The Role of Patient Education in Low Anterior Resection Syndrome: A Systematic Review.

Introduction
With advances in surgical techniques and neoadjuvant therapy, the survival rate of sphincter-preserving procedures for rectal cancer has significantly improved. However, the increase in sphincter-preserving rectal surgery has given rise to an increased incidence of postoperative bowel dysfunction in survivors of rectal cancer [1].
Low anterior resection syndrome (LARS) refers to the constellation of symptoms that can occur after sphincter-preserving rectal cancer surgery, including faecal incontinence, urgency and frequency. As the diagnosis of LARS is a clinical one, there exist multiple measures of its severity. Many of these measures are patient reported, such as the LARS score and Wexner score, and some include objective measures such as anal physiology measurements. LARS can be graded using the LARS score system—major LARS (score 30–42), minor LARS (score 21–29) and no LARS (score 0–20). Over 44% of patients who have undergone sphincter-preserving rectal surgery will experience major LARS [2]. Higher mean LARS scores have been shown to have a negative impact of quality of life, especially on physical and social well-being of patients [1–5].
Currently, there is no established standardised treatment strategy for LARS given the highly variable nature of the condition. Treatment is mostly empirical and symptom-based, which can involve lifestyle and pharmacological measures such as dietary modifications and anti-diarrhoeal medications for minor LARS, and interventions such as colonic irrigation, pelvic floor rehabilitation and sacral nerve stimulation for major LARS [6, 7].
There is no doubt that each modality has a role to play in the treatment of LARS, seemingly in an additive fashion. When used to its fullest, this combination of interventions can lead to significant symptom improvements, with each modality contributing in increments [8].
Current information available to patients on LARS is lacking [9]. Patients with LARS that have been interviewed in previous studies have also expressed a desire for more education and counselling about the syndrome before and after their surgery [10, 11].
Previous studies assessing the impact of patient education for colorectal cancer patients with stomas have shown a positive effect on patients’ psychosocial needs and quality of life [12, 13]. This study aims to assess whether patient education can improve the quality of life of colorectal cancer patients with LARS.

Methods

Search Strategy
This systematic review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered with PROSPERO: 42,023,434,601. An electronic search of the literature was conducted on PubMed, MEDLINE and EMBASE for articles published from 1946 to October 2023. This search strategy is detailed in the Appendix. Hand searching of relevant literature was reviewed to identify additional studies.

Inclusion and Exclusion Criteria
All titles and abstracts retrieved from the search strategy were screened by two independent reviewers, and conflicts were resolved by a third reviewer. Both comparative and non-comparative studies that reported on clinical outcomes of patients with LARS that underwent any form of educational intervention were included for this review, e.g. if an intervention such as pelvic floor rehabilitation specified an education component in the study. Case reports and conference abstracts were excluded. This process is summarised in the PRISMA diagram in Fig. 1.

Determining Study Quality
For non-RCTs, the risk of bias in non-randomised studies—of interventions (ROBINS-I) tool was used, which assesses risk of bias at the pre-intervention, at intervention and at post-intervention stages. For RCTs, the revised Cochrane risk-of-bias tool for randomised trials was used.

Outcomes of Interest
The primary outcome of interest was the incidence of major LARS, as defined by the LARS score. Secondary outcomes include quality of life scores and whether further intervention was required.

Results

Study and Patient Characteristics
Five studies [14–18] have been included in this review, with 368 patients in total. Two studies were RCTs [14, 18] and the three others [15–17] were prospective cohort studies. Three studies recruited only symptomatic patients postoperatively [14–16], while the two most recently published studies [17, 18] recruited all patients undergoing low anterior resection preoperatively.
Study sample sizes ranged from 8 to 137 patients. The mean age of patients was 63 years. In terms of risk factors for LARS, neoadjuvant therapy was given to 48% of patients in the four studies that reported its use, 64.4% of patients had a diverting stoma and the median timing of stoma closure ranged from 72 days to 20 months. All studies were assessed to have an overall low risk of bias. A summary of the included studies which have already been performed is shown in Table 1.

