Evaluating the clinical outcomes of thulium fiber laser (TFL) in comparison to holmium laser in the treatment of urinary tract stones – A systematic review

Introduction

The use of laser (light amplification by stimulated emission of radiation) energy in the field of urology had undergone tremendous progress over the years, this is especially true in the utilization of lasers in the fragmentation of urinary tract stones.^1,2 The first documentation of utilizing laser in the treatment of urinary tract stones dated back to 1968 by Mulvaney et al. in an in-vitro study, while the first published in-vivo study of laser lithotripsy was in 1986 by Watson et al.^3,4

Several types of lasers have been applied in urological procedures, such as pulsed dye laser, FREDDY (frequency-doubled double-pulse neodymium-doped yttrium aluminium garnet (Nd: YAG)), alexandrite laser, holmium laser, and many others.² Nevertheless, holmium: yttrium aluminum garnet (Ho: YAG) laser has proven itself to be superior compared to its rivals because of its ability to fragment all types of stones efficiently with acceptable safety profiles. Within the last two decades, Ho: YAG laser has become the gold standard in urinary tract stones fragmentation procedure until the recent appearance of a new competitor, thulium fiber laser (TFL).^5–9 Fried et al. conducted the first in-vitro trial of using TFL in fragmenting urinary tract stone and found TFL’s capabilities in disintegrating both soft and hard stones.¹⁰ Recent preclinical and clinical studies shows TFL holds more advantages over the Ho:YAG laser, in terms of better ablation efficiency and efficacy, lower retropulsion effect, and more durable laser fiber.^11–13

In this study, we aim to review the clinical outcomes (operating time, stone-free rate, retropulsion, and complication rate) of TFL in comparison to the current gold standard (Ho:YAG laser) in the treatment of urinary tract stones.

Methods

The report of this systematic review was prepared following the guidelines provided by the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement.^32,33 In July 2022, we conducted a systematic search of the PubMed (RRID:SCR_004846) and ScienceDirect databases. The search strategy involved the use of Boolean operators to combine the keywords and refine the search results. Table 1 presents the specific keywords that were utilized in each database during the search process. We limited the search to studies published between July 2018 to July 2022 and applied specific inclusion and exclusion criteria. Included studies were required to be written entirely in English, use Ho:YAG and TFL laser energy in urinary tract stone cases, and provide readily available full-text articles comparing clinical outcomes between TFL and holmium laser. We excluded studies discussing the use of laser energy for other conditions besides urinary tract stones and publications on the use of lasers besides TFL and Ho:YAG. In cases where articles were duplicated, we counted them as one instead of multiple entries. To ensure the validity of the search results, we manually performed the search using these criteria, and two co-authors conducted the data collection without utilizing any automated tools. The risk of bias in the selected studies was evaluated using the ROB-2 (Risk of Bias 2) (RRID:SCR_016393) tool for randomized controlled trials and the ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) tool for cohort studies.^14,15 The data collected from the studies included population characteristics (age, gender), stone characteristic (stone size, stone burden, stone density), type of lithotripsy procedures, number of patients, laser settings, operating time, lasing time, stone free rate, incidence of retropulsion, and complication rate. The collected data were then input into a spreadsheet using Microsoft Excel (Microsoft, 2021) (RRID:SCR_016137) and direct comparison of the clinical outcomes were formulated into separate charts.

Results

The search strategy produced a total of 106 manuscripts after omitting duplicated articles from both databases. After evaluating the title and abstract of the articles, a total of 89 studies were eliminated from further consideration. The full articles of the remaining 17 studies were then reviewed, and out of those, 13 studies were excluded as they were found to be an ex vivo study and in-vitro studies. Eventually, this review included four studies that met the inclusion criteria, involving a total of 544 procedures.³¹ The studies included in this review underwent a risk of bias assessment using the appropriate tools. However, the other two trials were graded as having some concern due to the randomization process. As for the retrospective cohort study conducted by Jaeger et al., it was deemed to have a moderate risk of bias. This assessment was based on the potential presence of confounding factors that could impact the outcomes of the study. The summary of risk of bias assessment are provided in Figure 1.

Figure 1. Risk of bias summary.

Data extraction and analysis were conducted based on these selected studies. The selected studies were conducted in four different countries: India, Norway, Russia, and the USA. The population characteristics are summarized in Table 2, while the outcomes of the studies (operating time, lasing time, stone free rate (SFR), retropulsion, and complication rate) for both TFL and Ho:YAG are summarized in Table 3.

