March's Paper of the Month assesses the impact of sacral neuromodulation on low anterior resection syndrome symptoms as measured by validated scores and bowel diaries.
Sacral Neuromodulation in Patients With Low Anterior Resection Syndrome: The SANLARS Randomized Clinical Trial
Franco Marinello, Doménico Fraccalvieri, Pere Planellas, Montse Adell Trapé, Julia M Gil, Esther Kreisler, Gianluca Pellino, Eloy Espín-Basany
Dis Colon Rectum 2024; 67: 435–447
What is known about the subject?
While patient prognosis and the possibility of sphincter preservation have improved significantly over the last few decades due to the increasing use and intensification of radiochemotherapy, functional impairment has also increased.
In particular, the combination of neoadjuvant radiochemotherapy with subsequent sphincter-preserving resection is associated with significant limitations, which are summarised under the term (Low anterior resection syndrome) LARS.
No specific treatment is yet available for this disease, which, depending on its severity, is associated with a significant reduction in quality of life.
This multicentre study was designed to prospectively evaluate the efficacy of sacral neuromodulation (SNM) in patients with major LARS and was based on usual clinical practice for SNM.
After a 3-week trial period, patients underwent permanent generator implantation if a 50% reduction in baseline LARS score was achieved. Immediately after IPG implantation, patients entered the double-blind, randomised crossover phase to receive either 4 weeks of active modulation (generator "ON") or sham stimulation (generator "OFF"). After a 2-week washout period, the sequence was reversed and the generator was switched ON or OFF for a further 4 weeks.
The primary endpoint was the clinical response with SNM to LARS symptoms as measured by the LARS score, with an expected reduction of 40% at 12 months after permanent generator implantation compared to baseline.
Secondary endpoints included assessment of faecal incontinence, health-related quality of life (HRQoL) and bowel function, as assessed by the St Mark's faecal incontinence score and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30.
What the study adds?
The mean baseline LARS score was 37.94 (±4.05) for the whole study group. After the 3-week testing period, the score showed a mean reduction of 59.12%, corresponding to 15.51 (±8.74) points (effect size, -22.43 [95% CI, -25.2 to -19.66] p < 0.001). IPG implantation was performed in 35 of 46 patients (76%).
However, at 6 and 12 months, the LARS score decreased by only 16.3% and 18.4%, respectively, compared to baseline (p < 0.001) and the primary endpoint was not met at 12 months.
In contrast, the mean St Mark's Continence Score at baseline was 18.63 (±3.84); at 6 and 12 months, it improved by 40.6% and 44.5%, respectively, compared to baseline (p < 0.001). Similarly, treatment satisfaction was reported by 82.8% of patients at baseline and 67.7% and 69.7% at 6 and 12 months, respectively; global health status and functioning (physical, role, emotional, cognitive and social) also improved at 6 and 12 months.
Thus, while the improvement in the LARS score observed after the testing phase was not maintained at 6 and 12 months follow-up with active stimulation, the HRQoL items improved substantially with active stimulation, raising the question as to how comprehensively the score reflects the patient's condition.
Implications for colorectal practice
While LARS encompasses all changes in bowel function resulting from rectal resection that can lead to a poorer quality of life, including faecal incontinence, urgency, increased stool frequency and fragmentation, it seems most appropriate to consider SNM in LARS patients with a faecal incontinence phenotype.
Since a significantly lower rate of patients with a history of anastomotic leakage underwent a successful testing phase, SNM does not appear to be a promising tool in this patient group.
Take home message
SNM is often recommended as the last resort before stoma creation, but these results show that it could be considered at an earlier stage in appropriate patients, after comprehensive counselling.
