CONSENSUS STATEMENT International Consensus Definition of Low Anterior Resection Syndrome Celia Keane, M.B.Ch.B.1 • Nicola S. Fearnhead, D.M.2 Liliana G. Bordeianou, M.D., M.P.H.3 • Peter Christensen, DM.Sci.4 Eloy Espin Basany, M.D.5 • Søren Laurberg, M.D., D.M.Sc.4 Anders Mellgren, M.D., Ph.D.6 • Craig Messick, M.B.Ch.B., M.D.7 Guy R. Orangio, M.D.8 • Azmina Verjee, B.Sc.9 • Kirsty Wing, B.Nurs.10 Ian Bissett, M.B.Ch.B., M.D.1,11 on behalf of the LARS International Collaborative Group* 1 Department of Surgery, University of Auckland, Auckland, New Zealand 2 Department of Colorectal Surgery, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom 3 Colorectal Surgery Centre/Department of Surgery at the Massachusetts General Hospital and Harvard Medical School, Boston, MA 4 Danish Cancer Society National Research Centre for Survivorship and Late Side Effect to Cancer in the Pelvic Organs, Department of Surgery, Aarhus University Hospital, Aarhus, Denmark 5 Colon and Recto Unit, Department of General Surgery, Vall de Hebron Hospital, Universitat Autonoma de Barcelona, Spain 6 Division of Colon & Rectal Surgery, Department of Surgery, University of Illinois at Chicago, Illinois 7 Department of Surgical Oncology, Section of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston and Sugar Land, Texas 8 Department of Surgery/School of Medicine, Louisiana State University, New Orleans, Louisiana 9 Bowel Disease Research Foundation, London, England, United Kingdom 10 Otago Community Hospice, Dunedin, New Zealand 11 Department of Surgery, Auckland City Hospital, Auckland, New Zealand BACKGROUND: Low anterior resection syndrome is OBJECTIVE: The aim of this collaboration was to develop pragmatically defined as disordered bowel function after an international consensus definition of low anterior rectal resection leading to a detriment in quality of life. resection syndrome that encompasses all aspects of the This broad characterization does not allow for precise condition and is informed by all stakeholders. estimates of prevalence. The low anterior resection DESIGN: This international patient-provider initiative syndrome score was designed as a simple tool for clinical used an online Delphi survey, regional patient consultation evaluation of low anterior resection syndrome. Although meetings, and an international consensus meeting. the low anterior resection syndrome score has good clinical utility, it may not capture all important aspects PARTICIPANTS: Three expert groups participated: that patients may experience. patients, surgeons, and other health professionals from Supplemental digital content is available for this article. Direct URL ci- Financial Disclosures: None reported. tations appear in the printed text, and links to the digital files are pro- vided in HTML and PDF versions of this article on the journal’s Web site Celia Keane and Nicola S. Fearnhead are dual first authors. (www.dcrjournal.com). Podium presentation at the meeting of The American Society of Colon and Funding/Support: This study was supported financially by the Euro- Rectal Surgeons, May 1 to 5, 2019; at the meeting of the Association of Colo- pean Society of Coloproctology (ESCP), the Auckland Medical Research proctology of Great Britain and Ireland, July 1 to 3, 2019; and at the meeting Foundation (AMRF), the Danish Cancer Society, and the Bowel Disease of the European Society of Coloproctology (ESCP), September 25 to 27, 2019. Research Foundation (BDRF). Dr Keane is funded by the Auckland Medical Research Foundation Ruth Spencer Fellowship. This article is being published concurrently in Diseases of the Colon & Rectum, Colorectal Disease, and ANZ Journal of Surgery. The articles are Dis Colon Rectum 2020; 63: 274–284 identical except for minor stylistic and spelling differences in keeping DOI: 10.1097/DCR.0000000000001583 with each journal’s style. Citation from any of the 3 journals can be used Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, when citing this article. Inc. on behalf of the American Society of Colon and Rectal Surgeons. This is an open access article distributed under the terms of the Crea- Correspondence: Ian Bissett, M.B.Ch.B., M.D., Department of Surgery, tive Commons Attribution-Non Commercial-No Derivatives License 4.0 University of Auckland, Private Bag 92019, Auckland 1142, New Zea- (CCBY-NC-ND), where it is permissible to download and share the work land. E-mail: i.bissett@auckland.ac.nz. provided it is properly cited. The work cannot be changed in anyway or used commercially without permission from the journal. *LARS International Collaborative Group: See Acknowledgments. 