Preoperative radiation with concurrent 5-fluorouracil for locally advanced T4-primary rectal cancer

In cT4-rectal carcinoma disease-free margins often cannot be obtained by primary surgery, and even if total en bloc resection is accomplished, local failure remains high with surgery alone. Herein we report on the curative resectability rate, acute toxicities, surgical complications, local control and 5-year survival rates achieved with a more aggressive multimodality regimen, including preoperative radiochemotherapy.

Between 1/1990 and 12/1998, a total of 31 patients with cT4-rectal cancer were treated at our institution. All patients presented with tumor contiguous or adherent to adjacent pelvic organs. Eight patients had synchronous distant metastases. A total radiation dose of 50.4 Gy with a small-volume boost of 5.4 to 9 Gy was delivered (single dose: 1.8 Gy). 5-FU was scheduled as a continuous infusion of 1000 mg/m2 per 24 hours on days 1 to 5 and 29 to 33. Six weeks after completion of radiochemotherapy, patients were reassessed for resectability.

After preoperative radiochemotherapy, 29/31 patients (94%) underwent surgery with curative intent. Resection of the pelvic tumor with negative margins was achieved in 26/31 patients (84%), 3 patients had microscopic residual pelvic disease. In 3/8 patients with distant spread at presentation a complete resection of metastases was finally accomplished. Toxicity of radiochemotherapy occurred mainly as diarrhea (NCI-CTC Grade 3: 23%), dermatitis (Grade 3: 16%) and leucopenia (Grade 3: 10%). Surgical complications appeared as anastomotic leakage in 3, wound infection in 2, fistula, abscess and hemorrhage in 1 patient, respectively. With a median follow-up of 33 months, local failure after curative resection was observed in 4 patients (19%), 3 patients (14%) developed distant metastases. The 5-year overall survival rate for the entire group of 31 patients was 51%, following curative surgery 68%.

A combination of high-dose preoperative radiochemotherapy followed by extended surgery can achieve clear resection margins in more than 80% of patients with locally advanced cT4 rectal tumor. An encouraging trend evolves for this multimodality treatment to improve long-term local control and survival.