Tandem Ureteral Stents for Malignant Ureteral Obstruction

Abstract

Objectives:

Malignant ureteral obstruction (MUO) is a devastating complication of cancer, and it is commonly treated by drainage via percutaneous nephrostomy (PCN). The objective of this study was to determine the efficacy, safety, and functional outcome of tandem ureteral stents (TUS) in the management of MUO.

Materials and Methods:

The medical records of all patients with MUO who underwent balloon dilation and TUS insertion in Sheba Medical Center between 2014 and 2018 were retrospectively analyzed. Safety was measured by intra- and postoperative complications, efficacy by time to event analysis, and failure by the requirement of PCN attributable to renal failure or infection. Independent risk predictors of TUS failure were determined by a multivariable Cox regression analysis.

Results:

A total of 103 procedures were performed on 81 patients during the study period. The median follow-up was 32 weeks (interquartile range [IQR] 24–67). Fifty-nine (72.9%) patients remained with TUS while 22 patients required PCNs. The median time to procedural failure was 4 months (IQR 2–8). Complications developed after 18 (22.2%) procedures. Two patients requested stent removal due to lower urinary tract symptoms. Independent predictors for TUS failure were metastasis (hazard ratio [HR] 3.03, 95% confidence interval [CI] 1.27, 7.23, p = 0.013) and prior PCN (HR 3.38, 95% CI 1.40, 8.13, p = 0.007).

Conclusions:

TUS is an efficient and safe management option for patients with MUO. It can alleviate renal failure without the need for an external PCN. Metastasis and prior PCN are associated with TUS failure.

Introduction

Malignant ureteral obstruction (MUO) may cause renal function impairment, renal colic, and infection. It may be the result of intrinsic ureteral obstruction or extrinsic compression by a primary tumor, metastases, or retroperitoneal lymphadenopathy.¹ MUO is commonly caused by ovarian, cervical, colorectal, and breast cancer, while genitourinary malignancies are less frequent.² The survival of these patients is grim, with a median survival of 6 and 8 months and a 1-year overall survival of less than 50%.^3,4

MUO has been traditionally managed by surgical reconstruction, however, the limited life expectancy of the patients and the high rate of complications call for a less radical and a more minimally invasive treatment option.⁵ The most common management options for MUO are drainage via a percutaneous nephrostomy (PCN) or an indwelling ureteral stent. Each has its merits; however, it is believed that indwelling stents provide a better quality of life (QOL), particularly in the long term.^6,7 Increased external compressive forces, mucous production, and urothelial sloughing uniformly cause stent failure,² and a PCN is eventually placed in most cases.

Single ureteral stent has a failure rate of about 40%, with most patients developing complications.² However, it is also possible to insert two stents side-by-side (tandem ureteral stents [TUS]), which improves the urine flow by better withstanding the compressive tumoral forces and allowing urine to flow between the stents. The use of TUS has thus far been explored only in small retrospective series.^8

–14 The object of this study was to determine the efficacy, safety, and functional outcome of TUS in the management of MUO, and to identify factors to predict success or failure of TUS.

Materials and Methods

Study population

After receiving institutional review board approval, we reviewed the medical records of all patients who underwent TUS insertion between June 2014 (when stiff TUS drainage was introduced in Sheba Medical Center) and October 2018 (study closure). All patients requiring upper tract drainage due to MUO were offered single ureteral stent, TUS, or PCN drainage, and those already with a PCN were offered have it exchanged for single or TUS. Advantages of TUS over single ureteral stents were presented to each patient.

We collected the following data: age, gender, side of obstruction, type of primary tumor, indication for TUS drainage (patients' preference, renal colic, renal failure, and infection), serum creatinine level, and severity of hydronephrosis, as graded by the Society for Fetal Urology Classification, before and after the drainage, obstruction site and length, and TUS failure.