274 DISEASES OF THE COLON & RECTUM VOLUME 63: 3 (2020) DISEASES OF THE COLON & RECTUM VOLUME 63: 3 (2020) 275 5 regions (Australasia, Denmark, Spain, Great Britain and symptoms from fecal incontinence and urgency, to evac- Ireland, and North America) and in 3 languages (English, uation difficulties. Consequent heterogeneity in reporting Spanish, and Danish). makes it impossible to accurately identify the prevalence of MAIN OUTCOME MEASURE: The primary outcome LARS.9–11 Development of a validated patient-reported out- measured was the priorities for the definition of low come measure, the LARS score, has improved the standard- anterior resection syndrome. ization of reporting.12 Prevalence of LARS using this tool is reported to be 41% (95% CI, 34%–48%).13 The LARS RESULTS: Three hundred twenty-five participants (156 score has good psychometric properties and has been vali- patients) registered. The response rates for successive dated in multiple languages.14–17 However, the LARS score rounds of the Delphi survey were 86%, 96%, and 99%. may significantly underestimate the impact of evacuatory Eighteen priorities emerged from the Delphi survey. dysfunction and may not accurately assess the impact of Patient consultation and consensus meetings refined symptoms on an individual patient’s quality of life.18 these priorities to 8 symptoms and 8 consequences that Like most patient-reported outcome measures, the LARS capture essential aspects of the syndrome. score was initially produced by expert clinician researchers LIMITATIONS: Sampling bias may have been present, who then consulted patient populations.12 Active involve- in particular, in the patient panel because social media ment of all major stakeholders, especially patients, early in the was used extensively in recruitment. There was also construction of any outcome measure is necessary to ensure dominance of the surgical panel at the final consensus that the resulting tool is fit for purpose, as outlined by the meeting despite attempts to mitigate this. COMET19 and COSMIN20 guidelines. The aim of this study is CONCLUSIONS: This is the first definition of low anterior to use an international patient-provider initiative with robust resection syndrome developed with direct input from methodology to produce a consensus definition of LARS. a large international patient panel. The involvement of This is the first phase of a wider project to construct a tool to patients in all phases has ensured that the definition accurately identify survivors who have LARS, assess severity, presented encompasses the vital aspects of the patient and enable evaluation of treatment approaches. experience of low anterior resection syndrome. The novel separation of symptoms and consequences may MATERIALS AND METHODS enable greater sensitivity to detect changes in low anterior resection syndrome over time and with intervention. Scientific Committee A Scientific Committee of patients and clinicians was convened to oversee the study. Clinician representatives KEY WORDS: Consensus definition; Low anterior were also lead investigators for each region involved in the resection syndrome; Patient reported; Rectal resection. study: Australasia, Denmark, North America, Spain, Great Britain and Ireland. Two patient representatives formed part of the Scientific Committee and contributed directly I nternationally, colorectal cancer is the third most com- to conception, methodology, recruitment, interpreta- mon cancer with 1.8 million cases reported in 2018.1 tion, and presentation of results. Ethical approval for this The introduction of stapling devices and other tech- study was granted by the University of Auckland Human niques has facilitated a rise in sphincter-saving surgery for Participants Ethics Committee (Ref 019179). rectal cancer.2 Total mesorectal excision and radiotherapy have dramatically improved oncological outcomes.3,4 Im- Participants proved survival has heightened awareness of survivorship Three groups of experts were enrolled in this study: patients issues, including bowel dysfunction.5 Consequently, cli- (panel A), surgeons (panel B), and other health care pro- nicians and researchers have been urged to look beyond fessionals (panel C). There is no agreed method of de- survival and recurrence as the sole measures of treatment termining required sample size for a consensus method success.6 Core outcomes sets that specify a minimum set Delphi survey,21 so a minimum recruitment target was set of outcomes to be measured have been proposed to reduce to balance the need for breadth of opinion and interna- the heterogeneity of outcome reporting and reporting bias tional involvement with resources available. Recruitment in clinical trials.7 The proposed core outcomes set for colo- target was 120 patients (24 per region), 60 surgeons, and rectal cancer surgery includes quality of life and functional 60 other health care professionals (12 of each per region). outcomes, highlighting the importance of these outcomes.7 Regional lead investigators were responsible for recruitment The term low anterior resection syndrome (LARS) in their region. Maximum diversity sampling (nonproba- describes “disordered bowel function after rectal resec- bilistic purposeful sampling) was used to recruit a wide tion, leading to a detriment in quality of life.”8 Although range of perspectives. The study was advertised via social pragmatic, this definition can incorporate a vast array of media through charitable colorectal cancer organizations 276 KEANE ET AL: LARS INTERNATIONAL CONSENSUS DEFINITION and peer support groups. Patient participants could volun- questionnaire.22,23 The Delphi survey consisted of 3 rounds, teer by registering online. Care was taken to enroll patient available to participants in 3 languages: Danish, English, participants who did not have a clinician-patient relation- and Spanish. The first round was sent to all eligible regis- ship with lead investigators. All participants completed an tered participants; patients, health