Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials

Seventy-five patients with complete bowel wall penetration and/or positive lymph nodes at the time of initial “curative surgery” had planned single or multiple reoperations at the University of Minnesota. Tumor due to rectal carcinoma was found in 52. Four were converted to disease-free status. Areas of failure were analyzed in detail. Distant metastasis (DM) alone was uncommon. Peritoneal seeding (PS) was rare. Local failure and/or regional lymph node metastases (LF-RF) occurred as the only failure in nearly 50% of the failure group and as some component in 92%. Patterns of failure are fairly predictable if anatomical factors and initial pathologic extent of tumor are considered. Postoperative irradiation may be a logical adjuvant in view of the high percentage of local-regional failures and the ability to identify subgroups of patients at highest risk for such failure.

Areas of failure found at reoperation (second or symptomatic look) following "curative surgery" for adenocarcinoma of the rectum. Clinicopathologic correlation and implications for adjuvant therapy.

A randomized clinical trial was conducted by the European Organization for Research and Treatment for Cancer (EORTC) Gastrointestinal Cancer Cooperative Group to study the effectiveness of irradiation therapy administered in a dosage of 34.5 Gy, divided into 15 daily doses of 2.3 Gy each before radical surgery for rectal cancer (T2, T3, T4, NX, MO). Four hundred sixty-six patients were entered in the clinical trial between June 1976 and September 1981. Tolerance and side effects of preoperative irradiation were acceptable. The overall 5-year survival rates were similar in both groups. When considering only the 341 patients treated by surgery with a curative aim, the 5-year survival rates were 59.1% and 69.1% in the control group and in the combined modality group, respectively (p = 0.08). The local recurrence rates at 5 years were 30% and 15% in the control group and the adjuvant radiotherapy group, respectively (p = 0.003). Although this study did not show preoperative radiotherapy to have a statistically significant benefit on overall survival, it does have a clear effect on local control of rectal cancer. Therefore, before performing radical surgery, this adjuvant therapy should be administered to patients who have locally extended rectal cancer.

Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC).

Background. From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial to evaluate the role of preoperative radiotherapy. Methods. Patients were given either 25 Gy during 5 to 7 days before surgery or underwent surgery alone. Results. At a median follow-up time of 107 months (range, 62-144 months) the incidence of pelvic recurrence among 684 curatively operated patients was significantly lower among those who also received radiotherapy (P < 0.001) in all Dukes' stages. No significant difference was observed between the treatment groups with regard to frequency of distant metastases or overall survival. The time to local recurrence or distant metastasis and survival was significantly prolonged in the irradiated group. However, the postoperative mortality was 8% in the radiotherapy group compared with 2% in the surgery only group (P = 0.01). Conclusions. Preoperative short term radiotherapy reduced the incidence of pelvic recurrences and prolonged survival related to rectal cancer compared with surgery alone. The postoperative morbidity was significantly higher in the irradiated group. Cancer 1995 ;75 : 2269-75.

The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma

Silencing of genes by aberrant promoter hypermethylation is now recognized as a crucial component in cancer initiation and progression. Highly sensitive assays have been developed to assess gene-promoter methylation in biological fluids. The detection of methylated genes in sputum could lead to the development of a screening test to non-invasively identify early cancer in high-risk people.

Gene-promoter hypermethylation as a biomarker in lung cancer.

In a prospective randomized trial, 700 patients with a confirmed histological diagnosis of adenocarcinoma of the rectum or rectosigmoid were randomized to receive radiotherapy prior to operation (2000 to 2500 rads in two weeks) or surgery alone. Five year observed survival in the 453 patients on whom "curative" resection was possible was 48.5% in the X-ray treated group compared with 38.8% in controls, while in the 305 having low lying lesions requiring abdominoperineal resection, survival in the treated group was 46.9% compared with 34.3% in controls. Although suggestive of a treatment benefit, neither is considered statistically significant. Histologically positive lymph nodes were found in 41.2% of the control group and in only 27.8% of the patients receiving radiotherapy. Reveiw of all patients who died during the study shows a consistently lower death rate from cancer in the radiotherapy group. Although this study suggests a treatment benefit from preoperative radiotherapy, further studies now in progress by this group and others are necessary to determine the optimal dose regimen.

Preoperative radiotherapy for colorectal cancer.

Long-term survivors after resection of lung carcinoma.

Preoperative irradiation in a moderate dose schedule (2,000–3,000 rads∕two weeks) followed promptly by surgery has had a favorable effect, when matched with controls, on the survival of male patients with operable and resectable adenocarcinoma of the rectum, particularly when the lesion is low-lying and requires an abdominoperineal resection. There is a significant reduction in the finding of positive lymph nodes in the treated group (27%) compared with the controls (40%). With 700 men already in the study, life table survivals at five years are documented at 40.4% for irradiated patients who undergo abdominoperineal resection vs. 27.5% for the control group. This favorable effect appears dose-related.

George A. Higgins

Papers

Preoperative radiotherapy for colorectal cancer.

Long-term survivors after resection of lung carcinoma.

Preoperative irradiation of operable adenocarcinoma of the rectum and rectosigmoid colon.

Preoperative Radiation Therapy for Carcinoma of the Lung: Report of a National VA Controlled Study1

The long term survival of patients with visceral carcinoma.