Pretreatment Diagnosis of the Small Renal Mass: Status of Renal Biopsy in the United States of America

Abstract

Introduction:

We surveyed United States of America-based urologists to characterize practice patterns and indications to perform a renal mass biopsy for small renal masses.

Materials and Methods:

Members of the American Urological Association who practice in the United States were invited to participate in a 11-question web-based survey that was distributed via SurveyMonkey^® from December 2016 to January 2017.

Results:

There were 1131 respondents. The respondents equally represented all regions of the United States; the majority were in private practice. Overall, 32% of American urologists would “never” perform a biopsy of a renal mass ≤4 cm. Those who saw fewer than five small renal masses per year were more likely to “never” perform a renal biopsy on either a renal mass ≤4 cm or a renal mass 2–3 cm compared with those who saw more than five small renal masses per year (p < 0.001). Urologists who practiced at an academic hospital were more likely to perform a renal biopsy on both a renal mass ≤4 cm and a renal mass 2–3 cm compared with private practice and government-based urologists (p < 0.001 and p = 0.008 respectively). The primary reason for not performing a biopsy, cited by 68% of responding urologists, was that the results of a biopsy “would not change their management of the renal mass.” Respondents independently performed only 2% of biopsies; however, almost half stated that they would be interested in learning office-based ultrasound-guided biopsy of a small renal mass.

Conclusions:

Among members of the American Urological Association, biopsy of a small renal mass remains an underutilized diagnostic procedure, especially in light of 6000 unnecessary surgeries annually; nonuniversity-based urologists and those who see <5 renal mass cases each year infrequently perform a biopsy. Currently, interventional radiologists perform almost all small renal mass biopsies.

Introduction

There has been a significant rise in the incidental detection of small renal masses (≤4 cm) in the United States of America secondary to the increased use of cross-sectional abdominal imaging.¹ The treatment paradigm historically has been extirpative therapy with diagnosis dependent solely upon surgical excision. Of concern is that almost 20% of small renal masses are benign; as a result more than 6000 benign renal lesions undergo surgical excision, by either partial or radical nephrectomy, each year in the United States.² Given the significant heterogeneity in the biological aggressiveness of renal cortical neoplasms³ and the wide range of treatment options available coupled with improvements in renal imaging and renal biopsy techniques, renal mass biopsy has been proposed as a method to help the clinician formulate a diagnosis before offering treatment. It could be inferred that at a minimum, 20% of patients with a small renal mass could benefit from an increase in the practice of renal biopsy; indeed, this percentage is likely higher given that many of these tumors are found to be low-grade malignancies that could be could be surveilled, particularly in older and more ill populations.

Recently, the American Urological Association released updated guidelines on the management of the clinical stage I renal mass. These guidelines do not support the use of renal mass biopsy in healthy patients or older patients who presumably due to their advanced age may only consider conservative management options regardless of biopsy results.⁴ However, it is our contention that the role of biopsy to preclude nonbeneficial surgery in one-fifth of patients with a small renal mass needs to be revisited given refinements in imaging, and in biopsy technique, which together have increased the safety and accuracy of renal biopsy while decreasing the morbidity and, for those masses amenable to office-based biopsy, the cost.⁵

Four previous surveys on assessing urologists' practice patterns for dealing with a small renal mass were performed between 2005 and 2010.^6

–9 Of those, three specifically addressed renal mass biopsy indications and practice patterns with a total of 662 responses worldwide among which only 142 responses came from urologists in the United States.^6,8,9 Given the passage of nearly a decade, improvements in biopsy technique and outcome along with the prior small sample size regarding the utilization of renal mass biopsy in the United States, we sought to update current practice patterns and further characterize today's decision-making process surrounding renal mass biopsy in general, and for small renal mass biopsy in particular.

Materials and Methods

After obtaining institutional review board approval, an 11-question survey was designed by three endourologists at the University of California, Irvine with over 50 years of combined experience in the management of small renal masses while also taking into account the questions posed in the aforementioned studies. It was subsequently distributed via SurveyMonkey^®, a web-based survey provider (Appendix 1). All questions were close-ended, multiple-choice, and assessed the demographics of the respondents, their type of practice, and respondent's decision-making process regarding renal mass biopsy.

Invitations to participate in the web-based survey were sent to members of the American Urological Association practicing in the United States of America. The initial request to participate in the survey was sent on December 30, 2016, with reminders sent weekly to those who had not completed the survey within 3 weeks. The survey was closed on January 30, 2017.

Statistical analysis

Data from all responders who answered at least one survey item are described using descriptive statistics (frequencies and percents for categorical data). Responses to questions on practice patterns were compared among subgroups defined by practice region, practice type, hospital size, and number of renal mass patients treated annually. All variables were categorical thus departures from expected were tested using two-sided Pearson chi-square tests or chi-square tests for linear trend with significance level of 0.05. Analysis was conducted using SYSTAT v13 (Systat Software, Inc., Chicago, IL).

Results

A total of 6731 invitations were distributed. Of the 3489 individuals that opened the survey, 1131 (32.4%) submitted a response, among whom 721/1131 (64%) completed all questions on the survey and 1013/1131 (90%) completed 50% or more of all survey questions. The number of urologists that responded to each question is included in Appendix 1. The majority of respondents were practicing urologists (98.8%), representing a nearly equal distribution among Eastern, Midwestern, Southern and Western regions (Table 1).

Table 1.