care professionals, and enrollment registration form to obtain demographic details surgeons. Subsequent rounds were only sent to participants and, for patients, eligibility criteria and treatment informa- who completed the previous round and were accompa- tion. Participants who completed a registration form were nied by a graphical summary of how each expert group deemed to have given their consent to participate in the responded to each question (“item”) in the previous round study; an additional consent form was not required. (See Appendix A, http://links.lww.com/DCR/B127). Survey Monkey platform was used to manage surveys. Patient rep- Panel A resentatives sent newsletters to maintain participant en- Patients were eligible to participate if they had undergone gagement and highlight focus on patient perspective. an anterior resection for rectal cancer more than 12 months In each survey, participants were asked to rank each earlier with or without diverting ileostomy, providing any item on a 1 to 9 point Likert scale from Not Important (1) to ileostomy had then been closed for at least 6 months and Essential (9) for the definition of LARS, with an additional that adjuvant treatment had been completed. Patients who response option Unable to comment (0) (see Appendix A for did not meet the inclusion criteria, who were receiving on- the format of a question, http://links.lww.com/DCR/B127). going treatment for recurrent or metastatic disease, or who Likert rankings of 7 to 9 in any round were considered to in- had cognitive impairment, were excluded. Poor bowel func- dicate high-priority items, ratings of 4 to 6 indicated mod- tion was not a requirement for eligibility; patients with erate-priority items that were important but not critical good bowel function were also encouraged to participate. for the definition, and rankings of 1to 3 were low priority. The Scientific Committee applied a priori decision rules to Panel B determine which items progressed to the next round (see Surgeons were recruited via lead investigators in con- Appendix B, http://links.lww.com/DCR/B128). During the sultation with relevant societies: Association of first round, participants were invited to provide additional Coloproctology of Great Britain and Ireland (ACPGBI), items important for the definition of LARS. Thematic anal- Royal Society of Medicine Section of Coloproctology ysis of all additional items was undertaken and these items (RSM Coloproctology), Colorectal Surgical Society of were included in round 2 (see Appendix C for questions Australia and New Zealand (CSSANZ), Colon and Rectal included in each round, http://links.lww.com/DCR/B129). Surgery Section of Royal Australasian College of Surgeons Round 3 incorporated items that met consensus criteria for (RACS), European Society of Coloproctology (ESCP), and “high priority” in round 1 or round 2 and items that had American Society of Colon and Rectal Surgeons (ASCRS). not met consensus in round 2. Panel C Phase 2: Patient Consultation Meetings Other specialists who treat or conduct research into LARS Each region convened a patient consultation meeting to elicit were identified by lead investigators and invited to par- detailed information on patient views by using the nominal ticipate. This panel included specialist nurses, biofeedback group technique.24 A uniform template of phase 1 results was specialists, physiotherapists, gastroenterologists, oncolo- prepared, and the discussion was centered around items that gists with special interest in functional outcome after had not met consensus in the Delphi survey. The meetings rectal cancer treatment, and pelvic floor specialists with allowed discussion of items that may have been misrepre- an interest in managing LARS. sented or divided votes due to overlap. Face-to-face meetings were held in London, Barcelona, and Aarhus. Because of ge- Longlisting of Potential Outcomes ographical constraints, 2-hour teleconference meetings were Systematic review of literature published between 1986 and held for Australasian and North American patient expert 2016 that reported functional outcomes after sphincter-pre- panels using the Zoom web-based conferencing platform. serving rectal resection was undertaken to produce a com- Online meetings were recorded and transcribed. prehensive list of bowel function outcomes that were then tested in a pilot study. The results of this review have been Phase 3: Consensus Meeting published9 and were used in round 1 of the Delphi survey. Participants who completed all 3 Delphi survey rounds Participants were invited to add novel items during round 1. were invited to attend the international multidiscipli- nary consensus meeting held in Nice, France, at the 2018 Phase 1: Online Delphi Survey Annual ESCP meeting. Feedback from all patient consul- Delphi methodology aims to produce a conver- tation meetings was presented before discussion to achieve gence of opinion using multiple iterative rounds of a final consensus. Polling was used to assess whether items DISEASES OF THE COLON & RECTUM VOLUME 63: 3 (2020) 277 that had met “high priority” consensus during the Delphi and D, http://links.lww.com/DCR/B129 and http://links. survey were required for the definition and to determine lww.com/DCR/B130). whether related items could be amalgamated. Round 