The estimated glomerular filtration rate (eGFR) was calculated using the MDRD formula.¹⁵ In patients with acute renal failure, serum creatinine level was measured on the week following the procedure. Follow-up protocol included outpatient visit 2 months postoperatively with urinalysis, urine culture, CBC, SMAC, and renal ultrasonography with postvoid residual urine. If significant residual urine volume was measured—behavioral modifications were recommended. Patient satisfaction and complaints were qualitatively recorded at every follow-up visit. In addition, flexible cystoscopy was performed 6 months after the procedure, to evaluate stent encrustation and shorten the time to stent exchange if necessary.

Procedural failure was defined as the need to insert a PCN to better drain the renal unit. The reason for failure and the time to failure were also recorded. Lastly, the date and reason for patient demise were noted.

Surgical technique

All procedures were performed by an endourological society fellowship-trained surgeon (N.K.) who used the same surgical technique for all patients. The patient was positioned in the dorsal lithotomy position, and the genitalia were prepped and draped. With the patient under general anesthesia, a rigid cystoscope with a 30-degree lens was inserted into the bladder. Bilateral ureteral orifices (UOs) were identified, after which a 0.038-inch Glidewire (Terumo, Tokyo, Japan) was used to cannulate the UO. A 10F dual-lumen catheter was inserted over the guidewire with its tip just proximal to the UO. A retrograde pyelogram was performed using diluted contrast material to define the location and extent of external compression.

In case of difficulty passing a guidewire through the obstructed segment a semi-rigid ureteroscopy was performed. In extreme cases of obstruction this maneuver enables visualization of the narrow lumen. In addition, it provides better buttress for the guidewire and prevents backward coiling of the guidewire's floppy tip.

A 4 cm/18F ureteral balloon dilation catheter was used to dilate the stricture up to 20 atmospheres. Several dilatations were sometimes needed, particularly in cases of long strictures. A 14F ureteral dilator was then advanced over the guidewire up to the level of the renal pelvis to ensure sufficient accommodation of the ureter, after which a 10F dual-lumen catheter was reinserted, and a second guidewire was passed into the kidney.

Finally, two 6F double-pigtail stiff Percuflex ureteral stents (Boston Scientific, Marlborough, MA) were placed simultaneously over these guidewires under fluoroscopy. The proximal curls were positioned within the kidney and the distal curls were formed in the bladder. If doubt exists, cystoscopy is performed to confirm the position of the distal coils. Fluoroscopy was used to verify drainage of contrast material from the kidney. Stent exchange was typically performed every 9 and 12 months in accordance with the stent manufacturer's recommendation of doing so up to 365 days. This stent is relatively stiff and of unique composition that allows it to remain functional for an extended period of time.

Statistical analysis

We used continuous variables to describe the median (interquartile range [IQR]), and frequency (proportions) to describe categorical variables. Wilcoxon signed rank test was used to compare continuous variables before and after TUS drainage. Cox proportional hazard regression analysis was used to assess independent predictors of time to TUS failure. Statistically significant predictors on univariate Cox analysis were included in the multivariate Cox analysis. Statistical significance was defined as p < 0.05, and all analyses were performed on SPSS v.23 (IBM).

Results

The study patients' characteristics are detailed in Table 1.

Table 1.

Patients and Stricture Characteristics

Characteristic	N
Patients	81
Number of renal units	103 (22 with bilateral stents)
Age, years median (IQR)	60 (49–70)
Gender, female, n (%)	61 (75.3)
Primary tumor site, n (%)
Breast	10 (12.3)
Gastrointestinal	20 (24.6)
Genitourinary	8 (9.9)
Gynecologic	35 (43.2)
Other	8 (9.9)
Metastasis, n (%)	37 (45.6)
Line of treatment, n (%)
Primary	56 (69)
Secondary	25 (31)
eGFR before drainage, median (IQR)	50.7 (34.6–66.7)
Prior nephrostomy tube, n (%)	31 (38.2)
Prior surgery, n (%)	58 (71.6)
ASA score, n (%)
1	1 (1.2)
2	11 (13.5)
3	63 (77.7)
4	6 (7.4)
Strictures, n (%)
Side, right (renal units), n (%)	54 (52.4)
Ureteral obstruction site (renal units), n (%)
Proximal	22 (21.4)
Middle	19 (18.4)
Distal	62 (60.2)
Length of stricture, cm, median (IQR)	3.8 (2.3–6.0)

eGFR = estimated glomerular filtration rate; IQR = interquartile range.

