Preoperative radio/chemo-radiotherapy in combination with intraoperative radiotherapy for T3-4Nx rectal cancer

Abstract

Aims. To analyse the results of a single institution experience of combined preoperative radio/chemo-radiotherapy and intraoperative electron-radiation therapy (IORT) for locally advanced rectal cancer and to compare the results with surgery alone retrospectively.

Methods. The study cohort comprised 99 patients with clinical T3-4NxM0 adenocarcinoma of the rectum who had received preoperative radio/chemo-radiotherapy, radical surgery, and IORT [Group I]. Until 1998, 67 patients were treated with radiation only [Group Ia], and after 1999, 32 patients were concurrently given tegafur and uracil (UFT) [Group Ib]. 68 patients with clinical T3-4NxM0 rectal cancer were treated with surgery alone [Group II].

Results. The median follow-up was 67 months in Group I and 83 months in Group II. Local recurrence rate was 2% in Group I, which was significantly lower than 16% in Group II (p=0.002). Both disease-free survival and overall survival in Group I were significantly better than those in Group II (p=0.04, p=0.02, respectively). Sphincter preservation was possible in 78% in Group Ib, which was significantly more than 42% in Group Ia (p=0.002).

Conclusions. The combined preoperative radio/chemo-radiotherapy and IORT for clinical T3-4Nx rectal cancer significantly reduces local recurrence and improves prognosis. Combination of preoperative radiotherapy and oral UFT improves the feasibility of sphincter-preservation.

Introduction

Local recurrence after surgery of rectal cancer is still a major problem. McCall et al. reviewed 10,465 cases in 51 papers from 1982 through 1992, and reported local recurrence rates ranging from 16% in Dukes B to 29% in Dukes C rectal cancer.¹ After the introduction of total mesorectal excision (TME), local recurrence rate was reported to be reduced to 5–19%,2., 3., 4. however, Boley et al. reported it to be higher in Stage III disease (23%).⁵ Recently, local recurrence rates have been reported to exceed 20% in cases where the circumferential resection margin (CRM) was 1 mm or less in the resected specimen, suggesting that even with TME, the extent of resection is not sufficient in some cases.6., 7., 8. Obtaining sufficient distance between tumour and CRM is often difficult and depends on the site and size of the tumours.

Preoperative or post-operative radiotherapy decreased local recurrence rate significantly. However, the effect on overall survival was marginal.⁹ Combined modality adjuvant treatment with radiation therapy and 5-fluorouracil (5-FU)-based chemotherapy is more effective than either radiation therapy or chemotherapy alone.10., 11.

Intraoperative radiotherapy (IORT) has been used to treat primary unresectable colorectal cancer, residual colorectal cancer after resection, and recurrent colorectal cancer.12., 13. Good local control has been achieved when IORT was administered in combination with preoperative radiotherapy in patients evaluated as having undergone ‘complete resection’ or having ‘microscopic disease,’ although the reports were not based on randomised clinical trials.14., 15., 16. IORT has conventionally been used to irradiate the tumour bed or only areas where the tumour was adherent or fixed.¹⁴ However, local recurrences occur even in patients with no penetration of the tumour through the rectal wall. The dose distribution of 6–9 MeV electron beam is homogeneous at tissues 1–2 cm beneath the surface of the irradiated site. We developed a new concept to create the IORT-induced tumour-free margin just beneath the dissected surface of the pelvis. Therefore, we delivered electron beam, as uniformly as possible, to the dissected surface just after the removal of the rectum.17., 18.

This paper compares retrospectively the outcome of patients who received preoperative radio/chemo-radiotherapy combined with intraoperative electron beam radiation therapy (Group I) to that of patients who had surgery alone (Group II).