Comparison of the prognosis of four different treatment strategies for acute left malignant colonic obstruction: a systematic review and network meta-analysis

Colorectal cancer (CRC) is ranked third and second among global cancer morbidity and mortality, respectively. The incidence rate of CRC is third in men and fourth in women [1]. Approximately 30% of CRC patients have acute colonic obstruction, and the overall prognosis is poor [2]. Compared with elective surgery for CRC without left-sided malignant colonic obstruction, emergency resection (ER) with left-sided malignant colonic obstruction is associated with a higher risk of mortality and morbidity [3].

Twenty years ago, colonic stent (CS) implantation was first used to restore the lumen opening of patients with malignant obstruction of the left colon as a bridge to surgery (BTS) [4]. The current clinical treatments for patients with malignant obstruction of the left colon include CS-BTS, transanal colorectal tube (TCT)-BTS, decompressing stoma (DS)-BTS, and ER. Research on the treatment of left obstructive colorectal cancer is gradually increasing. A meta-analysis showed that CS-BTS improved short-term surgical outcomes compared with ER but had similar long-term tumor and survival outcomes [5]. Compared with TCT-BTS, CS-BTS in the treatment of acute left malignant intestinal obstruction had a higher decompression efficiency, safety, and technical success rate; had fewer complications; and could avoid the formation of stoma [6]; moreover, DS-BTS has more primary anastomoses than ER [7]. TCT-BTS can increase primary resection/anastomosis compared to ER, but the long-term outcomes are similar [8]. Although many RCTs and many standard paired meta-analyses have been published to date, upon comparing the available treatment strategies for left obstructive colorectal cancer, there is still controversy regarding the best treatment strategy.

An important disadvantage of these RCTs and standard pairwise meta-analyses on this topic is that they can only directly compare two treatments, not all available treatments at once. A network meta-analysis can simultaneously compare all treatment strategies available for left obstructive colorectal cancer. Another advantage of network meta-analysis is that it combines direct and indirect evidence from trials to facilitate indirect comparisons between multiple treatments that have not been directly studied before and comparative studies [9, 10]. The purpose of this study was to conduct a systematic review of the literature to determine the relevant comparative treatment strategies available for left obstructive colorectal cancer, collect all published relevant data, and conduct a network meta-analysis to compare the long-term survival and short-term effects of the different treatment strategies.

Our computer-aided search yielded 2705 publications from PubMed, MEDLINE (Ovid), Embase (Ovid), Web of Science, and Cochrane Library after removing the duplicate literature. By screening the titles and reading abstracts, we excluded another 2495 obviously irrelevant documents. Further full-text screening of 210 publications was carried out, and 161 articles were excluded (Fig. 1). Ultimately, this network analysis contained 48 articles, including 7 RCT experiments (8 RCT literatures) [16‐23] and 40 non-RCT experiments [8, 24‐62]. The characteristics of the included studies (first author, journal, country, treatment strategy, basic characteristics of the study population, etc.) are summarized in Table 1. The risk of bias and literature quality assessment of each study included in the analysis are summarized in Supplementary Table 2. For RCT experiments, the risk of bias tool based on the Cochrane collaboration found that the quality of the included trials met the research standards. For non-RCT experiments, a NOS score of 7–9 indicates that the quality of the included trials meets the research standards.

This is the first network meta-analysis that can simultaneously compare several different treatment strategies for left-sided malignant colonic obstruction. The European Society of Gastrointestinal Endoscopy 2020 Guidelines recommend colon stents as a bridge to elective surgery in acute malignant obstruction of the left colon; at the same time, when the patient is not suitable for colonic stent placement, or when there is no professional for stent placement, decompression stoma is an effective choice as a bridge for selective surgery [63]. This network meta-analysis showed that patients with CS-BTS and DS-BTS strategies had a better prognosis than patients with ER strategies, while patients with DS-BTS strategies had better OS than patients with CS-BTS strategies. The previous standard paired meta-analysis and RCT comparison between CS-BTS and ER in the treatment of acute left colonic malignant obstruction proved that although CS-BTS increased the hospital stay, and it also increased the primary anastomosis rate. At the same time, postoperative complications, anastomotic leak, short-term mortality, wound infection, initial stoma, and permanent stoma were significantly reduced [16, 17, 19, 20, 64‐69]. Similarly, our research proves that the CS-BTS strategy can increase primary anastomosis and reduce permanent stoma and short-term mortality compared with the ER strategy. Previous paired meta-analyses and RCT comparisons of CS-BTS and ER in the treatment of acute left colonic malignant obstruction proved that the long-term results are similar [5, 16, 21, 22, 70‐74], but our study proved that the long-term survival of CS-BTS is better than that of ER. The reasons for our analysis are as follows: ER often belongs to the state of incomplete surgical preparation, the general nutritional and immune status of patients is worse, and it is more likely to lead to tumor recurrence; longer recovery time after ER may lead to delayed chemotherapy; ER pays more attention to speed while neglecting lymph node dissection. Under these comprehensive factors, the long-term survival rate of ER is even worse. At same time, it may also be because we included more studies and the analysis method of the included studies adopted an intention-to-treat analysis.

