Medical Expulsive Therapy after Extracorporeal Shock Wave Lithotripsy: A Systematic Review and Network Meta-Analysis

Abstract

Purpose

Medical expulsive therapy (MET) after extracorporeal shock wave lithotripsy (ESWL) remains a subject of debate. We aimed to evaluate the comparative efficacy and safety of various pharmacological interventions using a network meta-analysis (NMA) of 21 randomized controlled trials (RCTs).

Materials and Methods

A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted through 2024 (Open Science Framework registered). We included only purely pharmacological RCTs, strictly excluding non-randomized studies and device-assisted trials. A Bayesian NMA was performed to estimate odds ratios and the surface under the cumulative ranking curve (SUCRA) for stone-free rates and complications.

Results

Twenty-one RCTs involving 3262 patients were analyzed. The tamsulosin-tadalafil combination was identified as the most effective strategy (SUCRA: 93.8%), followed by tamsulosin-corticosteroid (78.2%) and boron supplementation (67.9%). Notably, while silodosin is often superior for single intact stones, it ranked relatively low in the post-ESWL setting (SUCRA: 20.9%). All agents showed acceptable safety profiles without significant serious adverse events compared to controls.

Conclusion

The tamsulosin-tadalafil combination represents the optimal pharmacological adjunct to ESWL. Our findings suggest that effective post-ESWL MET requires a broad therapeutic approach targeting multi-segmental ureteral relaxation and inflammation to clear fragment “showers,” distinguishing it from the management of solitary ureteral stones.

Graphical Abstract

INTRODUCTION

Extracorporeal shock wave lithotripsy (ESWL) remains a cornerstone of minimally invasive management for renal and ureteral calculi, owing to its well-established efficacy and favorable safety profile.¹ However, the ultimate success of ESWL is not solely defined by the fragmentation of the stone, but rather by the subsequent spontaneous passage of these fragments through the ureter. Residual fragments that fail to pass can lead to recurrent renal colic, hematuria, and obstructive complications such as “steinstrasse,” which frequently necessitate auxiliary surgical interventions and escalate the overall healthcare burden.²

To facilitate the expulsion of fragments following ESWL, medical expulsive therapy (MET) has been extensively investigated.³ Historically, alpha-blockers—most notably tamsulosin—have been the most widely utilized agents, leveraging their ability to reduce ureteral smooth muscle tone.⁴ While numerous traditional meta-analyses have confirmed the benefits of tamsulosin in improving stone-free rates (SFR) and reducing analgesic requirements, the pharmacological landscape of MET is rapidly diversifying.⁵ Newer therapeutic options, including highly selective alpha-blockers (e.g., silodosin), phosphodiesterase type 5 inhibitors (PDE5is; e.g., tadalafil), beta-3 agonists (e.g., mirabegron), and even mineral or herbal supplements (e.g., Boron, Phyllanthus niruri), have emerged as potential adjunctive treatments.

Despite the proliferation of randomized controlled trials (RCTs) investigating these agents, the majority of existing literature focuses on head-to-head comparisons between a specific drug and a control group. This has created a clinical challenge for urologists: there is a lack of direct evidence to determine which specific pharmacological class or combination therapy offers the superior clinical outcome in the post-ESWL setting. Furthermore, the safety profiles of these diverse agents—ranging from ejaculatory dysfunction associated with silodosin to headaches or back pain linked with PDE5is—must be meticulously balanced against their expulsive efficacy to optimize patient-centered care.⁶,⁷

Consequently, we conducted a comprehensive systematic review and network meta-analysis (NMA) to compare and rank the efficacy of all currently available MET agents in improving SFR after ESWL. In addition to efficacy, we performed a detailed systematic evaluation of the safety profiles and complication rates associated with each therapy. Our study aims to provide a robust, evidence-based hierarchy of MET options to guide clinical decision-making and enhance treatment outcomes following shock wave lithotripsy.

