Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience.
OBJECTIVE
To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer.


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 T4NI 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. > or = 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.
Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
N A
NA
Janjan
V S
VS
Khoo
J
J
Abbruzzese
R
R
Pazdur
R
R
Dubrow
K R
KR
Cleary
P K
PK
Allen
P M
PM
Lynch
G
G
Glober
R
R
Wolff
T A
TA
Rich
J
J
Skibber
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001003:Anal Canal; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil