Large, randomized trials show that postoperative chemoradiation decreases local recurrence and improves survival in rectal cancer patients with T3 or node positive disease. In multiple studies, overall local failure rates were about 10%. Overall 5-year survival rates were approximately 55% to 65%, or about 10% to 15% better than surgery alone.

However, 7-year survival rates in a large Intergroup study (INT 0114) about to be published are 56%, compared with 64% at 5 years. In addition, the local failure rate was 17% at 7 years, as opposed to 14% at 5 years. These data suggest a need to await longer-term follow-up to better understand the impact of current treatments.

The data also suggest a need for new strategies in postoperative chemoradiation. A current Intergroup trial (INT 0144), closed to accrual approximately 18 months ago, evaluates the relative benefit of continuous infusion versus bolus 5-fluorouracil. Results from this study will emerge over the next 2 to 3 years.

Some rectal cancer patients may not even need adjuvant treatment. Emerging data suggest that postoperative chemoradiation is not necessary in certain subgroups with T3 or node positive rectal cancers. Thus, these patients could avoid the significant toxicities of adjuvant treatment. Confirmatory randomized trials need to be undertaken. At this time, oncologists still consider postoperative chemoradiation the standard of care.

Preoperative therapy has a number of potential advantages. These include an increase in sphincter preservation and lower incidence of acute side effects.

Twelve randomized studies, mostly European, look at a short course of preoperative radiation, without chemotherapy. Only one, the Swedish Rectal Cancer Trial, shows an improvement in local control and survival with preoperative radiation alone. A current Swedish Rectal Cancer Trial compares a short intensive course of radiation versus a long standard course of radiation.

Meanwhile, investigators are incorporating other cytotoxic and biological agents into the preoperative combined modality treatment of rectal cancer. One such study of 5-fluorouracil continuous infusion plus irinotecan produced high complete response rates. The regimen now forms the basis of a new Radiation Therapy Oncology Group phase II randomized study. Preliminary results suggest higher response rates than 5-fluorouracil alone.