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

Background and purpose: To evaluate the influence of response to preoperati ve infusional chemoradiation on outcome parameters among patients with loca lly advanced rectal cancer. Materials and methods: Preoperative chemoradiotherapy, 45 Gy in 25 fraction s over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m(2) per day ), was given to 117 patients. As determined by pretreatment endorectal ultr asound (EUS), 96% of cases were Stage T3, and 51% had EUS evidence of perir ectal adenopathy, Surgery was performed approximately 6 weeks after chemora diation therapy. Postoperatively adjuvant systemic therapy, consisting of 4 00-425 mg/m(2) of 5-fluorouracil plus 20 mg/m(2) leucovorin for 5 days, was administered every 28 days for six cycles. Outcome parameters of local con trol (LC), freedom from distant metastases (DMC), disease-free survival (DF S) and cancer specific survival (CSS) were evaluated relative to primary tu mor characteristics. Results: The final post-treatment pathological tumor stages were complete r esponse in 27%, Tis-2 N0 in 26%, T2 N1 in 5%, T3 N0 in 21%, T3 N1 in 15%, T 4 N0 in 5% and T4 N1 in 1%, Down-staging occurred in 61% of cases. The pret reatment primary tumor size only influenced rates of local control (P < 0.0 3) and had no other influence on outcome parameters. Pretreatment evidence of perirectal lymph node involvement had no impact on outcome parameters. P athologic 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 r elationship held only when responders were compared to non-responders. No d ifference was observed based on the level of downstaging at the primary tum or. Correspondingly, DFS was improved when non-responders were compared to downstaged patients (P < 0.01), Response to preoperative chemoradiation fai led tb affect rates of LC or CSS. For the group as a whole, adjuvant chemot herapy improved only CSS (P < 0.03), Adjuvant chemotherapy was given to 74 patients, 36 of whom had responded to preoperative chemoradiation. Improvem ents were only seen in DFS (P < 0.03) when down-staged patients were compar ed to the non-responders who received adjuvant chemotherapy. In addition, t he DFS rates were lower in the non-responder group who received adjuvant ch emotherapy 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 subseq uent development of distant metastases is reduced in the more than 60% of p atients 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 b e given for strategies that base selection of subsequent adjuvant chemother apy on response to preoperative chemoradiation, (C) 1999 Elsevier Science I reland Ltd. All rights reserved.