MATERIALS AND METHODS

Study protocol and eligibility criteria

This systematic review and NMA was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for network meta-analyses and the Participants, Interventions, Comparators, Outcomes, and Study Design (PICOS) framework.⁸,⁹,¹⁰ The study protocol was prospectively registered in the Open Science Framework (OSF; https://doi.org/10.17605/OSF.IO/52MZS). Eligibility was strictly limited to RCTs investigating pharmacological interventions as MET following ESWL.

The inclusion criteria were established as follows: 1) adult patients (≥18 years) diagnosed with renal or ureteral calculi who underwent ESWL; 2) studies comparing various MET agents—including alpha-blockers (e.g., tamsulosin, silodosin, alfuzosin), PDE5is (e.g., tadalafil), beta-3 agonists (e.g., mirabegron), or supplements (e.g., boron, Phyllanthus niruri)—with placebo, active controls, or standard care; and 3) reporting of clinical outcomes such as SFR, pain or colic episodes, and adverse events (AEs). To ensure the highest level of evidence and the validity of the network, we included only RCTs published as full-text peer-reviewed articles. Observational studies, non-randomized prospective or retrospective studies, case reports, review articles, editorials, scientific congress abstracts, and studies without available full text were strictly excluded.

Ethical review and approval were waived for this study because it is a systematic review and meta-analysis of previously published studies and does not involve direct contact with human subjects or the use of identifiable private information, in accordance with the Bioethics and Safety Act of the Republic of Korea.

Information sources and search strategy

A comprehensive literature search was performed across major electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL), from their inception until January 2025. The search strategy was designed to identify all relevant RCTs investigating MET following ESWL. The detailed search strings and keywords used for each database are provided in Supplementary Table 1 (only online). No language restrictions were applied to minimize publication bias. In addition, the reference lists of retrieved articles and previous systematic reviews were manually screened to identify any further eligible studies.

Two independent reviewers (Y.J.M. and J.Y.J.) screened the titles and abstracts of the identified records. Full-text articles of potentially relevant studies were then independently assessed for eligibility based on the predefined inclusion and exclusion criteria. Any discrepancies during the screening and selection process were resolved through discussion or by consulting a third senior reviewer (J.Y.L.). The detailed process of study selection is depicted in the PRISMA flow diagram (Fig. 1).

Fig. 1. PRISMA flow diagram regarding the selection of eligible studies. The flow diagram depicts the systematic literature search and selection process. A total of 15435 initial records were identified, and after rigorous screening, 21 RCTs were included in the final network meta-analysis. ^*including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL); ^**Duplicate records removed. RCT, randomized controlled trial; ESWL, extracorporeal shock wave lithotripsy.

Quality assessment and certainty of evidence

The methodological quality of the included RCTs was independently assessed by two reviewers using the Revised Cochrane Risk-of-Bias tool for randomized trials (RoB 2.0; Cochrane Methods Bias Group, Bristol, England, United Kingdom).¹¹ Risk of bias was evaluated across five domains: 1) bias arising from the randomization process; 2) bias due to deviations from intended interventions; 3) bias due to missing outcome data; 4) bias in the measurement of the outcome; and 5) bias in the selection of the reported result. Based on the signaling questions, each domain was categorized as having “low risk of bias,” “some concerns,” or “high risk of bias.” The overall risk of bias for each study was determined by the highest risk identified in any single domain. Any disagreements in the assessment were resolved through consensus or consultation with a third reviewer.

The certainty of evidence for the NMA results was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for NMAs.¹² The evidence for each pairwise comparison and the overall ranking was assessed based on four key components: study limitations (risk of bias), indirectness, inconsistency, and imprecision. The certainty of evidence was categorized into four levels: high, moderate, low, or very low. Publication bias was assessed using comparison-adjusted funnel plots if more than 10 studies were available for a specific comparison.

