More on the Treatment of Anal Margin Carcinomas

May 1, 1997

Anal carcinomas are an uncommon group of heterogeneous lesions that have represented a therapeutic enigma for many years. The mere rarity of these cancers alone has proven to be a major impediment to the formulation of a standardized

Anal carcinomas are an uncommon group of heterogeneous lesions thathave represented a therapeutic enigma for many years. The mere rarity ofthese cancers alone has proven to be a major impediment to the formulationof a standardized approach to treatment planning.

Much of our current knowledge about the natural history and the biologyof these tumors derives from small, single-institution, retrospective reviewsof questionable scientific merit that extended over long periods and lackedappropriate control groups or utilized historical controls. These datahave been further criticized due to the anatomic definition of the componentsof the anal canal and anal margin and the nonstandardization of the stagingsystems used until the American Joint Committee on Cancer (AJCC) and InternationalUnion Against Cancer (UICC) systems became widely accepted after 1987.[1,2]

In addition, treatment modalities for anal cancer have varied with individualinstitutional experience and bias. Compounding this even further, therehas been variation even within individual institutions in terms of thechemotherapy regimens utilized, methods of delivering radiation therapy(interstitial implant vs external beam), and whether a single modalityor combined approach was employed. Important therapeutic end points, suchas disease-free survival and site of first failure, have also been glaringlyomitted from many of these published series.

Collectively, the nonuniformity of the existing data prevents them frombeing subjected to meaningful statistical evaluation. The article by Drs.Mendenhall, Copeland, and associates of their institutional experienceand their review of the literature, published in the December issue ofONCOLOGY (10[12]:1843-1854, 1996), addresses some of these important issuesand stands as a commendable attempt to formulate a structured approachto the treatment of this rare entity.

Treatment Approaches

It is clear that the management of this disease represents another exampleof the necessity for a multimodality approach to solid tumors. This approachmandates consultation among surgeons, medical oncologists, and radiationoncologists to formulate the therapeutic strategy that ensures the bestoutcome, measured not only by disease-free and overall survival but also,importantly, by functional preservation.

The primary goals of treatment have evolved to include not only localcontrol and improved survival but also preservation of normal anal function.Although an abdominoperineal resection was the preferred approach in thepast, with time, it has become well accepted that perianal lesions arenot as invasive and do not metastasize to regional lymph nodes as frequentlyas their anal canal counterparts,[3] and therefore, do not necessitatethis radical treatment.

Many series have subsequently reported on the feasibility of local excisionfor early-stage, small tumors that do not demonstrate invasion of the surrounding,deeper tissue. In a previous institutional review of 16 patients treatedfor perianal squamous cell carcinomas by Schraut et al at The Universityof Chicago, the concept of local excision for treatment of the tumors wassupported by a 67% absolute 10-year survival.[4] This paralleled the experienceof Papillon et al, who, in a 1992 review of epidermoid carcinoma of theanal margin, clearly demonstrated the benefit of local excision in controllingthe disease and concomitantly preserving sphincter function.[5] Local recurrenceswere generally controlled by repeat excision or by the more radical abdominoperinealresection. Abdominoperineal resection was used successfully in 3 of 10patients in the series of Cutuli et al[6] and in 2 of 8 patients in theCleveland Clinic series.[7]

A number of conclusions can be drawn from a review of the literature,such as that provided by Mendenhall et al. These conclusions agree withour own experience. We concur with Mendenhall et al that early T1 and T2lesions may be treated with either local excision with clear margins orradiotherapy. One can accept the relatively high local recurrence ratewith these approaches since the recurrences tend to be amenable to furtherexcision, radiotherapy, or abdominoperineal resection for cure.

Stage T2 and more advanced lesions should be considered for prophylacticgroin irradiation due to the significant likelihood of regional nodal disease.In their series of 57 patients, Papillon et al found a high incidence ofinguinal lymph node recurrence in those individuals with T2-T3, N0 tumors.[5]This was their rationale for elective bilateral inguinal irradiation atthe time of treatment of the primary lesion. Other investigators, suchas Cutuli's group, found no inguinal recurrences in patients with N0 tumorswho received prophylactic groin irradiation.[6] In all of these series,there was minimal treatment-associated morbidity. Taking these data intoconsideration, it seems reasonable that, in patients with T2 or more advancedlesions, groin irradiation be instituted at the time of treatment of theprimary cancer. It is unclear at present whether this therapy achievesstatistically improved disease-free or long-term survival.

More advanced T3 and T4 cancers are best treated with the combinationof cytotoxic chemotherapy and radiation therapy, with abdominoperinealresection reserved for patients with poor sphincter function (manifestedby fecal incontinence) and for those fortunate individuals who experiencea significant clinical response with downstaging of their tumors to allowfor consideration of potentially curative surgery. There does not appearto be any role for prophylactic regional lymph node dissection.

Role of Lymph Node Dissection

The role of either hypogastric lymph node/extended pelvic lymph nodedissection or radical groin dissection has been a topic of debate for manyyears. According to our institutional experience and the experience ofother surgeons, perianal squamous cell carcinoma rarely metastasizes topelvic lymph nodes, and thus, does not warrant routine dissection. Inguinalnode involvement--a well accepted, poor prognostic factor--occurs withrelatively high frequency in patients with more advanced tumors. However,since radical groin dissection is attended by considerable morbidity andsevere disability, it is difficult to justify a prophylactic dissectionon theoretical grounds alone. Inguinal lmph node dissection is still usedfor local control of nodal disease.

Importance of Follow-up

Lastly, one important, seemingly obvious point in the management ofcancers of the anal margin is the need for careful, close interval follow-upby examination and proctoscopy for early detection of local or nodal recurrences.Given the sometimes indolent pattern of these tumors, such follow-up shouldbe continued for at least 10 years.

References:

1. American Joint Committee on Cancer: Manual For Staging of Cancer,3rd ed. Philadelphia, JB Lippincott, 1987.

2. Hermanek P, Sobin LH: TNM Classification of Malignant Tumors, 4thed. New York, Springer Verlag, 1987.

3. Beahrs OH, Wilson SM: Carcinoma of the anus. Ann Surg 184:422-428,1976.

4. Schraut WH, Wang CH, Dawson PJ, et al: Depth of invasion, location,and size of cancer of the anus dictate operative treatment. Cancer 51:1291-1296,1983.

5. Papillon J, Chassard JL: Respective roles of radiotherapy and surgeryin the management of epidermoid carcinoma of the anal margin. Dis ColonRectum 35:422-429, 1992.

6. Cutuli B, Fenton J, Labib A, et al: Anal margin carcinoma: 21 Casestreated at the Institute Curie by exclusive curative radiotherapy. RadiotherOncol 11:1-6, 1988.

7. Al-Jurf AS, Tumbull RB, Fazio VW: Local treatment of squamous cellcarcinoma of the anus. Surg Gynecol Obstet 148:576-578, 1979.