Medical Policy Title: Periureteral Bulking ARBenefits Approval: 10/26/201

Size: px

Start display at page:

Download "Medical Policy Title: Periureteral Bulking ARBenefits Approval: 10/26/201"

Rosaline Stewart
5 years ago
Views:

1 Medical Policy Title: Periureteral Bulking ARBenefits Approval: 10/26/201 Agents as a Treatment of Vesicoureteral Reflux (VUR) Effective Date: 01/01/2012 Document: ARB0278 Revision Date: Code(s): Cystourethroscopy (including ureteral catheterization); with subureteric injection of implant material L8603 Injectable bulking agent, collagen implant, urinary tract, 2.5 ml syringe, includes shipping and necessary supplies L8604 Injectable bulking agent, dextranomer/hyaluronic acid copolymer implant, urinary tract, 1 ml, includes shipping and necessary supplies L8606 Injectable bulking agent, synthetic implant, urinary tract, 1 ml syringe, includes shipping and necessary supplies Public Statement: Administered by: Severe vesicoureteral reflux may damage the kidney through mechanical or immunological mechanisms, and increases the risk of pyelonephritis and kidney scarring. Traditional treatment for high grade reflux has been open surgery. An option is the use of bulking agents at the vesicoureteral junction to minimize reflux. Use of these agents is covered as an alternative to surgery. Medical Policy Statement: Periureteral bulking agents as a treatment of vesicoureteral reflux grades II IV when surgical intervention is otherwise indicated is considered medically necessary and is covered. Background: Page 1 of 7

2 In most cases, VUR is diagnosed during evaluation of UTI. About one third of children with UTIs are found to have VUR. The average age for the onset of UTI is 2 3 years, corresponding to the age when toilet training occurs. There also appears to be a genetic predisposition to VUR, and siblings may also be examined. The gold standard for diagnosis is voiding cystourography, a procedure that involves catheterization of the bladder. The severity of reflux is described by a grade, typically with the International Reflux Study Group grading system, which grades severity from I (reflux partway up the ureter) to V (massive reflux of urine up the ureter with marked tortuosity and dilation of the ureter and calyces). Determination of VUR grade is not exact, however, due to factors such as bladder pressure, which may vary at the time of measurement. In general, more severe reflux is associated with higher rates of renal injury. Spontaneous resolution and treatment success also varies with reflux grade. Treatment strategies include bladder training, antibiotic prophylaxis, and surgical modification of the ureters to correct the underlying reflux. VUR is likely to resolve spontaneously over a period of 1 5 years; lower grades of reflux (i.e., grades I and II) are associated with a higher probability of spontaneous resolution. The decision to administer prophylactic antibiotic treatment depends both on the probability of spontaneous resolution and the level of parental concern for potential adverse effects of long-term antibiotic treatment, which can include allergic reactions and development of treatment-resistant bacteria resulting in breakthrough UTIs. Open surgical treatment is typically reserved for patients with high-grade reflux (grades III and IV) or as salvage therapy for those who are noncompliant with antibiotic therapy or have breakthrough UTIs while receiving prophylactic therapy. Surgical management involves lengthening the intramural ureter by modification of the ureterovesical attachment with reimplantation of the ureters. Success rates for open surgery are reported to be above 98% for reflux grades III and IV; and about 80% for reflux grade V. In addition to surgery-associated morbidity, obstruction and reoperation rates have been reported to be as high as 9%. The use of bulking agents in the treatment of VUR has been reported for over 20 years and has been suggested as an alternative to either antibiotic or surgical therapy. Bulking agents can be injected into tissue around the ureteral orifices to minimize reflux. The STING procedure (subureteral trans-urethral injection) involves the endoscopic injection of a bulking agent into the submucosal bladder wall just below the ureteral opening. In the more recently used modified STING procedure, the needle is placed in the ureteral tunnel and the bulking agent is injected into the submucosal intraureteral space. When successfully injected the compound tracks along the length of the detrusor tunnel and establishes a coapted ureteral tunnel. This endoscopic procedure can be performed in an outpatient setting. A variety of bulking agents have been tested for biocompatibility and absence of migration. Some of the compounds used in clinical studies are collagen (Contigen, Zyderm, Zyplast), polytetrafluoroethylene paste (Teflon), polydimethylsiloxane (Macroplastique ), calcium hydroxyapatite (Coaptite ), and dextranomer/hyaluronic Page 2 of 7

