A 2-year prospective study on the evolution of Low Anterior Resection Syndrome (LARS) following rectal cancer surgery

Abstract

Purpose

This study investigated the evolution of Low Anterior Resection Syndrome (LARS) over 2 years following Total Mesorectal Excision (TME) for rectal cancer.

Methods

In this prospective cohort study, patients were recruited from three Belgian hospitals between January 2017 and January 2021. The primary outcome was the evolution of LARS, assessed with the LARS score at 1, 6, 12, and 24 months postoperatively or after stoma closure. The proportion of patients in each LARS category (no, minor, major) was analyzed, and transitions over time were examined using Bowker’s test of symmetry. The secondary outcome was health-related quality of life, measured using the Short Form-12 (SF-12) at the same time points.

Results

Of 180 patients who underwent TME for rectal cancer, 87 (48.3%) completed the LARS score at all time points. At 1 month postoperatively, 66 patients (75.9%) had major LARS, decreasing to 51 patients (58.6%) at 6 months (p = 0.028). No significant changes were observed thereafter (p = 0.43 and p = 0.45 for 6 to 12 months and 12–24 months, respectively). Among the 51 patients with major LARS at 6 months, 10 patients (20%) improved by 12 and 24 months. Between 1 month and later time points, approximately 60% remained in the same category, 30% improved, and 10% deteriorated. Mean SF-12 physical and mental scores were similar across LARS categories at all time points.

Conclusion

The majority of spontaneous improvement in LARS occurred within the first 6 months postoperatively, with little improvement thereafter. These findings highlight the need for early proactive management rather than expectant follow-up.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00384-025-05009-2.

Introduction

Colorectal cancer is the third most common cancer in both men and women, with approximately 35% of cases located in the rectum [1, 2]. Multimodal treatment (radio-chemotherapy and radical surgery) of rectal cancer has significantly improved local control and long-term survival over the years [3].

Given the improved 5-year survival rates, postoperative gastrointestinal function and related quality of life (QoL) have become increasingly important [4]. A wide spectrum of bowel symptoms, including variable bowel function, altered stool consistency, increased frequency, urgency, incontinence, and emptying difficulties, collectively impact QoL. These symptoms and consequences have been summarized in an international consensus definition [5] and are referred to as Low Anterior Resection Syndrome (LARS) [6–11].

Several risk factors have been identified that influence the development of severe LARS, including younger age, female gender, total mesorectal excision (TME), low tumor height, neo-adjuvant radiotherapy, and time to stoma closure [12, 13].

While these risk factors contribute to the development of severe LARS, understanding how symptoms evolve post-surgery is crucial. In the prospective cohort study of Harji et al., approximately half of the patients experienced severe LARS at 1 month post-surgery, with the prevalence of severe LARS decreasing to around 12% by 12 months [14]. This contrasts with the findings of Sun et al., whose systematic review reported 44% of patients with major LARS at 12 months, and Sandberg et al., who reported 63% of patients at the same time point [15, 16]. From 1 to 2 years postoperatively, Sandberg et al. observed a slight reduction in major LARS from 63 to 56% [16]. Additionally, Pieniowski et al., who measured LARS at two time points with a 5-year gap (range 7.1–16.1 years postoperatively at the second follow-up), found no significant differences in LARS distribution between follow-ups (p = 0.455), with 49% of patients still experiencing major impairment at the second follow-up [17].

The discrepancies in LARS prevalence during the first year postoperatively, along with limited data on long-term symptom evolution, highlight the need for a better understanding of LARS evolution. Additionally, no studies have examined transitions between LARS categories over time. Therefore, this study aims to assess LARS in rectal cancer patients post-restorative surgery, focusing on transitions between LARS categories over 2 years.

Methods

Study design and participants

This multicentric prospective cohort study (one academic and two peripheral hospitals) included patients recruited between January 2017 and January 2021. Inclusion criteria were (1) undergoing a Low Anterior Resection (LAR) with TME for rectal cancer and (2) the ability to complete the administered questionnaires, with or without assistance. Exclusion criteria included patients who (1) underwent other colorectal surgeries (e.g., Hartmann procedure, abdominoperineal excision, transanal endoscopic microsurgery, or sigmoid resection), (2) were fecal incontinent prior to surgery, (3) had neurological disorders, or (4) had previous pelvic surgery, pelvic radiation, or LAR for non-cancer reasons. The reporting of this study adheres to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for cohort studies, as recommended by the EQUATOR Network.