2 included 24 items that did not meet con- sensus in round 1 and 15 new items generated by both Data Analysis patients and clinicians from round 1. The patient panel Descriptive statistics including percentages and median again produced the most discriminatory rankings. (range) are presented. The χ2 test was used for compari- Patient representatives on the steering group raised con- sons between categorical data. Correlations were assessed cerns that certain items were being ranked lower because using the nonparametric Spearman rho (ρ) test. IBM SPSS of wording issues and split voting. The steering group Statistics for Macintosh Version 24.0 and GraphPad Prism recognized that patients were less likely than clinicians v.7 for Mac OS X (GraphPad Software, La Jolla, CA) were to discard important symptoms and so the majority cri- used for the statistical analyses. terion was lowered from 67% to 55% to ensure impor- tant items were not lost before the final round of voting. Eighteen items progressed to round 3 based on the cri- RESULTS teria that the majority (55%) of patient panelists ranked an item as high priority and less than 33% of panelists The study methodology and number of participants at ranked it as a low-priority item. each stage are summarized in Figure 1. Round 3 included 29 items: 11 from round 1 and 18 items from round 2. Two items were reworded based Participants on survey feedback and advice from patient representa- Three hundred twenty-five participants registered: 156 tives. Inability to cope with bowel function was reworded patients, 96 colorectal surgeons, and 73 health care profes- to need to use coping strategies to manage bowel function. sionals; 55 from Australasia, 53 from Denmark, 44 from Effect on sexual function was reworded to impact on sexu- Spain, 93 from Great Britain and Ireland, and 80 from ality and sexual life. A discernible cutoff point was evident North America. Details of participants registered for each above which the proportion of participants giving a high- expert panel are shown in Table 1. Participants complet- priority ranking sharply increased, and the proportion of ing each Delphi survey round were invited to participate participants giving a low- or moderate-priority ranking in the next rounds, so the response rate denominator is sharply decreased. This cutoff point (majority of 70%) was the number of participants in the previous round. Overall the criterion on which all items were assessed for inclusion response rates were 86% (278/325) for round 1, 96% in round 3. Appendix E, http://links.lww.com/DCR/B131, (268/278) for round 2, and 99% (265/268) for round 3. shows expert panel and overall rankings for all items. Response rates for each region and expert panel are shown Eighteen items met consensus criteria: clustering/ in Figure 2. fragmentation, incomplete emptying, difficulty empty- ing, stool frequency, soiling, fecal incontinence, urgency, Delphi Survey inability to defer defecation, variable/unpredictable bowel Round 1 contained 37 items. The patient panel produced function, dissatisfaction with bowel function, preoccupa- the most discriminatory rankings, but overall group and tion with bowel function, toilet dependence, need to use patient panel rankings were similar. Eight items were coping strategies to manage bowel function, fear and/or ranked “high priority” (scores of 7–9 out of 9) by the ma- anxiety over bowel control, effect on quality of life, effect jority (67%) of all 3 panels and a further 5 items were on overall well-being, effect on lifestyle/daily activities, ranked “high priority” by the majority (67%) of the pa- and effect on social activities. tient participants, so these items progressed directly to round 3. Incontinence (of any kind): unintended passage of Patient Consultation Meetings solid, liquid or gaseous fecal material was removed because In total, 42 patients participated in 5 meetings. Carers also it was redundant (the responses to this were highly cor- attended and contributed. One important concept iden- related with the responses to the questions regarding solid tified as missing was effect on mental health/psychological stool incontinence (ρ = 0.84) and liquid fecal incontinence consequences of changes in bowel function. There was ge- (ρ = 0.88)). Two items that met the criterion for high pri- neral agreement that pain related to defecation or to the ority were amalgamated to reduce splitting of the vote be- urge to defecate was important despite variable interpre- tween related items (ρ = 0.59): Stool frequency: number of tations of tenesmus. There was agreement that impact on bowel movements per 24 hours and Stool frequency >4 per 24 sexuality and sexual life and effect on ability to perform hours. No items in round 1 met the consensus criterion for usual work are very important but needed rewording. “low priority”; therefore, all other items were represented Patients suggested expanding effect on ability to perform in round 2 for further consideration (see Appendices C usual work to include roles within family, community, 278 KEANE ET AL: LARS INTERNATIONAL CONSENSUS DEFINITION and other organizations, not just paid employment. There agreement that some items may be amalgamated because was agreement that the impact of LARS on sexuality was they represented similar