3 acid copolymer (Deflux or Dx/HA). In 2001, Deflux received pre-market approval from the U.S. Food and Drug Administration (FDA) for the treatment of children with vesicoureteral reflux (VUR) grades II-IV. Contraindications include patients with nonfunctioning kidney(s), duplicated ureters, active voiding dysfunction, and ongoing urinary tract infection. Note: Polytetrafluoroethylene may migrate, causing serious adverse events; this agent is not FDA-approved. Coaptite, Macroplastique, and Tegress are categorized by the FDA as Agent, Bulking, Injectable for Gastro-Urology Use. These are currently indicated for the treatment of stress urinary incontinence. A 2004 Cochrane review focused on treatment of primary VUR. This review analyzed the published randomized studies of surgery (including open surgery or endoscopic use of bulking agents), antibiotic prophylaxis of any duration, and non-invasive techniques, such as bladder training. Outcome measures included final health outcomes, such as incidence of UTI, renal parenchymal abnormalities, development of hypertension, or renal function impairment. Correction of VUR and obstruction following VUR correction were also evaluated. Eleven randomized controlled trials were identified, 2 of which involved Deflux. (These 2 trials are reviewed in greater detail below.) Overall, the authors concluded that no significant differences in the risk for UTI or renal parenchymal injury were found in a meta-analysis of 7 trials with 847 evaluable patients combining antibiotic prophylaxis with combined surgery and antibiotics. This finding challenges the assumptions underlying the treatment of VUR, since one would expect a reduction in UTI if the hypothesis is correct that VUR is a modifiable risk factor for UTI and renal parenchymal damage. No differences between treatment groups were demonstrated for the endpoints of hypertension and chronic renal failure, but the trials were not powered to detect these endpoints and follow-up time was too short. Furthermore, data from available randomized trials did not provide evidence as to whether the current practice of diagnosing and treating children with VUR confers important health benefits, since no adequately powered trials have included a no treatment arm. The only positive finding from the meta-analysis was a reduction in the incidence of febrile UTI in children surgically treated; however, the clinical significance of this finding is uncertain. For example, if one assumes a relatively high baseline 20% risk of a UTI, about 9 children would need to be treated with combined reimplantation surgery and antibiotics compared with antibiotics alone to prevent 1 febrile UTI during the ensuing 5 years. A 2009 comparison of 2 cohorts of children treated at a single institution compared success rates with Deflux and mini-ureteroneocystostomy (mini-unc), a modified extravesical ureteroneocystostomy performed through a 2 cm. groin incision (Ashley, 2008). A total of 99 children were treated with one of these procedures, 57 had a mini- UNC and 42 had Deflux injections. The groups were similar at baseline, except that children in the mini-unc group had higher-grade VUR (all grades were included, most children had grade II or III disease), and 5 had a solitary kidney. About 80% of each cohort returned for the 3-month follow-up and received a voiding cystourethrogram (VCUG) examination. All 47 of the patients in the mini-unc group, and 26 of the 33 in the Deflux group (78%) demonstrated surgical cure; 4 children in the mini-unc group Page 3 of 7

4 later experienced complications that required urological intervention or rehospitalization. The authors concluded that mini-unc has a better success rate than Deflux injection, with a low complication given the higher-grade VUR of the patients in this group. Due to lack of randomization and differences in VUR grade, outcomes cannot be directly compared. A number of case series of bulking agents have been published and they generally report higher rates of successful elimination of reflux with low-grade reflux and lower in those with high-grade reflux (Lavelle, 2005) (Capozza, 2004). One of the larger case series was by a European group and reported on 692 children (1,101 ureters) treated with the STING procedure (Puri, 2006). Ninety-six percent of the 1,101 ureters treated (mostly grade III or IV) had completely resolved (grade 0) and the rest had downgraded to grade I after 1 (86%), 2 (12%), or 3 (2%) injections. Patients with neurogenic bladder, bladder diverticulum, ureterocele, and urethral valves were excluded from analysis. Among the studies reporting longer term success rates, most but not all have had high rates of treatment success. Another study by the European research group assessed outcomes in 209 ureters (about 125 consecutively treated infants) (Dawrant, 2006). One injection of Dx/HA was reported to adequately resolve VUR (complete resolution to grade 0 or improvement to grade I II) in 80% of ureters, and the remaining 20% required multiple injections. There were no recurrences of symptomatic bacteriuria during the study period (median follow-up of 7 years; ranging from 6 months to 20 years). Other studies have shown stability of implant size by ultrasound for up to 3 years 10 months, with over 96% of patients remaining free of VUR as measured by voiding cystourography for 2 5 years after treatment (Puri, 2006) (Lackgren, 2001). On the other hand, a retrospective series published in 2009 reported a 73% (246/337 ureters in 219 patients) success rate at post-operative voiding cystourecystourethregram (Lee, 2009). A total of 150 ureters were reevaluated at 1 year with another VCUG. Seventyfour percent (111 of 150 ureters) had long-term success. Including the initial treatment failures, the overall one-year success rate was 46.1% (111 of 241 ureters). Data were missing at 1 year on 74 patients (96 ureters). If all 96 had lasting success at 1 year, the overall success rate would be 61.4% (207 of 337 ureters). As discussed above, VUR may resolve spontaneously without intervention; therefore, the absence of a comparator group limits interpretation of these case series. According to case series data, there are low morbidity rates associated with injection of periureteral bulking agents. Temporary postoperative ureteral obstruction may occur in less than 0.7% of patients following injection of bulking agents; this can be treated with ureteral stenting until the problem resolves (Vandersteen, 2006). In comparison, an average 2% (range of 0% to 9%) ureteral obstruction and reoperation rate has been reported following ureteral reimplantation (Elder, 1997). References: Page 4 of 7

