The Role for Active Monitoring in Urinary Stones: A Systematic Review

Abstract

Background and Purpose:

All urinary stones may not need prompt active treatment. The aim of our study was to identify urinary stones that can be actively monitored safely.

Materials and Methods:

We performed a systematic review of the natural history and the role of active monitoring for urinary stones.

Results:

Thirty-seven studies have selected. Of symptomatic ureteral calculi <4 mm, 38% to 71% will pass spontaneously while only 4.8% of stones <2 mm will need intervention during surveillance. Follow-up with history, physical examination, urinalysis, and plain radiography every 2 weeks for 1 month is necessary. If spontaneous passage does not occur within this period, intervention is recommended. When shockwave lithotripsy for caliceal stones is prospectively compared with observation, there is no difference in stone-free rates (28% vs 17%), need for additional treatment (15% vs 21%), or visits to a general practitioner (18.5% vs 20.8%). Patients under observation may need more invasive procedures and may be more commonly left with residual stone fragments >5 mm (58% vs 30%). Isolated, nonuric acid calculi <4 mm may be most amenable to active monitoring. Physical examination, urinalysis, and CT scan performed on an annual basis up to year 2 or 3, followed by intervention, are recommended. Lower pole stones <10 mm could be actively monitored on an annual basis by alternating ultrasonoraphy with CT scan, provided the patients are adequately informed. Up to 58.6% and 43% of patients with residual fragments after shockwave and percutaneous lithotripsy, respectively, may become symptomatic or require intervention during follow-up. Noninfected, asymptomatic fragments, <4 mm postextracorporeal lithotripsy, and <2 mm postpercutaneous surgery could be followed expectantly on an annual basis, in combination with medical therapy.

Conclusion:

Active stone monitoring has a certain role in the treatment of patients with urinary stones. The success is largely dependent on the stone size, location, and composition, as well as the time after the diagnosis. Medical therapy is a useful adjunct to observation.

Introduction

U rinary stone prevalence is gradually increasing around the world, rising from 3.8% to 5.2% during the 1990s in the United States¹ and from 4% to 4.7% in Germany and 6.8% to 10.1% in Italy from 1979 to 2001 and 1986 to 1998, respectively.^2,3

The cause of increasing stone prevalence is not clearly established. Several factors such as diet, fluid intake, climate and seasonal factors, inheritance and genetics, age and sex, and associate diseases may be responsible. It is also possible, however, that rather than a true increase in prevalence, the above findings represent the detection of more asymptomatic stones found incidentally because of more widespread application of CT and ultrasonography, imaging modalities more sensitive for stone detection than plain radiography.¹

A decade ago, it was shown that only a fraction of 10% to 20% of patients actually becomes symptomatic from a new stone each year and only half of symptomatic patients ultimately need surgical intervention.^4
–6 Primary urinary stone treatment depends on stone-related factors, anatomic factors, clinical factors, and technical factors. Taking into consideration the fate of residual stone fragments after different treatments⁷ as well as the fact that appropriate medical therapy can decrease the risk of stone recurrence and stone re-growth⁸ and improve stone spontaneous passage rates,⁹ urologists are confronted with several dilemmas when they evaluate a patient with stones.

We have tried to identify patients with stones who can be treated safely with active monitoring, focusing mainly in symptomatic stones of small diameter with a high likelihood of spontaneous passage, newly asymptomatic stones, and residual stone fragments (RFs) after definitive treatment.

Materials and Methods

A systematic review based on summary information tha was obtained from published papers was performed. This review did not include a meta-analysis because of the wide diversity of studies regarding their design, number of patients included, lack of data, and variety of definitions and inclusion and exclusion criteria, which may have led to inappropriate or even misleading statistical results. Furthermore, the majority of the studies identified were observational in nature and as a result, the statistical combination of results may produce spurious and misleading results. Table 1 describes the protocol followed in the current review.

Table 1.

