Chemoradiation for adenocarcinoma of the anus.
OBJECTIVE
To assess the efficacy and limitations of definitive chemoradiation for adenocarcinoma of the anal canal and to propose a treatment strategy that addresses the limitations of treatment.


METHODS
Between 1976 and 1998, 16 patients with localized adenocarcinoma of the anal canal were treated with radiotherapy with or without chemotherapy with curative intent. Available histologic slides were reviewed for evidence of primary adenocarcinoma of anal duct origin. The treatment results for these patients were compared with those of a group of patients with epidermoid histologic features who were all treated with definitive chemoradiation (55 Gy with concurrent 5-fluorouracil and cisplatin, n = 92) between 1989 and 1998. The hospital records were reviewed for all patients. Patients with epidermoid carcinoma presented with more advanced primary tumors (42% vs. 19% Stage T3 or greater). All adenocarcinoma patients were treated with radiotherapy (median dose 55 Gy): 11 received concurrent 5-fluorouracil-based chemotherapy and 5 received radiotherapy alone. The initial surgical procedures included abdominoperineal resection, excisional biopsies (n = 5), and local excision (n = 1). Abdominoperineal resection was performed as salvage therapy after local recurrence in 5 patients. The Kaplan-Meier method was used to calculate 5-year actuarial pelvic control, distant disease control, disease-free survival, and overall survival. The median follow-up was 45 months (range 5-196) for patients with adenocarcinoma and 44 months (range 9-115) for patients with epidermoid histologic features.


RESULTS
Both local and distant recurrence rates were significantly greater in the adenocarcinoma patients. Of 16 patients with adenocarcinoma, 7 (5-year actuarial rate 54%) had recurrence at the primary site compared with 16 (5-year actuarial rate 18%) of 92 patients with epidermoid histologic features (p = 0.004). Distant disease developed in more patients with adenocarcinoma (5-year actuarial rate 66%) than in patients with epidermoid carcinoma (5-year actuarial rate 10%, p <0.001). The 5-year actuarial disease-free survival and overall survival rate for adenocarcinoma patients was 19% and 64%, respectively, compared with 77% (p <0.0001) and 85% (p = 0.017) for those with epidermoid carcinoma.


CONCLUSIONS
Patients with localized adenocarcinoma of the anus treated with definitive chemoradiation had high rates of pelvic failure and distant metastasis compared with comparably staged patients with epidermoid histologic features treated similarly. On the basis of these limitations, we recommend preoperative chemoradiation followed by abdominoperineal resection to maximize pelvic disease control and consideration of adjuvant chemotherapy to address the problem of micrometastatic disease.
Papagikos
Michael
M
Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Crane
Christopher H
CH
Skibber
John
J
Janjan
Nora A
NA
Feig
Barry
B
Rodriguez-Bigas
Miguel A
MA
Hung
Arthur
A
Wolff
Robert A
RA
Delclos
Marc
M
Lin
Edward
E
Cleary
Karen
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011879:Radiotherapy Dosage; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil