What more do we want from neoadjuvant treatment strategies in rectal cancer?

Abstract

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? First of all, the observation that neoadjuvant chemoradiation (CRT) could result in complete tumor eradication, also known as complete pathological response is now considered one of the major advantages of neoadjuvant therapy in patients with rectal cancer [9]. Patients with complete pathological response (pCR) are associated with improved oncological outcomes [10]. Therefore, development of alternative neoadjuvant strategies that could maximize pCR rates is highly desirable. Also, even though increased rates of sphincter preservation have been considered another advantage of the neoadjuvant strategy, none of the randomized studies have demonstrated any superiority in sphincter preservation rates in experimental arms of these studies [11]. However, in select patients with clinical and radiological evidence of pCR (complete clinical response [cCR]), alternative organ-preserving treatment strategies have been suggested [12,13]. Therefore, a substantial increase in pCR and cCR rates could benefit patients by improving oncological outcomes and truly affecting sphincter or even organ preservation rates [9]. Therefore, maximization of pCR/cCR rates is an excellent reason for the search of improved neoadjuvant treatment regimens. But radiation therapy comes at a significant cost for patients, even though some