Adjuvant preoperative radiotherapy in patients with rectal carcinoma. Adverse effects during long term follow-up of two randomized trials.

BACKGROUND

Adjuvant preoperative radiotherapy of patients with primary rectal carcinoma improves local control and survival, but also may increase the risk of early postoperative morbidity and mortality. In addition, the possible late adverse effects of this treatment are largely unknown.

METHODS

The present study was based on 1027 curatively operated patients included in 2 prospective randomized trials of preoperative radiotherapy for rectal carcinoma patients (Stockholm I and Stockholm II Trials). The goal was to assess whether long term intercurrent morbidity and mortality were increased in patients allocated to the preoperative treatment. A computerized linkage of the randomized patients to a population-based registry of the Stockholm County Council was used to study hospital admissions for six groups of a priori defined diseases, putatively related to late adverse effects of the radiation.

RESULTS

Preoperative radiotherapy significantly increased the incidence of venous thromboembolism (P = 0.01), femoral neck and pelvic fractures (P = 0.03), intestinal obstruction (P = 0.02), and postoperative fistulas (P = 0.01). For arterial disease and genitourinary tract diseases, no difference in risk was found between irradiated and non irradiated patients. Radiotherapy significantly reduced rectal carcinoma deaths in both trials and also improved overall survival in the Stockholm II trial. The late intercurrent mortality was similar in irradiated and nonirradiated patients.

CONCLUSIONS

Although high dose, short term, preoperative radiotherapy can improve outcome after surgery for rectal carcinoma, there also may be an increased risk for long term morbidity. Refinement of the radiotherapy technique and a more accurate selection of patients suitable for the treatment will probably further improve the results, at least in regard to treatment-related complications.