Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: To evaluate the influence of response to preoperative infusional chemoradiation on outcome parameters among patients with locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy, 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2 per day), was given to 117 patients. As determined by pretreatment endorectal ultrasound (EUS), 96% of cases were Stage T3, and 51% had EUS evidence of perirectal adenopathy. Surgery was performed approximately 6 weeks after chemoradiation therapy. Postoperatively adjuvant systemic therapy, consisting of 400-425 mg/m2 of 5-fluorouracil plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for six cycles. Outcome parameters of local control (LC), freedom from distant metastases (DMC), disease-free survival (DFS) and cancer specific survival (CSS) were evaluated relative to primary tumor characteristics. RESULTS: The final post-treatment pathological tumor stages were complete response in 27%, Tis-2 N0 in 26%, T2 N1 in 5%, T3 N0 in 21%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Down-staging occurred in 61% of cases. The pretreatment primary tumor size only influenced rates of local control (P < 0.03) and had no other influence on outcome parameters. Pretreatment evidence of perirectal lymph node involvement had no impact on outcome parameters. Pathologic evidence of nodal involvement did affect DMC (P < 0.002) and DFS (P < 0.003). Pathologic evidence of response did influence freedom from the development of distant metastases (P < 0.004). On pairwise analysis this relationship held only when responders were compared to non-responders. No difference was observed based on the level of downstaging at the primary tumor. Correspondingly, DFS was improved when non-responders were compared to downstaged patients (P < 0.01). Response to preoperative chemoradiation failed to affect rates of LC or CSS. For the group as a whole, adjuvant chemotherapy improved only CSS (P < 0.03). Adjuvant chemotherapy was given to 74 patients, 36 of whom had responded to preoperative chemoradiation. Improvements were only seen in DFS (P < 0.03) when down-staged patients were compared to the non-responders who received adjuvant chemotherapy. In addition, the DFS rates were lower in the non-responder group who received adjuvant chemotherapy even when they were compared to down-staged patients who did not receive adjuvant chemotherapy (P < 0.04). CONCLUSION: Consistent with other reports, disease free survival and subsequent development of distant metastases is reduced in the more than 60% of patients who respond to preoperative infusional chemoradiation. Evidence of response appears more significant than the degree of response. At present, no impact is seen on cancer specific survival rates. Consideration should be given for strategies that base selection of subsequent adjuvant chemotherapy on response to preoperative chemoradiation.

Locally advanced rectal cancer: surgical complications after infusional chemotherapy and radiation therapy.

PURPOSE: To compare the surgical complication rate after further experience with infusional chemotherapy and radiation therapy for locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative radiation therapy (45 Gy in 25 fractions over 5 weeks) and concurrent continuous infusion of 5-fluorouracil (300 mg.m-2.d-1) were given to 117 patients with rectal cancer. Approximately 6 weeks after therapy, surgery was performed. RESULTS: The histopathologic cancer stages were Tis-2N0 in 30 patients (26%), T2N1 in six (5%), T3N0 in 24 (21%), T3N1 in 18 (15%), T4N0 in six (5%), and T4N1 in one (1%); a complete response to preoperative therapy was histopathologically confirmed in 32 patients. A decrease in cancer stage allowed a sphincter-saving procedure in 68 patients (58%) and abdominoperineal resection in 49 patients (42%). Only one patient developed fistula; nine patients, perioperative wound complications; and four patients, pelvic infection. In the authors' previously reported chemotherapy and radiation therapy results (same protocol), eight (22%) of 37 patients developed fistulas and five (14%) developed pelvic abscess; in the authors' previous experience with preoperative radiation therapy only (median total dose, 45 Gy; dose range, 40.0-59.4 Gy), results were similar. CONCLUSION: Surgical complications after chemotherapy and radiation therapy are statistically significantly (P < .05) reduced with further experience.