Factors Associated with Diagnostic Accuracy When Performing a Preablation Renal Biopsy

Abstract

Background and Purpose:

Long-term treatment of patients undergoing definitive management of a small renal mass depends largely on the final pathology determination. Preablation renal biopsy (PABx) is often the only source of determining pathology in patients undergoing thermal ablation of a small renal mass. We sought to evaluate patient and tumor characteristics that may play a role in determining the accuracy of a PABx obtained during radiofrequency ablation (RFA).

Methods:

This retrospective study included a review of our prospectively collected database of all laparoscopic and CT-guided RFA (LRFA; CTRFA) performed in our center from November 2001 to July 2013. Three 18-gauge core biopsies were obtained per tumor. Pathology samples were stratified into diagnostic (group 1) and nondiagnostic (ND) (group 2). We used univariate and multivariate analysis to identify potential biopsy result-modifying factors including patient characteristics (age, body mass index [BMI]), biopsy approach (CTRFA vs LRFA), tumor size, orientation, depth, and polarity.

Results:

A total of 463 treatments in 411 patients were evaluated. Of these, 66% were CTRFA while 34% were LRFA. Mean patient age was 67.4 years (31–88), mean BMI was 28.3 kg/m² (16.6–47.2), and mean tumor size was 2.6 cm (0.3–5.5). There was a total of 73 (15.8%) ND biopsies. On multivariate analysis, CTRFA and medial tumors managed with either CTRFA or LRFA were found to be associated with an increased likelihood of a ND biopsy.

Conclusion:

PABx obtained in patients undergoing CTRFA and from medial tumors managed with either CTRFA or LRFA were more likely to be ND. Future RFA patients should be counseled appropriately. Additional biopsy cores may be needed in these subgroups. Further prospective studies are warranted to confirm these findings.

Introduction

Definitive treatment of a small renal mass includes surgical resection or thermal ablation,¹ following which patients are stratified into low-, intermediate-, or high-risk groups, based on the tumor pathology and stage. This stratification aids in subsequent decision-making when planning a follow-up protocol schedule² as well as deciding on the need for adjuvant systemic therapy.

While surgical resection inherently results in a specimen suitable for pathologic evaluation, thermal ablation does not. As such, a preablation renal biopsy (PABx) is commonly obtained before the procedure. Biopsies obtained in the context of percutaneous thermal ablation are typically guided by CT, whereas those obtained during laparoscopic ablation are commonly directed by surgical ultrasonography (US) and visual guidance.

Improvement in imaging, biopsy technique, immunohistochemistry staining, and new molecular markers have improved the accuracy of renal biopsies. Currently, sensitivities of 80% to 92% and specificities of 83% to 100% are reported.³

The primary aim of this study was to identify patient and tumor characteristics that may play a role in determining the accuracy of a PABx obtained at the time of radiofrequency ablation (RFA). This, in turn, would aid in future RFA patient counseling.

Methods

For this retrospective study, we reviewed our prospectively collected database of all consecutive laparoscopic and CT-guided RFA treatments performed in our single center between November 2001 and July 2013. Institutional Review Board approval for the present study was obtained.

Our RFA technique has been described previously.⁴ In general, laparoscopic RFA (LRFA) was performed under general anesthesia, via a transperitoneal approach. The renal mass was identified using a combination of intracorporeal US and direct vision. Before ablation, three renal biopsy cores, from different aspects of the mass, were obtained using an 18-gauge Tru-Cut® biopsy needle. Next, RFA was delivered using an impedance-based generator.

CT-guided RFA (CTRFA) was performed by a joint urology and interventional radiology team under general anesthesia, with the patient in the prone position. Under CT guidance, three renal core biopsies were obtained, and ablation was performed in an identical protocol as that used for LRFA.

Treatment parameters were prospectively recorded into a RFA database. We reviewed patient characteristics (age, sex, body mass index [BMI]), tumor properties such as size, orientation (anterior, posterior, medial, lateral), depth (endophytic, mesophytic, exophytic), polarity (upper pole, midpolar, lower pole), and biopsy approach (CTRFA vs LRFA). Surgeon experience was reported as a scale numerical variable by assigning a serial number to each consecutive treatment (1=first case, 2=second case, and so forth).

Pathology samples were stratified into diagnostic (group 1) and nondiagnostic (ND) (group 2) based on the recommendations made by the International Consensus Panel on small renal mass biopsy.⁵ ND samples included insufficient material, inconclusive, and benign renal parenchyma. All pathologically confirmed malignant and benign histology results were classified as diagnostic.

Statistical analysis

Continuous numerical variables are reported by their means and range, while categorical variables are described as counts and percentages. For univariate analysis, independent samples t test was used to compare means of continuous numerical variables while the Pearson chi-square test was used to compare proportions of categorical variables.

