Complete primary repair versus modern staged repair for bladder exstrophy-epispadias complex: a systematic review and meta-analysis

Introduction

Bladder exstrophy-epispadias complex (BEEC) is a rare congenital malformation of the genitourinary system, occurring in approximately 1 in 30,000 to 50,000 live births, with a male-to-female ratio of about 2.3:1 [1][2]. Classic bladder exstrophy is the most common and clinically relevant form and is characterized by an exposed bladder plate, pubic diastasis, and epispadias. Without surgical reconstruction, patients may develop continuous urinary incontinence, recurrent infection, progressive renal injury, and psychosocial impairment [3].

Two reconstructive strategies dominate contemporary management. Modern staged repair of exstrophy (MSRE), as developed from the Jeffs approach, begins with neonatal bladder and abdominal wall closure, followed by epispadias repair at approximately 6 to 12 months and bladder neck reconstruction at about 4 to 6 years when bladder capacity is adequate [4]. Complete primary repair of exstrophy (CPRE), introduced by Mitchell and Bagli, combines bladder closure, epispadias repair, and partial bladder-neck reconstruction during one neonatal operation [5][6].

The optimal approach remains uncertain. Comparative studies are mostly retrospective, single-center, and limited by small samples, heterogeneous continence definitions, and variable follow-up. Reported continence after CPRE ranges from 23% to 80%, while multi-institutional data suggest that few patients achieve continence with spontaneous voiding after one CPRE procedure [7]. MSRE outcomes also vary by institutional experience [8]. Whether the potential reduction in planned operations with CPRE offsets greater risks of closure failure, urinary tract infection, and reoperation remains unclear [9].

Objective. This systematic review and meta-analysis evaluated whether CPRE, compared with MSRE, is associated with differences in continence and functional outcomes, surgical complications and reoperations, and renal or urologic outcomes in patients with classic bladder exstrophy or BEEC [10].

Materials and methods

Protocol and registration. This systematic review and meta-analysis was conducted according to PRISMA 2020 guidance [11][12]. The protocol was registered prospectively in PROSPERO (registration number: CRD420261292831).

Eligibility criteria. Eligible studies compared CPRE, including technical variants, with MSRE in patients with classic bladder exstrophy or BEEC. Outcomes of interest included continence and functional endpoints, surgical complications and reoperations, and renal or urologic complications. Randomized and nonrandomized comparative cohort studies were eligible regardless of date, language, or sample size. Non-comparative studies, isolated epispadias, cloacal exstrophy, case reports, editorials, narrative reviews, expert opinion, and non-human or cadaveric studies were excluded.

Search strategy and selection of studies. PubMed/MEDLINE, Scopus, Europe PMC, and Epistemonikos were searched from inception to April 1, 2026. MeSH terms and keywords for BEEC were combined with terms for complete primary repair and staged reconstruction; equivalent strategies were adapted for each database. Reference lists of included studies and relevant reviews were hand-searched, and trial registries were screened for completed unpublished comparative studies. The full search strategy is provided in Additional file 1.

Data extraction. Two investigators independently extracted study characteristics, patient demographics, surgical techniques, use of osteotomy, follow-up duration, and functional, surgical, and renal outcomes using a standardized form. Extracted data were checked by another independent investigator.

Risk of bias assessment. Risk of bias was assessed with the Newcastle-Ottawa Scale (NOS) for nonrandomized studies [13]. The scale evaluates selection, comparability, and outcome ascertainment. Studies were classified according to Agency for Healthcare Research and Quality standards as good, fair, or poor quality.

Outcome measures. Functional outcomes included overall continence, spontaneous voiding without clean intermittent catheterization (CIC), dry interval greater than 2 to 3 hours, and subsequent bladder neck reconstruction. Surgical outcomes included bladder dehiscence, urethrocutaneous fistula, urethral stricture, redo bladder closure, and overall reoperation. Renal and urologic outcomes included febrile urinary tract infection (UTI), vesicoureteral reflux (VUR), new or worsening hydronephrosis, and renal impairment or scarring.

Data synthesis and statistical analysis. Analyses were conducted in R software v3.13 (The R Foundation for Statistical Computing, Vienna, Austria). Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis with restricted maximum likelihood estimation. Heterogeneity was assessed with the I² statistic, interpreted as 0 – 25% low, 26 – 50% moderate, 51 – 75% substantial, and > 75% considerable. Leave-one-out sensitivity analyses were performed for outcomes with substantial heterogeneity or disproportionate study weighting. Funnel plots and Egger's regression were exploratory [14]. Statistical significance was set at p < 0.05.