Steps of the Systematic Review

Review question	Identify stones that can be subjected safely to active monitoring
Inclusion criteria	Urinary stone disease
	Studies on stone's natural history
	Studies on observation, watchful waiting, or active monitoring of stones
	Studies on spontaneous stone passage
	Studies of symptomatic stones of small diameter
	Studies of newly/incidentally diagnosed asymptomatic stones
	Studies of residual stone fragments after definitive treatments
Search strategy
Years covered	1975–2009
Key words	Using the MeSH terms “urinary stones,” “renal and ureteral stones,” “natural history,” “observation,” “active monitoring,” “surveillance,” “watchful waiting,” “conservative treatment,” “expectant management,” “medical therapy,” “expulsion therapy,” “residual fragments,” and “surgical treatment”
Sources	Medline, MeSH, EMBASE, and Cochrane databases
Search for unpublished data	No
Language restrictions	English
Select studies	Human/English language/RCTs/Clinical trials/Review articles/Meta-analysis/Practice guidelines and Editorials
	Eligibility checked by all authors
	No blinding of observers to authors, institutions, and journals
Assessment of trial quality	No
Analysis-data extraction	Data extraction by all authors
Number of studies included	37
Type of studies per stone category	Symptomatic stones of small diameter: 9 Observational, 4 reviews
	Asymptomatic or incidentally diagnosed stones: 2 RCTs, 4 observational, 1 review
	Residual stone fragments: 1 RCT, 12 observational, 4 review
Number of studies excluded with reasons	473 (irrelevant to topics, repeated publications, upgraded publications, studies included in subsequent meta-analysis)
Statistical model	None
Stratified by trial quality	No
Individual patient data	Not included

RCT = randomized controlled trial.

Results

Symptomatic stones of small diameter

Urologists are often confronted with the decision of whether to observe a stone, which led a patient to the emergency department, in hopes of spontaneous passage, or to intervene surgically. Although the majority of ureteral stones are small enough to pass spontaneously,¹⁰ there is no doubt that in patients with large stones, coexisting infection, severe obstruction, intractable pain, or renal insufficiency, prompt surgical intervention is mandatory.

Spontaneous passage of symptomatic single ureteral calculi is size and time dependent.¹¹ A meta-analysis comprising 2704 patients treated before the advent of shockwave lithotripsy (SWL) and ureteroscopy (URS), showed that when comparing passage rates based on stone size, regardless of location in the ureter, stones <4 mm and >6 mm had spontaneous passage rates of 38% and 1.2%, respectively.¹² More recent reviews reported that distal ureteral stones <5 mm passed spontaneously with a rate of 71% to 100%, whereas stones from 5 to 10 mm passed with a rate of 25% to 46%.^13,14 There is a roughly linear relationship between stone size and likelihood of spontaneous passage, with reporting passage rates of 87%, 72%, 47%, and 27% for stones measuring 1, 4, 7 and 10 mm, respectively.¹⁵ Spontaneous passage rates are higher for distal ureteral stones (45%–71%) compared with middle (22%–46%) and proximal ureteral stones (12–22%).^12,16

Two thirds of stones pass spontaneously within 4 weeks of the onset of symptoms, with the average time to spontaneous passage being 1.6 weeks for stones <4 mm, compared with 2.8 weeks for those 4 to 6 mm.¹² Moreover, the rate of complications is directly related to the duration of symptoms, reaching 20% when symptoms last >4 weeks compared with 7% if symptoms are <4 weeks in duration.¹² The importance of symptom duration was reported by several other authors, who concluded that if significant progress has not occurred after 1 month of observation, intervention is usually necessary.^12,17

Stones <2 mm have a 4.8% chance of needing intervention during surveillance compared with a 50% chance for stones 4 to 6 mm.¹⁰ Stones of 5 to 7 mm in diameter may be safely treated conservatively, provided that the renal function is normal. In a recent study, 28% and 52% of patients with ureteral stones >4 mm underwent immediate and early intervention, respectively, for diminished renal function discovered by radioisotope renography. Twenty-eight percent of the patients had silent loss of renal function at presentation and would have been managed by conservative therapy only if renography had not been performed. Intervention for reduced function at ≤7 days gave better results, in terms of attainment of normal/improved renal function, than in patients undergoing intervention after 7 days. The proportion of patients needing early intervention increased with increasing stone size.¹⁸

Several authors have developed predictive models and artificial neural networks to predict the likelihood of spontaneous passage. These have been created with historic retrospective data or case series.^10,19 Most studies agree that duration of symptoms before seeking medical attention and degree of hydronephrosis may have some influence on outcome.

