Non-Operative Management of Patients with Rectal Cancer: Lessons Learnt from the OPRA Trial

SIMPLE SUMMARY: The management of rectal cancer has become increasingly more complex. Over the recent year, the use of chemotherapy and radiation before surgical intervention has been accepted as a new standard. As a consequence, between a third and half of the patients undergoing upfront therapy experience a clinical complete response with no residual rectal tumor remaining in the bowel lumen. These patients could potentially avoid the risks of surgery and undergo a close surveillance protocol, known as watch and wait. However, the identification of ideal candidates for this strategy remains challenging due to the lack of objective criteria. Ongoing studies are investigating optimal treatment algorithms to further expand the indications for watch and wait. ABSTRACT: Over the past decade, the management of locally advanced rectal cancer (LARC) has progressively become more complex. The introduction of total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathological complete response, resulting in excellent long-term oncological outcomes. As a result, non-operative management (NOM) of LARC patients with a clinical complete response (cCR) after neoadjuvant therapy has gained acceptance as a potential treatment option in selected cases. NOM is based on replacement of surgical resection with safe and active surveillance. However, the identification of appropriate candidates for a NOM strategy without compromising oncologic safety is currently challenging due to the lack of an objective standardization. NOM should be part of the treatment plan discussion with LARC patients, considering the increasing rates of cCR, patient preference, quality of life, expectations, and the potential avoidance of surgical morbidity. The recently published OPRA trial showed that organ preservation is achievable in half of rectal cancer patients treated with TNT, and that chemoradiotherapy followed by consolidation chemotherapy may an appropriate strategy to maximize cCR rates. Ongoing trials are investigating optimal algorithms of TNT delivery to further expand the pool of patients who may benefit from NOM of LARC.