This study¹ was awarded best paper in a session of the AUA 2023 Annual Meeting² and is summarized here and previously in the AUANews.³

The 73 study participants (38 treatment group, 35 control group) were already undergoing endoscopic stone treatment for a primary stone, defined as large kidney or obstructing ureteral stones. All subjects also had secondary stones, defined as small (≤6 mm) asymptomatic stones located in the contralateral kidney for a primary renal stone, or either the ipsilateral or contralateral kidney of a primary ureteral stone. We prospectively randomized these subjects to either have their primary and secondary stones treated (treatment group) or just the primary stones (control group). The primary outcome was relapse, which was measured by future emergency department (ED) visits, stone surgeries, or stone growth localized to the side with the small, asymptomatic secondary stones. After a median 4.2 years of follow-up, the treatment group had 82% lower risk of relapse (HR 0.18, 95% CI 0.07-0.44) with 16% relapses (6 of 38) in the treatment group and 63% relapses (22 of 35) in the control group (see Figure and Table). The treatment group also had 75% longer time to relapse than the control group (1,632 days [SE 73] vs 934 days [SE 122]). The removal of the small, asymptomatic renal stones in the treatment group added a median of 25.6 minutes (IQR 18.5-35.2) to surgery. There were no differences between groups in acute ED visits within 2 weeks after surgery, all of which occurred because of stent pain, and no differences in subjects reporting stone passage after surgery. Treatment of secondary stones did not affect new stone formation (37% in the treatment group vs 43% in the control group), despite aggressive efforts to pursue prevention. We concluded that among patients undergoing surgical removal of ureteral or significant kidney stones, removal of small, asymptomatic kidney stones during their surgery dramatically reduced relapse at the cost of about 25 minutes of surgery time without increasing surgery-related ED visits. Our work was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases Grant P01 DK043881 and from resources through the Veterans Affairs Puget Sound Health Care System. The ClinicalTrials.gov number was NCT02210650. The 4 sites were University of Washington (Principal investigator: J.D. Harper), VA Puget Sound Health Care System (Principal investigator: M.D. Sorensen), University of Minnesota (Principal investigator: M.S. Borofsky), and Indiana University (Principal investigator: J.E. Lingeman).

Figure. Cumulative incidence plots of relapse measured by emergency department (ED) visits, surgery, and stone growth on computed tomography (CT) exams (A), and ED visits and surgery only (B). The small circles represent subject censor events in the study.

The relapse rate of our control group (63% in 52 months) is similar to rates of relapse of untreated symptomatic stones published in the AUA guidelines (43% relapse in 32 months).⁴ Likewise, the added surgery time, 25 minutes, is similar to previous reports of additional time required (16 minutes) by removing asymptomatic kidney stones during ipsilateral ureteroscopy for a ureter stone.⁵ Also, our data add to a growing body of evidence that supports the efficacy and safety of single-setting treatment of ureteral and kidney stones, combining ureteroscopy and percutaneous nephrolithotomy, and performing bilateral modern-era endoscopic procedures.^6-8

Some limitations of our study include our study size was relatively small, and the small number of non-White participants attenuated generalization to other groups. Surgeons were unblinded as to treatment group postprocedure, but this limitation is likely counterbalanced to some degree by the shared patient care model and high rates of preventive evaluation in both study arms. Furthermore, all surgeons were fellowship-trained experts, and including a quality of life score may have been interesting.

Overall, at the time of surgery for a primary kidney or ureteral stone, additional treatment of small, asymptomatic stones that are located in a separate area is supported by our data. This dramatically reduces relapse, and is likely quite cost-effective (2.4-fold decrease) by reducing future surgeries and ED visits.^9,10 In our study, the control group experienced 36 relapse events in 35 patients, and we agree with the conclusions of Dr Streeper and Dr Hsi’s debate on the benefit of preemptive endoscopic surgery to remove small asymptomatic renal stones,^11,12 that a single relapse event per patient might well justify prophylactic surgery on all patients.

Lastly, we are privileged to consider and contemplate prophylactic removal of additional stones because of the improvements and advancements in endoscopic and other technologies to treat stones. Despite these advances, residual fragments remain after 30%-65% of procedures and were present in 18% (7 of 38) of the treatment group in the current study including all 6 relapses.^13,14 Like many others, our team continues to research improving efficacy and reducing risk of treating stones, which will further tip the scales toward earlier intervention. One particular focus is the use of noninvasive transcutaneous ultrasound to break and reposition stones and fragments to facilitate their clearance in awake patients: a median fragmentation of 90% of stone volume to <2 mm in 10 minutes was reported with burst wave lithotripsy,¹⁵ and 89% of distal ureteral stones treated with burst wave lithotripsy and ultrasonic propulsion in awake, nonanesthetized patients passed in a mean time of 3.9 days.¹⁶ A randomized controlled trial on clearing residual fragments with ultrasonic propulsion will soon be submitted. As technologies lower the barrier to treatment, especially with little or no anesthesia and a transition out of the operating room and into the clinic, we expect the barriers to prophylactic treatment will similarly decrease.