Cost-effectiveness of observation vs surgery depends on the likelihood of spontaneous passage, stone location, stone size, and success rates for SWL or URS.²⁰ In the United States, observation was the most cost-effective approach to ureteral stones, demonstrating a $1200 cost advantage for distal ureteral stones and a $400 cost advantage for proximal ureteral stones. Parameters potentially increasing total observation cost, however, such as additional visits to the emergency department or loss of work secondary to pain, were not taken into account.²¹

In an attempt to increase the spontaneous ureteral stone passage rate, the addition of pharmacotherapeutics has been advocated. A contemporary meta-analysis incorporating 693 patients showed that patients who were given calcium-channel blockers or alpha-blockers had a 65% greater likelihood of stone passage than those not given such treatment.⁹ This increase in likelihood of spontaneous stone passage using medications was recently found to be associated with an $1132 cost-advantage over observation alone for distal ureteral stones.²² Despite the differences in various countries, it seemed that universally the combination of observation and medical therapy was further cost-effective by decreasing the need for expensive surgical intervention, such as ureteroscopy.²² These findings disagree with the results of a subsequent contemporary double-blind placebo controlled study, which showed that tamsulosin did not improve spontaneous passage in patients with distal ureteral stones of 7 mm or less.²³ An explanation of this conflict could be attributed to the fact that the vast majority of the studies on medical expulsive therapy are small, single-center studies, limiting the strength of conclusions.²⁴ Therefore, large multicenter, placebo-controlled trials are needed.

There are no definitive data on how and when patients with small symptomatic ureteral stones should be monitored. Some authors suggest that every patient should be evaluated by a urologist at initial diagnosis and follow-up could be obtained every 2 weeks until spontaneous stone passage or intervention.^10,12 Follow-up should consist of a genitourinary history with emphasis on pain, narcotic requirements, stone passage, or recovery, physical examination and urinalysis, and plain radiography in most cases.^10
–12 When the stone is not easily visualized on plain radiography, intravenous urography (IVU) or CT should be obtained.^10,12,15 There are findings indicating that renography could be used in patients who present with a ureteral calculus of 4 to 7 mm to identify those renal units with diminished function and provide timely intervention in those units that need it.¹⁸ Whether a stone of ≤4 mm can cause similar renal functional impairment and subsequently necessitates formal initial and follow-up renal impairment studies is unknown.¹⁸

Taking into consideration that watchful waiting for ureteral stones <5 mm in diameter may significantly increase the patient's state of anxiety,²⁵ individual preferences after a thorough counseling about treatment choices, degree of invasiveness, and spectrum of complications will guide urologists and patients to select the best treatment option.²⁶

Asymptomatic and/or incidentally diagnosed renal stones

Before the introduction of minimally invasive therapies, urologists were reluctant to remove incidentally found, asymptomatic caliceal stones because of the high morbidity associated with open surgery. The introduction of SWL coincided with an increase in the percentage of small, <10 mm in diameter, caliceal stones that were being treated from 36% to more than 50%.^27,28 Subsequently, excellent stone-free rates and pain relief after the removal of small caliceal stones by SWL, percutaneous nephrolithotomy (PCNL), or URS have been reported.^29
–31 Therefore, a symptomatic caliceal stone should be treated.

