Clinical Investigation
Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience

https://doi.org/10.1016/S0360-3016(99)00099-1Get rights and content

Abstract

Purpose: To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer.

Materials and Methods: Preoperative chemoradiotherapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed.

Results: The pathological tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor downstaging occurred in 72 (62%) cases. Only 3% of cases had pathologic evidence of progressive disease. Pretreatment tumor size (< 5 cm vs. ≥ 5 cm) was the only factor predictive of tumor downstaging (p < 0.04). A decrease of >1 T-stage level was accomplished in 45% of those downstaged. Overall, a sphincter-saving (SP) procedure was possible in 59% of patients and an abdominoperineal resection (APR) was required in 41% of cases. Factors predictive of SP included downstaging (p < 0.03), age > 40 years (p < 0.007), pretreatment tumor distance, 3 to 6 cm from the anal verge (p < 0.00001), tumor size <6 cm (p < 0.02), mobility (p < 0.004), tumor stage <T4 (p < 0.01), and uN negative (p < 0.008). SP was performed in 23 patients (72%) with a CR and in 48 (67%) of downstaged cases. Among the 69 tumors located < 6 cm from the anal verge, 29 (42%) were resected with a SP. The level of response was important for tumors located < 6 cm from the anal verge because a SP was performed in 9 of the 17 (53%) CRs in this group while only 20 of 52 patients (38%) had a SP when residual disease was present after CTX/XRT. For tumors located > 6 cm from the anal verge, SP was performed in 14 of the 15 (93%) patients with a CR and 32 of 33 (97%) of patients with residual disease (p < 0.00004).

Conclusions: Significant tumor downstaging results from preoperative chemoradiation allowing sphincter sparing surgery in over 40% of patients whose tumors were located < 6 cm from the anal verge and who otherwise would have required colostomy.

Introduction

Preoperative radiation, administered alone or in combination with chemotherapy, has been used to cause tumor regression and allow complete resection of the rectal cancer with a sphincter saving procedure 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. Other advantages for the use of preoperative radiation include a lower total dose of radiation, and easier displacement of the small bowel from the radiation field 19, 20, 21, 22, 23, 24, 25, 26, 27. No excess surgical complications have been reported as a result of preoperative radiation 4, 8, 22, 23, 28. A survival advantage, largely due to the decreased rates of local recurrence, has also been reported in the Swedish Rectal Cancer Trial 22, 23, 29, 30, 31, 32.

The significance of the level of downstaging after preoperative chemoradiation relative to the ability to perform a sphincter sparing procedure and the risk for local recurrence is still not completely described. Berger and colleagues (33) evaluated the residual tumor cell density after preoperative chemoradiation. Factors predictive for tumor downstaging included higher total radiation doses, tumor differentiation, preoperative tumor stage, and length of time between completion of radiation and surgery. No factor was found to be predictive of a complete pathologic response. In univariate analysis, the postoperative stage was statistically significant for survival. No assessment was performed that related the level of response with the type of surgical intervention performed or the rate of local control.

Our study evaluates the influence of the level of tumor downstaging on the ability to perform sphincter-sparing surgery after preoperative chemoradiation in locally advanced rectal cancer. Tumor location, pathologic characteristics, and rates of local control relative to the surgical procedure performed will be presented.

Section snippets

Materials and methods

Preoperative chemoradiotherapy was administered to 117 patients treated by a single surgeon (JS) from 1991–1995 with locally advanced rectal cancer. Locally advanced rectal cancer was defined as tumor extension through the bowel wall, based on clinical, endorectal ultrasound and/or radiographic evaluations, without associated distant metastases. Diagnostic studies performed at presentation included proctoscopy or colonoscopy, computed tomography (CT) of the abdomen and pelvis, chest x-ray, and

Results

The pretreatment stage distribution, as determined by endorectal ultrasound (u) in 102 patients, included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases. Endorectal ultrasound was not performed in 13% of cases (15 patients) because of an obstructing tumor; 10 of these cases were staged clinically and radiographically as T3. Therefore, a total of 96% of cases (n = 108) were classified as having a stage T3 tumor. The 2 patients with uT2N0 disease were included because the

Discussion

Sphincter preservation is the primary goal of preoperative irradiation for locally advanced rectal cancer. The addition of chemotherapy during the course of preoperative radiation is advocated based on the high risk for disseminated disease and use of chemotherapy as a radiation sensitizer 4, 5, 8, 10, 14, 16, 38, 39, 40. Preoperative chemoradiation has been shown to reduce both the size and the proliferative activity of rectal tumors when compared to pretreatment levels 10, 41. Using

Acknowledgements

This work was supported in part by Grants P01 CA 06294, T32 CA 77050, P30 CA 16672 awarded by the National Cancer Institute, Department of Health and Human Services.

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