Ureteroscopic Biopsy of Upper Tract Urothelial Carcinoma: Comparison of Basket and Forceps

Abstract

Purpose:

To compare two different biopsy devices for upper tract urothelial carcinoma (UTUC) and evaluate the pathologic result obtained by these devices.

Patients and Methods:

From January 2008 to December 2010, 414 ureteroscopies were performed and 504 biopsies were taken for evaluation of UTUC. Two biopsy devices were compared: 2.4F stainless steel flat wire basket and 3F cup biopsy forceps. The effect of the biopsy device on obtaining an adequate pathologic specimen was evaluated using univariate and multivariate binary logistic regression analysis. We also investigated whether tumor grade determination was affected by the biopsy device among patients with a diagnostic biopsy.

Results:

Diagnosis was successful in 63% and 94% in the forceps and basket groups, respectively (P<0.0001). Among biopsies with a definite diagnosis of UTUC, specific grade was determined in 80% and 93% in the forceps and basket groups, respectively (P=0.033). In subgroup analysis of tumors larger than 10 mm in diameter, diagnosis was obtained in 80% and 94% in the forceps and basket groups, respectively (P=0.037). Cytologic evaluation was found to increase diagnostic rates.

Conclusions:

The stainless steel flat wire basket was shown to be superior to the 3F cup biopsy forceps in terms of obtaining tissue diagnosis and providing specific grade.

Introduction

Upper tract urothelial carcinoma (UTUC) is a rare malignancy, which accounts for only 5% to 7% of renal tumors and 5% of urothelial tumors.¹ The number of newly diagnosed cases in 2013 in the United States is estimated to be between 5900 and 7300.² Although radical nephroureterectomy (RNU) has been considered the gold standard treatment for patients with UTUC, endoscopic advancements have achieved favorable treatment outcomes and renal preservation rates in selected cases, even in patients with a normal contralateral kidney^3,4 Recent reports show equivalent cancer-specific survival compared with RNU for low-grade disease.^5,6 Careful selection of patients for endoscopic treatment is crucial. Accurate preoperative staging for UTUC is unreliable, but tumor grade is suggestive of stage^7,8 Endoscopic visualization is only 70% accurate in determining the presence or grade of UTUC.⁹ Obtaining a more accurate tissue diagnosis is an essential step in determining treatment for patients with UTUC. Currently, the most accurate technique for diagnosis of upper tract lesions has been ureteroscopy with biopsy.^8,10

Consistently sampling sufficient tissue for pathologic evaluation remains challenging. The small working channels of ureteroscopes limit the size of biopsy devices, which may provide insufficient tissue for accurate diagnosis.^11,12 The two most commonly used biopsy devices are the 3F cup biopsy forceps and the 2.4F stainless steel flat wire basket¹³ (Fig. 1).

FIG. 1.

The two most commonly used ureteroscopic biopsy devices: 3F cup biopsy forceps and stainless steel flat wire basket.

Despite the importance of reaching an accurate diagnosis, an ideal method to procure adequate tissue has not yet been described. The purpose of this study was to compare diagnostic yield obtained by either forceps or basket and to assess whether one of the devices is superior.

Patients and Methods

In a study approved by the Institutional Review Board, we retrospectively reviewed the records of patients who underwent ureteroscopic procedures for UTUC between the years 2008 to 2010 at our tertiary care institution. During this period, 127 consecutive patients underwent 414 ureteroscopies for newly diagnosed UTUC or as surveillance for previously diagnosed UTUC. New patients received a diagnosis during evaluation of hematuria or filling defects on contrast studies, or were referred by outside urologists.

Biopsies taken from different lesions along the upper tract during a single procedure were recorded as separate entries. A total of 504 entries were reviewed. Exclusion criteria included ureteroscopies in which tumor was not visualized, tumors that were managed without obtaining a biopsy, cases in which the operative report did not indicate the biopsy device used, or whenever both forceps and basket were used for biopsy of the same lesion. A total of 303 entries were analyzed after exclusions.

Data extracted included patient demographics, presence of ureteral stent before the procedure, tumor size and location, type of biopsy device, and the pathology result. In 18 operative reports, tumor size was described as “small” but not specified. In these cases, a tumor size of 2 mm was used. Similarly, in three cases, the tumor was described as “large” and involved multiple calices. This was substituted with 40 mm.