Despite the differences in procedures (URS, RIRS, and PCNL), laser settings (different frequency, different laser energy, and different laser fiber), and population (adult and pediatric cases), all four studies demonstrated that the operating time of TFL group was shorter compared to Ho:YAG group (24,7-78 minutes vs 32,4-84 minutes, respectively). Three studies by Martov et al., Ulvik et al., and Mahajan et al. found these differences to be statistically significant. The comparison of the operating time in both laser group is shown in Figure 2.

Figure 2. Operating time comparison between Holmium:Yttrium-Aluminum-Garnet (HO:YAG) and thulium fiber laser (TFL).

^pp value < 0.005 between the two groups.

In Figure 3, it is evident that patients in the TFL group had a higher stone free rate (SFR) compared to the holmium group. This finding was consistent across all four studies included in this review. Ulvik et al. and Jaeger et al. both demonstrated a statistically significant higher SFR for the TFL group (p-value <0.005). Interestingly, the location of the stone played a significant role in determining the SFR. As mentioned by Jaeger et al., higher SFR was observed in cases of ureteral stones, while the lowest SFR was observed in cases where stones were located in the lower pole of the kidney.

Figure 3. SFR comparison between Holmium:Yttrium-Aluminum-Garnet (HO:YAG) and thulium fiber laser (TFL).

^pp value < 0.005 between the two groups.

Only one of the four articles, led by Martov et al., reported on the incidence of retropulsion between the two laser types. They classify the retropulsion into three categories such as no retropulsion, mild retropulsion (if no additional devices were needed or the stone migration occurred within the ureter) and severe retropulsion (if either antimigration device or flexible ureteroscope was used due to the migration into calices). Martov et al. found the absence of retropulsion in nearly all cases of the TFL group and no severe retropulsion were observed in this group, on the other hand, no retropulsion was seen in 31% (27 out of 87) of the patients and severe retropulsion were observed in 18% (16 out of 87) patients in the Ho:YAG group (Figure 4).

Figure 4. Retropulsion comparison between Holmium:Yttrium-Aluminum-Garnet (HO:YAG) and thulium fiber laser (TFL).

The reported complications across these four studies were varied. Jaeger et al. found no intraoperative complication during procedures for both the Ho:Yag and TFL group, while Martov et al. reported several intraoperative complications, such as ureteral perforation, fragment migration, and bleeding during the management of ureteral stones. Nevertheless, there was no statistically significant difference in the rate of intraoperative complications in both laser treatment groups. On the contrary, Ulvik et al. reported a significantly higher rate of intra-operative complication (such as bleeding that impairs vision, perforation, and mucosal abrasion) in Ho:YAG group compared to TFL Group (16 out of 60 patients (27%) vs 5 out of 60 patients (8%) respectively, p<0.05). In another study attempting to evaluate the safety and effectiveness of TFL in mini PCNL procedures, Mahajan et al. reported higher rate of prolonged hematuria in TFL group compared to Ho:YAG group (13 out of 59 cases (22%) vs 2 out of 66 cases(3%) respectively, p<0.05). All four studies included in the analysis utilized the Clavien-Dindo classification systems to assess postoperative complication, and all four studies reported similar postoperative complications in both groups.

Discussion

As a novel lithotripsy technology, TFL has emerged as an attractive alternative to Ho:YAG laser due to its unique architecture, which leads to a higher stone ablation rate and lower retropulsion, as demonstrated in in-vitro studies.^11,16 Supporting these findings, clinical studies have also shown that TFL outperforms Ho:YAG in terms of operating time, retropulsion, and SFR during lithotripsy.^17–20

In this systematic review, three out of the four trials showed that the TFL group had a significant shorter operation time than the Ho:YAG group. This could be attributed to TFL’s ability to operate at a much higher frequency of up to 2000Hz.²¹ Pre-clinical and clinical studies have found that higher frequency regimen was associated with greater ablation efficacy and ablation speed.^21–24 However, It is important to note that using high-frequency and high-energy settings may lead to the disturbance of the endoscopic view due to an increase in dust and microbleeding.^9,25,26 Despite this, both Ulvik O et al. and Martov et al. found that the incidence of bleeding that compromised intraoperative vision was considerably less in TFL group when compared to Ho:YAG, resulting in fewer pauses during the operation and ultimately shorter operating time.^19,20 Additionally, TFL operates at a wavelength of 1940 nm which closely matches the absorption coefficient peak of liquid water. This attribute results in a higher water absorption coefficient compared to Ho:YAG laser, with the TFL absorption coefficient being four times higher (3 mm^-1 vs 14 mm^-1, respectively).^10,21 This property leads to better ablation efficacy as it lowers the ablation threshold of urinary stones, resulting in a more efficient and effective ablation process. In fact, the TFL can achieve a higher ablation rate using the same laser settings or achieve the same stone ablation result using lower energy settings.^21,25

