Colorectal cancer is the 2nd and 3rd most common cancer in respectively women and men, of which about 40% is located in the rectum. The gold standard treatment for rectal cancer (RC) is a low anterior resection, combined with chemoradiotherapy. However, given the improved 5-year survival rate, functional outcomes such as bowel symptoms, become increasingly important. Furthermore, bowel symptoms have a lasting adverse impact on quality of life (QoL).(1) The combination of these  bowel symptoms and their impact on QoL has been summarized in an international consensus definition(2) and is referred to as the Low Anterior Resection Syndrome (LARS). 
Although there are numerous studies in the literature investigating LARS until one year-post surgery, only Sandberg et al.(3) included a two-year follow-up period. Consequently, the primary aim of this study was to investigate the evolution of LARS until 2 years post-surgery. Furthermore, to date, there have been no long-term prospective studies examining factors associated with the development of persistent LARS. Therefore, the secondary aim of this study was to identify the risk factors associated with the development of persistent LARS.

One hundred and twenty-three patients who underwent Total Mesorectal Excision (TME) for rectal cancer were included in this prospective cohort study. Exclusion criteria encompassed various surgical procedures (Hartmann procedure, abdominoperineal excision, transanal endoscopic microsurgery, sigmoid resection), preoperative fecal incontinence, neurological disorders affecting bowel function and previous pelvic surgery, pelvic radiation, or LAR for non-cancer reasons.

First, to investigate the evolution of LARS until 2 years post-surgery, the LARS score was assessed preoperatively, and at 1,12 and 24 months post-surgery. As a secondary outcome, to identify patient characteristics of individuals experiencing persisting debilitating bowel symptoms, multiple measurement tools were deployed: the LARS score (continuous score), the COREFO questionnaire and the Short Form 12 (SF-12 Physical and Mental Component Summary (PCS and MCS)) to assess the impact on the participants’ quality of life. Risk factors were obtained from medical records and included patient-related factors (age, Body Mass Index (BMI), gender, and smoking status), cancer-related factors (tumor height), and treatment-related factors (neoadjuvant therapy, reconstruction technique, anastomosis technique, and adjuvant therapy).

Descriptive statistics were used to determine the proportion of patients experiencing LARS (LARS) one month post-surgery and to assess whether these patients subsequently experienced improvements in their LARS category at 24 months post-surgery.
Quantitative data were analysed using Mann-Whitney U-tests and Kruskal-Wallis tests to identify the risk factors associated with the development of persistent LARS measured with the LARS score, the COREFO and the SF-12 at 12 months and 24 months post-surgery. A statistical significance level of p<0.05 was set, with two-sided p-tests conducted.

Of the 123 patients who underwent TME for rectal cancer, 103 and 62 patients were followed up to 1 year and 2 years respectively. 

At one month post-surgery, 23% of the patients experienced no LARS. Among this group, 15% persisted having no LARS, while 2% experienced a worsening to minor LARS, and 6% to major LARS.
At one month post-surgery, 11% of the patients exhibited minor LARS. Among them, 2% faced a resolution to no LARS, 6% persisted having minor LARS, and 3% experienced an exacerbation to major LARS 24 months post-surgery.
Additionally, 66% of the patients experienced major LARS at one month post-surgery. Among this group, 6% demonstrated a remission to no LARS, 18% transitioned to minor LARS, and 42% persisted with major symptoms 24 months post-surgery.

Patients younger than 50 years showed a greater decline in SF-12 PCS scores at both 12 months and 24 months, as well as in SF-12 MCS scores at 12 months, compared to patients older than 70 years. Furthermore, females experienced a greater decline in LARS score at 12 months and 24 months than males.  Similarly, patients with a low tumor height (0-5 cm from anal verge) experienced a greater decline in SF-12 PCS score at 24 months compared to those with a high tumor  height (11-15 cm). At 12 months post-surgery, patients with manually sewn anastomotic sutures exhibited a greater decline in COREFO scores compared to those with double-stapled sutures. Furthermore, participants who underwent adjuvant chemoradiotherapy showed less decline in COREFO scores compared to those receiving chemotherapy alone.
Conversely, BMI, neo-adjuvant therapy, reconstruction technique and smoking where not associated with persistent bowel symptoms at 12 or 24 months after TME.

The findings of this prospective cohort study revealed three key points. Firstly, one-third of the patients experiencing no LARS at one month post-surgery (14%), developed LARS symptoms at 24 months post-surgery. Secondly, among patients classified as experiencing major LARS at one month (66%), only one-third of patients improved to no or minor LARS at 24 months. 
Finally, younger age, male gender, low tumor height, double-stapled anastomotic sutures and adjuvant chemoradiotherapy influenced the development of persistent bowel symptoms negatively. In contrast, BMI, neo-adjuvant therapy, reconstruction technique, and smoking showed no association with persistent bowel symptoms.

Although there are numerous studies in the literature investigating LARS until one year-post surgery, only one study included a two-year follow-up period. In this study, we observed that only one-third of patients with initial major LARS improved to no or minor LARS at 24 months after surgery. Finally, younger age, male gender, low tumor height, double-stapled anastomotic sutures and adjuvant chemoradiotherapy influenced the development of persistent bowel symptoms negatively.

Pieniowski EHA, Nordenvall C, Palmer G, Johar A, Tumlin Ekelund S, Lagergren P, Abraham-Nordling M. Prevalence of low anterior resection syndrome and impact on quality of life after rectal cancer surgery: population-based study. BJS Open. 2020;4(5):935-42.
Keane C, Fearnhead NS, Bordeianou LG, Christensen P, Basany EE, Laurberg S, et al. International Consensus Definition of Low Anterior Resection Syndrome. Dis Colon Rectum. 2020;63(3):274-84.
Sandberg S, Asplund D, Bisgaard T, Bock D, González E, Karlsson L, et al. Low anterior resection syndrome in a Scandinavian population of patients with rectal cancer: a longitudinal follow-up within the QoLiRECT study. Colorectal Dis. 2020;22(10):1367-78.

Continence 12S (2024) 101676
DOI: 10.1016/j.cont.2024.101676