Stent-Associated Symptoms After Two-Stage Ureteroscopy: Results from STENTS

Abstract

Objective:

To compare patient-reported stent-associated symptoms (SAS) after first- and second-stage unilateral ureteroscopy with ureteral stent placement for treatment of urinary stones.

Methods:

Participants enrolled in the Study to Enhance Understanding of Stent-Associated Symptoms (STENTS) underwent unilateral URS with ureteral stent for urinary stones and completed patient-reported outcome measures to assess SAS. Differences in pain intensity were evaluated at baseline and following first- and second-stage URS procedures. A propensity score–matched cohort of participants who underwent single-stage URS were compared to participants undergoing a two-staged procedure.

Results:

Of the 424 participants who underwent unilateral URS, 40 (9.4%) had an unplanned staged procedure. Most participants (75%) undergoing a staged procedure had a narrow ureter or stricture. The median time to second procedure was 14.0 days, with second procedure mean operative time 25 minutes greater than first stage. Preoperative pain intensity was similar before both procedures, whereas postoperative pain was lower after the second procedure compared to the first. In the matched cohort, patients reported comparable pain on POD 1, but lower pain scores in the two-stage group on PODs 3 and 5. Urinary symptoms were improved on PODs 1 and 3 after the second procedure compared to the first stage.

Conclusion:

Despite a longer procedure time, pain intensity appears to be lower after a second-stage procedure compared to the first. These results may be useful in counseling patients who require staged treatment.

Introduction

Staged ureteroscopy (URS) is a reasonable treatment option for patients with a stone burden too large to treat in one setting or with ureters too narrow to accommodate the ureteroscope.^1,2 Staged URS is recommended to reduce adverse events associated with longer operative times that may occur when attempting to treat a large stone burden in a single setting.^3–5 Additionally, failed retrograde ureteral access in non-stented patients occurs for approximately 6–16% of adults and 25% of children.^6–9 Typically, a ureteral stent is placed in these cases to allow for passive dilation and facilitate future instrumentation. This approach has been shown to be effective in porcine models to increase luminal ureteral circumference an average of 4 Fr.¹⁰ A preexisting ureteral stent has also been associated with more successful access sheath placement and larger access sheath insertion in retrospective series.¹¹

Postoperative pain and stent-associated symptoms (SAS) following staged URS have not been evaluated, however remain important for preoperative counseling and furthering the understanding of stent-related ureteral pain. Using data derived from the Urinary Stone Disease Research Network (USDRN) Study to Enhance Understanding of Stent-associated Symptoms (STENTS), we performed a prospective cohort study using the subset of patients who underwent unplanned staged URS to: 1) investigate patient-level changes in SAS from first-stage to second-stage procedure and 2) compare the time course and severity of SAS in those with a preexisting stent compared to the overall group that underwent single-stage surgery without a stent in place.

Methods

Population

STENTS is a multicenter, prospective, observational cohort study of individuals undergoing URS and ureteral stent placement for treatment of a ureteral or renal stone. A description of the STENTS protocol has been published.¹² Patients with suspected infection stones or urinary tract infection were excluded. We examined a subset of participants who underwent staged URS to assess SAS following each stage and to compare SAS in this cohort to those undergoing a single-stage procedure.

Data Collection

Participants completed the Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity 3a questionnaire, PROMIS pain interference 6b, and the Urinary Score of the Ureteral Stent Symptom Questionnaire (USSQ-U) to assess pain intensity, pain interference and urinary symptoms, respectively. Data were collected prior to first- and second-stage procedures as baseline measures and on postoperative days (PODs) 1, 3, 5, and 7–9; although questionnaires were administered on PODs 7–9, very few were completed, and therefore these were not included in our analysis. Trained research coordinators recorded intraoperative data at the time of URS as previously reported.¹²

Statistical Analysis

Baseline characteristics were reported as mean (standard deviation [SD]) and median (25^th, 75^th percentiles) for continuous variables, and as count (percentage) for categorical variables. Continuous variables were compared using two-sample t-test or Wilcoxon rank-sum test depending on the normality of the data distribution. Categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test, as appropriate. A paired t-test was used to compare first- and second-stage outcomes. A 2:1 propensity score–matched cohort was generated from the single-stage unilateral STENTS cohort.¹³ Matching was performed based on clinical center, age, sex, stone location, stone size, and procedure time. Kruskal–Wallis tests were used to compare single-stage, first-stage, and second-stage pain intensity scores across different timepoints. Two-sided significance testing was used with a conventional significance level of 0.05. No adjustments were made for multiple comparisons. All statistical analyses were performed using Statistical Analysis Software version 9.4 (SAS Institute Inc., Cary, NC).

