100 patients treated with radiation alone.  9.1% increase in non-anal cancer deaths was seen in the first 5 years following chemoradiation, which was not seen after 10 years. ‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬‫ـــ‬‫ــــــــــــــــــــــــــــــــــــــــــ‬ Northover J, GlynneJones R, SebagMontefiore D, et al.: Chemoradiation for the treatment of epidermoid anal cancer: 13year followup of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer 102 (7): 11238,, 2010
  12. 12. The choice of chemotherapy during concurrent chemo-radiation has been the subject of several trials. Analysis of an intergroup trial (Flam M, et al. J Clin Oncol 1996) that compared radiation therapy plus 5FU and MMC with radiation therapy plus 5FU alone in patients with anal cancer demonstrated lower colostomy rates as well as higher colostomy free and disease free survival (DFS) with the addition of MMC.
  13. 13. The intergroup, randomized, phase III trial (RTOG 9811) examined whether MMC could be replaced by cisplatin in combination with 5FU during concurrent chemoradiation:  In the cisplatin arm of this study, two cycles of induction 5FU and cisplatin were given before concurrent chemoradiation with 5FU and cisplatin.  The MMC arm had improved local control and colostomy free survival, but no improvement was found in DFS or overall survival (OS).  Longterm follow up of the RTOG9811 trial has been published and demonstrated superior 5-year DFS and OS. One potential explanation for the inferiority of the cisplatin arm is delay in time to radiation, given the induction strategy employed in this study.
  14. 14.  A strategy of maintenance chemotherapy with 5FU and cisplatin after chemoradiation with 5FU and MMC or 5FU and cisplatin was evaluated in the ACTII trial, and 3- year PFS was not improved (74% with maintenance chemotherapy vs. 73% without maintenance Chemotherapy.  Induction chemotherapy and dose intensification were examined in the UNICANCER ACCORD03 trial, which did not demonstrate an advantage in colostomy free survival with induction chemotherapy with 5FU and cisplatin or with radiation dose intensification.
  16. 16.  Capecitabine is an accepted alternative to 5-FU in CCRT based in retrospectve studies.  Cetuximab (Anti-EGFR ) is effective with accepted toxicity profile when combined with Cisplatin-5FU and RTx, based in phase II studies.  Brachytherapy: There are currently limited data on the use of HDR brachytherapy in anal cancer and lack of consensus on the optimal fractionation schedule. Curative brachytherapy as a single modality is not recommended, but may be applicable as a boost following response to CCRT.
  17. 17.  Standard salvage therapy for those patients with either gross or microscopic residual disease following chemoradiation therapy has been abdomino-perineal resection.  Alternately, patients may be treated with additional salvage chemoradiation therapy in the form of 5FU, cisplatin, and a radiation boost to potentially avoid permanent colostomy.  Because of the small number of cases, information that can only come from patient participation in Well designed clinical trials is needed to improve the management of anal cancer. Patients with stages II, III, and IV disease should be considered candidates for clinical trials.
  18. 18. • Approximately 10%–20% of patients suffer distant relapse. • The most common sites of metastatic spread are to the para- aortic nodes, liver, lungs and skin, which usually appear relatively late and in the context of local persistence or recurrence of disease following treatment. • The prognosis in this group is poor with only 10% of patients with distant metastases surviving 2 years or more, but long- term survivors are described. • Patients with small volume or isolated metastatic disease should be further discussed by an appropriate Multi- disceplinary team, in case there are surgical or CRT options.
  19. 19. • There is no consensus on the standard chemotherapy treatment. The choice of chemotherapy is often influenced by previously used agents in the initial CRT regimen, but regimens with good documented activity are limited and generally have produced unsatisfactory results. • Otherwise fit patients with symptomatic metastatic or recurrent disease not amenable to surgery should be considered for chemotherapy; combination of cisplatin+5-FU. • Activity is also reported for carboplatin, doxorubicin, taxanes and irinotecan ± cetuximab, or combinations of these agents. • Responses are rarely complete and usually of short duration.
  20. 20. Combinations of 5-FU based CCRT and other cytotoxic agents e.g Mitomycin C = (MMC), have been established as the standard of care, leading to complete tumour regression in 80%–90% of patients, with locoregional failures of 15%.
  21. 21.  Adenocarcinoma arises from the columnar epithelium of the anal canal and its incidence is low accounting for less than 5 % of all anal malignancies.  Extension of rectal cancer into the anal canal is the more common presentation. Occasionally, adenocarcinoma may occur in patients with ulcerative colitis or Crohn disease who have ileal pouch-anal anastomosis.  APR should be offered for early-stage disease.  For locally advanced disease (T3 or any T with N + ), a multimodality approach should be considered. Patients treated with APR had significantly improved 5-year OS than those treated with radiation alone.
  22. 22.  Anorectal melanoma is rare and accounts for less than 3 % of all malignant melanomas and less than 1 % of all anal canal tumors.  The 5 -year OS rate is generally less than 20 % . The initial stage at presentation largely determines OS.  Ross et al. from the M. D. Anderson Cancer Center reviewed a series of 32 patients with melanoma treated with either APR or local resection.  Local recurrence was lower in the APR group (29 % for APR; 5 8 % for local excision) . However, there was no difference in OS between the two groups ( 19 . 5 months for APR; 18 .9 months for local resection ) .  Most authors recommend local excision of anorectal melanoma if adequate margins could be achieved.