One hundred three consecutive procedures were performed on 81 patients (median age 60 years [IQR 49–70]). Seventy-eight (75.7%) procedures were performed on female patients. The insertion was on the right side in 54 (52.4%) patients. The most common primary malignancy site was the gynecologic system (43.2%), while the genitourinary system was the cause of obstruction in only 8 (9.9%) patients. Multiple lines of systemic therapy were used in 56 (69.1%) patients. Fifty (48.5%) renal units were obstructed by metastatic deposits, while the rest were obstructed at the primary site of disease. Most of the patients (n = 58, 71.6%) had undergone surgery before TUS insertion.

The most common indication for kidney decompression was acute kidney injury (n = 53, 65.4%), followed by patient request to exchange a PCN with a TUS (25.9%). The most common site of ureteral obstruction was the distal ureter (n = 62, 60.2%). The median length of obstruction was 3.8 (2.3–6) cm. The pre- and postdrainage median eGFRs were 54.1 (IQR 41.1–72.3) and 68.9 (IQR 57.4–83.1), respectively. The eGFR was significantly higher after drainage (p < 0.001). During the study period, in three patients the procedure failed due to inability to pass a guidewire through the obstruction, and they are not included in this cohort.

Complications developed after 18 (22.2%) procedures (Table 2). Urinary tract infection was the most common complication, occurring in 10 patients (12.3%), 3 of whom had a PCN due to urosepsis. All three cases of hematuria resolved spontaneously. Out of the five patients who had significant lower urinary tract symptoms (LUTS), three were treated conservatively with analgesics and anticholinergic medications, and the other two patients failed medical treatment and requested removal of the stents. Out of the 31 patients who had a prior PCN insertion, 30 (96.7%) were satisfied with the TUS and did not request to go back to PCN.

Table 2.

Post-Tandem Ureteral Stent Drainage Complications

Complication	Frequency, n (%)
Hematuria	3 (3.7)
LUTS	5 (6.1)
UTI	10 (12.3)

LUTS = lower urinary tract symptoms; UTI = urinary tract infections.

Hydronephrosis improved after 72 (69.9%) procedures and did not change in 27 (26.2%) procedures. Hydronephrosis worsened in a single renal unit (0.9%). Three (2.9%) procedures did not have sufficient imaging data to assess change in hydronephrosis. No significant encrustation was observed in follow-up cystoscopy.

Factors that predicted TUS failure are detailed in Table 3. The median follow-up time was 32 (IQR 24–67) weeks. Twenty-one (25.9%) patients died during the study period, and the median time to death was 9 (IQR 3–15) months. Drainage with TUS failed in 22 patients (27.1%) and a PCN tube was inserted. The median time to failure was 4 (IQR 2–8) months. Two of the patients with TUS failure who had a nephrostomy tube before TUS insertion, had a single stent before having a nephrostomy tube. Independent predictors for shorter time to TUS failure were metastasis (HR 3.03, 95% confidence interval [CI] 1.27, 7.23, p = 0.013) and prior PCN (HR 3.38, 95% CI 1.40, 8.13, p = 0.007).

Table 3.