5 Arant BS.(1992) Medical management of mild and moderate vesicoureteral reflux: follow up studies of infants and young children. A preliminary report of the Southwest Pediatic Nephrology Study Group. J Urol, 1992; 148(5 pt 2): Ashley R, Vandersteen D.(2008) Outcome analysis of mini-ureteroneocystostomy versus dextranomer/hyaluronic acid copolymer injection for unilateral vesicoureteral reflux. J Urol 2008; 180(4 suppl): Capozza N, Caione P.(2002) Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis. J Pediatr, 2002; 140: Capozza N, Lais A, et al.(2004) The role of endoscopic treatment of vesicoureteral reflux. J Urol, 2004; 172 (4 pt 2): Cerwinka WH, Scherz HC, Kirsch AJ.(2007) Endoscopic treatment of vesicoureteral reflux associated with paraureteral diverticula in children. J Urol 2007; 178(4 pt 1): Cooper CS.(2009) Diagnosis and management of vesicoureteral reflux in children. Nat Rev Urol 2009; 6(9): Dawrant MJ, Mohanan N, Puri P.(2006) Endoscopic treatment for high grade vesicoureteral reflux in infants. J Urol 2006; 176(4 pt 2): Elder JS, Diaz M, Caldamone AA, et al.(2006) Endoscopic therapy for vesicoureteral reflux: a meta-analysis. I. Reflux resolution and urinary tract infection. J Urol 2006; 175(2): Elder JS, Peters CA, et al.(1997) Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol, 1997; 157: Garin EH, Orta-Sibu N, Campos A.(2002) Primary vesicoureteral reflux in childhood. Adv Pediatr, 2002; 49: Hayn MH, Smaldone MC, Ost MC et al.(2008) Minimally invasive treatment of vesicoureteral reflux. Urol Clin North Am 2008; 35(3): Hodson EM, Wheeler DM, Vimalchandra D et al.(2007) Interventions for primary vesicoureteric reflux. Cochrane Database Syst Rev 2007; (3):CD Jodal U, Smellie JM, et al.(2006) Ten-year results of randomized treatment of children with severe vesicoureteral reflux. Final report of the International Reflux Study in Children. Pediatr Nephrol, 2006; 21: Page 5 of 7

6 Keating MA.(2005) Role of periureteral injections in children with vesicoureteral reflux. Curr Opin Urol, 2005; 15: Lackgren G, Wahlin N, Skoldenberg E, et al.(2001) Long-term follow-up of children treated with dextranomer/hyaluronic acid copolymer for vesicoureteral reflux. J Urol 2001; 166(5): Lavelle MT, Conlin MJ, Skoog SJ.(2005) Subureteral injection of Deflux for correction of reflux: analysis of factors predicting success. Urol, 2005; 65: Lee EK, Gatti JM, DeMarco RT et al.(2009) Long-term followup of dextranomer/hyaluronic acid injection for vesicoureteral reflux: late failure warrants continued followup. J Urol 2009; 181(4): McMillan ZM, Austin JC, Knudson MJ et al.(2006) Bladder volume at onset of reflux on initial cystogram predicts spontaneous resolution. J Urol 2006; 176(4 pt 2): Menezes MN, Puri P.(2007) The role of endoscopic treatment in the management of grade V primary vesicoureteral reflux. Eur Urol 2007; 52(5): Mevorach RA, Hulbert WC, Rabinowitz R, et al.(2006) Results of a 2-year multicenter trial of endoscopic treatment of vesicoureteral reflux with synthetic calcium hydroxyapatite. J Urol 2006; 175(1): Oswald J, Riccabona M, et al.(2002) Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children. Urol, 2002; 60: Puri P, Pirker M, Mohanan N et al.(2006) Subureteral dextranomer/hyaluronic acid injection as first line treatment in the management of high grade vesicoureteral reflux. J Urol 2006; 176(4 pt 2): Smellie JM, Poulton A, Prescod NP.(1994) Retrospective study of children with renal scarring associated with reflux and urinary retention. Br Med J, 1994; 308: Tamminen-Mobus T, Brunier E, et al.(1992) Cessation of vesicoureteral reflux for 5 years in infants and children allocated to medical treatment. The International Reflux Study in Children. J Urol, 1992; 148(5 pt 2): Vandersteen DR, Routh JC, Kirsch AJ, et al.(2006) Postoperative ureteral obstruction after subureteral injection of dextranomer/hyaluronic acid copolymer. J Urol 2006; 176(4 pt 1): Wheeler DM, Vimalachandra D, et al.(2004) Interventions for primary vesicoureteric reflux. The Cochrane Database Syst Rev, 2004;3:CD Page 6 of 7

7 Application to Products This policy applies to ARBenefits. Consult ARBenefits Summary Plan Description (SPD) for additional information. Last modified by: Date: Page 7 of 7

Periureteral Bulking Agents as a Treatment of Vesicoureteral Reflux. Original Policy Date

MP 7.01.82 Periureteral Bulking Agents as a Treatment of Vesicoureteral Reflux Medical Policy Section Surgery Issue 12/2013 Original Policy Date 12/2013 Last Review Status/Date Reviewed with literature