Fast-track surgery versus traditional perioperative care in laparoscopic colorectal cancer surgery: a meta-analysis

Colorectal cancer is the third most commonly diagnosed cancer in men and the second most commonly diagnosed cancer in women [1]. Surgery, which is still the most common treatment for colorectal cancer, remains a high-risk procedure with clinically significant postoperative stress, complications, and a lengthy postoperative hospital stay. Standard elective colorectal resection is associated with a complication rate of 8% to 20% and a postoperative stay of 8 to 12 days [2]. The high complication rate and long hospital stay necessitate changes to the management of colorectal cancer.

Laparoscopy for colorectal surgery was first reported in 1991 by Fowler [3]. Many studies have shown that this technique can result in a shorter postoperative hospital stay, a lower requirement for postoperative pain control, and more rapid gastrointestinal recovery than can open surgery, without comprising safety [4, 5]. Fast-track surgery (FTS), also termed an enhanced recovery program, was initiated by the Kehlet group in 2001 [6, 7]. This program combines several methods, such as patient education, epidural or regional anesthesia, minimally invasive techniques, no routine use of drains or nasogastric tubes, optimal pain control, and early enteral nutrition and ambulation [6]. Its purpose is to reduce the stress response, shorten the hospital stay, improve recovery, and reduce the complication rate [2]. Many randomized controlled trials (RCTs) and meta-analyses have demonstrated that FTS is applicable and effective in colorectal surgery [8‐11].

Indeed, both the laparoscopic technique and FTS are able to enhance recovery and shorten the postoperative hospital stay. Hypothetically, we can assume that incorporation of FTS into laparoscopic surgery can result in the most rapid postoperative recovery. However, this theory is not evidenced-based because very few published comprehensive systematic reviews or meta-analyses on the enhanced recovery effects of FTS in patients undergoing laparoscopic colorectal surgery have been retrieved from the databases. At the same time, well-designed comprehensive studies to provide solid evidence for further studies are needed [12, 13]. Moreover, the individual studies that have investigated this issue have yielded conflicting results. Thus, we conducted the present meta-analysis of published studies to evaluate the effects of FTS in patients undergoing laparoscopic colorectal cancer surgery.

Over the past 20 years, FTS and laparoscopic techniques have become the two primary methods of reducing surgical stress and improving recovery after colorectal surgery, thus providing better short-term outcomes. Combining the two approaches would hypothetically result in the most rapid recovery. Thus, we conducted the present study to provide evidence in support of this theory. Our results suggest that both the postoperative hospital stay, time to first bowel movement and the time to first flatus were shorter in the FTS group than in the traditional care group after laparoscopic colorectal surgery. Two recent meta-analyses [11, 26] that compared FTS with traditional care for all types of colorectal surgery suggested that hospital stays were shorter in the FTS group, which is in agreement with our findings. Furthermore, because both FTS and laparoscopy can reduce surgical stress and improve recovery, incorporation of FTS into laparoscopic surgery is not superfluous and may have a combined effect in enhancing recovery and shortening the postoperative hospital stay.

Safety is always of utmost concern in clinical practice. Although reducing the complication rate is one of the aims of FTS, concerns have been expressed about the increased risk of severe complications such as pulmonary embolism and anastomotic leakage [27]. Previous meta-analysis of FTS in all types of colorectal surgery suggested that FTS neither compromise nor enhance safety [11, 26]. However, our results suggest that FTS is associated with a significantly lower complication rate than traditional care is. This is a surprising result. First, this finding may have been caused by the adequate fast-track elements in the included studies. Second, this result may have been associated with the combined effect of laparoscopic techniques and FTS with available expertise of the medical team [2, 28]. Another concern about FTS is the potentially higher readmission rate reported by some hospitals [29]. After pooling the data, FTS was associated with a relatively lower readmission rate. This finding may be attributed to the rigid and strict discharge criteria in the FTS protocols of the included studies [11]. Based on our results, we can conclude that FTS is feasible and can enhance safety after laparoscopic colorectal cancer surgery. Adequate fast-track elements and rigid and strict discharge criteria are two important factors that contribute to this conclusion.

As mentioned above, adequate fast-track elements applied in the included studies were an important prerequisite for the encouraging results. This is also why we excluded studies with fewer than six fast-track elements. We did not include the study by Chalabi et al. [30] because they applied a “RAPID protocol”, which is a simplified fast-track protocol that contains only three fast-track elements. However, distinctions among the fast-track elements were not preventable among the included studies. This may also explain the heterogeneity in some outcome measures.