Statistical analysis

NMA was performed to integrate both direct and indirect evidence for SFR across various MET agents. All statistical analyses were conducted using R version 4.5.2 (R Foundation for Statistical Computing, Vienna, Austria), primarily utilizing the “multinma” and “netmeta” packages, and the “robvis” package was employed to generate risk-of-bias plots. We employed both frequentist and Bayesian frameworks to ensure the robustness of the results, using a random-effects model to account for potential heterogeneity between studies.

The primary outcome, SFR, was expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CIs) or credible intervals (CrIs). To determine the relative hierarchy of the interventions, we calculated the Surface Under the Cumulative Ranking curve (SUCRA) values; a higher SUCRA value indicates a higher probability of the treatment being the most effective.

Statistical heterogeneity across the included studies was assessed using the I² statistic, with I² > 50% indicating significant heterogeneity. Consistency between direct and indirect evidence was evaluated using the node-splitting method and the design-by-treatment interaction model. A p-value<0.05 was considered statistically significant for all tests. Publication bias was evaluated using comparison-adjusted funnel plots to detect potential small-study effects.

RESULTS

Study selection

The initial database search identified a total of 15435 potentially relevant records. After removing duplicates, 13432 records were screened based on titles and abstracts. Of these, 187 articles underwent full-text assessment for eligibility. Following a rigorous evaluation against the predefined inclusion and exclusion criteria, 21 RCTs were finally included in this NMA.¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³,²⁴,²⁵,²⁶,²⁷,²⁸,²⁹,³⁰,³¹,³²,³³ During the full-text review, specific attention was paid to study design and intervention type. Notably, the study by Micali, et al.³⁴ was excluded as it was identified as a non-randomized prospective study, and the study by Xu, et al.³⁵ was excluded because it utilized a physical vibratory device (EPVL) rather than a purely pharmacological intervention. Other reasons for exclusion included insufficient reporting of outcome data and publication solely as meeting abstracts.

Study characteristics and quality assessment

A total of 3262 patients were enrolled across the 21 included RCTs, with publication dates ranging from 2002 to 2023. The studies were conducted across diverse geographical regions, including Italy, India, Egypt, Taiwan, Korea, Brazil, Bulgaria, Mexico, and Iran. The MET agents evaluated in this NMA encompassed tamsulosin, silodosin, alfuzosin, nifedipine, terazosin, tadalafil, and boron supplements. The majority of studies focused on ureteral stones, while several specifically addressed fragment clearance following ESWL for renal calculi (Table 1).

Table 1. Characteristics of the Included Studies.

Study	Year	Country	Study design	Intervention	Control
Porpiglia, et al.13	2002	Italy	RCT	Nifedipine, deflazacort	Control/usual care
Gravina, et al.14	2005	Italy	RCT	Tamsulosin, standard medical therapy	Standard medical therapy alone
Bhagat, et al.15	2007	India	DB-PC-RCT	Tamsulosin	Placebo
Naja, et al.16	2008	India	OL-RCT	Tamsulosin	Usual care
Agarwal, et al.17	2009	India	OL-RCT	Tamsulosin during SWL course	Usual care
Wang, et al.18	2009	Taiwan	RCT (3-arm)	Tamsulosin; terazosin	Placebo
Hussein19	2010	Egypt	RCT	Tamsulosin, NSAID PRN	NSAID PRN alone
Georgiev, et al.20	2011	Bulgaria	OL-RCT	Standard care+tamsulosin OCAS	Standard care alone
Singh, et al.21	2011	India	RCT	Tamsulosin	Usual care (Hydration/NSAID)
Vicentini, et al.22	2011	Brazil	DB-PC-RCT (3-arm)	Tamsulosin; nifedipine retard	Placebo
Elkoushy23	2012	Egypt	PC-RCT	Tamsulosin	Placebo
Cho, et al.24	2013	Korea	SB-RCT	Alfuzosin, NSAID PRN	NSAID PRN alone
Mohamed25	2013	Egypt	RCT	Tamsulosin	Placebo
Ahmed, et al.26	2016	Egypt	RCT	Tamsulosin, analgesia	Analgesia alone
De Nunzio, et al.27	2016	Italy	RCT (3-arm)	Tamsulosin; silodosin	Placebo
Jain, et al.28	2020	India	RCT (3-arm)	Tamsulosin; tamsulosin+deflazacort	Control/Analgesics-only
Neeli29	2021	India	OL-RCT	Tamsulosin, tadalafil	Active control: Tamsulosin
Hashem, et al.30	2022	Egypt	PC-RCT	Tamsulosin	Placebo
Maldonado-Valadez, et al.31	2022	Mexico	RCT	Tamsulosin, diclofenac PRN	Diclofenac PRN alone
Jalali, et al.32	2023	Iran	RCT	Boron supplement	Tamsulosin
Sadanala, et al.33	2023	India	TB-RCT	Tadalafil	Tamsulosin