Given the small number of studies available, five protocols of future studies [19–23] related to education for LARS patients have been included for analysis of content and method of delivery. Three of these studies recruit all patients undergoing low anterior resection either preoperatively or prior to their ostomy reversal, while the other two recruit patients symptomatic with LARS postoperatively. This may reflect a contemporary trend towards an increasingly proactive approach to healthcare and intervention.

Delivery and Contents of Education Intervention
The majority of education interventions were delivered in the postoperative period after sphincter-preserving surgery or ileostomy closure; only the study by Harji [15] introduced the education intervention in the preoperative period. Education was delivered in multiple methods, including in-person sessions that were either individual or in groups, phone reviews and online modules. In future study protocols, a specific information booklet for LARS and online and phone applications are being produced for RCTs [19–23]. The contents of the education interventions mainly included advice on dietary changes and toileting habits that are used to manage LARS, detailed information about LARS itself and the functional outcomes that can be expected postoperatively, as well as disease experience of other similar patients [14–18]. The length of the education intervention varied, ranging from 2 to 12 months after the initial operation. A summary of the education interventions and follow-up is shown in Table 2.

Comparison and Co-interventions
In the included RCTs, the control groups received standard care, which included the education intervention, while the intervention groups received pelvic floor muscle training (PFMT) alongside standard care [14, 18]. In two of the prospective cohort studies [15, 16], patients received stepwise care depending on the severity and response of their symptoms, starting from educational intervention only, then medications, PFMT and transanal irrigation (TAI), and finally surgical intervention. In future RCTs, online and phone applications will be compared to a standard written information booklet for LARS [19–23].

Impact on LARS
Four of the five included studies [14–16, 18] described the impact of their interventions on LARS. Van der Heijden et al. [14] reported no significant difference in the change of LARS score in the pelvic floor rehabilitation (PFR) group compared to standard care (mean difference: PFR − 2.4 vs. control − 2.3, p = 0.93). Kim et al. [18] reported an average difference in LARS score of − 2.28 in the intervention group compared to the control group, and a lower prevalence of major LARS in the intervention group at 3 months (52.4% vs. 71.4%). Harji et al. [15] reported that with their rehabilitation programme, the prevalence of major LARS decreased from 48 to 12%, and the prevalence of Wexner score > 4 decreased from 59 to 22% in 12 months. Seventy-seven percent of patients from Harji’s cohort only required education and anti-diarrhoeal drugs to improve their LARS symptoms during the 12-month follow-up period. Dalsgaard et al. [16] reported that 51.2% of their patients required basic treatment, i.e. education and medications only, and within this group, the prevalence of major LARS decreased from 97 to 57%.

Quality of Life
Quality of life measures were reported by three studies [14, 15, 18]. The two RCTs used the European Organisation of Research and Treatment of Cancer (EORTC QLQ-CR29) questionnaire to assess quality of life, while Harji et al. used the EQ-5D questionnaire. Van der Heijden et al. [14] reported no significant difference between the two groups in the final EORTC scores, but there was a clinical difference in favour of the intervention group in relevant domains such as anxiety and urinary frequency. Kim et al. [17] also reported no significant differences between the two groups in all functional and symptom scores of the EORTC questionnaire, except for lower abdominal pain scores in the intervention group. Harji et al.’s study [15] only measured quality of life at the end of follow-up and found no difference in EQ-5D questionnaire scores between patients with major or minor LARS.
Olivia et al.’s study [17] reported descriptive outcomes after implementing their online educational modules for LARS. Their participants described that the online educational module provided credible information on LARS, which was delivered at an appropriate reading level and had useful accompanying illustrations. The patient forum on the online module allowed participants to share their own experiences and provide emotional support to one another. A satisfaction survey was provided at the end of their follow-up, and seven of the eight participants were ‘mostly’ or ‘very’ satisfied with the information provided by the online educational modules, and all eight participants would recommend it to other rectal cancer survivors with LARS.