underlying concepts. not solely due to changes in sexual function, but related more broadly to the impact on intimacy. Change in stool Final Consensus Meeting consistency was considered important, but diarrhea was Thirty-five Delphi participants attended the facilitated mostly inevitable and was not itself the problem, whereas consensus meeting (Fig. 3). Discussion was structured unpredictability of bowel movements and paste-like stool around items that had met consensus but had potential to consistency made it difficult to evacuate. There was general be amalgamated and items for which there were significant Literature review 35 items from review pilot study 1 item from the pilot Participant recruitment Patient panel n = 156 Health professional panel n = 73 Surgeon panel n = 96 Online Delphi survey Round 1 – 37 items Overall response rate 86% Patients 123, healthcare professionals 63, surgeons 92 Round 2 – 39 items Overall response rate 96% Patients 114, healthcare professionals 63, surgeons 91 Round 3 – 29 items Overall response rate 99% Patients 111, healthcare professionals 63, surgeons 91 Meetings in London (10 patients), Aarhus (9 patients), Patient consultation meetings Barcelona (12 patients), Australasia (7 patients online) and North America (7 patients online). Face-to-face meetings in Nice, France, 35 Attendees: Consensus Meetings Patients 6, healthcare professionals 7, surgeons 22 Consensus Statement FIGURE 1. Study methodology. DISEASES OF THE COLON & RECTUM VOLUME 63: 3 (2020) 279 TABLE 1.   Participant characteristics presentation of patient participant quotes as well as post- ers of statements from patient participants during previous Health professional phases. The meeting opened with presentations from each Patient panel panel Surgeon panel regional lead investigator summarizing the patient consulta- Characteristics (n = 155) (n = 73) (n = 96) tion meetings. During group discussion of each item, patient Sex (female %/male %) 66/34 92/8 31/69 representatives were invited to articulate the patient voice. Age, % Consensus meeting discussion clarified that symp-  20–29 y 0 5 1 toms should be differentiated from impact or con-  30–39 y 6 10 8  40–49 y 19 28 28 sequences of LARS. Figure 4 describes outcomes  50–59 y 32 39 31 throughout each phase of the study (details in Appendix  60–69 y 30 18 25 F, http://links.lww.com/DCR/B132). Eight symptom  70–79 y 13 0 8 complexes and 8 consequences were agreed on as the Years in practice, median 20 (1–42) 11 (1–40) (range) most important priorities for definition of LARS (Fig. 5). Year since surgery, 3 (1–15) To meet the definition of LARS, a patient must have had median (range) an anterior resection (sphincter-preserving rectal resec- Treatment included 55 radiotherapy, % tion) and have at least 1 of these symptoms that results Treatment included 69 in at least 1 of these consequences. Increased stool fre- chemotherapy, % quency was compared to preoperative stool frequency. Temporary stoma, % 86 Repeated painful stools includes pain on urge, on passing Satisfied with bowel function, % a bowel movement, and/or after passing a bowel move-  Yes 21 ment. Emptying difficulties include difficulty emptying  Sometimes 36 the bowel for any reason, a feeling that the bowel has not  No 43 completely emptied after passing a bowel movement, and need to return to the toilet multiple times to empty the discrepancies in ranking among groups. Real-time elec- bowel. Fecal incontinence is defined as the unintended tronic polling was used to identify whether a consensus passage of a large volume of fecal material. Fecal urgency had been reached after discussion of each item. The crite- is the need to rush to the toilet to defecate and/or the in- rion for consensus was 70% of attendees. ability to delay passing a bowel movement. Soiling is the Visual aids were used to ensure that patient voice was pre- involuntary passage of a small amount of material onto sent during the meeting, including continuous PowerPoint clothing or sanitary item. Response rate (%) 100 90 80 70 60 50 40 30 20 10 Patient Healthcare Surgeon Australasia Denmark Spain UK USA professionals Expert panel response rate Regional response rate Round 1 Round 2 Round 3 FIGURE 2. Response rate for each group. Round 1 (left, blue bar) to round 3 (right, green bar). The response rate is given as a percentage above each bar (the denominator for the response rate calculation is the number of participants who completed the previous round). 280 KEANE ET AL: LARS INTERNATIONAL CONSENSUS DEFINITION 22 10 8 7 7 6 6 4 Patients Healthcare Surgeons Australasia Denmark Spain UK USA Professionals Expert panel attendance Regional attendance FIGURE 3. Attendance at the final consensus meeting by group and by region. DISCUSSION considered to be of the highest priority when defining LARS. This international patient-provider initiative used robust Low anterior resection syndrome has previously been methodology throughout 3 phases to reach a consensus pragmatically defined as “disordered bowel function after definition of LARS. This is the first attempt to define rectal resection, leading to a detriment in quality of life.”8 LARS that from conception has incorporated multiple This broad definition does not allow the precise measure- stakeholders and prioritized patient views. The major