RCT, randomized controlled trial; DB-PC, double-blind placebo-controlled; OL, open-label; SB, single-blind; TB, triple-blind; PC, prospective controlled; MET, medical expulsive therapy; SWL, shock wave lithotripsy; NSAID, non-steroidal anti-inflammatory drug; PRN, pro re nata (as needed); OCAS, oral controlled absorption system.

Control/usual care: typically includes hydration and analgesics on demand.

Methodological quality assessment using the RoB 2.0 tool revealed that most studies were categorized as having “some concerns” or being at “high risk” of bias, often due to insufficient detail regarding allocation concealment or blinding of participants and personnel. However, the studies by Bhagat, et al.¹⁵ and Hussein,¹⁹ which were initially scrutinized for potential attrition bias, were re-evaluated as having a “low risk of bias” in the “missing outcome data” domain (Domain 3) after confirming exceptionally low dropout rates of 3.3% and 0%, respectively. This rigor in data reporting supports the reliability of the primary outcomes. The overall distribution of the risk of bias for the 21 included trials is summarized in Supplementary Figs. 1 and 2 (only online).

NMA of stone-free rate

Network geometry

After excluding one non-randomized trial and one device-based study, the final network for SFR comprised 21 RCTs evaluating 11 distinct pharmacological strategies (Supplementary Fig. 3, only online). The network remained well-connected, with “No MET” serving as the central reference node. Tamsulosin monotherapy continued to be the most frequently investigated intervention, acting as the primary hub for indirect comparisons.

Relative efficacy (relative to no MET)

The Bayesian random-effects NMA demonstrated that specific combination therapies and supplements significantly improved the odds of achieving a stone-free state compared to the control group (Supplementary Fig. 4, only online). The tamsulosin+tadalafil combination emerged as the most potent therapy, with a posterior mean OR of 7.85 (95% CrI: 2.39 to 26.84).

Among other interventions, tamsulosin+steroid (OR 4.14, 95% CrI: 1.38 to 13.74) and boron supplements (OR 3.00, 95% CrI: 1.19 to 7.69) showed robust efficacy, demonstrating statistically significant superiority over No MET. Nifedipine+steroid also showed a favorable profile (OR 1.14, 95% CrI: 0.00 to 2.29), with its lower CrI just touching the line of no effect. Tamsulosin monotherapy maintained a consistent clinical benefit (OR 0.78, 95% CrI: 0.51 to 1.06). Conversely, silodosin, alfuzosin, and terazosin did not reach statistical significance in improving SFR compared to No MET in this specific post-ESWL setting.

Treatment ranking and SUCRA analysis

Ranking probabilities and SUCRA curves confirmed the hierarchy of treatment efficacy (Fig. 2 and Supplementary Fig. 5, only online). Tamsulosin+tadalafil was unequivocally identified as the optimal strategy, with the highest probability of being the best treatment (P_rank1=0.64) and the lowest mean rank of 1.62.

Fig. 2. Rankogram of MET agents. The bar chart illustrates the probability of each treatment achieving a specific rank (1st to 11th) among all evaluated interventions. The tamsulosin-tadalafil combination shows the highest probability of being ranked first (Rank 1). MET, medical expulsive therapy.