Ethics

Institutional review boards at all participating clinical centers approved the protocol. Adult participants provided written informed consent to participate. Adolescents aged 17 years and younger provided their informed consent, and their parents provided parental permission.

Results

First Stage vs. Second Stage

Of 424 patients who underwent unilateral URS in STENTS, 40 (9.4%) patients had a staged procedure (Table 1). The median cohort age was 60.0 years (interquartile range (IQR) 48.5, 67.0), and most patients were male (68%). The median BMI for patients was 28.1 kg/m² (IQR 23.5, 35.6). The median largest stone diameter was 11.0 mm (IQR 6.0, 16.3), and most patients had a dominant renal stone treated (55%). For most of the participants (75%) requiring a staged procedure, the reason was narrow ureter or stricture. There were 10 participants who had incomplete lithotripsy owing to poor visualization due to blood or debris, or inability to pass a ureteral access sheath. Median time to second procedure was 14.0 (IQR 13.8–21.0) days, with a mean operative time 25 minutes longer for the second-stage procedure (first stage vs. second stage, p<0.001) (Table 1). Laser lithotripsy was performed more often during the second stage compared to the first (25% in first stage vs. 83% in second stage), and there was increased use of a ureteral access sheath in the second procedure (10% in first stage vs. 65% in second stage).

Table 1.

Patient, Operative, and Stone Factors

Variable	Staged	Single Stage (Propensity Score–Matched)	p-value
N	40	78
Age, years (median, 25th ,75th percentile)	60.0 (48.5, 67.0)	57 (47.0, 64.8)	0.409
Stone burden, mm (median, 25th ,75th percentile)	11.0 (6.0, 16.3)	10.0 (6.3, 15.8)	0.641
Operative time (second procedure), min (median, 25th,75th percentile)	59.5 (44.0, 80.5)	60.0 (40.0, 80.3)	0.880
Operative time (first procedure) min (median, 25th,75th percentile)	34.5 (22.0, 55.3)	-
BMI (median, 25th,75th percentile)	28.1 (23.5, 35.6)	30.8 (26.3, 35.5)
Days to second stage (median, 25th-75th percentile)	14.0 (13.8, 21.0)	-
Sex, n (%)			0.301
Female	13 (32.5%)	33 (42.3%)
Male	27 (67.5%)	45 (57.7%)
Stone location (as reported for second stage), n (%)			0.973
Ureteral	11 (27.5%)	22 (28.2%)
Renal	22 (55.0%)	45 (56.4%)
Ureteral and Renal	4 (10.0%)	8 (10.3%)
Unknown	3 (7.5%)	4 (5.1%)

Differences in pain intensity were evaluated at baseline and following first- and second-stage procedures. PROMIS pain intensity was similar preoperatively despite having a stent before the second-stage procedure, placed during the first stage (p=0.220, Table 2). Pain intensity was significantly lower at all corresponding time points following the second-stage procedure when compared to first stage (Figure 1A). PROMIS pain interference was lower on POD 3 after second stage compared to first stage (p= 0.016, Figure 1B) but was similar at all other timepoints between the two groups. As expected, urinary bother measured by USSQ-U was worse at baseline prior to the second procedure with the presence of an indwelling ureteral stent (p<0.001). Postoperative urinary symptoms were, however, comparatively less following the second-stage procedure by POD 1 and POD 3 (Figure 1C).

Table 2.

