Adjuvant radiochemotherapy in high-risk rectal cancer results of a prospective non-randomized study

Aims and background: In 1990 the National Institutes of Health Consensus Co nference recommended adjuvant combined therapy for patients with radically resected rectal cancer at high risk for relapse (i.e, stage II-III). The pu rpose of our prospective non-randomized study was to verify the feasibility and effectiveness of postoperative radiochemotherapy in terms of improveme nt in disease-free and overall survival in this patient subgroup. Study design: From January 1990 to October 1998, 191 consecutive patients w ith radically resected stage II-III rectal cancer were treated. A total of 159 patients with a 24-month follow-up were assessable for toxicity and sur vival. Anterior resection was performed In 129 (81%) and abdomino-perineal resection in 30 (19%) patients. Fifty-four (34%) stage II and 105 (66%) sta ge III patients entered the study. Within 45-60 days of surgery, all patien ts received 5-fluorouracil chemotherapy at the dose of 500 mg/m(2) as an iv bolus on days 1-5, every 4 weeks, for 6 cycles. Chemotherapy cycles III an d IV were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy consisted of 45 Gy/25 fractions plus a boost dose of 5. 4 Gy. Results: After a median follow-up of 57 months (range, 25-123), overall rec urrent disease was reported in 58 (36%) patients: local, systemic, and both local and systemic relapses in 12 (8%), 37 (23%) and 9 (6%) cases, respect ively. According to local extension, recurrence rates were 15% and 48% in s tage II and III, respectively. Five-year overall and disease-free survival were 71% and 66%, respectively. Overall survival was 87% in stage II and 62 % in stage III patients, and disease-free survival was 84% and 56% in stage II and III disease, respectively. According to univariate and multivariate analyses, significant prognostic factors for better tumor control were: st age (II vs III, P < 0.001), the number of involved nodes (less than or equa l to 3 vs > 3, P < 0.0001), and no extracapsular node invasion (P < 0.0001) . The recommended dose of the combined radiochemotherapy regimen was genera lly well tolerated. The incidence of any grade 3 acute toxicity (according to the WHO scale) was 13% diarrhea, 11% proctitis, 5% perineal dermatitis a nd 4% myelosuppression. Four (3%) patients had radiotherapy-related severe late toxicity which required surgery. Conclusions: The study provided recurrence rates and survival similar to ot her adjuvant radiochemotherapy regimens published in the literature. Howeve r, in view of the low 5-year survival rate recorded in stage III patients, a different approach should be investigated.