Outcome measures

The primary outcome was the percentage of patients in each LARS category at 1, 6, 12, and 24 months postoperatively or after stoma closure, as well as the percentage of patients who transitioned between LARS categories over time. This outcome was assessed using the LARS score, which is validated in Dutch, ranges from 0 to 42, and is divided into three categories: no LARS (0–20), minor LARS (21–29), and major LARS (30–42) [18, 19].

The secondary outcome was health-related quality of life, evaluated using the Short Form-12 (SF-12), consisting of two domains—Physical Component Summary (PCS) and Mental Component Summary (MCS) —each based on six questions [20, 21]. Scores were collected at the same time points as for the primary outcome, with both domains ranging from 0 (lowest level of health) to 100 (highest).

All patients had regular follow-up visits with their abdominal surgeon, during which specific complaints could be discussed and treatments (e.g., dietary advice, loperamide, ondansetron, transanal irrigation) prescribed in a patient-tailored manner.

Statistical analysis

Analyses were performed using SAS software, version 9.4 of the SAS System for Windows. Only patients who completed the LARS score at all time points were included in the statistical analysis. Descriptive statistics were utilized to summarize baseline patient characteristics. Mann-Whitney U tests, independent t-tests, and χ² tests were used to compare the baseline characteristics between included patients and those who were lost to follow-up. A Sankey diagram was used to visually represent the proportion of patients in each LARS category (no LARS, minor LARS, and major LARS) at each time point and to highlight the transitions between categories over time. Furthermore, Bowker’s test of symmetry (an extension of McNemar’s test for paired proportions) was used to evaluate the changes in LARS categories over time. Finally, mean and standard deviation values for SF-12 PCS and MCS scores were calculated within each LARS category at 1, 6, 12, and 24 months to describe health-related quality of life.

Ethical approval

This study was approved by the local ethical committee of the University Hospitals Leuven (s59761) and both the Ethical Committees of the OLV Hospital Aalst and the General Hospital Groeninge in Kortrijk. The trial was registered at the Netherlands Trial Register (NTR6383). All participants provided written informed consent.

Results

General results

Of the 346 patients who underwent TME for rectal cancer, 77 (22.3%) were excluded: 47 did not meet the inclusion criteria, 9 had language barriers, 9 had specific comorbidities, 8 had a permanent stoma, and 4 were missed during consultation (Fig. 1). This left 269 eligible patients, of whom 89 (33.1%) declined participation, resulting in 180 patients. Among these, the final sample size consisted of 87 patients (48.3% of the eligible sample) who completed the LARS score at all time points up to 2 years.

Fig. 1.

Flowchart of participant recruitment

Patient characteristics

Among the 87 patients, the mean age at the time of TME was 60 years and the mean BMI was 26. Baseline characteristics of both the included patients and those who were lost to follow-up are presented in Table 1. Furthermore, this table shows no significant or clinically relevant differences in baseline characteristics between the 87 patients who remained in the study and the 93 patients who were lost to follow-up (p > 0.05).

Table 1.