The question of whether we should treat small, asymptomatic calculi still remains difficult to answer. Studying disease process and management outcome may enlighten the natural history of these stones and guide the decision for intervention. For children, patients with a solitary kidney, patients in high-risk professions such as pilots, and women considering pregnancy, treatment of an asymptomatic caliceal stone may be indicated.

Several studies have described the natural history of caliceal stones (Table 2). The majority were retrospective in nature, lacked a comparative arm, and recruited asymptomatic stones of any diameter. Two retrospective studies with a mean patient follow-up of 31.6 months⁵ and 7.4 years,³² respectively, early indicated that expectant management of caliceal stones was associated with a significant risk of increase in size (45%), development of symptoms (32% and 68%), and necessity for intervention (53% and 40%). The risk of a symptomatic episode or need for intervention was found to be approximately 10% per year,⁵ with a cumulative 5-year event probability of 48.5% and 83% in the two studies, respectively.^5,32 The incidence of an event peaked at year 3,⁵ and only 11% of patients remained symptom-free after 10 years.³² Stones that did pass spontaneously did so early, with about 30% of stones passing in 2 years and progressively fewer during subsequent years.³²

Table 2.

Studies for Follow-up of Asymptomatic Renal Stones

	Hübner 1990 ³²	Glowacki 1992 ⁵	Keeley 2001 ⁴	Burgher 2004 ³³	Inci 2007 ³⁴
Number of patients	62	107	99	300	24
Type of study	Retrospective	Retrospective	Prospective	Retrospective	Prospective
Follow-up (mean) (months)	88.8	31.6	26.4	39	52.3
Stone size (mm)	–	–	<15	10.8	8.8
Stable %	55	68	–	–	–
Symptoms and/or disease progression	–	32	–	77	33.3
Spontaneous passage	16	15	17	–	–
Intervention necessary	40	53	15	26	11

These initial data indicated that for asymptomatic caliceal stones in general, active surveillance was mandatory for the first 2 to 3 years, while intervention should be considered after this period. Most frequently, annual follow-up evaluating symptoms and the status of the stone by abdominal radiography, renal tomography, ultrasonography, or noncontrast CT was proposed.^5,32,33 During the last years, there is a shift toward CT as the primary imaging modality for follow-up of calculus disease.³³

Stratification of risk of progression according to stone size, location, and composition was performed in a recent retrospective study of 300 male patients who were observed for a mean of 3.26 years.³³ The mean cumulative stone diameter at presentation was 10.8 mm (range 1.0–74.0 mm), and 48% of the patients had multiple calculi. Overall, 77% of the patients demonstrated progression, with 26% needing intervention, with the risk of intervention being 50% at 7.25 years.

Stone size at presentation was positively associated with failure of observation. Patients with stones that were >15 mm were deemed to fail observation, because 29% needed intervention, pain developed in 57%, 71% had stone growth, and 100% had at least one of the three. Those patients with an isolated stone ≥4 mm on presentation were 26% more likely to fail observation than patients with smaller solitary calculi. Stone growth was less common in those patients with upper-pole and interpolar stones (47%) compared with lower pole stones (61%). Using stone number, size, and location together was a more powerful predictor of progression than either alone. Isolated small <4 mm upper-pole stones were less likely to result in failure than larger upper-pole calculi. Furthermore, intervention rates were lower in those with small <4 mm solitary upper-pole stones than in those with small stones at other sites. The most common reason for observation failure for small upper-pole calculi was stone growth (50%). Finally, only urine and serum uric acid concentrations correlated positively with the rate of stone growth. Based on the above results, the authors concluded that isolated nonuric acid upper-pole calculi <4 mm may be most amenable to active monitoring on an annual basis.