For multivariate analysis, we used a binary logistical regression model including all variables found to be significant on univariate analysis.

All calculations were performed using SPSS Statistics software (v.21, IBM Corporation, Armonk, NY).

Results

A total of 463 RFA treatments in 411 patients were performed. Of these, 66% were CTRFA while 34% were LRFA. A PABx was obtained at the time of the procedure. Patient and tumor characteristics are presented in Table 1. Mean patient age was 67.4 years (31–88), mean BMI was 28.3 kg/m² (16.6–47.2), and mean tumor size was 2.6 cm (0.3–5.5).

Table 1.

Baseline Demographics and Patient Characteristics

Approach	CTRFA	LRFA	P value	Total
Number of treatments, N (%)	304 (65.7)	159 (34.3)		463 (100)
Age (years)	66.6 (31–88)	69.0 (33–88)	0.041	67.4 (31–88)
Sex, N (%)
Female	94 (30.9)	45 (28.3)		139 (30)
Male	210 (69.1)	114 (71.7)		324 (70)
BMI (kg/m²)	28.8 (18.1–47.2)	27.8 (16.6–41.8)	0.048	28.3 (16.6–47.2)
Tumor size (cm)	2.5 (0.3–5.5)	2.8 (1.0–5.0)	0.003	2.6 (0.3–5.5)
Tumor orientation, N (%)
Posterior	220 (72.4)	32 (20.1)	0.000	213 (50)
Anterior	22 (7.2)	87 (54.7)		79 (18.5)
Lateral	23 (7.6)	23 (14.5)		46 (10.8)
Medial	10 (3.3)	9 (5.7)		19 (4.1)
Pathology, N (%)
Diagnostic	241 (79.3)	142 (89.3)	0.013	383 (82.7)
Nondiagnostic	57 (18.8)	16 (10.1)		73 (15.8)
No biopsy	6 (2)	1 (0.6)		7 (1.5)
Stage, N (%)
T_1a	279 (91.8)	133 (83.6)	0.008	412 (89)
T_1b	25 (8.2)	26 (16.4)		51 (11)

CTRFA=computed tomography radiofrequency ablation; LRF=laparoscopic radiofrequency ablation; BMI=body mass index.

Pathology results are detailed in Table 2, stratified by biopsy approach. Overall, a biopsy was obtained in 456 (98.4%) treatments. Of these, 73 (16%) biopsies were found to be ND, of which 78% were obtained during CTRFA and 22% during LRFA. In seven (1.5%) treatments, no biopsy was obtained at the time of the procedure.

Table 2.

Pathology Results Stratified by Biopsy Approach

Parameter n (%)	CTRFA	LRFA	Total
Diagnostic
Clear-cell	128 (42.1)	80 (50.3)	208 (44.9)
Papillary	36 (11.8)	23 (14.5)	59 (12.7)
Chromophobe	9 (3.0)	6 (3.8)	15 (3.2)
Oncocytoma	41 (13.5)	27 (17.0)	68 (14.7)
Unclassified RCC	11 (3.6)	1 (0.6)	12 (2.6)
AML	16 (5.3)	5 (3.1)	21 (4.5)
Nondiagnostic
Benign	29 (9.5)	13 (8.2)	42 (9.1)
Indeterminate	25 (8.2)	3 (1.9)	28 (6.0)
Other	3 (1.0)	0 (0)	3 (0.6)
No biopsy	6 (2.0)	1 (0.6)	7 (1.5)
Total	304 (65.4)	159 (34.6)	463 (100)

CTRFA=computed tomography radiofrequency ablation; LRF=laparoscopic radiofrequency ablation; AML=acute myeloid leukemia.

Univariate analysis revealed a statistically significant higher risk for a ND biopsy in patients who underwent CTRFA compared with those who had LRFA. The likelihood for a ND biopsy was also higher when the tumor size was smaller, in patients with an elevated BMI undergoing LRFA, and in those undergoing CTRFA for a tumor oriented medially (Table 3).

Table 3.

Univariate and Multivariate Analysis

	Univariate analysisP value	Multivariate analysis
Parameter		Odds ratio	95% CI	P value
Approach: (CTRFA)	0.013	2.27	1.00–5.12	0.048
Size	0.046	0.87	0.64–1.18	0.369
BMI	0.024	1.01	0.96–1.07	0.621
Age	0.083	0.99	0.97–1.01	0.327
Polarity	0.734	1.16	0.60–2.21	0.662
Depth	0.512	0.84	0.43–1.16	0.581
Orientation (medial)	0.060	8.79	1.46–52.73	0.017
Surgeon experience	0.013	1.00	0.99–1.00	0.846

Biopsy approach (CTRFA vs LRFA); polarity (lower pole, midpolar, upper pole); depth (endophytic, mesophytic, exophytic); orientation (anterior, posterior, medial, lateral, anterior-lateral, posterior-lateral).

