Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum.
OBJECTIVE
In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group.


BACKGROUND
The optimal treatment of large rectal carcinomas remains controversial; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems.


METHODS
Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy-proven lesions > 3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates.


RESULTS
The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens. Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes. In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (< 5%). Cox-Mantel analysis of Kaplan-Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p = 0.031) for protocol versus control patients.


CONCLUSIONS
This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.
Chari
R S
RS
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Tyler
D S
DS
Anscher
M S
MS
Russell
L
L
Clary
B M
BM
Hathorn
J
J
Seigler
H F
HF
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015996:Survival Rate
D002945:Cisplatin; D005472:Fluorouracil