Long-course versus short-course radiation therapy

There are two approaches commonly used for radiation therapy:

In Europe, preoperative radiation therapy is commonly delivered alone in 1 week (5 Gy × five daily treatments) followed by surgery one week later, rather than the long-course chemoradiation therapy approach used in the United States. One reason for this difference is the concern in the United States for heightened late effects when high radiation doses per fraction are given.

A Polish study randomly assigned 316 patients to receive either preoperative long-course chemoradiation therapy (50.4 Gy in 28 daily fractions with 5-FU/LV) or short-course preoperative radiation therapy (25 Gy in five fractions).[46] Although the primary end point was sphincter preservation, late toxicity was not statistically significantly different between the two treatment approaches (7% for the long-course group vs. 10% for the short-course group). Of note, data on anal sphincter and sexual function were not reported, and toxicity was determined by the physician, not patient reported.

The choice of long-course versus short-course radiation therapy for rectal cancer is an area of active study, and it is not known which is superior. Generally, long-course chemoradiation therapy results in a higher biologically equivalent dose being delivered to the patient (along with chemosensitization, most commonly with capecitabine or 5-FU), which would theoretically result in improved local control. This is supported by the RAPIDO trial, where a higher local recurrence rate was seen in the patients who received short-course radiation therapy rather than those who received long-course chemoradiation therapy.[35]

Alternatively, short-course radiation therapy requires a shorter break from stronger systemic therapy. Therefore, if a patient is at a relatively higher risk of local recurrence than distant recurrence, long-course chemoradiation therapy may be preferred, but if the patient is at a higher risk of distant recurrence, short-course therapy may be preferred to allow a quicker return to chemotherapy. Many physicians also do not offer short-course chemoradiation therapy when a nonoperative management approach is used, as it has not been studied, and given the potentially lower local control rates due to the lower biologically equivalent dose as compared with long-course chemoradiation therapy. The optimal sequencing of radiation therapy and chemotherapy when given as a part of total neoadjuvant therapy is still being evaluated. There are also some clinical situations where short-course radiation therapy may not be preferred, such as when a rectal stent is present (which may result in greater rectal toxicity).