Ureteroscopy was performed using a “no touch technique” whereby the urinary tract is visualized before the insertion of guidewires to avoid trauma or bleeding that might obscure small tumors. During ureteroscopy, multiple urine samples from the following locations were obtained for cytologic evaluation: Urinary bladder, tumor site, renal pelvis, postbiopsy aspirate, and postlaser treatment aspirate. When the forceps were used, multiple biopsies were taken from the same lesion until grossly visible tumor was noted in the sample container. While using the basket, the tumor is trapped between the wires, which are subsequently closed snugly but not completely. The specimen is removed en bloc, thus avulsing a piece of tumor.

With either device, if a relatively large tumor is secured, the ureteroscope, biopsy device, and specimen are removed as a single unit to avoid loss of tissue in the working channel. The specimen is then promptly delivered to the cytopathology laboratory fresh in physiologic saline. It is then processed with the Cytospin technique. Cell block is also prepared from any visible tissue in the sample.¹⁴

The effect of the biopsy device on retrieval of an adequate pathologic specimen was evaluated using univariate and multivariate binary logistic regression analysis. We adjusted for the following putative confounders: Age, sex, side, tumor size, tumor location (ureter vs kidney), and presence of a previously placed ureteral stent. We also examined whether the biopsy device was associated with higher rates of grade determination among patients with diagnostic pathology. To test the robustness of the results, we stratified our cohort and repeated the same analysis among patients with larger tumors (≥10 mm in diameter).

Statistical analysis was performed using SPSS version 19. A P value of <0.05 was considered statistically significant.

Results

The present study includes 303 biopsies taken during ureteroscopy for UTUC, divided into the forceps group (237) and the basket group (66). Mean tumor size was 7 mm (±11.4) and 21 mm (±12.9) for the forceps and basket groups, respectively (P<0.0001). Table 1 summarizes patient characteristics, side and location of the tumor, and presence of ureteral stent.

Table 1.

Patient Characteristics

	Total	Forceps (n=237)	Basket (n=66)	P value
Mean age±SD (years)	73 (10.3)	73 (9.7)	72 (12.1)	0.08
Mean tumor size±SD (mm)	10 (12.9)	7 (11.4)	21 (12.9)	<0.0001
Gender
Male	155 (51%)	121 (51%)	34 (52%)	0.9
Female	148 (49%)	116 (49%)	32 (48%)
Side
Right	156 (51%)	116 (49%)	40 (60%)	0.09
Left	147 (49%)	121 (51%)	26 (40%)
Location
Kidney	183 (60%)	149 (63%)	34 (52%)	0.1
Ureter	120 (40%)	88 (37%)	32 (48%)
Stent
Yes	57 (19%)	33 (14%)	24 (36%)	<0.0001
No	242 (81%)	200 (86%)	42 (64%)

SD=standard deviation.

Overall successful diagnosis was achieved in 70% of the cases. Stratified by biopsy device, diagnosis was obtained in 63% in the forceps group compared with 94% in the basket group (univariate analysis, odds ratio [OR] 8.990, 95% confidence interval [CI]=3.162–25.563, P<0.0001, Table 2). On multivariate analysis, use of a basket was identified as a single, independent predictor of obtaining pathologic diagnosis (adjusted OR 6.329, P=0.004, Table 3). Of note, tumor size was not associated with a successful diagnosis (adjusted OR 1.034, P=0.069, Table 3).

Table 2.

Pathology Outcomes of Biopsies Obtained with Forceps vs Basket

	Forceps	Basket	P value
Diagnosis success rate	(150/237) 63%	(62/66) 94%	<0.0001
Rate of grade determination	(85/106) 80%	(55/59) 93%	0.033
Diagnosis success rate for large tumors	(44/55) 80%	(50/53) 94%	0.037

Table 3.

Multivariate Analysis of Obtaining a Pathology Result

	OR	95% CI	P value
Biopsy device	6.329	1.796–22.301	0.004
Age	0.969	0.938–1.002	0.065
Sex	0.684	0.338–1.208	0.191
Side	0.787	0.443–1.399	0.415
Tumor size (mm)	1.034	0.997–1.071	0.069
Location	0.827	0.462–1.479	0.522
Stent	0.330	0.107–1.021	0.054

OR=odds ratio; CI=confidence interval.

Among those positive for a cancer diagnosis, tumor grade was specified in 80% and 93% in the forceps and basket groups, respectively (univariate analysis, OR 3.397, 95% CI 1.106–10.43, P=0.033, Table 2). This association, however, was not significant on multivariate analysis (Table 4).

Table 4.