Early research shows that, compared with the ER strategy, the DS-BTS strategy is a safe and effective treatment for acute left obstructive colon cancer [7]. Although the DS-BTS strategy had the same early mortality, complications, and anastomotic leakage as the ER strategy, the DS-BTS strategy increased the length of hospital stay and resulted in a significant increase in primary anastomosis and a significant decrease in permanent stoma [7, 54, 55, 62]. This network meta-analysis found that the anastomotic leakage and length of hospital stay were similar in the previous study, but our study showed that the early mortality rate of the DS-BTS strategy was significantly lower than that of the ER strategy. The difference in this strategy may be that DS-BTS is divided into two operations, the first operation is relatively small, and the surgical trauma is relatively small, so the early mortality rate is relatively low. The DS-BTS strategy requires two operations, which increases the patient’s hospital stay and costs [75]. Our study proved that the 5-year OS and DFS of the DS-BTS strategy are significantly better than those of the ER strategy. The DS-BTS strategy increases the patient’s hospital stay and costs but returns good long-term survival. Previous studies have proved that compared with the ER strategy, the DS-BTS strategy can significantly increase the production of lymph nodes [55], which is an important prognostic factor for colorectal malignancies. Perhaps because of this increased lymph node production, the obstructive colorectal cancer 5-year OS is significantly increased. This may be one of the important reasons why DS-BTS strategy leads to better 5-year OS and DFS than ER strategy.

Previous meta-analyses and RCTs showed that the CS-BTS strategy has fewer complications, a lower stoma rate, a higher primary anastomosis rate, and higher technical and clinical success rates than the TCT-BTS strategy in the treatment of acute left malignant intestinal obstruction [6, 76, 77]. Perhaps because the guide wire of the stent is small, it is easy to pass through the narrow part of the region. At the same time, when the stent is placed, the guide wire is more likely to make the stent reach the front end of the tumor [6], resulting in higher technical and clinical success rates of the CS-BTS strategy than the TCT-BTS strategy. Compared with the CS decompression strategy, the TCT strategy has an equivalent decompression effect [78]. However, patients with the TCT-BTS strategy require long-term retention of the anal decompression tube in the anus, which is associated with a great psychological burden and a bad mental state, which may be the reason for the worse prognosis compared to CS-BTS. Compared with the ER strategy, the TCT-BTS strategy has similar permanent stoma, short-term mortality, and long-term survival rates, but it increases the primary anastomosis rate [8, 61]. This network meta-analysis showed that there were no significant differences between the CS-BTS strategy and the TCT-BTS strategy in terms of primary anastomosis, mortality, anastomotic leakage, permanent stoma, and long-term survival. At the same time, the TCT-BTS and ER strategies have similar permanent stoma rates, short-term mortality, and long-term survival, and the increased primary anastomosis rates are similar to previous studies.

Compared with elective surgery for CRC without left malignant colon obstruction, emergency surgery with left malignant colon obstruction usually requires multiple operations, prolongs the hospital stay, and is associated with higher mortality and morbidity [3]. Current research shows that for curable acute left-sided malignant colonic obstruction patients, CS and DS are both effective decompression methods [51], but there is still controversy regarding the prognosis of tumors [52‐54]. At the same time, the DS-BTS strategy requires more temporary colostomies and incisional hernias [51]. The DS-BTS strategy requires more surgical procedures to reinstate the stoma and repair the incision hernia. This network meta-analysis found that all short-term results of CS-BTS and DS-BTS were similar, except that the hospital stay in DS-BTS was longer. However, the long-term result is that the 5-year OS of the DS-BTS strategy is significantly better than that for the CS-BTS strategy. DS-BTS offers a better long-term survival than CS-BTS, which can be accompanied by some serious complications, including stent re-blocking, displacement, and intestinal perforation [79], and ER might be necessary, which could cause a poor prognosis. The abovementioned complications after DS-BTS decompression are relatively rare. It is worthwhile to implement a DS-BTS strategy for a better 5-year survival, notwithstanding a longer hospital stay and reoperation rate due to DS-BTS.

This network meta-analysis yielded short-term results similar to those of previous studies. In addition, we also obtained the long-term survival results of several treatment strategies. CS-BTS and DS-BTS significantly increased the 5-year OS compared with ER. Early large-scale studies and RCTs have shown that for acute left colonic obstructive malignant tumors, surgery after the remission of intestinal obstruction can significantly improve the short-term outcome (mortality [19, 54], primary anastomosis [8], stoma [16, 17, 20, 61]). For example, after the intestinal obstruction is relieved, the decrease of the stomata rate is related to the relief of oedema in the intestinal tract [80]. It is possible that relief of edema in the intestinal tract can increase primary anastomoses, decrease anastomotic leakage, and decrease mortality. Finally, it seems that in the treatment of acute left obstructive colonic malignancies, preoperative removal of the obstruction can improve the patient’s 5-year OS and DFS (whether it is CS-BTS or DS-BTS), possibly because the removal of intestinal obstruction can improve the patient’s nutritional status, enhance immunity, provide the opportunity to prepare the bowel, reduce the state of inflammatory stress, and increase the tumor R0 resection rate and more thorough lymph node dissection.

This research involves several limitations that must be considered. Since there are only 8 RCTs in the included 48 articles, and the RCT studies compared CS-BTS and ES, other treatment strategy studies are non-RCTs, which may cause some deviations in the results. The inclusion criteria limit the need for intentional analysis; this deviation should be minimized as much as possible.

In comprehensive literature research, we find that CS-BTS and DS-BTS strategies can bring better 5-year OS and DFS than ER. DS-BTS strategies have a better 5-year OS than CS-BTS strategies. Without considering the hospital stays, DS-BTS strategy is the best choice.