Pain Intensity, Interference, and Urinary Symptoms: First-, Second-, and Single-Stage Ureteroscopy

Variable	First Stage		Second Stage		Paired First vs Second Stage		Propensity Score–Matched Single Stage		Second vs Single Stage
	N	Mean (SD)	N	Mean (SD)	N	p-value	N	Mean (SD)	p-value
PROMIS Pain Intensity (Scale 0–100)	40						78
Baseline	26	44.1 (19.8)	38	47.6 (16.3)	26	0.220	57	49.1 (20.2)	0.807
POD 1	33	59.4 (16.8)	34	55.3 (18.0)	29	0.025	64	61.7 (16.4)	0.080
POD 3	32	57.1 (17.4)	35	47.9 (16.0)	30	<0.001	63	57.1 (15.8)	0.009
POD 5	29	51.3 (16.5)	34	46.1 (17.4)	27	0.048	51	59.5 (17.0)	0.001
PROMIS Pain Interference
Baseline	28	11.9 (6.7)	35	12.8 (6.7)	28	0.431	67	12.7 (6.9)	0.879
POD 1	30	14.3 (7.4)	30	15.7 (7.1)	26	0.358	63	18.5 (6.7)	0.087
POD 3	32	16.5 (6.9)	30	14.1 (7.1)	29	0.016	65	18.6 (6.3)	0.002
POD 5	27	15.0 (7.6)	32	13.5 (6.9)	25	0.175	50	18.8 (6.7)	<0.001
USSQ-U
Baseline	36	20.7 (4.2)	39	25.1 (6.1)	36	<0.001	74	21.9 (5.6)	0.008
POD 1	33	31.5 (7.4)	32	27.7 (6.1)	27	0.005	69	32.2 (7.0)	0.001
POD 3	34	29.3 (7.4)	34	25.0 (6.2)	31	0.001	70	29.9 (6.4)	<0.001
POD 5	29	26.6 (6.4)	34	25.1 (5.6)	26	0.052	51	27.9 (6.9)	0.076

POD = postoperative day; PROMIS = Patient-Reported Outcomes Measurement Information System; USSQ-U= Ureteral Stent Symptom Questionnaire-Urinary score.

Figure 1.

(A) PROMIS pain intensity over time, (B) PROMIS pain interference over time, and (C) urinary symptoms over time, for first stage vs. second stage ureteroscopy. PROMIS = Patient-Reported Outcomes Measurement Information System.

Second Stage vs. Propensity Score–Matched Single Stage

A propensity score–matched cohort of 78 patients undergoing single-stage URS were compared to the second stage of those who underwent staged URS. By design, the matched cohort did not differ from the staged cohort based on operative time, stone size, stone location, age or sex (Table 1). PROMIS pain intensity did not differ prior to second-stage procedure or on POD 1 following second-stage procedure when compared to a single-stage procedure (Table 2). Pain intensity was significantly less on PODs 3 and 5 after second-stage procedure compared with single stage (p=0.009 and p=0.001, respectively) (Table 2). Pain interference did not significantly differ at baseline or on POD 1 but was significantly less following the second stage compared to a single-stage procedure on PODs 3 and 5 (p=0.002 and p<0.001, respectively). Urinary bother as measured by USSQ-U was worse at baseline prior to a staged procedure compared with single-stage procedure (p=0.008); however, on PODs 1 and 3, USSQ-U scores were lower for those undergoing a staged procedure compared to a single-stage procedure (Table 2). When comparing all three categories (single-, first-, and second-stage procedures), pain intensity was significantly less after the second-stage procedure on PODs 3 and 5 (p= 0.02 and p <0.01) compared to first stage and single-stage procedures (Figure 2).

Figure 2.

Pain intensity over time for single-, first-, and second-stage ureteroscopy. Comparison across all three groups using Kruskal Wallis test

Discussion

This multicenter, prospective, observational study evaluating SAS after a staged procedure has several important findings. We found that despite a longer operative time and more extensive instrumentation, such as laser usage and use of access sheath, pain intensity and urinary symptoms were comparably less following a second-stage procedure, consistent with prior results from STENTS where operative factors were not associated with postoperative pain.¹³ Pain intensity and interference also remained lower after a second-stage procedure when compared to a cohort of single-stage URS patients later in their postoperative courses. These results were achieved by frequent assessment of self-reported symptoms following each stage, controlling for differences between individuals and allowing improved evaluation of procedural and temporal contributions to measurement outcomes, a significant strength of this study. Comparison of SAS in patients after a staged procedure with a propensity score–matched cohort of patients who underwent a single-stage procedure allowed for assessment of symptoms with and without a ureteral stent in place at the time of surgery. These unique aspects allowed for a novel evaluation of SAS in the staged setting.