Thus, to provide better evidence, we performed a subgroup analysis based on each fast-track element for two major outcomes: the duration of the postoperative hospital stay and the total postoperative complication rate, each of which can separately represent the efficacy and safety of FTS. Our results indicate the importance of the fast-track element “no bowel preparation” because the difference in the duration of the postoperative hospital stay between the FTS and traditional care group was not significant in the studies without the element “no bowel preparation”. Two comprehensive studies also suggested that bowel preparation is unnecessary [31, 32]. Several RCTs showed that bowel preparation was associated with a prolonged hospital stay and higher complication rate [33, 34]. Therefore, “no bowel preparation” should be a priority when establishing a fast-track protocol in the future. Additionally, differences in the total postoperative complication rate between the FTS and traditional care group were not significant in the subgroup analysis of many elements. Notably, subgroup analysis results of the element “wound infiltration with local analgesia” deviated greatly from statistical significance (OR, 0.82 [0.41–1.63]; p = 0.57). At the same time, the effect of local infiltration analgesia is questionable [35]. RCTs and meta-analysis on this topic have also shown controversial results [36‐38]. Therefore, we do not recommend integration of the element “wound infiltration with local analgesia” into FTS. More high-quality RCTs are required to provide more solid evidence regarding this element.

Another issue regarding the fast-track elements is that no presented FTS guidelines are particular for laparoscopic surgery, and some useful fast-track elements are debatable in laparoscopic surgery. In particular, epidural analgesia has been proven to provide better pain relief, reduce perioperative stress, reduce postoperative complications, and shorten the hospital stay after open surgery [6, 39]; however, its role in laparoscopic surgery remains controversial. On one hand, six studies used epidural analgesia, which showed wide acceptance. The beneficial effect of epidural analgesia in pain control has also been confirmed by many studies [40, 41]. On the other hand, epidural analgesia during laparoscopic surgery is not advocated by some authors. The meta-analysis conducted by Levy et al. [40] suggested that no analgesia protocol showed more overall benefits than did other protocols during laparoscopic surgery. Another meta-analysis showed that epidural analgesia fails to shorten the hospital stay following laparoscopic colorectal surgery [41]. Moreover, even Kehlet [2], who initiated FTS, demonstrated that epidural analgesia might not be necessary in laparoscopic colorectal surgery and can be replaced by non-opioid analgesia. Given the limited number of studies in this specific clinical area, more evidence is required to determine the role of epidural analgesia in the fast-track protocol for laparoscopic colorectal surgery.

Patient selection is also a debatable issue in FTS. Feroci et al. [42] suggested that patients >75 years of age with an American Society of Anesthesiologists (ASA) physical status score of 3 or 4 have high complication rates, prolonged hospital stays, and negative compliance. Male sex is another predictor of negative compliance. Among the included studies, the baseline characteristics were comparable between the FTS and control groups in the studies published by Poon et al. [22], Vassiliki et al. [24], and all RCTs. Compared with the traditional care group, Gouvas et al. [21] enrolled more male patients, Esteban et al. [23] enrolled more patients with high ASA scores, and Huibers et al. [25] enrolled more patients with advanced-stage tumors in the FTS group. Male sex, a high ASA score, and advanced-stage tumors were factors associated with poor outcomes. Thus, the effect of FTS may have been more significant without these baseline differences. The differences in patient selection among the different studies is another issue. Wang et al. [16] focused on elderly patients with a higher mean age than in other studies. Vassiliki et al. [24] enrolled more patients with ASA scores of 3 and 4. The ratio of patients with advanced-stage tumors in the study by Poon et al. [22] was also relatively higher than in other studies. Although all of these studies showed results favoring FTS, the above-mentioned differences may be another factor that contributed to the heterogeneity.

A previous meta-analysis [43] was conducted on this topic. In contrast to their study, we included CCTs and one new RCT [20]. We also excluded three RCTs [44‐46] that were included in the above-mentioned meta-analysis by mistake. Most importantly, we excluded the study by Wang [44] because in that study, FTS and traditional care were compared in all types of colorectal surgery, not only in laparoscopic surgery. We also excluded the studies by van Bree [45] and Veenhof [46] because they exhibited overlap of patients and authors with the study by Vlug [18]. Thus, we suppose that our study provides better evidence.Several limitations of this meta-analysis should be considered. First, some variables such as the skill and experience of the operating surgeon, efficacy of perioperative care, and quality of anesthesia may have differed between the FTS and traditional care groups. Thus, further high-quality, large-scale, and multicenter RCTs should be performed with consideration of these differences between the two groups. Second, 5 of 10 studies were not RCTs, which may have compromised the statistical power. Third, the surgery type varied among the studies, and subgroup analysis was not performed because of unextractable data. Finally, as mentioned above, considerable heterogeneity was observed in our study. Despite of these limitations, our meta-analysis shows some favorable results and conclusions regarding the effects of FTS after laparoscopic colorectal surgery. In particular, we found that FTS can enhance safety. At the same time, no obvious publication bias was observed by performing a funnel plot on the rate of postoperative complications (Figure 8).

In laparoscopic colorectal cancer surgery, FTS can significantly shorten the postoperative hospital stay, accelerate the postoperative recovery, and, notably, enhance safety when compared with traditional care. In the future, more high-quality and well-designed studies are needed to provide more solid evidence.