Retropulsion is defined as undesirable stone movement during laser lithotripsy.¹¹ Martov et al. demonstrated that TFL had lower incidence of retropulsion, which is attributed to smaller bubbles produced during lithotripsy, therefore generating less pressure that pushed the stones away.²¹ Another factor that contributed to the lower retropulsion rate is TFL’s capabilities to be operated in a much lower pulse energy than the minimum of 0.2 J required for Ho:YAG.^16,25

In this review, SFR depends on the location of the stones. Higher SFR is observed in ureteral stones, while stones located in lower pole have the lowest SFR. Ulvik et al. and Jaeger et al. reported a significantly higher SFR in the TFL group compared to the Ho:YAG group, attributed to the TFL’s superior ablation efficacy and better endoscopic view.^18,19 Higher SFR rate would be beneficial for both patients and surgeons since it reduces the needs for subsequent procedure. Furthermore, shorter operation time also leads to lower cost for both the patients and health care institution, as stated by Ryan JR et al.²⁷

Considering the safety profile of TFL, Ulvik et al. reported a lower rate of intraoperative complications such as bleeding that impairs vision, perforation, and mucosal abrasion in the TFL group, which is attributed to TFL’s higher absorption coefficient leading to lower penetration depth and thus increasing the safety profile of TFL.^19,21,25 On the other hand, Mahajan et al. found a higher rate of prolonged hematuria in TFL group during Mini PCNL procedures, however, it was self-limiting and therefore could be treated conservatively. According to Mahajan et al., the hematuria is likely caused by thermal stress injuries to the mucosa, which occur due to reduced irrigation and visibility resulting from the presence of stone fragments.¹⁷ Hardy et al. mentioned the possibility of higher intraurethral temperature using TFL during lithotripsy. The higher temperature produced by TFL may be due to higher water absorption coefficient and the use of high frequency.²⁸ However, this claim has been contradicted by several studies that indicate a relatively similar increase in temperature in both Ho:YAG and TFL.¹¹ Furthermore, in the study led by Æsøy et al. it is indicated that using larger laser fiber generate higher intrarenal temperature in porcine model, which gives TFL an advantage since it uses a smaller laser fiber.²⁹ Nevertheless, mitigating thermal induced damage should always be the surgeon’s priority by maintaining irrigation fluid, intermittent laser activation, using cooled irrigation fluid, or avoid using high power setting to minimize thermal injury.³⁰ Æsøy et al. advised that laser with high power settings (≥20 Watt) should be used with caution to prevent thermal injury since the activation of high power settings easily surpass the temperature threshold (42°C) that cause cellular damage, meanwhile the activation of laser with settings 2,4 W (0,4 J and 6 Hz) and 8 W (0,8 J and 10 Hz) were able to maintain the intrapelvic temperature within the safety limit.²⁹ Additionally, Hardy et al also recommended to avoid using frequency higher than 500 Hz in order to minimize thermal damage.²⁸

The limitations of this review include heterogeneity in procedures and laser settings, a limited number of included studies, and the lack of registration and protocols. Firstly, the heterogeneity in procedures and laser settings among the selected studies introduces variability and may affect the comparability of the results. The use of different procedures such as URS, RIRS, and PCNL, as well as variations in laser settings including frequency, energy, and fiber used, can influence the outcomes and make it challenging to draw definitive conclusions.

Secondly, the relatively small number of included studies (only four studies) may limit the generalizability of the findings and reduce the overall strength of evidence. With a limited number of studies, there is a higher possibility of chance effects, and the findings may not fully represent the entire population or provide robust evidence.

Thirdly, we acknowledge the review was conducted without prior registration in a public database and without predetermined protocols. The absence of registration and protocols may introduce potential biases and affect the transparency and reproducibility of the review. Without predefined protocols, there is a risk of selective reporting and data analysis, which can influence the validity of the findings. Future research should aim to address these limitations by registering studies and following established protocols to ensure transparency and minimize bias.

Conclusion

In conclusion, TFL has demonstrated efficient fragmentation of urinary tract stones with shorter operation time and higher SFR compared to Ho:YAG laser while still maintaining patient safety. However, the limited availability of clinical studies on TFL and lack of consensus on optimal laser settings for lithotripsy indicate a need for further research in this area. Additional randomized clinical trials comparing the two laser systems could provide valuable insights for future treatment options.