The management of lower-pole renal calculi is one of the most controversial topics in endourology. In a retrospective review of observation for caliceal stones, among patients with lower-pole stones, 61% demonstrated progression in stone size. Baseline stone size was not a predictor of failure of observation in these patients.³³ The intervention time of asymptomatic lower-pole calculi remains controversial. In a prospective study, of 24 patients with a lower-pole stone of mean size of 8.8 mm (range 2–26 mm), 33.3% experienced size progression and 11.1% needed intervention. There was no need for intervention during the first 2 years of follow-up, while three patients required SWL, URS, and PCNL because of pain, an obstructing ureteropelvic stone, and stone growth at months 30, 62, and 67 of follow-up, respectively. The spontaneous passage rate was 50% for stones <5 mm, 16% for stones 5 to 10 mm, and 0% for stones >10 mm. Of the renal units, 18.5 % were stone-free at the end of follow-up.³⁴

Taking into consideration the associated morbidity of surgical intervention, current available data support that lower-pole stones <10 mm can be managed expectantly if asymptomatic. Patients should be informed of the possibility of stone-related symptom progression or need for future intervention.³⁵ All patients should undergo a detailed evaluation including noncontrast spiral CT and urinalysis at the initial visit.³⁴ Thereafter, patients could be evaluated on an annual basis for development of symptoms, urinary tract infection, and stone growth. CT in even years, ultrasonography in odd years, and plain radiography of the kidneys, ureters, and bladder (KUB) in between has been proposed for stone follow-up.³⁴

Two randomized controlled trials that compare SWL with observation for asymptomatic stones exist. Although the end point of the first study was the incidence of new onset hypertension after SWL, the authors reported the intervention rates in 79 patients with asymptomatic caliceal and pelvic stones of <2 cm who were simply observed. At 2 years, 21.5% of patients in the control arm needed intervention for symptoms, although these interventions were not described. A longer follow-up resulted in 43% of patients needing or requesting intervention. Unfortunately, the authors do not comment on the stone burden after treatment or on admission rates for those patients who were treated with SWL.³⁶

In the second trial, patients with caliceal stones <15 mm in total diameter were randomized to undergo SWL (n = 113) or observation (n = 115).⁴ Mean follow-up was 2.2 years (range 1–5 yrs). At an annual follow-up schedule, each patient was assessed with KUB radiography, urine culture, and blood urea and serum creatinine assay. Patients also completed a health and quality-of-life questionnaire. There was no difference between the two groups in stone-free rates (28% vs 17%); need for additional treatment, including analgesics, antibiotics, SWL, stent insertion, and URS (15% vs 21%); or in visits to a general practitioner (18.5% vs 20.8%). There was a difference, however, in the nature of additional treatments. Ten patients in the observation group needed invasive procedures vs none in the SWL group. The SWL group had fewer patients (30%) with residual stone fragments >5 mm compared with the observation group (58%). There was no evidence of differences in the symptoms, quality of life, or renal function tests between the arms of the trial.⁴

It is difficult to create a follow-up schedule based on the findings of the above trials. This is mainly because of the lack of documentation of the exact time to stone growth, symptom acquisition, and need for intervention in these studies. Given the fact that SWL did not improve the clinical outcome of patients with small asymptomatic caliceal stones,⁴ annual follow-up of these patients may be sufficient. The impact of ureteroscopic intrarenal surgery on the progression of asymptomatic renal calculi remains to be evaluated. The latter may alter the way these patients should be treated and followed.

Postprocedural residual fragments

“Clinically insignificant residual stone fragments” (CIRF), defined as residual calculi <4 to 5 mm in diameter that are asymptomatic and not composed of struvite or associated with infection,^37
–39 represent a common and still controversial problem of SWL, PCNL or URS.

Several studies have stressed the fate of RFs after SWL (Table 3).^{6,40

–48} For a mean follow-up range between 6 and 57 months, spontaneous stone passage was noted in 11% to 92.7% of cases. The spontaneous clearance rate was highest for stones that were located in the ureter and lowest for the lower-pole stones. Stone remained stable in 11% to 52.6% of the cases, while stone regrowth was encountered in 2% to 78%. A recent review showed that among patients with CIRF, 25% will become stone free, 50% will remain symptom free, 20% will experience a clinically significant stone episode, and 4% to 25% of patients will need a secondary intervention, mostly a repeated SWL.³⁹ The authors concluded that if there are no clinical symptoms, any endoscopic procedure should be considered as overtreatment.³⁹

Table 3.