Discussion
There is increasing awareness of LARS and its impact not only on functional outcomes but also on a patient’s quality of life [2]. LARS is associated with functional symptoms such as diarrhoea and incontinence, which in turn can lead to social withdrawal, sleep pattern disturbances and mental distress, ultimately leading to poorer quality of life [24]. Previous studies with patient interviews suggest that there is minimal preoperative or postoperative education about LARS, and counselling provided by clinicians on LARS largely surrounded pharmacological management rather than education about the expected functional change or psychosocial impact of LARS [11, 25]. Given the lack of credible resources and treatment protocols for LARS, rectal cancer patients require more access to better information and counselling about LARS in order to manage their symptoms more effectively [9–11].
More recent studies recognise that the treatment of LARS is most effective when detected and initiated early, leading to the development of the MANUEL and BOREAL protocols, and this is another area where perioperative education can really come to the fore, prompting patients to seek attention and treatment early, and encouraging clinicians to systematically step up treatment modalities as required [7, 15].
Education interventions for colorectal cancer patients with stomas have been shown to provide improvements in psychosocial adjustment and self-management skills with a stoma. Overall costs after patient education interventions were also less than standard care [12]. To our knowledge, this is the first systematic review of education interventions in colorectal cancer patients with LARS.
Our results suggest that education interventions have a role to play in improving the symptoms of LARS, or at least in mitigating its impact on patients’ lives. In the included RCTs, even the control groups that only received an education intervention experienced improvements in the mean LARS scores. Most patients within the Harji and Dalsgaard cohort studies experienced significant improvement in LARS symptoms with only perioperative education and use of medical therapy, indicating both the significance of early and appropriate therapy, which is an outcome that is hoped to be achieved through education. In terms of quality of life, there were no significant differences between the intervention and control groups for the EORTC QLQ-CR29 questionnaires, suggesting that education alone can be beneficial in improving the quality of life in a patient with LARS.
These marginal gains must not be overlooked, as the implementation of an educational intervention is cost-effective and easily disseminated, making it a crucial component for LARS intervention in any setting, regardless of resource constraints.
As alluded to previously, the multi-modality nature of the treatment of LARS is such that although each intervention can contribute to symptom improvement incrementally when used to its fullest, the reality of practicing within a resource-limited healthcare system is that not every centre (and thus not every patient) will have access to resources to implement more resource intensive treatments for LARS such as PFMT, TAI or SNS [26]. Therefore, it is important to study each component both individually and in tandem to identify their impact on LARS. Future studies looking at education interventions alone for LARS will ideally provide more information on its impact. However, we also acknowledge that this may be impractical, as many patients may require escalation in therapy in order to improve their LARS symptoms.
The different modes of education delivery and dissemination seen in the included studies also show that education for LARS is becoming more accessible to patients. In the post COVID-19 pandemic era, many domains of medicine have developed online and remote methods of disseminating education [27]. Through the use of mobile applications, online modules and remote reviews with clinicians, patients experiencing LARS will be able to receive the education and counselling even if they are socially isolated [17–20, 23]. An additional benefit of online resources is that patients with LARS can become connected and support one another through their experiences [17].
Overall, there is a paucity of research in the use of education interventions in LARS, despite the potential benefits that they can provide. A significant limitation to this review is the lack of comparison of education interventions to a control group, given that through the natural progression of LARS, it is anticipated that there is some symptom improvement over time; however, its magnitude is yet unclear. Further research should ideally assess standardised outcomes, such as changes in LARS scores, effects of patient-reported outcome measures and quality of life measures (e.g. EORTC questionnaires), in order for data to be meta-analysed in the future.

Conclusion
This systematic review demonstrates that education interventions have a role to play in reducing the prevalence of LARS following resection for rectal cancer. This can be delivered in many ways but generally includes education about the pathophysiology of the disease, dietary and lifestyle modifications to improve bowel function, as well as potential interventions that can be undertaken in a step up fashion. It is a cost-effective, easily initiated intervention, which is often studied in conjunction with other co-interventions. However, the marginal gains that can be derived from it must not be overlooked, and given the paucity of studies focused on the topic, there is significant potential for further research to determine its true effect, as well as optimal content and delivery methods.

Electronic supplementary material
Below is the link to the electronic supplementary material.