Goals: To evaluate the role of length of the interval between 5 × 5 Gy and surgery.
Methods: PubMed was searched to perform a systematic review.
Results: There were 10 studies on 5 × 5 Gy with delayed surgery (no of patients (n) = 1343), and six studies on 5 × 5 Gy with consolidation chemotherapy delivered over a long interval prior to surgery in a tight sequence (n = 244). In total, there were four randomized studies, five phase II studies, and seven retrospective studies. Trials that compared immediate with delayed surgery after 5 × 5 Gy showed a benefit in terms of lower rate of severe acute post-radiation toxicity (4.2 % absolute difference) in the immediate-surgery group. However, this benefit was counterbalanced by the increase in minor postoperative complications (13 % of absolute difference) in the group with immediate surgery compared with that with the delayed surgery. The pathological complete response (pCR) rate was about 10 % higher in the delayed-surgery group. There were no differences in sphincter preservation and R0 resection rate between the two groups. Small studies suggest no differences in the oncological outcomes. Regarding elderly patients who were unfit for chemotherapy, short-course radiotherapy with delayed surgery produced favourable outcomes for "unresectable" cancer or for small cancer after full-thickness local excision. A watch-and-wait policy in complete responders after short-course radiotherapy is feasible. A pCR of over 20 % was recorded after short-course radiotherapy and consolidation chemotherapy compared with about 10 % after 5 × 5 Gy and delayed surgery. Favourable outcomes after short-course radiotherapy and consolidation chemotherapy were observed in patients with potentially resectable stage IV disease.
Conclusions: Evidence showed that 5 × 5 Gy with delayed surgery can be used routinely for the management of elderly patients who are unfit for chemotherapy in case of "unresectable" cancer or early cancer prior to local excision. Short-course radiotherapy with consolidation chemotherapy is a promising treatment that can be used routinely for potentially resectable stage IV disease.