Fate of Residual Stone Fragments After Shockwave Lithotripsy

Series	No. of patients	Mean follow-up in months (range)	Stable (%)	Regrowth (%)	Stone free (spontaneous passage) (%)
Beck 1991⁴⁰	53	26.6	11	78	11
Moon 1993⁴²	248	6	–	–	92.7
Streem 1996⁶	160	23 (1.6–88.8)	43.5	10	46.5
Buchholz 1997⁴³	55	54	12.7	2	85.3
Zanetti 1997⁴¹	129	12 (3–12)	43.5	10	46.5
Candau 2000⁴⁴	83	40.6 (7–96)	29	37	34
Khaitan 2002⁴⁵	81	15 (6–60)	17.3	58.7	24
Afshar^* 2004⁴⁶	26	46	31	69	–
Osman 2005⁴⁷	76	57 (52–63)	27.3	21.4	51.3
El-Nahas 2006⁴⁸	154	31 (7.3–80.2)	52.6	33.8	13.6

Pediatric population.

The natural history and clinical significance of small, asymptomatic, non–infection-related stone fragments after SWL were prospectively evaluated in four studies.^6,43,45,47 In total, 463 patients with CIRF <5 mm in diameter were prospectively followed for a mean period of 15 months⁴⁵ to 4.9 years.⁴⁷ Stone-free status, a stable or increased amount of residual stone ranged from 23.8% to 78.9%, 10.7% to 41.9% and 2% to 58.6%, respectively. Between 41.4 and 100% of the patients remained asymptomatic, while 0% to 58.6% had a symptomatic episode or needed intervention 1.6 to 85.4 months after SWL. The intervention was relatively noninvasive and consisted of either repeated SWL or retrograde endoscopy. As the stone burden and number of stone fragments increased, and when the fragments were located in the lower calices, the risk of CIRF becoming clinically significant increased.^6,45,47 Also, as the duration of follow-up increased, the rate of complications increased.⁴⁵ Metabolic defects, when treated adequately, did not decrease the regrowth rate.^45,47

The results of these studies indicate that while patients with small CIRF after SWL could be followed expectantly, a significant number would need intervention or have symptomatic episodes during follow-up. As a consequence, the term CIRF after SWL may not be appropriate, and these stones should be actively monitored.

This was confirmed in a prospective randomized comparative study⁴⁹ of SWL re-treatment vs surveillance only in patients with persistent caliceal RFs after primary SWL. After a 3-month follow-up, significant decreases in residual debris were observed in the re-treated group, while changes in the control group were negligible. The authors suggested that considering the low morbidity of outpatient SWL, SWL re-treatment of completely fragmented but persistent stone debris appears to be justified to render the kidney stone free. Still, the advantages of a higher stone-free rate by SWL re-treatment must be weighted against potentially higher side effects and the additional cost.

There is no consensus regarding the monitoring of small residual fragments after SWL. In the light of the aforementioned data, active surveillance until these stones become symptomatic, increase in size, or need intervention is justified. Follow-up schedules are difficult to design because the tests and the intervals necessary were not specifically recorded in the majority of these studies.^{39,41
–43,46,47,49} When described, standard follow-up comprised clinical examination, urine culture, radiographic studies, and/or renal ultrasonography at 3,^40,45 6,^6,40,48 or 12^6,44 month intervals. Such an intense follow-up, however, may not be indicated. Stone clearance occurs asymptomatically in most of the patients and therefore rarely necessitates any auxiliary procedures.³⁹ Moreover, although the clearance rate is higher at 6 months,^42,45,48 spontaneous clearance is a continuous process that may last up to 24 months.^39,43,48 In addition, only 15% of patients with residual fragments will experience symptomatic events or need further treatment in the first year of follow-up.⁴¹ Furthermore, stone fragments that cleared spontaneously did not recur within 5 years of follow-up.⁴⁷ In lieu of this evidence and taking into consideration that stone recurrence in general is about 8% per 12 months,³⁹ one could support the initial follow-up performed at 6 months, followed by an annual active monitoring schedule for those patients who were not clear at that time.⁴⁴

