Radiation therapy (RT) delivered preoperatively has clearly shown to improve local disease control after radical surgery in rectal cancer [1–3]. In fact different options including short-course or long-course regimens have been extensively studied with similar good long-term local disease control [4–6]. Also, the addition of chemotherapy with fluoropyrimidine to radiation led to further improvement in local disease control of these patients [7,8]. At a first glance, the issue of local recurrence in rectal cancer had been solved with widespread introduction of preoperative RT with or without concomitant chemotherapy. So why do we keep searching for alternative treatment options for the already successful neoadjuvant approach? What are we looking for?