Predictors of Tandem Stent Drainage Failure

Predictor	Success	Failure	Univariate analysis			Multivariate analysis
Predictor	Success	Failure	HR	95% CI	p	HR	95% CI	p
Patient characteristics
Age, years, median (range)	60 (27–85)	60.5 (33–83)	0.99	0.97, 1.02	0.956
Primary tumor site, n (%)
Genitourinary	4 (6.8)	4 (18.3)	Ref.	Ref.	0.995
Breast	7 (11.9)	3 (13.6)	0.73	0.14, 3.64	0.705
Gastrointestinal	15 (25.4)	5 (22.7)	NA	NA	0.966
Gynecologic	28 (47.4)	7 (31.8)	1.14	0.23, 5.57	0.865
Other	5 (8.5)	3 (13.6)	1.01	0.24, 4.06	0.993
Metastasis, n (%)	24 (50.7)	13 (59.1)	2.71	1.14, 6.44	0.024	3.03	1.26, 7.23	0.013
eGFR before drainage, median ± SD, IQR	56.1 ± 25.4	52.2 ± 27.9	0.99	0.97, 1.01	0.310
Elevation in eGFR after insertion of tandem stents, mean ± SD	19.6 ± 35.4	10.9 ± 23.3	1.01	0.99, 1.02	0.193
Previous treatments
Nephrostomy tube, n (%)	9 (15.3)	12 (54.5)	3.03	1.27, 7.26	0.013	3.38	1.40, 8.13	0.007
Surgery, n (%)	45 (76.3)	13 (59.1)	0.57	0.23, 1.36	0.205
Radiation, n (%)	29 (49.2)	15 (68.2)	1.16	0.46, 2.90	0.744
Chemotherapy, n (%)	45 (76.3)	16 (72.7)	1.49	0.57, 3.91	0.400
Stricture characteristics
Obstruction site, n (%)
Proximal ureter	8 (13.6)	7 (31.8)	Ref.	Ref.	0.686
Mid-ureter	15 (25.4)	3 (13.7)	1.45	0.55, 3.75	0.446
Distal ureter	36 (61.0)	12 (54.5)	0.87	0.24, 3.12	0.837
Length of stricture, cm, median (IQR)	4.0 (3.0–6.0)	3.5 (2.0–6.0)	1.13	0.98, 1.30	0.071

Bold indicates statistical significance (p < 0.05).

CI = confidence interval; HR = hazard ratio; SD = standard deviation.

Discussion

Our study demonstrates several important issues about TUS. First, they are safe, with complications having occurred in 18 patients (22.2%), and only 5 of them requiring insertion of a PCN tube. Second, they are effective in relieving the malignant obstruction, with a success rate of 72.9% over a median follow-up time of 33 weeks. Third, they are well tolerated, with only five patients (6.1%) having reported significant LUTS, of whom three were managed medically and only two patients requested removal of the stents. To the best of our knowledge, this is the largest study to date to have examined the safety, efficacy, and functional outcome of TUS drainage for MUO.

MUO is a urological sign of advanced malignant processes and carries with it a grim prognosis. These patients are usually morbid, with frequent hospitalizations and a significant reduction of their QOL. As such, all efforts should focus on relieving the ureteral obstruction and to avoid complications of renal failure, while maintaining the highest possible QOL.⁴

Minimally invasive management options include PCN, metallic stent, and TUS insertion, of which PCN is least favored by urologists and oncologists because of its external nature and reduced QOL measures.⁶ Metallic stents rely on stronger materials and a coil design to better withstand the external compressive forces present in MUO. TUS provide an additional lumen and allow for extra-luminal flow between the stents.²

The use of TUS was introduced two decades ago, and only small retrospective series have been published on its efficacy in treating MUO.^8,10

–14 The largest series to date, by Elsamra and colleagues,¹² included 34 patients who underwent 132 TUS insertions for MUO. The patients had their TUS renewed every 3 months regardless of whether or not there had been TUS failure. The median follow-up in that study was 17.4 months, and no complications were reported. Eighteen (53%) patients died or were transferred to a hospice during the study period, and 14 (41%) patients experienced TUS failure. The median survival was longer for patients without a history of TUS failure compared with those with a failure history (433 days vs 66 days, p = 0.007).¹²

More recently, Varnavas et al.¹⁴ described their experience with TUS insertion for MUO involving 15 patients who underwent 22 TUS insertions. TUS failure occurred in 3 (20%) patients, all within 3 months of insertion. The median overall survival was shorter among patients who experienced TUS failure compared with those without failure (45.6 days vs 162.5 days, p < 0.05). Eleven (50%) patients died during the study period.¹⁴ The most common indication for TUS insertion was acute kidney injury (65.4%), followed by patient preference of TUS over PCN (25.9%).