Tamsulosin+steroid followed as the second most effective option (mean rank 3.18), while boron (mean rank 4.21) and nifedipine+steroid (mean rank 4.21) shared the third tier of efficacy. Tamsulosin monotherapy was positioned in the middle of the ranking (mean rank 5.67). The control group (No MET) and silodosin were consistently ranked among the least effective strategies, with mean ranks of 9.45 and 8.93, respectively.

Heterogeneity and model Fit

The model showed excellent convergence with potential scale reduction factors (R̂) of 1.00 for all parameters. The estimated between-study heterogeneity was low to moderate (τ=0.27, 95% CrI: 0.01 to 0.71), indicating that the pooled estimates were reliable across the included RCTs.

Consistency and heterogeneity

Assessment of inconsistency

To validate the transitivity assumption of the network, we evaluated local inconsistency using the node-splitting method. This analysis separates direct evidence from indirect evidence to detect any significant discrepancies (Supplementary Fig. 6, only online). As detailed in the node-splitting analysis, there was no evidence of statistically significant inconsistency between direct and indirect estimates for any of the comparisons (p>0.05). Specifically, the comparisons for nifedipine vs. No MET (p=0.637), silodosin vs. No MET (p=0.349), and terazosin vs. No MET (p=0.472) showed high concordance between data sources. Although the comparison for tamsulosin+steroid vs. No MET showed a trend toward discrepancy (p=0.060), it did not reach statistical significance. Consequently, the consistency assumption was accepted for the entire network, justifying the combination of direct and indirect evidence.

Heterogeneity

Global heterogeneity across the included studies was assessed within the Bayesian framework. The estimated standard deviation of random effects (τ) was 0.27 (95% CrI: 0.01 to 0.71), indicating a low to moderate level of heterogeneity. This suggests that while there is some variability in effect sizes across studies—likely due to differences in stone size or patient demographics—it is not substantial enough to compromise the validity of the pooled estimates.

Certainty of evidence

The certainty of evidence for the primary outcome (SFR) ranged from low to moderate across the network comparisons. The evidence supporting the top-ranked intervention, tamsulosin plus tadalafil, was graded as moderate, primarily downgraded due to the risk of bias inherent in the included trials. Similarly, tamsulosin monotherapy and tamsulosin-corticosteroid combinations demonstrated moderate certainty. Conversely, the evidence for boron supplementation and silodosin was rated as low, owing to study limitations and imprecision derived from wide CrIs. A detailed summary of findings is provided in Supplementary Table 2 (only online).

Safety and complications

As summarized in Supplementary Table 3 (only online), the majority of reported AEs were mild (Clavien-Dindo grade I), transient, and resolved without intervention. The safety profiles varied distinctly by pharmacological class. Tamsulosin was primarily associated with vascular symptoms such as dizziness and orthostatic hypotension. In contrast, silodosin was frequently linked to ejaculatory dysfunction, specifically retrograde ejaculation, while tadalafil (monotherapy or combination) showed a unique propensity for backache and facial flushing.

Notably, boron supplements demonstrated a superior safety profile with significantly fewer AEs compared to standard alpha-blocker therapy.³² Beyond drug-specific side effects, the use of MET appeared to be protective against stone-related complications; the incidence of renal colic and “steinstrasse” was notably higher in the control (No MET) groups, suggesting that accelerating fragment expulsion mitigates obstructive risks.

Publication bias

The potential for publication bias and small-study effects was assessed using a comparison-adjusted funnel plot (Supplementary Fig. 7, only online). Visual inspection of the plot revealed a generally symmetrical distribution of the included studies around the summary effect line, suggesting the absence of substantial bias. This observation was statistically corroborated by Egger’s regression test, which indicated no significant asymmetry (p=0.539). Consequently, the findings of this NMA are considered robust and unlikely to be compromised by selective reporting or publication bias.