Radiologic studies usually include plain abdominal radiography and/or ultrasonography.^{39

–49} The most sensitive method of detecting residual stones is undoubtedly CT. Fragments down to 1 mm are visible, and even radiolucent uric acid or cystine calculi are shown with a density that compares with that of calcium-containing stones.⁴⁵ In practical terms, however, precision imaging of a very small fragment is probably an unnecessary, time-consuming, and expensive procedure. Sonography provides comparable precision and detects stones down to a diameter of 2 mm.⁴⁵

The fate of residual stones after PCNL was retrospectively examined in 187 patients.⁵⁰ The most common site of RF was the lower calix (57.7%), and the mean size of RF was 38.6 ± 52 mm². Up to 45% of the patients passed RFs spontaneously at a mean follow-up of 24 months (range 1–100 mos). Of the stones that passed spontaneously, 65.47% did so in 3 months. RF < 25 mm² and those situated in the renal pelvis had the best chance of clearance. In addition, a history of previous intervention, renal failure, and metabolic hyperactivity were predictors of persistence of RF. Unfortunately, the exact follow-up schedule was not defined in this series.

The natural history of RFs after PCNL was recently studied in 42 patients who were prospectively observed for a median period of 41 months and were evaluated for a stone-related event, defined as growth of a RF, need for emergency department visit, hospitalization, or additional intervention attributable to the RF.⁵¹

The median diameter of the largest RF was 2 mm, with 60% of fragments 2 mm or smaller and 79% smaller than 5 mm. Forty-three percent of patients experienced a stone-related event with a median time to occurrence of 32 months (range 4–95 mos). Of these patients, 61% needed a secondary surgical procedure that included 5 URSs, 2 PCNLs, 2 SWLs, 1 nephrectomy, and 1 ureteral stent placement. The estimated 3- and 5-year event-free probabilities were 74% and 48%, respectively.

On multivariate analysis, a maximum RF size >2 mm and location in the renal pelvis or ureter independently predicted a stone-related event. The probability of needing a second surgical procedure correlated with RF size. Eight percent of patients with RFs <2 mm underwent surgical re-treatment compared with 53% of patients with RFs >2 mm. When stratified by maximum RF size, the estimated 3- and 5-year event-free survival rates were 87% and 65%, respectively, for 2 mm or smaller RFs, and 56% and 33%, respectively, for RFs larger than 2 mm. When considering RF location in the renal pelvis/ureter vs other caliceal locations the estimated 3 and 5-year event-free survival rates were 33% and 17%, respectively for RFs in the renal pelvis/ureter, and 79% and 52%, respectively for RFs in the calices. These results indicate that patients with RFs larger than 2 mm or those with fragments located in the renal pelvis or ureter should be treated promptly. Second-look flexible nephroscopy was proposed to be of benefit for these patients.

According to the study design, patients with residual fragments <2 mm were actively monitored at least every 6 months for the first 2 years and annually thereafter with history, physical examination, serum chemistry studies, urine culture, and CT. The need for such an intense schedule still needs to be verified. Taking into consideration that the majority of these stones will pass spontaneously without causing any symptoms during the first year of follow-up, an annual follow-up with a CT scan could be sufficient.

Several authors have addressed the issue of medical therapy in the management of RFs after SWL or PCNL (Table 4).^52

–56 In a retrospective study,⁵² patients receiving medical therapy experienced a significant decrease in the stone-formation rate from a median of 1.17 to 0.00 stones per patient per year, compared with those patients not receiving medical therapy, who experienced a minimal decrease from a median of 1.33 to 0.77 stones per patient per year. The medically treated patients had a significantly greater stone remission rate (63.9% vs 23.1%) and lower stone burden increase (27.8% vs 61.6%) than the untreated patients. Regarding patients with CIRF, 16% of those who were treated medically demonstrated fragment growth compared with 54.5% of the untreated patients. This retrospective study early indicated that medical therapy may control active stone formation in patients with residual stone fragments after SWL.⁵²

Table 4.