Baseline characteristics of the patients

			Included cases (n = 87)	Missing cases (n = 93)	P-value
Age
		< 50 years	16 (18.39)	18 (19.35)	0.99
		≥ 50–70 years	54 (62.07)	57 (61.29)
		≥ 70 years	17 (19.54)	18 (19.35)
Gender
		Female	62 (71.26)	61 (65.59)	0.41
		Male	25 (28.74)	32 (34.41)
BMI
		≤ 25.0	46 (52.87)	50 (53.76)	0.67
		25.1–30.0	29 (33.33)	34 (36.56)
		> 30.0	12 (13.79)	9 (9.68)
Smoking
		No	78 (89.66)	82 (88.17)	0.75
		Yes	9 (10.34)	11 (11.83)
Tumor height
		Low (0–5)	44 (50.57)	47 (50.54)	0.10
		Mid (6–10)	38 (43.68)	32 (34.41)
		High (11–15)	5 (5.75)	14 (15.05)
Neoadjuvant therapy
		No	30 (34.48)	34 (35.56)	0.09
		Chemotherapy	4 (4.60)	0 (0.00)
		Radiotherapy	8 (9.20)	4 (4.30)
		Chemoradiotherapy	45 (51.72)	55 (59.14)
Surgery technique
	Laparoscopic		82 (94.25)	84 (90.37)	0.40
	Open		3 (3.45)	3 (3.23)
	Laparoscopic converted to open		7 (2.30)	6 (6.45)
Reconstruction technique
	Straight		55 (63.22)	55 (59.14)	0.78
	Side to end		21 (74.14)	73 (74.73)
	Colonic J-pouch		11 (12.61)	15 (16.13)
Anastomosis
	Single stapled		37 (47.53)	26 (77.96)	0.12
	Double-stapled		30 (34.48)	38 (40.86)
	Manual		70 (77.99)	29 (31.18)
Anastomotic leakage
	None		79 (90.80)	82 (88.17)	0.42
	Grade A		0 (0.00)	0 (0.00)
	Grade B		1 (1.15)	0 (0.00)
	Grade C		7 (8.05)	11 (11.83)
Stoma type
	No		17 (19.54)	13 (13.98)	0.53
	Ileostomy		61 (70.11)	66 (70.97)
	Colostomy		6 (6.90)	7 (7.53)
	Ileostomy after leakage		3 (3.45)	7 (7.53)
Time to stoma closure (days)
	Mean (range)		156 (0–577)	135 (0–672)	0.15
Adjuvant therapy
	No		46 (52.87)	48 (51.61)	0.39
	Chemotherapy		41 (47.13)	43 (46.24)
	Chemoradiation		0 (0.00)	2 (2.15)
Duration radiotherapy
	Missing		0 (0.00)	1 (1.08)	0.74
	None		34 (39.08)	34 (36.56)
	Short course		10 (11.49)	8 (8.60)
	Long course		43 (49.43)	50 (53.76)
Baseline LARS Score at 1 M
	Major LARS		66 (75.86)	70 (84.34)	0.26
	Minor LARS		8 (9.20)	7 (8.43)
	No LARS		13 (14.94)	6 (7.23)
	Missing		0	10

Values in round brackets are percentages

Anastomotic leakage graded according to the classification by Starr and Fazio: Grade A, anastomotic leakage requiring no active therapeutic intervention; Grade B, active intervention but manageable without surgery: antibiotics, interventional drainage, transanal lavage/drainage; Grade C, anastomotic leakage requiring surgery

Evolution of LARS

Figure 2 presents the Sankey diagram illustrating the evolution of symptoms in the 87 included patients with LARS following TME. At 1 month postoperatively, 66 patients (75.9%) were classified as having major LARS. Between 1 and 6 months postoperatively, a significant change in the LARS categories was observed (p = 0.028) with the prevalence of major LARS decreasing from 75.9% to 58.6%. Starting from 6 months, the percentage of patients in each LARS category did not change significantly (p = 0.43 and p = 0.45 for change from 6 to 12 months and from 12 to 24 months, respectively) with a stable proportion of patients with major LARS and a small non-significant decrease in the prevalence of no LARS. Among the 51 patients with major LARS at 6 months, only 10 patients (20%) experienced improvement to no LARS or minor LARS at both 12 and 24 months.

Fig. 2.

Sankey Diagram: Evolution \ of LARS from 1 month to 6, 12, and 24 months post-operatively or post-stoma closure (number of patients with corresponding percentages in parentheses). Vertical bars, prevalence at time point; wavy lines, transition between time points from one category to another

Online resource 1 presents the percentage of patients who remained in the same LARS category, improved, or worsened between time points. Between 1 month and 6, 12, and 24 months, approximately 60% remained stable, 30% improved, and 10% deteriorated. From 6 to 12 months, 70% remained in the same category, 10% improved, and 20% deteriorated. Between 6 and 24 months, 60% remained stable, while 20% improved and 20% deteriorated. Finally, between 12 and 24 months, 70% remained stable, 20% improved, and 10% worsened.

Quality of life

Mean SF-12 physical and mental health scores were similar across LARS categories at all time points.

Discussion

This is the first prospective cohort study that investigated the percentage of patients transitioning between LARS categories over time.

