Discussion
vascular injuries, tumor, early-stage disease
SYSTEMIC DISEASE, RECURRENCE, TUMOR, METASTASIS, POSTOPERATIVE COMPLICATIONS, POSTOPERATIVE COMPLICATION, MINOR, POSTOPERATIVE COMPLICATION, WEST, RECTAL CANCER
As a new technique, CME remains under investigation. Although renewed attention to meticulous surgical technique certainly has its merits, routine implementation of CME seems currently unfounded for several reasons. First, in contrast to rectal cancer, local recurrence originating from an incomplete or non-optimal removal of colonic mesentery is rare in CC and usually is a manifestation of a systemic disease. Second, although CME may increase nodal counts and therefore staging accuracy, this is unlikely to affect survival because the observed relationship between nodal counts and outcome in CC is most probably not causal but confounded by a range of different clinical variables. Third, several lines of evidence suggest that metastasis to locoregional nodes occurs early and is a stochastic rather than a stepwise phenomenon in CC, reflecting the tumor host-metastasis relationship.Available data document that CME with central vascular ligation (CVL) often is a more demanding procedure than standard right hemicolectomy, almost always has a longer duration (10–90 min or longer depending on the completeness of the learning curve), can carry a higher morbidity (longer time to first flatus and major vascular injuries above all), and also is more challenging based on the high variability of vascular anatomy. These issues support the actual debate on the reasons to implement the CME for the treatment of RSCC at least in referral centers.Above all, three main items currently remain under investigation: the efficacy of CME in increasing the LN yield, the risk of intra- and postoperative complications particularly concerning major vessels injuries, and mostly the relationship between CME and the improvement of survival outcomes.During the past decade, several systematic reviews and meta-analysis have effectively evaluated these items with the aim to crown CME as the standard of care for RSCC or definitively to reject it.Unfortunately, these studies had many limitations. First, most of the studies were case series of a prospective or retrospective nature, and no level 1 evidence from RCTs is available. Second, these studies were not homogeneous concerning the outcomes of interest (safety, quality, oncologic outcomes) because most of them had important missing outcomes. Third, most of the included patients had early-stage disease (60.6% stage 0, I, or II). These limitations represent confounding factors for the final analysis. In the end, most of these studies concluded that well-designed RCTs are necessary to strengthen the evidence base and eventually to justify the implementation of routine use of CME.Actually, only two RCTs comparing CME and non-CME in RSCC are available in the literature.The current study not only is the third RCT conducted in the world, but also is the first Western multicenter nationwide high-volume phase 3 superiority trial comparing CME with non-CME for RSCC. In this trial, the quality of surgery provided in the CME arm was assessed with the previously reported four indicators. The length of the specimen was similar between the two groups. However, the length of resected ICA and MCA, the area of resected mesentery, and its integrity rate were significantly superior in the CME arm. This observation was documented in all the participating centers, confirming the high quality of surgery performed. The quality of CME provided to the enrolled patients also was evaluated with Benz classification.Despite strict quality control, noncompliance (see definitions in the Methods section) was identified in 21.5 of the CME procedures and contamination in 20.7% of the non-CME procedures. The only significant correlation was between the magnitude of noncompliance per patient and the type of approach (Table These protocol violations may potentially have been responsible, in the intention-to-treat analysis, for an underestimation of the difference in number of LNs harvested between the two arms. However, significant underestimation appears unlikely because although the patients undergoing CME had a moderate grade of noncompliance, the number of nodes yielded was significantly higher in this group than in the non-CME group.Nevertheless, we should accept the continued occurrence of minor deviations considering the complexity of this trial. Consistent with the design of the study, this interim analysis documented that the median number of LNs harvested in the CME group was significantly higher than in the non-CME group (25 vs. 20). Although a significant relationship between the number of nodes removed and patients’ survival has not been documented with sufficient evidence to date, providing a higher number of nodes with a demanding procedure that includes a super-extended LN dissection is essential to demonstrate any oncologic benefits and to continue enrollment of patients.Postoperative complications were described as comparable in the CME and non-CME arms of both previous RCTs. However, the RELARC trialAlthough both the AgrusaTo our best knowledge this trial is the first multicenter high-volume RCT from the West comparing the safety and feasibility of CME with standard right hemicolectomy for patients with RSCC. In this interim analysis, only the short-term outcomes are reported, whereas survival outcomes have not matured to date and are expected in January 2027.The current trial had some limitations. First, it involved only Italian referral centers for colorectal surgery with experienced surgeons and does not represent the reality of primary care facilities in which surgeons have less expertise. Second, only patients with a BMI of 30 kg/mIn conclusion, data available from this interim analysis document that the quality of surgery measured by the length of the specimen, the area and integrity rate of the resected mesentery, and the length of IC and MC vessels was higher in CME arm, confirming that CME is an extended procedure compared with non-CME. In addition, the interim data show that CME significantly increases the number of LNs harvested without increasing vascular injuries, postoperative complication rates, postoperative mortality, or length of hospital stay. Hence CME is a safe and feasible technique, particularly when performed by experienced surgeons in referral centers.