ment of LARS. The LARS score was developed to overcome finding of this consensus definition is that both symptoms inconsistencies in reporting functional outcome and was and consequences are important. The study has identi- designed to be a quick clinical evaluation tool to screen fied 8 symptom complexes and 8 consequences that are patients for LARS.12 The LARS score has been widely FIGURE 4. Priorities identified in each phase of the study. DISEASES OF THE COLON & RECTUM VOLUME 63: 3 (2020) 281 FIGURE 5. Consensus definition of low anterior resection syndrome. To meet the definition, a patient must have had an anterior resection (sphincter-preserving rectal resection) and experience at least 1 of these symptoms that results in at least one of these consequences. adopted but appears to suffer from insensitivity to evacu- active in peer support groups may allow wider dissemina- atory dysfunction and may overestimate the impact on tion of the proposed definition. quality of life for some patients.18 Weighting of the LARS The overarching difference between the current results score response categories makes the LARS score differen- and the previously published LARS score and BFI is that tially responsive to change in certain dimensions (such as the outcome is a definition not a scoring system. However, urgency) and may mean that more subtle improvements there is some overlap that is worthy of comment. Both the on other dimensions are not documented. There is also LARS score and BFI enquire about stool frequency, incon- a high rate of LARS in the general population. When the tinence, urgency, and clustering or fragmentation, which LARS score was applied to the Danish population, 19% is consistent with the proposed definition. The BFI also of women and 10% of men aged between 50 and 79 years investigates diarrhea or loose stool, soiling, emptying dif- experience symptoms that meet the criteria for major ficulties (incomplete evacuation), and whether patients LARS.25 This reflects the high sensitivity but low speci- have to alter their activities because of bowel function, ficity of the LARS score. The more comprehensive Bowel which are all concepts that reached consensus in the cur- Function Instrument (BFI) developed at Memorial Sloan rent work. However, the LARS score and the BFI include Kettering Cancer Centre was also designed to measure flatus incontinence, which did not reach consensus for in- bowel dysfunction after sphincter-preserving surgery but clusion in the proposed definition. The BFI also inquires has not been used widely in the literature.26 about dietary restrictions and distinguishes between daily The major methodological difference between this and nocturnal symptoms, which was not borne out in the work and previous attempts to measure LARS is the consensus work. The LARS score incorporated quality of patient-provider approach. Patients were not only par- life by weighting the response categories based on a statis- ticipants, but also investigators. Active steps were taken tical association with the overall effect of bowel function throughout to ensure that the patient perspective was on the quality of life, whereas the BFI simply included a recognized and amplified. This key factor is likely to have question about altering activities because of bowel func- contributed to a more efficacious definition that accurately tion. The consensus work suggests that the impact on captures real-world clinical experience. Engagement of the LARS is such an important component that it is necessary wider patient community through advertising the project to specify the various dimensions that may be impacted by via social media and involvement of patient participants the symptoms of LARS. 282 KEANE ET AL: LARS INTERNATIONAL CONSENSUS DEFINITION There are multiple novel components identified in an easily recognizable visual aid will hopefully allow for this work that may be due to the early and consistent inclu- greater awareness of LARS from both patients and clini- sion of the patient perspective. In particular, the concept cians, and will hopefully enable more patients to receive of variable or unpredictable bowel function and altered professional help for their symptoms. We do not expect stool consistency may align better with patient experience. the work presented here to directly improve the assess- Patient participants reported that diarrhea was less of an ment of the prevalence of LARS, nor the assessment of issue than unpredictable movements and paste-like con- LARS over time or with treatment, but we will base subse- sistency that makes evacuation difficult. Clear differenti- quent work toward these aims on the priorities identified ation into symptoms and consequences is novel. Further here. work is needed to transform the definition presented here into a scoring system, but we suggest that inclusion of specific patient-centered consequences may allow devel- CONCLUSION opment of a refined tool with greater discrimination of This is the first attempt to define LARS using robust meth- changes that occur over time and with treatment. odology that included multiple stakeholders, particularly Our study attempted to obtain a broad range of patients. This novel approach has identified that both opinion from all important stakeholders across a di- symptoms