Pilot study of concurrent cisplatin, 5-fluorouracil, and external beam radiotherapy prior to radical surgery +/- intraoperative electron beam radiotherapy in locally advanced cervical cancer

Purpose. The purpose of this study was to describe the feasibility of a com bined preoperative chemoradiation program followed by radical surgery in ad vanced cervical cancer. Materials and methods. From February 1988 to April 1997, 40 patients with c arcinoma of the cervix were treated with preoperative external beam radioth erapy to 45 Gy in 5 weeks. Patients received concurrent continuous infusion cisplatin (20 mg/m(2)) and 5-fluorouracil (1500 mg) chemotherapy during th e first (days 1-4) and fifth (days 22-25) weeks of the radiation course. Ra dical surgery was performed 4-6 weeks after the completion of the preoperat ive treatment. Intraoperative radiotherapy was given to 20 patients, based on intraoperative assessment. Results. Toxicity associated with chemoradiation was usually mild except in two patients who presented WHO grade 4 bone marrow aplasia. Three patients developed postoperative ureterovaginal fistula, and five patients develope d long-term hydronephrosis that needed ureteral stenting. Clinical response was observed in 95% of the patients (55% complete response). The analysis of the surgical specimens revealed complete pathological response in 67.5% of the cases and partial pathological response in 32.5%. As expected, the d egree of pathological response was predicted by the degree of clinical resp onse (P = 0.001). Nine-year local control, distant metastases-free survival , disease-free survival, and overall survival were 86, 84, 81, and 85%, res pectively. Patients displaying a complete pathological response had statist ically significant improved local control (P = 0.004), distant metastases-f ree survival (P = 0.009), disease-free survival (P = 0.002), and overall su rvival (P = 0.038). Conclusions. Cisplatin plus 5-fluorouracil preoperative chemoradiation is a ctive and usually well tolerated in locally advanced carcinoma of cervix, i nducing a high rate of clinical and pathological complete responses. When t his therapy is followed by radical surgery, the local control rates are exc ellent, even in patients with advanced stages or poor response. These impro ved local control rates may be achievable only through extensive surgical r esection, with a parallel increase in the complication rates. (C) 1999 Acad emic Press.