Which is the best treatment of pediatric upper urinary tract stones among extracorporeal shockwave lithotripsy, percutaneous nephrolithotomy and retrograde intrarenal surgery: a systematic review

Pediatric urolithiasis is an important global medical issue, particularly in regards to the selection of different treatments by care providers. The primary risk factors of forming stones among children include geographical conditions, climates, and diet customs. Additionally, the morbidity is opposite to the level of economic development; the morbidity is 1 to 5% in developed nations and 5 to 15% in developing nations [1]. Nevertheless, rates of pediatric urolithiasis have increased in developed countries. Extracorporeal shockwave lithotripsy (SWL) has long been considered as the first-line therapy for pediatric urolithiasis less than 20 mm [2]. There is a growing trend in the management of pediatric urolithiasis with endourologic procedures due to the technological advances and miniaturization of instruments. SWL, percutaneous nephrolithotomy (PCNL), and retrograde intrarenal surgery (RIRS) have become standard therapeutic options for adult urinary stones and can be extended to pediatric stones.

SWL is still the first choice for pediatric renal stones since it is the least-invasive approach for managing pediatric urolithiasis. The indications of SWL for pediatric urolithiasis are similar to those of adults, according to the European Association of Urology (EAU) guideline, and the stone fragments are more easily passed by pediatric patients than adult patients [3]. Similarly, the American Urological Association (AUA) guideline recommends that clinicians offer SWL or RIRS as first-line therapy for pediatric patient with a total renal stone burden under 20 mm [4]. However, the high retreatment rates and the potential biological effects on the immature kidneys and adjacent tissues may limit the range of application of SWL.

Age is not a limiting factor, since there are appropriately sized PCNL instruments for children, and this approach has even been reported in a 5-month-old infant [5, 6]. In children, PCNL is recommended to manage renal stones larger than 20 mm [3, 4], especially multiple renal stones. The most common complications are fever and bleeding with some serious cases requiring blood transfusions to prevent ischaemia. The necessary radiation exposure and its effects on pediatric renal function remain controversial [7].RIRS is considered as an ideal choice for medium and large-sized pediatric renal or ureteric stones. With their smaller diameter, excellent optical properties, relatively wider range of motion, and the multiple secure and effective lithotripsy techniques available, increasing numbers of urologists prefer to treat pediatric upper urinary tract stones using ureteroscopy [8, 9]. Nevertheless, ureteroscopy, especially flexible ureteroscopy, is quite a challenge for clinicians who lack the necessary training. In addition, the high purchase and maintenance costs of RIRS result in this technique not being available in every medical centre.

In adults, any of the above three procedures could be recommended to patients with stones smaller than 20 mm located in the renal pelvis and upper or middle calices [3]. Although the indications for treatment in pediatric urolithiasis are similar to those of adults, the unique considerations, such as a smaller anatomical structure and immature kidneys, make it vital to identify the most effective and safest procedure for children. To evaluate the efficacy and safety of SWL, PCNL, and RIRS in the management of pediatric upper urinary tract stones, we performed a systematic review, synthesizing the available high-level studies.

Pediatric urolithiasis, which has a high risk of a relapse, can currently be managed by SWL, PCNL, RIRS, and laparoscopic or open surgery. Regardless of the selection of treatment modalities, the final objective is to render the pediatric patient stone free and to reduce the recurrence risk to a minimum. The results from this systematic review illustrated that PCNL presented a significantly higher overall SFR (OR 2.69, 95% CI 1.48 to 4.91, p = 0.001), higher single-session SFR (OR 4.67, 95% CI 1.68 to 12.98, p = 0.003), and higher EQ. (OR 5.49, 95% CI 3.73 to 8.06, p < 0.00001) compared with SWL. The RCT of SWL vs PCNL conducted by Kumar A, et al. [17] proved that PCNL was more efficient for stone sizes of 10–20 mm than SWL (EQ: 86.96% vs 53.33%), and the identical conclusion was also reached by the retrospective case controlled studies. Although the pooled results demonstrated the overall SFR and single-session SFR of PCNL were both significantly higher than SWL, there was no significant difference in several studies in terms of the overall SFR (PCNL vs SWL: 96% vs 86.3%; 88% vs 88%; 89.2% vs 88%; 94.9% vs 84.6%) [15, 16, 18, 20]. Considering the lower retreatment rate and auxiliary procedure rate, these studies claimed that PCNL is a feasible and more efficient treatment for pediatric renal stones.