Medical Therapy Effect on Residual Stone Fragment Activity

	Stone free		Stone size unchanged or decreased		Stone size increased ^a
Reference	Medical therapy	Control	Medical therapy	Control	Medical therapy	Control
Cicerello^b 1994⁵³	80.5%	36%	75%	52.6%	5%	47%
Soygur^b 2002⁵⁴	44.4%	12.5%	56.6%	25%	–	62.5%
Sarica^b,d 2006⁵⁵	–	–	81.8%	27.2%	18.2%	72.8%
Fine 1995⁵²	58.3%	38.4%	13.9%	0%	27.8%	61.6%
Kang^c 2007⁵⁶	77%	21%

Regrowth and/or recurrence rate included.

Randomized controlled studies.

Stone remission rates after percutaneous nephrolithotomy.

Study in children.

These results were confirmed by prospective and randomized trials.⁵³ After 1 year of follow-up, RF <5 mm in diameter disappeared in up to 74% of calcium oxalate patients and in up to 86% of infection stone patients who were treated with citrate. In the control group, the percentages were 32% and 40%, respectively. During the 12-month follow-up, RF growth or reaggregation occurred in 47% of the calcium oxalate control patients compared with 5% of the calcium oxalate citrate-treated patients. None of the treated or control infection stone patients in whom stone fragments persisted at the end of follow-up had growth or reaggregation of residual fragments.⁵³

Similar results were found in another prospective randomized comparative study. Of 34 patients with lower-pole RFs after SWL, the group who were receiving citrate therapy showed a significantly higher stone fragment disappearance rate (45.5% vs 12.5%) and less stone recurrence rate (56.6% vs 87.5%) compared with the control group at 12 months of follow-up.⁵⁴

Finally, there is some evidence to suggest that medical management can control active stone formation in patients with RFs after PCNL.⁵⁶ Patients receiving medical therapy exhibited a lower median stone-free rate (0.02 vs 1.00 stones per patient per year) and a higher remission rate (77% vs 21%) compared with patients not receiving medical therapy, supporting the role of medical treatment in inhibiting new stone formation or growth in patients with residual fragments after PCNL.⁵⁶

Conclusion

Active stone monitoring may have a certain role in the treatment of stone patients. The success is largely dependent on the stone size, location, and composition as well as the time elapsed after the diagnosis. Most symptomatic ureteral stones <4 mm, especially those located in the distal ureter, will pass spontaneously. Follow-up could be obtained with plain radiography every 2 weeks for 1 month. If spontaneous passage does not occur within this period, intervention is recommended. SWL for small asymptomatic renal caliceal stones does not appear to offer any advantage to patients in terms of stone-free rate, quality of life, renal function, symptoms, or hospital admissions. Observation may be associated with a greater risk of necessitating more invasive procedures. Active monitoring on an annual basis with a CT scan up to year 2 or 3 is recommended. Asymptomatic lower pole stones <10 mm in diameter could be actively monitored on an annual basis alternating ultrasonography with CT, provided patients are adequately informed. The size and location of residual stone fragments after SWL or PCNL are the major predictors for symptoms developing or requiring intervention. Early re-SWL and second-look nephroscopy are recommended after primary SWL and PCNL, respectively. Residual fragments <4 mm after SWL and <2 mm after PCNL could be actively monitored on an annual basis. Finally, medical therapy is a useful adjunct to observation in all the above situations.

Disclosure Statement

Dr. de la Rosette is a consultant for Boston Scientific, a consultant for Cook, and an investigator for Storz and Olympus. The other authors have no disclosures to report.

Footnotes

Abbreviations Used

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