Results

Study selection. The search identified 1,113 records. After 487 duplicates were removed, 626 records were screened and 616 were excluded. Nine reports were sought for full text, 1 could not be retrieved, and 8 studies were assessed for eligibility and included in the final meta-analysis (Fig. 1) [4][9][15 – 20].

Study characteristics. The 8 included studies were published from 2005 to 2026 and comprised 878 patients with BEEC (315 CPRE, 563 MSRE) (Table 1). Seven studies were retrospective and 1 was prospective. Studies were conducted in North America, Europe, and Asia. Age at initial surgery ranged from neonatal repair to a median of 17 months, and follow-up ranged from about 1 year to 18 years where reported. Techniques included Mitchell, Mitchell-Bagli, delayed primary, and single-stage Erlangen CPRE variants compared with staged closure, epispadias repair, and later bladder neck reconstruction. Osteotomy use varied widely across centers.

Risk of bias in included studies. Seven studies were classified as good quality and 1 as poor quality (Table 2). Selection and outcome domains were generally strong, with mean scores of 3.75 / 4 and 2.88 / 3, respectively. Comparability was the most frequent limitation: 3 studies used multivariable adjustment for key confounders [4][9][20], whereas others lacked formal adjustment. The study by A.A. Khawaja et al. (2012) was rated poor because of a comparability score of 0, reflecting gender imbalance without adjustment [19].

Meta-analysis results. Functional and continence outcomes. Overall continence did not differ significantly between CPRE and MSRE (RR 0.98, 95% CI 0.52 to 1.84, p = 0.95) (Fig. 2), with moderate heterogeneity (I² = 51.4%). Spontaneous voiding without CIC (RR 0.94, 95% CI 0.55 to 1.62, p = 0.82), dry interval > 2 to 3 hours (RR 0.91, 95% CI 0.76 to 1.10, p = 0.35), and subsequent bladder neck reconstruction (RR 0.77, 95% CI 0.53 to 1.10, p = 0.15) were also comparable.

Surgical complications and reoperations. Bladder dehiscence did not differ significantly between approaches (RR 0.50, 95% CI 0.14 to 1.76, p = 0.28). No significant differences were found for urethrocutaneous fistula (RR 1.22, 95% CI 0.65 to 2.30, p = 0.54) or urethral stricture (RR 2.40, 95% CI 0.34 to 16.89, p = 0.38). CPRE was associated with higher redo bladder closure (RR 1.99, 95% CI 1.54 to 2.58, p < 0.0001) (Fig. 3) and overall reoperation (RR 1.64, 95% CI 1.15 to 2.34, p = 0.006; Fig. 4).

Renal and urologic complications. CPRE was associated with a higher incidence of febrile UTI (RR 1.61, 95% CI 1.21 to 2.14, p = 0.001; Fig. 5). VUR (RR 0.99, 95% CI 0.80 to 1.22, p = 0.90), new or worsening hydronephrosis (RR 1.22, 95% CI 0.36 to 4.16, p = 0.75), and renal function or scarring outcomes (RR 1.25, 95% CI 0.30 to 5.26, p = 0.76) were not significantly different between groups.

Sensitivity analyses. Leave-one-out analyses showed that overall continence remained non-significant regardless of which study was omitted, although heterogeneity varied. The higher redo-closure risk with CPRE depended on the B.M. Inouye et al. (2018) cohort; after excluding this study, the pooled estimate became non-significant (RR 0.98, 95% CI 0.29 to 3.28, p = 0.97). Hydronephrosis remained non-significant across all iterations, with persistent between-study variability [9].

Publication bias. Egger's regression was exploratory because few studies contributed to most outcomes. No statistically significant funnel-plot asymmetry was detected for outcomes with at least 3 contributing studies, including overall continence, redo bladder closure, overall reoperation, febrile UTI, VUR, and hydronephrosis. Outcomes with only 2 studies could not be assessed; therefore, publication bias cannot be excluded.