The rate of unilateral staged procedure in this study was 9.4% (40/424), whereas failed ureteral access was 7.1% (30/424), consistent with previously reported rates.^8,9 In this staged cohort, the main differentiator between the first stage and the second stage was the presence of an indwelling ipsilateral ureteral stent at baseline (for a median duration of 14 days). One might expect that a new insult such as a second-stage URS could result in worsening pain. In patients undergoing second-stage URS, SAS did increase in the short-term following URS; however, this effect was quicker to return to baseline and less intense compared with initial stent placement. This increase in SAS, albeit diminished, immediately following second-stage URS may be attributed to ureteral or renal manipulation in pre-stented ureters. These findings are consistent with results from STENTS with greatest pain intensity occurring in the early post-operative period and returning to near baseline by POD 7–9¹³. This may explain the similarity in preoperative pain intensity in first and second stages of the procedure, as most secondary procedures occur after POD 7 to allow for adequate ureteral dilation, with a median stent duration of 14 days in the current study.

The finding that SAS are worse after the first compared to second stage URS suggests that a large proportion of symptoms are due to the initial stent placement and that perhaps some symptoms may be mitigated by ureteral changes associated with an indwelling stent over time. This is consistent with findings from porcine studies, where ureteral stent placement has been shown to passively dilate the ureter over time, with an increase in ureteral diameter by approximately 4 Fr after 1 week of stent placement.¹⁰ Transcript-level changes also suggest an inflammatory profibrotic response to ureteral stenting¹⁴ with a time-dependent decrease in peristalsis.¹⁵ Our findings indicate that the perception of pain and urinary symptoms may be modulated by tissue changes in response to an indwelling stent over time.¹⁴ These changes may result in a less painful experience following a secondary procedure in a pre-stented ureter. As in clinical practice, staged URS was not planned in any of the selected cases, and importantly, all participants were without a stent in the prior 60 days at the time of the index procedure. Although 40% of the previously reported overall STENTS cohort had a history of prior ureteral stent, only severe pain with a prior stent predicted an increase in SAS.¹³ Thus, a distant history of stenting does not appear to have the same effect on SAS as a preexisting stent at the time of surgery, as shown in this study. This suggests that if ureteral changes are implicit in pain perception, these changes may return to normal once the stent is removed.

It is important to note that this study is a post hoc analysis and was not powered to assess for differences in SAS between first and second-stage URS procedures and has several limitations. It is possible that ureteral changes induced by stent placement alone may not be responsible for the decrease in SAS and that psychosocial factors may play a role between two consecutive procedures, a notable finding in STENTS¹³ in which the experience of recent stent placement may influence the perception of pain following a subsequent procedure. Preoperative psychosocial factors such as depression and anxiety have been found to be associated with postoperative pain scores in the STENTS cohort¹³ as well as in other fields, such as bariatric surgery.¹⁶ In this cohort, we did not use psychosocial instruments to measure changes in anxiety between first- and second-stage URS to assess for this contribution to symptoms. Standardized preoperative counseling has been shown to impact postoperative pain perception in other surgical disciplines.¹⁷ In this study, participants received preoperative counseling routinely employed by the treating surgeon. A post-operative medication regimen was also not standardized and was at provider discretion. Last, our results may have selection bias of patients with inherently difficult or constrictive anatomy as the staged procedures were unplanned.

Despite these limitations, this is the first study to report on the temporal relationship in patient-reported outcomes following staged ureteroscopic stone removal with the important finding of decreased pain intensity and urinary symptoms following second stage compared with the initial stage procedure. These results suggest that ureteral stenting could reduce pain in the subsequent procedure. This may be useful when considering a second-stage procedure or when counseling patients who must undergo second-stage URS, as they may be reassured that pain and urinary symptoms following their second procedure may be less than after the first.

Conclusion

Despite a longer procedure time and more extensive instrumentation during second-stage URS, when most of the stone treatment occurred, postoperative pain intensity and urinary symptoms were reported to be lower compared to the first stage. These results may be useful in counseling patients who may require a staged procedure. Our findings also raise the possibility that perception of pain may be modulated over time and may respond to physiologic changes induced by stent placement and ureteral dilation.