DISCUSSION

This NMA provides a comprehensive and updated synthesis of the efficacy and safety of various MET as an adjunct to ESWL.³ Our analysis of 21 RCTs suggests that the combination of tamsulosin and tadalafil has the highest probability of being the most effective pharmacological strategy for increasing SFR within this network, followed by tamsulosin-corticosteroid combination therapy²⁸,²⁹ and boron supplementation.³² However, it is important to note that these probability-based SUCRA rankings reflect relative statistical performance and should not be interpreted as absolute guarantees of clinical superiority for every patient.

A key strength of this study lies in the robustness of its dataset and the methodological rigor in handling multi-arm trials.³⁶ A previous meta-analysis by Brain, et al.⁵ included 21 RCTs in their qualitative synthesis; however, their quantitative analysis was limited to a pair-wise meta-analysis of only 17 studies, as they failed to appropriately integrate multi-arm trials without data loss or fragmentation. In contrast, our study utilized advanced Bayesian NMA modeling to fully incorporate all 21 RCTs, preserving the integrity of the network and ensuring that all randomized comparisons contributed to the final treatment hierarchy.³⁶ Furthermore, we maintained a high level of homogeneity by strictly excluding non-randomized designs, such as Micali, et al.,³⁴ and physical device-based interventions like the vibratory EPVL used in Xu, et al.,³⁵ thereby providing the most reliable evidence-based ranking for purely pharmacological MET to date.

The clinical performance of silodosin in this post-ESWL context warrants particular attention, especially when compared to its established role in spontaneous stone passage. According to a recent meta-analysis by Jung, et al.,³⁷ silodosin significantly outperformed tamsulosin for the treatment of ureteral stones (RR 1.10), boasting higher SFR and shorter expulsion times due to its superior selectivity for α1A-adrenoreceptors in the distal ureter.

However, our NMA revealed that in the post-ESWL setting, silodosin did not achieve the same level of dominance in the probabilistic rankings. As astutely pointed out by the reviewers, it is crucial to note that direct evidence comparing silodosin to a control group (No MET) in this network is limited to a single trial,²⁷ making definitive conclusions regarding its inferiority to tamsulosin challenging. This discrepancy in the network hierarchy might theoretically be explained by the physiological differences between the passage of a single intact stone and the “shower” of multiple small fragments and grit generated by ESWL. While the highly distal-selective blockade of silodosin is ideal for an isolated stone, we hypothesize that the broader α_1A/1D blockade of tamsulosin may offer a more stable therapeutic advantage for the clearance of post-lithotripsy debris.³⁸

This hypothesis is further supported by the high ranking of the tamsulosin-tadalafil combination. The synergistic effect of α1A/1D antagonism and PDE5 inhibition facilitates profound ureteral relaxation throughout the entire ureteral lumen, which is essential for the unimpeded passage of fragments across various segments.³⁹ Additionally, the superior performance of boron supplementation and corticosteroid combinations suggests that managing the post-ESWL inflammatory response is as critical as muscle relaxation. Boron likely reduces inflammatory cytokines and oxidative stress induced by the mechanical trauma of shock waves,⁴⁰ while steroids suppress sub-urothelial edema, thereby preventing the formation of “steinstrasse.”¹³

Beyond efficacy, the structured evaluation of safety outcomes is paramount for clinical decision-making. As summarized in our findings, while MET agents generally present mild and transient AEs, their distinct side-effect profiles must guide individualized therapy. For instance, the vascular side effects (e.g., dizziness, orthostatic hypotension) predominantly associated with broad alpha-blockers like tamsulosin contrast sharply with the high rates of ejaculatory dysfunction (retrograde ejaculation) linked to silodosin. Furthermore, the addition of PDE5 inhibitors introduced systemic effects such as backache and facial flushing, though these did not precipitate severe AEs leading to high dropout rates. Notably, boron supplementation demonstrated a particularly favorable safety profile with minimal side effects. Therefore, the optimal choice of post-ESWL MET requires a careful balancing of these distinct safety profiles against expected expulsive benefits.