CTRFA=computed tomography radiofrequency ablation; CI=confidence interval; LRFA=laparoscopic radiofrequency ablation.

On multivariate analysis (Table 3), only CTRFA and medially oriented tumors managed by either CTRFA or LRFA remained associated with an increased likelihood of resulting in a ND PABx (P=0.048; P=0.017, respectively).

Age, surgeon experience, tumor depth, and polarity did not play a role in the likelihood of resulting in a ND biopsy (Table 3).

Discussion

Data pertaining to long-term oncologic follow-up of renal ablative therapies are emerging and seem to suggest favorable outcomes, approaching those of open and laparoscopic nephron-sparing surgery.^6,7 As such, it is not unreasonable to assume that in the future, these procedures may be offered not only to the elderly and high surgical risk patients, but also to younger and healthier ones.

This scenario underscores the importance of obtaining an accurate and diagnostic renal biopsy. By virtue of their younger age, these patients will be subjected to many years of follow-up, which in turn relies heavily on the accuracy of the renal biopsy. The pathology result will aid in stratifying the patients into low-, moderate-, or high-risk groups as suggested by the American Urological Association guidelines on follow-up for clinically localized renal neoplasms.² Thus, the intensity, extent, and duration of the follow-up surveillance scheme rely on oncologic risk factors, which in turn depend heavily on obtaining reliable and definite preablation tumor pathology data.

An International Consensus Panel on small renal mass biopsy⁵ recently published its recommendations on indications, approaches, and pitfalls of renal biopsies. These recommendations were based on supporting literature and expertise of participating members from the field of urologic surgery, urologic pathology, and genitourinary radiology.

The accuracy and reliability of the biopsy in differentiating benign from malignant lesions was found to be in the range of 86% and 100% with a specificity approaching 100%. The rate of ND samples ranged from 0% and 47% in different series and appeared more frequent for smaller lesions and for those that seemed cystic on radiographic imaging. The panel recognized the need to standardize the nomenclature and offered to include in the ND category insufficient tissue for analysis as well as results that do not yield a diagnosis such as normal renal parenchyma and necrosis.

The rate of ND biopsies in patients undergoing evaluation of a documented renal mass has been reported to be in the range of 20%.^8,9 Predictors for a ND biopsy include: Nonsolid and cystic tumors, small renal mass diameter, less biopsy tissue available for pathologic analysis, and biopsies obtained during the earlier years of the study.

A PABx is obtained under CT or laparoscopic US guidance while extracorporeal US guidance is seldom used. Moreover, masses selected for ablation are less likely to be cystic, are typically smaller than 4 cm, and are deemed unsuitable for active surveillance. As such, the risk factors associated with a ND PABx may differ from those of a ND biopsy obtained in a nonablation setting. Identifying risk factors for a ND PABx may play a role when counseling future RFA patients and may assist in patient selection when considering management options for a small renal mass.

There are only a few studies that report the rate and risk factors for a ND renal biopsy within the preablation subgroup of patients. In one such study,¹⁰ PABx was obtained in 93% of cases, of which 10% were found to be ND when using the criteria we adopted for this article (unknown or ND pathology, benign renal parenchyma).

In the present study, only biopsy approach (CTRFA) and medial tumor orientation were found to be associated with a significant risk for a ND biopsy on multivariate analysis (Table 3).

An increased likelihood of a ND PABx in patients undergoing CTRFA compared with those undergoing LRFA is possibly secondary to better localization of the renal mass during LRFA, stemming from direct vision of the mass combined with the ability to place the ultrasound probe directly on the kidney or the exophytic component of the mass.

Medially located masses are likely to be in close proximity to the renal hilum and pose a targeting challenge because of their proximity to the main renal vasculature, renal pelvis, and ureter. The concern of injuring any one of these structures may inadvertently result in undersampling.

We recognize a limitation of our study. Renal biopsies obtained during LRFA were performed in the operating room by the urology team while those obtained during CTRFA were performed by an interventional radiologist in the CT suite. This may potentially limit comparison of these two approaches. Because both teams were highly experienced in image-guided renal targeting and access, it is unlikely operator dependent factors contributed to the higher rate of ND renal biopsies seen in CTRFA.

Conclusions

Final pathology is of paramount importance for determining the intensity of the future follow-up schedule in patients treated for renal-cell carcinoma. In this study, we analyzed risk factors for a ND PABx while focusing on biopsy approach and patient and tumor characteristics. Multivariate analysis showed biopsies obtained in patients undergoing CTRFA or those with medial renal tumors were more likely to be ND. Future RFA patients should be counseled appropriately. Biopsy cores should be carefully inspected for sufficient material, and additional cores may be needed in these subgroups. In addition, a pathologist should stand by to ensure the adequacy of the specimen. Further prospective studies are warranted to confirm these findings.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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