The pooled results revealed there was no significant difference in the SFR between PCNL and RIRS regardless of the stone size of the pediatric patients. Although Resorlu B, et al. [23] also reported that no significant difference of the SFR was found between PCNL and RIRS (94.3% vs 92.6%), if dividing patients into subgroups according to stone size, PCNL was apparently superior to RIRS (> 20 mm: 83.9% vs 50%; < 20 mm: 100% vs 87.3%). Nevertheless, the length of hospital stay was significantly shorter in RIRS pediatric patients in comparison with PCNL (PCNL vs RIRS: 3.1 ± 1.2 vs 1.7 ± 0.6, days) [23]. PCNL requires the creation and dilation of an access tract through the renal parenchyma, and this is deemed to be more invasive than RIRS or SWL. However, the application of micro-PCNL or even super-mini PCNL can reduce complication events with a very high single session SFR.

SWL is considered the most minimally invasive procedure among these 3 treatment modalities, and it is still the first-line therapy for pediatric renal stones. In our analysis, RIRS is a more effective procedure than SWL according to the higher single-session SFR (OR 2.35, 95% CI 1.21 to 4.55, p = 0.05) and higher overall SFR in pediatric patients with upper urinary tract stone size ≤20 mm, although comparative studies of SWL vs RIRS included in this review had no positive result in SFR, including from an RCT [28]. Furthermore, the biological effects of SWL may induce acute injury of the renal parenchyma and adjacent tissues due to the acute effects of SWL, such as focal hemorrhage, rupture of small veins, extravasation and pooling of blood, necrosis in vasculature, disintegration in podocytes and mesangial cells, blood within Bowman’s space and renal tubules, ischaemic changes, and infiltration by inflammatory cells [29]. Shock wave-induced transient tubular functional damage has been observed by Villanyi KK and colleagues [30]. Therefore, these authors recommended that consecutive treatments for pediatric renal stones should be spaced by at least 2 weeks. Although there is no clinical evidence about the long-term effect of SWL on pediatric kidneys [29], this effect should be kept in mind when SWL is chosen for pediatric renal stones due to the kidney still being in the growth and development stage.

In this review, higher overall complication rates and higher minor complication rates were only significantly found in the subgroup analyses of PCNL vs SWL. Although there was no significant difference in the various complication rates among the other subgroup analyses, blood transfusion was indicated exclusively in PCNL patients exclusively in our review. The highest transfusion rate, 13.64%, was reported by Saad KS, et al. [24]. Desoky EA and his colleagues [31] claimed that PCNL in the pediatric age group via the flank-free modified supine position was safe and effective in the management of renal pelvis stones of sizes 20–30 cm, and the SFR was similar to conventional PCNL in the prone position with only 1 (4.5%) blood transfusion.

Except for the results of subgroup analyses, there were no significant differences in all of the indexes of the complication rates comparing SWL with the other two treatments. This finding disagrees with the widespread recognition that SWL is the most minimally invasive procedure among these techniques. Moreover, steinstrasse formation was only observed in SWL (1.1–25%), except for 1 case of steinstrasse formation in PCNL [18] and another case in RIRS [22]. However, the fragment clearance after pediatric SWL is more efficient than in adults. D’Addessi A, et al. [28] indicated that, since the child’s ureter is shorter than an adult’s, this shorter length partially compensates for its narrower lumen, and the pediatric ureter is more elastic and distensible, promoting the passage of stone fragments. Finally, the small body volume of children reduces the loss of energy of the shockwaves in the process of release.