Multivariate Analysis of Obtaining a Specific Grade Among Biopsies with Upper Tract Urothelial Carcinoma

	OR	95% CI	P value
Biopsy device	2.489	0.712–8.701	0.153
Age	1.005	0.962–1.050	0.835
Sex	1.327	0.523–3.369	0.552
Side	0.950	0.379–2.381	0.913
Tumor size (mm)	1.048	0.993–1.106	0.090
Location	0.971	0.380–2.481	0.951
Stent	1.531	0.510–4.598	0.448

OR=odds ratio; CI=confidence interval.

Subgroup analysis of larger tumors (≥10 mm), demonstrated diagnosis in 80% and 94% in the forceps and basket groups, respectively. This was significant on univariate analysis (OR 4.167, 95% CI 1.092–15.902, P=0.037, Table 2), but not on multivariate analysis (Table 5).

Table 5.

Multivariate Analysis of Obtaining a Pathology Result for Tumors ≥10 mm

	OR	95% CI	P value
Biopsy device	2.628	0.606–11.389	0.197
Age	0.890	0.805–0.984	0.022
Sex	0.463	0.114–1.873	0.280
Side	0.602	0.148–2.455	0.479
Tumor size (mm)	0.999	0.950–1.051	0.973
Location	0.349	0.093–1.310	0.119
Stent	0.239	0.032–1.810	0.166

OR=odds ratio; CI=confidence interval.

Of the 303 biopsies, 91 (30%) resulted in nondiagnostic pathology. Of these, in 83 (91%) cases, the cytology was diagnostic (either urothelial carcinoma or benign) and 8 (9%) cases were suspicious for urothelial carcinoma.

Discussion

Although RNU has been the standard treatment for patients with UTUC, the loss of a renal unit can lead to deterioration of renal function. Nephron-sparing surgery for renal-cell carcinoma has been shown to be associated with preservation of renal function and increased overall survival.^15,16 Ureteroscopic management of UTUC may confer the same benefits of renal preservation as well as avoidance of major surgery. Because endoscopic surgery is reserved for patients with low-grade disease, patient selection is critical.

Currently, ureteroscopic biopsy is the most accurate means for grading and possibly staging UTUC.^8,10 Sample size, however, is limited secondary to small biopsy devices. Consequently, in many cases, the specimen is insufficient to establish an accurate diagnosis or may not survive processing. The aim of this study was to determine which of the two more commonly used biopsy devices yields better outcomes in terms of achieving proper pathologic results.

While using the basket, successful cytopathologic diagnosis was available in 94% of the cases, compared with only 63% of the cases when the forceps were used. This was significant both on univariate and multivariate analysis.

In addition, the basket was found to be superior in determining a specific tumor grade. Among biopsies with a definite diagnosis of UTUC, tumor grade was given in 93% vs 80% with the basket and forceps, respectively. This was significant on univariate analysis. Multivariate analysis demonstrated a trend toward better grade determination when the biopsy was taken using a basket (OR 2.5); however, this was not statistically significant (P=0.153). A larger sample size may be needed to increase the power to reach a statistically significant difference.

Cytology obtained during the same procedure was diagnostic in 91% of the cases in which cell block was noncontributory. These findings are consistent with previous reports from our group and have been attributed to the multiple specimens sampled before and after biopsy and treatment.¹⁴ When combining diagnostic site-specific cytology results with a 71% positive diagnostic rate from biopsy, the overall diagnostic yield approaches 97%.

Tumor size may be an important factor in diagnosis and treatment of UTUC. In this cohort, the average tumor size in the basket group was 21 mm, whereas the average tumor size in the forceps group was 7 mm. To overcome a selection bias, a subgroup analysis for large tumors (≥10 mm) was performed. In this subgroup, the basket still proved to be superior compared with the forceps in obtaining a diagnosis in 94% and 80% of the cases, respectively. This was significant in univariate analysis. Multivariate analysis demonstrated a trend toward higher diagnosis rates while using the basket (OR 2.6), but this was not statistically significant (P=0.197). Again, a larger sample size may be needed to increase the power to reach a statistically significant difference.

These findings may be explained by the larger amount of tissue obtained with the basket. The basket can also be used to debulk large papillary tumors by avulsing large pieces of tumor (Fig. 2). In contrast, the forceps are preferably used for sampling smaller, sessile, or nonpapillary lesions. Consequently, samples with the basket are generally larger than those obtained with the forceps. Other series have shown that larger biopsy specimens tend to correlate well with the grade of the final specimen.¹⁷

FIG. 2.