In this study, the most common complication after TUS insertion was urinary tract infection in 10 patients (12.3%), which can be attributed to the presence of a foreign body in the urine collecting system. Three of those patients were diagnosed with urosepsis and each had a PCN inserted (these cases were labeled TUS failures). We suggest that the use of prolonged prophylactic antibiotics may lower the infection rate and increase the time to infection. Three patients had hematuria and were managed expectantly, and five patients had significant LUTS (three of them were managed medically and the other two requested removal of the stents and underwent a PCN insertion). Since radiation can also affect bladder function and cause retention we routinely check postvoid residual and have our nursing staff instruct patients on behavioral modification when necessary.

We also demonstrated the efficacy of TUS in controlling renal failure, as evidenced by a higher eGFR rate and decreased hydronephrosis after drainage. TUS failure rates in our cohort (27%) are similar to those in earlier reports.¹² Renal failure in the presence of TUS was most commonly asymptomatic (82%), with only a minority of patients presenting with flank pain (18%). These patients usually suffer from chronic pain and are treated with high doses of analgesics. The latter can explain the paucity of symptoms from stent failure, along with the chronic nature of the obstruction.

In case of renal failure in the presence of TUS, it may be difficult to determine whether it is a true stent failure attributable to advancing disease and severe external compression (which can only be managed with PCN insertion), or a mere obstruction of the stents with blood clots or debris (which can be managed by replacing the stents).

Our results underscore the dismal oncologic outcomes of these patients who mainly require optimization of their QOL. Thus, flank pain is a compelling reason for altering management. Furthermore, these patients commonly carry external devices, such as central venous lines and stoma bags, which may well cause poor QOL and affect body image. The avoidance of any additional insult to their QOL must be prioritized. This is further emphasized by improved survival due to new oncologic treatments. Only two patients in our entire cohort requested removal of the stents, one of whom had a prior PCN and requested to return to carrying one. This is indicative of the potential QOL benefit of TUS over PCN.

Replacement of the stents was carried out every 9 and 12 months, compared to every 3 months for a PCN, and pointing to a clear advantage of TUS. In addition, a PCN can incidentally be pulled out of the collecting system due to its external nature, whereupon urgent reinsertion would be required. Although TUS replacement requires anesthesia and a visit to the operating room, patients can usually be discharged a few hours after undergoing the procedure.

Multivariate Cox regression analysis revealed two clinical factors that independently predicted TUS failure—metastasis and a prior PCN (Table 3). Metastasis is a direct measure of advanced disease. The fact that a prior PCN was associated with TUS failure can be due to selection bias, suggesting that these are patients with higher comorbidities or higher degrees of obstruction. Alternatively, a PCN may physiologically cause an inflammatory response and thus hamper TUS success. Nonetheless, these patients should be informed of a higher risk of failure (hazard ratio 3 for metastasis, and 3.3 for prior PCN).

Our study includes the largest cohort reported so far in the literature, but it has limitations that bear mention. First, its retrospective nature introduces selection bias. Second, we did not compare the efficacy of TUS with other methods of drainage. Third, we did not address patients with MUO who do not need drainage. Finally, we did not collect QOL quantitative measures that are important considerations in this patient population. However, since its introduction at our institution, TUS has become the preferred standard of care among both patients and physicians.

Conclusions

TUS is an efficient and safe management option for patients with MUO. It can provide relief of pain and treat renal failure without the need for an external PCN. Metastasis and prior nephrostomy are associated with TUS failure. A prospective study that includes QOL measurements is needed to better study the superior method for kidney drainage in cases of MUO.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Abbreviations Used

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