and consequences are important priorities in verse cultural, ethnic, and geographical area, but it was LARS. Acknowledging this by transforming these impor- limited by the resources available. Ideally, more than 5 tant priorities into a new tool to measure LARS may en- geographical regions could have participated. Strategies able better identification of rectal cancer survivors who were used to enhance the patient voice including: pref- experience bowel dysfunction, more accurately assess se- erence to patient panel rankings in the Delphi survey; verity, and enable more precise evaluation of treatment patient consultation meetings were held to allow prox- approaches for LARS. ies to take the patient voice to the consensus meeting; and visual aids were used to prompt awareness of the patient voice during the consensus meeting. However, ACKNOWLEDGMENTS these strategies are not substitutes for the presence of patient representatives, and we must acknowledge the As a Tripartite 2020 Vision collaborative study, the dominance of the surgical panel at final consensus de- authors thank the following societies for their support: spite attempts to mitigate this issue. There was a pos- The Association of Coloproctology of Great Britain sibility for sampling bias, in particular, in the patient and Ireland (ACPGBI), the Royal Society of Medicine panel, because social media was used extensively in pa- (RSM) Section of Coloproctology the Colorectal Surgical tient participant recruitment. However, many patient Society of Australia and New Zealand (CSSANZ) and/ participants were active members or even conveners of or the Colon and Rectal Surgery Section of the Royal support groups, and they endeavored to present ma- Australasian College of Surgeons (RACS), The European jority opinions from their wider groups. Society of Coloproctology (ESCP), The American Society The LARS score was designed as a simple tool for clin- of Colon & Rectal Surgeons (ASCRS). The Bowel Disease ical evaluation of LARS, and, although developed with ro- Research Foundation (BDRF) hosted and funded the UK bust methodology, it was not developed on the basis of patient meeting including travelling expenses for all pa- an accepted definition of LARS. This has resulted in the tient, nursing and trainee participants as well as meeting LARS score’s inability to capture evacuatory dysfunc- and administration costs. ESCP generously hosted the tion.18 To produce a more robust scoring system, we have final consensus meeting in Nice. The Auckland Medical developed a sequential approach; the initial phase is this Research Foundation and the Danish Cancer Society consensus definition based on broadly agreed upon pri- funded participant attendance at the final consensus orities of LARS, the second will involve transformation of meeting. these priorities into questions with weighting, and finally Bowel Cancer UK, Bowel Cancer NZ, Fight Colorectal the new tool will be assessed in both cross-sectional and Cancer assisted with advertising the study to allow for longitudinal validation studies. We have not attempted patient participant recruitment. We also thank Ethan to present a new “LARS score” in this article, merely the Hermanson for transcription of the North American pa- results of the initial phase. Before moving on to the trans- tient consultation meeting. formation, we need to assess whether the priorities we have presented are acceptable to the wider community. Lars International Collaborative Group We aimed to develop a definition that aligned with the pa- An V, Bryant A, Byrne C, Chen T, Croft S, Clark D, tient experience so that it will enable greater recognition Gladman M, Heriot A, Kariappa S, Keck J, Lubowski of LARS in routine clinical practice. The production of D, Dinning P, Khera A, Kirkwood K, Petersen D, DISEASES OF THE COLON & RECTUM VOLUME 63: 3 (2020) 283 Sloots K, Totten B, Weston M (Australia). Andersen 5. Denlinger CS, Barsevick AM. The challenges of colorec- P, Bachmann C, Barht H, Emmertsen K, Faaborg P, tal cancer survivorship. J Natl Compr Canc Netw. 2009;7: Gögenur I, Ingerslev P, Isaksen D, Iversen H, Iversen 883–894. L, Jacobsen K, Jansen T, Jocobsen I, Juul T, Kjar D, 6. McNair AG, Heywood N, Tiernan J, Verjee A, Bach SP, Fearn- head NS; ORACLE Collaboration. A national patient and Krogh K, Majgaard M, Mynster A, Neuenschwander public colorectal research agenda: integration of consumer per- A, Nielsen C, Nielsen R, Nielsen M, Nielsen T, Olsen J, spectives in bowel disease through early consultation. Colorectal Poulsen B, Rahr H, Snedker B, Sørensen G, Stolzenburg Dis. 2017;19:O75–O85. T, Vaabengaard P (Denmark). Acheson A, Andreyev 7. McNair AG, Whistance RN, Forsythe RO, et al. Core outcomes J, Bach S, Battersby N, Bradbury J, Brown S, Cecil T, for colorectal cancer surgery: a consensus study. PLoS Med. Chapman S, Chapman M, Chave H, Cook T, Cuffy L, 2016;13:e1002071. Davies J, Dawson C, Dixon J, Duff S, Edwards C, Geh 8. Bryant CL, Lunniss PJ, Knowles CH, Thaha MA, Chan CL. An- I, Hamilton C, Hancock L, Harji D, Hill J, Holtham S, terior resection syndrome. Lancet Oncol. 