Obtaining a large piece of tumor by using the stainless steel flat wire basket.

Although not specifically evaluated in this study, in our experience, we have found that the basket does not limit the deflection of the flexible ureteroscope as much as the forceps (Fig. 3). The superior deflection characteristics of the basket are likely secondary to its more flexible shaft. As a result, lower pole lesions are more accessible when using the basket.

FIG. 3.

Favorable deflection characteristics of the stainless steel flat wire basket compared with the 3F cup biopsy forceps.

This study did not show any benefit or detriment of preureteroscopy stent placement on biopsy results. In general, we avoid the insertion of a ureteral stent or the use of an access sheath to avoid ureteral trauma and edema, which may confound ureteroscopic as well as cytopathologic evaluation.

Conclusions

The stainless steel flat wire basket was shown to be superior in achieving pathologic diagnosis compared with the 3F cup biopsy forceps. The basket may also be superior in determining tumor grade. The forceps are useful for small and sessile lesions. Obtaining multiple site-specific specimens for cytology is important, because it may aid in diagnosis whenever cell block is noncontributory.

Footnotes

Disclosure Statement

Dr. Demetrius H. Bagley is a consultant for Bard and Cook.

Abbreviations Used

References

Sagalowsky

, Jarrett

, Flanigan

. Urothelial tumors of the upper urinary tract and ureter. In: Wein

, Kavoussi

, Novick

, Partin

, Peters

(eds): Campbell-Walsh Urology. 10th ed. Philadelphia: Elsevier Saunders, 2012, chap 53.

Siegel

, Naishadham

, Jemal

. Cancer statistics, 2013. CA Cancer J Clin, 2013; 63:11–30.

Chen

, Bagley

. Ureteroscopic management of upper tract transitional cell carcinoma in patients with normal contralateral kidneys. J Urol, 2000; 164:1173–1176.

Elliott

, Segura

, Lightner

, et al. Is nephroureterectomy necessary in all cases of upper tract transitional cell carcinoma? Long-term results of conservative endourologic management of upper tract transitional cell carcinoma in individuals with a normal contralateral kidney. Urology, 2001; 58:174–178.

Cutress

, Stewart

, Wells-Cole

, et al. Long-term endoscopic management of upper tract urothelial carcinoma: 20-year single-centre experience. BJU Int, 2012; 110:1608–1617.

Grasso

, Fishman

, Cohen

, Alexander

. Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma: A 15-year comprehensive review of 160 consecutive patients. BJU Int, 2012; 110:1618–1626.

Brown

, Matin

, Busby

, et al. Ability of clinical grade to predict final pathologic stage in upper urinary tract transitional cell carcinoma: Implications for therapy. Urology, 2007; 70:252–256.

Keeley

, Kulp

, Bibbo

, et al. Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma. J Urol, 1997; 157:33–37.

El-Hakim

, Weiss

, Lee

, Smith

. Correlation of ureteroscopic appearance with histologic grade of upper tract transitional cell carcinoma. Urology, 2004; 63:647–650.

10.

Williams

, Denton

, Minervini

, et al. Correlation of upper-tract cytology, retrograde pyelography, ureteroscopic appearance, and ureteroscopic biopsy with histologic examination of upper-tract transitional cell carcinoma. J Endourol, 2008; 22:71–76.

11.

Tavora

, Fajardo

, Lee

, et al. Small endoscopic biopsies of the ureter and renal pelvis: Pathologic pitfalls. Am J Surg Pathol, 2009; 33:1540–1546.

12.

Smith

, Stephenson

, Lane

, et al. Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: Implications for conservative management. Urology, 2011; 78:82–86.

13.

Abdel-Razzak

, Ehya

, Cubler-Goodman

, Bagley

. Ureteroscopic biopsy in the upper urinary tract. Urology, 1994; 44:451–457.

14.

Tawfiek

, Bibbo

, Bagley

. Ureteroscopic biopsy: Technique and specimen preparation. Urology, 1997; 50:117–119.

15.

Thompson

, Boorjian

, Lohse

, et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol, 2008; 179:468–473.

16.

Weight

, Lieser

, Larson

, et al. Partial nephrectomy is associated with improved overall survival compared to radical nephrectomy in patients with unanticipated benign renal tumours. Eur Urol, 2010; 58:293–298.

17.

Vashistha

, Shabsigh

, Zynger

. Utility and diagnostic accuracy of ureteroscopic biopsy in upper tract urothelial carcinoma. Arch Pathol Lab Med, 2013; 137:400–407.