Discussion

This meta-analysis of 8 comparative studies involving 878 children found no significant differences between CPRE and MSRE for continence, spontaneous voiding, dry interval, or subsequent bladder neck reconstruction. CPRE was associated with higher redo bladder closure, overall reoperation, and febrile UTI, whereas upper urinary tract outcomes were not significantly different. These findings reflect the central trade-off between the techniques: CPRE may reduce planned stages but may increase early infectious and closure-related morbidity, while MSRE distributes operative risk across planned stages.

The continence findings are consistent with previous literature. Continence rates after CPRE vary widely, and secondary interventions remain common even after successful initial closure [10]. Multi-Institutional Bladder Exstrophy Consortium data indicate that only 16.7% of patients achieved spontaneous voiding continence after single CPRE, with 40% achieving dry intervals greater than 1 hour at intermediate follow-up [7]. Institutional selection and referral patterns may partly explain differences observed in the cohorts reported by B.M. Inouye et al. (2018), A.K. Ebert et al. (2020), and K.J. Rathod et al. (2026) [9][18][20].

The higher febrile UTI risk with CPRE was the most consistent adverse association. Concomitant bladder neck reconstruction may produce early outlet resistance in a system where VUR is common after exstrophy closure [21][22]. This combination may promote ascending infection. In contrast, MSRE delays bladder neck reconstruction, maintaining a lower-pressure system during early childhood. Recent collaborative data suggest that concomitant bilateral ureteric reimplantation during CPRE may reduce postoperative VUR and pyelonephritis, but this strategy requires further evaluation [22].

Despite the UTI signal, pooled renal outcomes did not show significant differences. This should be interpreted cautiously because renal surveillance differed across studies, including ultrasound, serum creatinine, annual diethylenetriamine pentaacetic acid scanning, and dimercaptosuccinic acid radionuclide imaging. Such heterogeneity may underestimate subtle renal impairment. Longer standardized follow-up is needed before concluding that upper tract risk is equivalent between approaches.

Mechanical closure failure also requires caution. The redo-closure result was strongly influenced by the B.M. Inouye et al. (2018) referral-center cohort; removing that study eliminated statistical significance [9]. Referral centers may receive a disproportionate number of closure failures from outside institutions, inflating risk estimates. Nevertheless, the potential mechanical stress of one-stage reconstruction remains clinically plausible and should be considered alongside center experience and patient anatomy.

Variation in osteotomy use further complicates comparison. Rates ranged from 0% to 100% among included studies, reflecting institutional practice rather than standardized criteria. Osteotomy may facilitate tension-free closure and reduce dehiscence risk, especially when closure is delayed beyond 72 hours [23][24]. However, the model by K.J. Rathod et al. (2026) suggested no significant effect on continence after adjustment [20]. M.E. Chua et al. (2019) also emphasized that aggressive pubic approximation during CPRE can contribute to pelvic compartment syndrome and penile ischemia [17].

Several limitations should be acknowledged. Outcome-specific sample sizes were often small, ranging from 34 to 659 patients, and confidence intervals were wide for rare events. All included studies were observational and vulnerable to selection bias, reporting bias, and confounding by anatomy, surgeon preference, surgical era, center volume, immobilization, and osteotomy use. Definitions of continence also varied, limiting direct comparison. Formal tests did not detect publication bias, but the small number of studies per outcome substantially limits confidence in those tests.

In practice, neither approach can be recommended universally. CPRE may be appropriate in expert centers seeking to reduce scheduled stages and promote early bladder cycling, but the risks of closure failure and febrile UTI must be weighed carefully. MSRE may offer more reliable initial closure at the cost of planned staged operations. Prospective multicenter registries with standardized definitions, long-term follow-up, quality-of-life outcomes, cost-effectiveness data, and reproductive outcomes are needed.

Conclusion

This meta-analysis found no significant differences between CPRE and MSRE in continence, spontaneous voiding, dry interval, or subsequent bladder neck reconstruction. CPRE was associated with higher redo bladder closure, overall reoperation, and febrile UTI, while upper urinary tract outcomes were not significantly different. Because the evidence is observational and several analyses are underpowered, treatment should be individualized according to anatomy, family priorities, institutional expertise, and surgeon experience.

Keypoints

1. Continence and spontaneous voiding outcomes were not significantly different between complete primary and staged repair.
2. Complete primary repair was associated with higher redo bladder closure, overall reoperation, and febrile urinary tract infection.
3. Upper urinary tract outcomes were comparable, but renal assessment methods were heterogeneous.
4. Prospective multicenter data with standardized continence and renal definitions are needed.