Neoadjuvant therapy for adenocarcinoma of the rectum: Tumor response and acute toxicity

PURPOSE: This study was designed to evaluate the down-staging effect and ac ute toxicity of preoperative radiation and chemoradiation for primary adeno carcinoma of the rectum. METHODS: The results of pretreatment staging wish transrectal ultrasound and computed tomography were compared with final his tologic stage in 260 consecutive patients who underwent neoadjuvant therapy and proctectomy for primary adenocarcinoma of the rectum. Patients underwe nt short-course radiation (2,000 cGy in five fractions), long-course radiat ion (4,500 cGy in 25 fractions), or chemoradiation (4,500 cGy in 25 fractio ns with concurrent chemotherapy). RESULTS: Down-staging of one or more T st ages occurred in 116 of 260 (45 percent) patients overall (short-course rad iation 34/82 (42 percent), long-course radiation 55/122 (45 percent), chemo radiation 27/56 (48 percent), P = not significant). Down-staging of one or more N stages occurred in 85 of 178 (48 percent) patients overall (short-co urse radiation 12/45 (27 percent), long-course radiation 49/86 (57 percent) , chemoradiation 24/47 (51 percent), P = 0.003). Complete pathologic respon se was observed in 116 of 260 (6 percent) patients overall (short-course ra diation 4/82 (5 percent), long-course radiation 5/122 (4 percent), chemorad iation 7/56 (13 percent), P = 0.08). Resection with negative margins (dista l, proximal, and radial) was achieved in 211 of 227 patients 63 percent) in whom complete radial margin data were available. Permanent stomas were cre ated in 35 percent of patients; temporary stomas were created in 15 percent . Thirty-three Grade 3 or 4 toxicities occurred in 22 of 178 (48 percent) p atients overall during neoadjuvant therapy. Toxicity was more frequent in p atients receiving chemoradiation (14/56; 25 percent) and long-course radiat ion (8/122; 7 percent) than in those receiving short-course radiation (0/82 , 0 percent), P < 0.0001. Perioperative complications occurred in 93 patien ts overall (36 percent). The postoperative mortality rate was 0.4 percent ( 1/260). There was no significant difference in the com plication rate betwe en patients treated with short-course radiation (26/82; 32 percent), long-c ourse radiation (46/122; 36 per cent), and chemoradiation (21/56; 38 percen t). CONCLUSION: Neoadjuvant therapy for adenocarcinoma of the rectum is a w ell tolerated and can produce substantial clown-staging and a high curative resection rate. Chemoradiation can achieve high complete pathologic respon se rates, although toxicity during neoadjuvant therapy is greater than for radiation alone. Short-course radiation can achieve down-staging of both T stage and N stage.