Ureteral stent placement following ureteroscopy (URS) for treatment of urinary stone disease is commonly performed to maintain ureteral patency postoperatively when indicated, and to allow the ureter to heal in the event of injury.¹ Patients report a range of stent-associated symptoms (SAS), with some reporting an extremely burdensome experience.^2,3 Despite multiple studies examining stent characteristics and medication use for mitigating stent pain, the mechanisms and pathophysiology of SAS remain elusive. Further, there is very little information about who may be at risk for increased SAS. Factors that may contribute to an adverse experience post-URS and stenting include patient demographics, psychosocial features, prior pain and stone experiences, stone-related and operative factors, stent characteristics, and postoperative medication use. The aims of the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS) were to identify those at highest risk for the development of increased SAS and to determine patient, stone, and operative characteristics that may contribute to these symptoms. We also sought to assess the patient’s lived experience with a stent in place and to explore interference due to stent on normal life activities following stone treatment. We chose a patient-centered approach, using rigorous methods and expanding the use of existing outcome measures, drawing upon expertise from our multidisciplinary team, which included urologists, nephrologists, pain specialists, qualitative research experts, and psychometricians.

Study Design

The study design of STENTS has been previously described.³ Briefly, we performed a multicenter prospective observational cohort study, enrolling 424 patients aged ≥12 years undergoing unilateral URS for stone treatment with ureteral stent at 4 clinical centers. The initial 40 participants (nested qualitative cohort [NQC]) completed daily symptom assessments and interviews regarding their stent experiences. Informed by results from the NQC, the remainder of the 424 participants completed pain and urinary symptom questionnaires preoperatively (baseline) and on postoperative day (POD) 1, 3, and 5, day of stent removal, and 30 days following stent removal. These patient-reported symptom scores served as the outcome measures for this study.

NQC

The initial 40 participants completed daily assessment of self-reported measures to capture individual variation and evolution of symptoms over time. To this end, various instruments with conceptual overlap were utilized to assess pain, urinary symptoms, and the degree to which these symptoms affected quality of life. The daily symptom assessments in these patients demonstrated that symptoms peaked within the first 2 days after URS, and remained persistently elevated while the stent was in place.⁴ Semistructured interviews were performed after stent removal, which were recorded and analyzed. Themes emerging from these narratives, presented at AUA2022, suggest that there are substantial psychological impacts on patients while stented, which are not well captured by current patient-reported outcome instruments.

Figure. Stent-associated symptoms captured by pain, urinary symptoms, and the degree to which these symptoms affect one’s quality of life.

Quantitative Sensory Testing

We postulated that while peripheral sensitization of sensory nerves innervating the ureter likely influences stent-related pain, central sensitization may also play a role. Central sensitization is a physiological process wherein repeated or prolonged pain insults increase the neuronal excitability of the nociceptive pathways in the central nervous system, resulting in the development of hyperalgesia.^5,6 With hyperalgesia, an insult that is mildly painful translates to extreme pain, as in the case of stent pain that is seemingly disproportional to the degree of ureteral irritation. Intuitively, stone formers may be particularly prone to the development of central sensitization owing to recurrent renal colic and ureteral insults due to surgical intervention. Though excitability of neurons cannot be measured directly in humans, the manifestation of central sensitization can be assessed using quantitative sensory testing methods. Findings presented at AUA2022 suggest that hypersensitivity to pain and a higher degree of central sensitization preoperatively were associated with more severe postoperative pain, suggesting a physiological basis for the observed variation in severity of stent symptoms.

Factors Associated With More Severe Stent Symptoms

There was an increase in SAS across all domains on POD 1, and these gradually decreased such that by POD 5 the average pain intensity decreased by approximately 50%. Despite the decrease in pain intensity, interference due to pain remained elevated through POD 5, notably lagging behind the quantitative pain experience. Pain intensity was no longer statistically different from baseline by POD 7-9 with the stent in place, although quality of life was still adversely impacted. Urinary symptoms likewise demonstrated a distinct peak on POD 1, with a decline in symptoms thereafter, but remaining above baseline until stent removal. Similar to the relationship between pain intensity and interference, there was a delayed decrease in urinary bother compared to urinary symptoms.

As presented in a late-breaking abstract at AUA2022, a multivariable analysis showed that patient factors independently associated with greater pain intensity included younger age, history of prior severe stent pain or chronic pain condition, and baseline depressive symptoms measured by the Patient-Reported Outcomes Measurement Information System (PROMIS). These risk factors were additionally associated with higher interference due to pain. When using the 10-item Lower Urinary Tract Dysfunction Research Network symptom index (LURN SI-10), higher BMI and baseline depressive symptoms were associated with greater urinary symptoms and bother, while increasing age was associated with less bother. Risk factors associated with increased SAS did not change when factoring in postoperative medication use in a sensitivity analysis.

Summary

This multicenter prospective study evaluating patient psychosocial and physiological characteristics has revealed multiple important findings thus far, including: (1) although pain intensity decreases over time in the days following stent placement, interference due to pain remains elevated, suggesting that other unmeasured factors such as coping mechanisms may play a role in the stent experience, (2) older patients describe a lower pain intensity with no difference based on sex, (3) depressive symptoms, chronic pain conditions, and prior severe pain with a stent are risk factors for report of higher pain intensity, and (4) quantitative sensory testing correlation with greater SAS suggests there is a physiological difference that impacts the patient experience post-URS. Demonstration of central sensitization may identify new treatment avenues to manage pain via modulation of the neuroplasticity of the central nervous system. Importantly, stone and operative factors including ureteral instrumentation, use of access sheath, and stent characteristics were not associated with increased symptomatology. This initial work suggests that systematic, preoperative identification of patients at risk for severe symptoms is feasible, and development of a prediction model is ongoing. Additional planned analyses include examination of the experience of STENTS participants who underwent either bilateral URS or 2-stage URS, and health care utilization in the 30 days following stent removal. Finally, over 23,000 biological samples from 300 STENTS participants provide a wealth of opportunity for biomarker discovery research.