SWL had an undoubtedly shorter operative time than PCNL and RIRS, and it is usually performed as an outpatient treatment. All of the included studies preferred SWL over PCNL or RIRS, considering the operative time and hospital stay. However, with instrument miniaturization and other optimizations, RIRS has been increasingly performed, like SWL, as an outpatient procedure. The hospital stay of RIRS was also significantly shorter than PCNL, and this could reduce the medical cost, in spite of no significant difference being found in subgroup analyses. In addition to the relatively longer operative time and longer hospital stay, PCNL also presented a significantly longer fluoroscopy time than SWL or RIRS. Ristau BT and his colleagues [32] reported that radiation exposure was vital during treatment of pediatric stone disease, especially for defining the location of the stone when PCNL was performed. Therefore, these authors recommended that urologists should closely monitor the amount of radiation dose and limit the maximum effective dose to as low as reasonably achievable (ALARA) [33]. Specifically, ALARA principles mandated that the maximum effective dose should not exceed 50 mSv in any 1-year period, and an average dose less than 20 mSv per year over any 5-year period. In brief, the urologists should devote themselves to reducing the radiation hazard as much as possible.

Since SWL is mainly performed under ultrasonographic guidance, it becomes a more attractive option with lower radiation exposure than the other two treatments. However, SWL exhibited a significantly higher retreatment rate compared with the other two therapies, while the retreatment rate between PCNL and RIRS did not show any significant difference. Furthermore, SWL also caused a significantly higher auxiliary procedure rate than PCNL. Considering that the fragment clearance of children is more rapidly than that of adults after SWL, surgical approaches seem to be a last resort. Soygur T and his colleagues [34] suggested that expectant management was usually efficient even in patients who developed steinstrasse after SWL, except for patients with larger stones (> 20 mm), staghorn calculi or sepsis with an obstructed kidney. However, RIRS has a lower efficiency than SWL according to the EQ. In addition, every single EQ of RIRS from the included studies was less than 50% because the complete RIRS process includes one session for passive dilatation, one session for the lithotripsy and stent insertion, and one session for stent removal. Therefore, this technique requires more sessions under anaesthesia and more surgical risks.

When interpreting the results of our review, some limitations should be addressed. First, only 3 RCTs were available for final analysis, and more than half of the included studies were nonrandomized case control comparisons. Inevitably, patients and investigators cannot be double-blinded to the interventions. Allocation concealment was also not described in some RCTs. Furthermore, not all of the included articles were high-quality studies. A lack of more high-quality studies reduces the persuasiveness of our work. Second, no included study compared all three treatments head-to-head, and it was impossible to conduct a high-quality network meta-analysis since there were not enough relevant RCTs. Third, due to the nature of non-randomized studies, selection bias could be a major confounder, which might bias our conclusions. Finally, the heterogeneity among the studies was obvious for several parameters, which might be a result of the differences in pediatric inclusive criteria, physical environment, surgical skills, outcome definitions and standards, or imaging during follow-up. Even more concerning is the stone burdens were not similar among these included studies, and there was not enough data to execute a sufficient subgroup analysis.

In spite of these limitations, our study still has some merits and values. To the best of our knowledge, this is the first systematic review that has simultaneously analysed the efficacy and safety of SWL, PCNL, and RIRS simultaneously in the treatment of pediatric upper urinary tract stones. Furthermore, our work, updated with the most recent data, provides a newly reference for the selection of the ideal treatment modality in pediatric urolithiasis. However, it is noteworthy that making an optimal recommendation is unusually difficult, since the clinical option is based on the stone size, stone location, patient age, instrument caliber, previous interventions history, comorbidity, and other factors.

In summary, our review suggests that SWL performed as an outpatient procedure provides a shorter hospital stay and operative time, with a lower SFR, higher retreatment rate, higher auxiliary procedure rate, and relative lower EQ. PCNL presents a higher SFR than SWL and the highest EQ, but this is a technique accompanied by a longer fluoroscopy time and operative time than the other two modalities. RIRS offers a higher single-session SFR and lower retreatment rate than SWL but a lower EQ than SWL and PCNL, although a significantly shorter hospital stay than PCNL. Higher complication rates and higher minor complication rates were only significantly found in subgroup analyses of PCNL vs SWL. In other words, the complication rates are comparable among the three modalities, and most of these were minor complications.

The ultimate target of pediatric urinary stone management is to achieve extreme stone clearance with a safe and effective therapeutic regimen. To achieve this ideal target, urologists must choose the optimal individual modality, or combined other therapeutic regimens, according to the pediatric conditions and the goals of the parents.