Both our study and Harji’s found major LARS to be the most common classification at 1 month post-surgery [14]. However, the difference in the percentage of major LARS (75.9% in our study vs. 48% in Harji et al.) may be attributed to differences in baseline patient characteristics [14]. Specifically, patients in our study were, on average, 5 years younger, included 26% more women, and had a median stoma duration that was 48 days longer—factors known to increase the risk of developing LARS [14]. Conversely, the median tumor height in our study was 1.5 cm higher, and the rate of preoperative radiotherapy was 8% lower, both of which are associated with a reduced risk of LARS [14]. From 1 to 6 months postoperatively, major LARS decreased by approximately 20% in both studies [14]. Furthermore, in our study, the prevalence of major LARS remained stable at 58.6% from 6 months onwards, while Harji et al. reported a further reduction in major LARS, from 22% at 6 months to 12% at 12 months [14]. This difference may have been due to their stepwise treatment approach, which includes sacral nerve stimulation (SNS) at 6 months, followed by percutaneous endoscopic caecostomy (PEC) and antegrade enema at 9 months and colostomy at 12 months. However, this approach was only implemented in 23% of patients [14]. In our study, only 20% of patients with major LARS at 6 months showed improvement. These findings suggest that early intervention—similar to Harji’s approach—might be beneficial [14]. At 1 year postoperatively, the 58.6% prevalence of major LARS in our study aligned closely with the systematic review by Sun et al. (44%) and the prospective cohort study by Sandberg et al. (63%) [15, 16]. From 1 to 2 years postoperatively, the prevalence of major LARS in our study decreased slightly from 58.6% to 56.3%, similar to the reduction of Sandberg’s cohort (63% to 56%) [16].

A major strength of this study is being the first prospective longitudinal study with follow-up at 1, 6, 12, and 24 months postoperatively or stoma closure. Another strength is its comprehensive approach, as it not only examined the prevalence of major, minor, or no LARS but also analyzed the percentage of patients transitioning between LARS categories. Additionally, the multicentric design enhanced the generalizability of the results. However, the study has some limitations. First, the small sample size—due to 7 deaths and 86 withdrawals, leaving only 87 patients who completed the LARS score at all measurement points—may have led to response bias. Still, we assumed that the patients who were lost to follow-up were well represented by the patients included in the analysis (i.e., missing completely at random, MCAR). In particular, the main reason for the missing measurements was absenteeism of the employee responsible for the follow-up measurements. Nevertheless, the reduced sample size also limited the analysis of factors influencing persistent bowel symptoms, including age, gender, tumor height, neoadjuvant therapy, reconstruction technique, anastomosis, BMI, smoking, adjuvant therapy, and stoma. Second, 27 patients with minor or major LARS at 1 month postoperatively received pelvic floor muscle training between 1 and 4 months after TME, as previously reported by Asnong et al.[22] This may be considered a limitation since physiotherapy could have influenced the course of LARS. However, as the study demonstrated no sustained effects of physiotherapy on bowel symptoms beyond 6 months, its inclusion in our cohort is unlikely to have affected the overall findings.

Another limitation is that the type of treatments received (e.g., dietary advice, loperamide, ondansetron, transanal irrigation) and their timing were not systematically tracked. Future research should aim to systematically record these data to allow a more accurate assessment of their impact on outcomes. Furthermore, while the study relied solely on the LARS score questionnaire for measuring bowel symptoms, which could be subject to recall bias, it is important to note that the LARS score is currently considered the most reliable and valid tool for measuring functional outcomes in patients following rectal cancer surgery [23, 24]. Nonetheless, the fixed questions of the LARS score may overlook significant details that could be captured by more comprehensive tools, such as stool diaries [25]. Subsequent studies would benefit from incorporating a standardized bowel diary to provide an objective, real-time representation of LARS, encompassing a wider range of bowel symptoms. Finally, although the SF-12 was administered to assess health-related quality of life, no differences were observed between LARS severity categories. This may be due to the SF-12 being a general health questionnaire that is not specifically designed to capture the impact of bowel symptoms in patients with LARS.

Conclusion

This prospective cohort study is the first to longitudinally assess transitions between LARS categories following TME. While a significant improvement in bowel function was observed between 1 and 6 months postoperatively, symptom severity remained largely stable thereafter. Notably, 20% of patients with major LARS at 6 months improved by 12 and 24 months, indicating the persistence of symptoms in the majority of cases. Between 1 month and 6, 12, and 24 months, approximately 60% of patients remained in the same LARS category, 30% improved, and 10% deteriorated. These findings underscore the importance of early identification and proactive management of patients at risk of persistent major LARS.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

IG, AD, SF, and AA contributed to the conception and design of the study. Data acquisition was performed by IG, AD, AW, GB, YVM, BVG, LD, and AA. Data analysis and interpretation were carried out by LL, IG, AD, EC, ND, ADG, and AA. LL and IG were involved in drafting the manuscript. All authors critically revised the manuscript for intellectual content. They have all reviewed and approved the final version of the manuscript and agreed to be accountable for all aspects of the work.

Funding

C2-LIMPAC- KU Leuven,C2M23061,Fonds Wetenschappelijk Onderzoek,T000216N

Data availability

The datasets generated and analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.