Advances and controversies in treatment for locally advanced rectal cancer over the past decades: West meets East

摘要

The treatment of locally advanced rectal cancer (LARC) is still challenging and incorporation of new treatment options are being explored and continue to evolve. Total mesorectal excision (TME) with clear circumferential resection margin (CRM) has been accepted as a gold standard of surgery for LARC globally. Complete TME and negative CRM (1 mm) demonstrated improvement of overall survival and reduction in tumor local recurrence with less sexual and urinary dysfunctions. In this issue of the Annals of Gastroenterological Surgery, Kim et al1 reviewed challenging issues and shifting treatment strategy, and Toiyama et al2 reviewed centurial changes in the surgical treatment for LARC. Even though surgery is the mainstay of LARC treatment, the perioperative treatments also have major roles for further improving survival. In the West, the patients with LARC will undergo neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (NAC) followed by TME. However, nCRT contributes to local control significantly but not to overall survival sufficiently and the patients are likely to suffer from various adverse events as a result of the treatment. More recently, induction chemotherapy followed by CRT or upfront CRT followed by consolidation chemotherapy prior to TME, referred to as total neoadjuvant therapy (TNT), has been proposed. TNT, a new paradigm for LARC treatment, is associated with potential efficacy for higher pCR and CRM negative rates compared with nCRT alone or NAC because of greater compliance and earlier administration of full-dose systemic treatment. In addition, a more advanced concept in multidisciplinary treatment – the “watch and wait” strategy – has also developed to minimize long-term morbidity. There are many controversies in these treatments due to a lack of clear evidence regarding treatment protocols including regimens, interval between radiation and subsequent treatment, and adjuvant therapy issues. In Japan, these treatments prior to surgery are not standard until very recently, and lateral lymph node dissection (LLND) has been developed uniquely instead. The NCCN guideline does not recommend LLND unless metastases are clinically suspicious. However, the Japanese trial JCOG 0212 demonstrated the efficacy of LLND in reduction of local recurrence in the lateral pelvic compartment. Taking this result, some Western surgical communities have been actively expanding this procedure. At the moment, the role of prophylactic LLND vs TNT is still a subject of ongoing debate. Various international randomized controlled trials (RCTs) have demonstrated that laparoscopic colectomy has superior short-term outcomes and equivalent long-term survival to open resection, while there has been controversy regarding oncological safety of laparoscopic surgery for LARC. The results of several RCTs are inconsistent. The MRC-CLASSIC trial from the UK, the COLOR II trial from Europe, and the COREAN trial from South Korea revealed the equivalence in local recurrence and disease-free survivals. However, two last trials of the ACOSOG-Z6051 in North America and the ALaCaRT in Oceania failed to establish the noninferiority in positive rate of CRM, leading to widespread confusion and debate.3 Laparoscopic rectal cancer surgery with in-line rigid instruments is technically demanding and still highly challenging due to the limited operative field of the narrow pelvis. Several options have been introduced to overcome the technical limitations of laparoscopic surgery. Transanal TME (TaTME) providing better operative view and less obstructive procedures near the lower rectum is revolutionary. The development of TaTME is expected to improve oncological and functional outcomes and it may play a role as "a trump card" in such difficult cases as obese or male patients with a large tumor or narrow pelvis. The two-team approach is also attractive because of the significant reduction in operative time. However, its technical difficulty sometimes leads to unique co