Despite these insights, several limitations should be noted. Most notably, the timing of the SFR assessment varied widely across the included trials, ranging from 2 weeks to 3 months post-ESWL. We emphasize this substantial heterogeneity as a key limitation, as it carries a significant risk of distorting the estimated effect sizes; studies with longer follow-up periods naturally allow more time for spontaneous passage, which could confound the true pharmacological efficacy of the interventions. Crucially, the inherent clinical heterogeneity across the included trials must also be emphasized. Variations in baseline patient characteristics, stone burden, and specific ESWL protocols (e.g., energy settings, frequency) across the 21 RCTs inevitably introduce variability in treatment responses. Furthermore, the lack of uniform reporting on stone composition may have influenced the observed outcomes. While silodosin remains a potent option, its high rate of retrograde ejaculation compared to tamsulosin must be carefully weighed against its clinical benefits in individual patients.³⁷ Nevertheless, by rectifying the methodological shortcomings of previous analyses and integrating a refined dataset of 21 pure RCTs, this study establishes a new evidence-based framework for optimizing medical therapy after shock wave lithotripsy.

In conclusion, this NMA of 21 purely pharmacological RCTs identifies the combination of tamsulosin and tadalafil as the strategy that appears to be the most effective for enhancing SFRs after ESWL, though clinical heterogeneity must be factored into individual treatment decisions. Our findings demonstrate that while silodosin is highly effective for single intact stones, a broader therapeutic approach—addressing both multi-segmental relaxation and inflammatory response—is superior for clearing the debris generated by lithotripsy. These results provide a robust, evidence-based framework for clinicians to optimize MET and improve patient outcomes following shock wave lithotripsy.

SUPPLEMENTARY MATERIALS

Supplementary Fig. 1

Risk of bias summary for the included randomized controlled trials. Review of authors' judgments about each risk of bias item for each included study, assessed using the Cochrane Risk-of-Bias 2.0 tool. Studies are identified by their corresponding citation number in the reference list. Green (+), yellow (!), and red (-) symbols indicate low risk, some concerns, and high risk of bias, respectively.

Supplementary Fig. 2

Summary of risk of bias assessments. Weighted summary plot illustrating the proportion of studies with "low risk," "some concerns," and "high risk" of bias across each domain of the Cochrane RoB 2.0 tool.

Supplementary Fig. 3

Network geometry of comparisons for stone-free rate (SFR). Each node represents a treatment strategy, and the size of the node is proportional to the number of patients assigned to that intervention. The thickness of the connecting lines corresponds to the number of direct comparisons (studies) between the interventions. Tamsulosin and "No MET" (control) serve as the central hubs of the network.

Supplementary Fig. 4

Forest plot of relative treatment effects for stone-free rate (SFR) compared to No MET. The plot displays the posterior mean log odds ratios (logOR) with 95% credible intervals (CrIs) for each intervention relative to the control group (No MET). Estimates located to the right of the vertical line (logOR > 0) indicate a higher likelihood of achieving a stone-free state.

Supplementary Fig. 5

Surface Under the Cumulative Ranking curve (SUCRA). The plot represents the cumulative ranking probability for each treatment. A larger area under the curve (higher SUCRA value) indicates a higher overall efficacy. Tamsulosin combined with tadalafil demonstrates the highest SUCRA value, followed by tamsulosin-corticosteroid combination and boron supplementation.

Supplementary Fig. 6

Assessment of network inconsistency using the node-splitting method. Comparison between direct and indirect evidence for each split node. p-values > 0.05 indicate no significant inconsistency between direct and indirect estimates, supporting the validity of the network model.

Supplementary Fig. 7

Comparison-adjusted funnel plot for publication bias. The scatter plot evaluates small-study effects and potential publication bias. The symmetrical distribution of studies around the regression line, along with a non-significant Egger's test (p = 0.539), suggests the absence of substantial publication bias in the network.

Supplementary Table 1

Detailed Search Strategy for Electronic Databases

Supplementary Table 2

GRADE Summary of Findings for Stone-Free Rate (SFR)

Supplementary Table 3

Summary of complications and adverse events in included studies