2012;13:e403–e408. Jenkins J, Johnston R, Kapur S, Maxwell-Armstrong C, 9. Keane C, Wells C, O’Grady G, Bissett IP. Defining low anterior McArthur D, Moran B, Norton C, Nugent K, Pateman resection syndrome: a systematic review of the literature. Colo- L, Perston Y, Rockall T, Sagar P, Saunders M, Sebag- rectal Dis. 2017;19:713–722. Montefiore D, Senapati A, Singh B, Skaife P, Sykes H, 10. Chapman SJ, Bolton WS, Corrigan N, Young N, Jayne DG. A Smart N, Taylor C, Thorpe G, Tierney G, Voyce S, Walsh cross-sectional review of reporting variation in postoperative C, Warren O, Wheeler J, Woodward A (England). Winter bowel dysfunction after rectal cancer surgery. Dis Colon Rectum. 2017;60:240–247. D (Ireland). Abbott S, Beban V, Bennett M, Chadwick T, 11. Scheer AS, Boushey RP, Liang S, Doucette S, O’Connor AM, Collinson R, Corbett S, Dennett E, Eglinton T, Fraser Moher D. The long-term gastrointestinal functional outcomes A, Glue J, Hohaia D, Menzi E, O’Connor M, Stevenson following curative anterior resection in adults with rectal can- D, Wells C, Wolyncewicz S, Woodfield J (New Zealand). cer: a systematic review and meta-analysis. Dis Colon Rectum. Bence, K, Boutros M, Brueseke M, DeKorte J, Floruta C, 2011;54:1589–1597. Francone T, Frederick F, Grasso J, Gurland B, Higgins K, 12. Emmertsen KJ, Laurberg S. Low anterior resection syndrome Hull T, Keller D, Laffan A, Lovett S, Marlatt J, McAdams score: development and validation of a symptom-based scoring D, McCarthy C, Milch H, Natale S, Pappou E, Paquette system for bowel dysfunction after low anterior resection for I, Pulskamp S, Rich M, Savitt L, Shafi M, Steele S, rectal cancer. Ann Surg. 2012;255:922–928. Stein S, Tolbert M, Varma M, Vogler S, Vuong T, Wells 13. Croese AD, Lonie JM, Trollope AF, Vangaveti VN, Ho YH. K, Wexner S, Wo J, Wright J, Wunderlich C (North A meta-analysis of the prevalence of low anterior resection America). Campbell K, Lim M, Moug S, Oliphant syndrome and systematic review of risk factors. Int J Surg. R (Scotland). Labaka-Aretaga I, Ballester C, Belen- 2018;56:234–241. 14. Juul T, Ahlberg M, Biondo S, et al. Low anterior resection syn- Bueno A, Vaquer-Casas G, Jerez J, Castillo J, Paniagua- drome and quality of life: an international multicenter study. Cayetano G, Codina-Cazador A, Blanco-Colino R, de Dis Colon Rectum. 2014;57:585–591. la Portilla F, Pascual-Damieta M, Enriquez-Navascuez 15. Hou XT, Pang D, Lu Q, et al. Validation of the Chinese version JM, Martin-Fernández M, Araujo-Ferreiro M, Sanchez- of the low anterior resection syndrome score for measuring García C, Vico-García E, Gallego-García M, Jimenez bowel dysfunction after sphincter-preserving surgery among LM, Martinez-Sanchez C, Carrillo-Moreno J, Muñoz rectal cancer patients. Eur J Oncol Nurs. 2015;19:495–501. A, Ramirez L, Vigorita V (Spain). Adams R, Cornish J, 16. Juul T, Ahlberg M, Biondo S, et al. International valida- Davies M, Evans M, Torkington J, Turner J (Wales). tion of the low anterior resection syndrome score. Ann Surg. 2014;259:728–734. 17. Juul T, Battersby NJ, Christensen P, et al; UK LARS Study Group. REFERENCES Validation of the English translation of the low anterior resec- 1. World Health Organisation. Cancer: Key Facts. 2019. Cited Au- tion syndrome score. Colorectal Dis. 2015;17:908–916. gust 27, 2019. Available at https://www.who.int/en/news-room/ 18. Ribas Y, Aguilar F, Jovell-Fernández E, Cayetano L, Navar- fact-sheets/detail/cancer ro-Luna A, Muñoz-Duyos A. Clinical application of the 2. Ståhle E, Påhlman L, Enblad P. Double stapling technique LARS score: results from a pilot study. Int J Colorectal Dis. in the management of rectal tumours. Acta Chir Scand. 2017;32:409–418. 1986;152:743–747. 19. Williamson PR, Altman DG, Bagley H, et al. The COMET 3. Heald RJ, Ryall RD. Recurrence and survival after total meso- Handbook: version 1.0. Trials. 2017;18(suppl 3):280. rectal excision for rectal cancer. Lancet. 1986;1:1479–1482. 20. COMET Initiative. Guideline for Selecting Outcome Measure- 4. van Gijn W, Marijnen CA, Nagtegaal ID, et al; Dutch Colorectal ment Instruments for Outcomes Included in a Core Outcome Cancer Group. Preoperative radiotherapy combined with total Set. 2016. Cited August 27, 2019. Available at: http://www.com- mesorectal excision for resectable rectal cancer: 12-year fol- et-initiative.org/ low-up of the multicentre, randomised controlled TME trial. 21. Powell C. The Delphi technique: myths and realities. J Adv Nurs. Lancet Oncol. 2011;12:575–582. 2003;41:376–382. 284 KEANE ET AL: LARS INTERNATIONAL CONSENSUS DEFINITION 22. Hsu CC, Sandford BA. The Delphi technique: making sense of 25. Juul T, Elfeki H, Christensen P, Laurberg S, Emmertsen KJ, Bag- consensus. Pract Assess, Res Eval. 2007;12:1–8. er P. Normative data for the low anterior resection syndrome 23. Dalkey N, Helmer O. An experimental application of the Delphi score (LARS Score). Ann Surg. 2019;269:1124–1128. method to the use of experts. Manage Sci. 1963;9:458–467. 26. Temple LK, Bacik J, Savatta SG, et al. The development of a 24. Centers for Disease Control and Prevention. Gaining consen- sus among stakeholders through the nominal group technique. validated instrument to evaluate bowel function after sphinc- 2018. Cited August 27, 2019. Available at: https://www.cdc.gov/ ter-preserving surgery for rectal cancer. Dis Colon Rectum. healthyyouth/evaluation/pdf/brief7.pdf 2005;48:1353–1365. Bookmark DC&R on Your Phone Access mobile-optimized content when you’re on the go! 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