Management of Rectal Cancer: Short- vs. Long-Course Preoperative Radiation

There is considerable debate on the optimum approach to neoadjuvant therapy in rectal cancer. This review of major published studies of short-course preoperative radiation and the more conventional approach of long-course neoadjuvant chemoradiation was undertaken in an effort to understand the potential advantages and disadvantages of each of these approaches. Studies were evaluated with regard to patient selection, clinical outcomes, and toxicities. Short-course preoperative radiation has shown a clear advantage over surgery alone in reducing local recurrence rates and improving survival of patients with rectal cancer. However, studies using short-course preoperative treatment have included a significant number of early (30%; Stage I/II) and more proximal cancers yet appear to have higher positive margin rates, higher abdominoperineal resection rates, and lower aggregate survival than patients treated with long-course neoadjuvant chemoradiation. Although long-course preoperative chemoradiation is associated with higher rates of reversible acute toxicity, there appears to be more significant and a higher rate of late gastrointestinal toxicity observed in short-course preoperative radiation studies. Patient convenience and lower cost of treatment, however, can be a significant advantage in using a short-course treatment schedule. Selective utilization of either of these approaches should be based on extent of disease and goals of treatment. Patients with distal cancers or more advanced disease (T3/T4) appear to have better outcomes with neoadjuvant chemoradiation, especially where downstaging of disease is critical for more complete surgical resection and sphincter preservation.

Introduction

Neoadjuvant therapy is widely accepted as the current standard of care in the treatment of advanced rectal cancer. However, there is considerable debate regarding the best approach to neoadjuvant therapy. Early studies with preoperative radiation, although showing a consistent reduction in local recurrence rates, had failed to show a survival advantage 1, 2, 3, 4. The Swedish Rectal Cancer Trial (5) was the first randomized study to show that a “short course” of preoperative radiation (5 Gy × 5) alone, without chemotherapy, followed by immediate surgery, resulted in a significant improvement in 5-year survival and a reduction in the local recurrence rate for all stages of cancer. The experience in the United States has largely focused on a more protracted or “long course” of preoperative radiation using conventional doses of 1.8–2 Gy per fraction over 5–6 weeks, for a total dose of 45 to 50.4 Gy. Several institutional studies have reported exceptionally good survival with this more conventional approach with considerable downstaging of tumor, improved resectability rates, and low pelvic recurrence rates 6, 7, 8. The significant differences in these approaches, “short- vs. long-course pre operative radiation,” have led to some confusion as to the most optimum approach to preoperative radiation in the management of this disease. In a recent editorial in the Journal of Clinical Oncology, Kachnic et al.(9), discussed the role of neoadjuvant therapy for T3, N0 rectal cancers. It was suggested that because there is an 18% overstaging for these cancers in spite of endorectal ultrasound staging (10) and a 22% understaging (11), a compromise approach to treatment would be to use short-course (5 Gy × 5) preoperative radiation as per the Swedish (5) and Dutch (12) experiences. Kachnic et al.(9) also made an argument that short-course treatment would allow patients with positive nodes to receive adjuvant chemotherapy. Because the standard of care in patients receiving preoperative chemoradiotherapy is to administer adjuvant chemotherapy postoperatively regardless of the pathologic findings, as evidenced by the clinical practice guidelines published by the National Comprehensive Cancer Network, this argument of Kachnic et al.(9) becomes irrelevant. The question remains as to whether the short-course treatment should be considered a compromise between no preoperative radiation and the long-course treatment or whether there are pros and cons to each treatment that need to be clearly understood and appropriately used. The purpose of this review is to get a clear understanding of each of these approaches to neoadjuvant radiation for rectal cancer.