Demographics of Survey Respondents

	Total (%)
Profession
Urologist	1116 (98.8)
Urology Resident	6 (0.5)
Physician Assistant/Nurse Practitioner	3 (0.3)
Other	4 (0.4)
Region
Eastern	298 (29.5)
Midwestern	237 (23.4)
Southern	240 (23.7)
Western	236 (23.3)
Practice type
Academic Hospital	256 (25.3)
Private Hospital	644 (63.6)
Veteran's Administration Hospital (VA)	28 (2.8)
Other	84 (8.3)
Hospital size
0–99 Beds	72 (7.1)
100–199	163 (16.1)
200–299	264 (26.0)
300–399	185 (18.2)
400+	331 (32.6)
Annual number of patients treated with a renal mass
0–5	104 (10.3)
5–10	172 (17.0)
10–15	258 (25.5)
20+	477 (47.2)

Regarding renal masses that are ≤4 cm and 2–3 cm, 31.8% and 35.0% of urologists, respectively, would never consider obtaining a biopsy. Notably, urologists in a university practice were more likely than those working in other practice settings to perform a biopsy on ≤4 cm small renal mass (80.7% vs 63.9%, p < 0.001) and on a 2–3 cm small renal mass (71.9% vs 62.7%, p = 0.008). Furthermore, urologists who saw over five patients per year with a small renal mass were more likely to perform a biopsy than those who saw less than five small renal mass patients per year, 71.3% vs 42.2% (p < 0.001) (Table 2). There was no difference in biopsy practice based on hospital size (p = 0.356).

Table 2.

Frequency of Performing Biopsy in a Small Renal Mass ≤4 cm and 2–3 cm Based on Practice Type and Number of Patients with a Renal Mass Treated Annually

		Never biopsy	Consider biopsy	p Value
Renal mass ≤4 cm
Practice type	Academic (%)	49 (19.3%)	205 (80.7%)	<0.001
Practice type	Private, VA, other (%)	272 (36.1%)	482 (63.9%)	<0.001
# of patients seen annually	0–5	59 (57.8%)	43 (42.2%)	<0.001
	5–10	68 (39.5%)	104 (60.5%)
	10–15	71 (27.6%)	186 (72.4%)
	20+	121 (25.4%)	355 (74.6%)
Renal mass 2–3 cm
Practice type	Academic (%)	71 (28.1%)	182 (71.9%)	0.008
Practice type	Private, VA, other (%)	280 (37.3%)	471 (62.7%)	0.008
# of patients seen annually	0–5	56 (55.4%)	45 (44.6%)	<0.001
	5–10	65 (38.0%)	106 (62.0%)
	10–15	85 (33.1%)	172 (66.9%)
	20+	143 (30.2%)	331 (69.8%)

Respondents were asked to rank eight potential reasons for not performing a biopsy (Fig. 1), from most compelling to least. The majority of urologists (68%) responded that it would not change their management. The next two most important reasons not to do a biopsy were the risk of a false negative biopsy (10.2%) and risk of a nondiagnostic biopsy (9.7%), followed by risk of complications (3.9%), lack of infrastructure (3.3%) risk of tract seeding (2.7%), cost (1.6%), and risk of a false positive biopsy (0.6%).

FIG. 1.

Most important indication not to perform a renal mass biopsy.

Respondents were also asked to indicate who performs a renal biopsy in their practice environment. Only 2% of urologists perform renal biopsies independently while 4% perform a renal biopsy concurrently with an interventional radiologist; in sum, 94% of urologists defer to interventional radiologists to perform the biopsy (Table 3). Of interest, almost half of the urologists surveyed (48.3%) stated that they would be interested in learning office-based ultrasound-guided biopsy of a small renal mass.

Table 3.

Renal Mass Biopsy Physician of Record

Type of physician	Total (%)
Interventional radiology	949 (94)
Urologist	20 (2)
Both	39 (4)
Other	4 (<1)

Furthermore, respondents were asked whether recent literature had changed their attitude toward renal mass biopsy; 55% of respondents reported that it had for small renal masses <3 cm, while 11% noted a similar change in approach for tumors up to 7 cm. Those individuals practicing in a university setting vs private or government-based were more likely to have changed their attitude toward renal biopsy based on recent literature, 70% vs 65% (p < 0.001). Attitude toward renal biopsy was trending to more likely change in favor of renal biopsy, with increasing number of renal masses seen annually (p = 0.053).

There was no regional variation on the number of patients with a small renal mass seen by the urologists who responded (p = 0.413). For a ≤4 cm small renal mass, urologists in the Midwestern region were more likely to obtain a renal mass biopsy followed by the Western, Eastern, and Southern regions (p = 0.036). For a 2–3 cm small renal mass, Midwestern urologists again were more likely to obtain a renal mass biopsy followed by the Western, Southern, and Eastern regions (p = 0.002). Of note, when comparing urologists who obtain a renal mass biopsy ≥50% of the time, there was no statistical difference across regions.

Discussion

According to the Centers for Disease Control and Prevention's National Center for Health Statistics there will be 63,990 cases of kidney cancer diagnosed in 2017.¹⁰ Currently, according to the Surveillance, Epidemiology, and End Results program, in 2013 the percentage of kidney cancers diagnosed in the localized stages ranges up to 73% depending on race and sex.¹¹ This trend for small, localized tumors has been proposed to be a reflection of earlier diagnosis primarily as a result of the widespread and increased use of computed tomography (CT) examinations in the United States of America^1,11

Despite excision of these tumors, by partial or radical nephrectomy, survival of patients with kidney cancer has not changed significantly. Robust increase in the diagnosis and intervention of small renal masses without an associated reduction in mortality further confounds contemporary practice. Surgical extirpation remains the gold standard treatment for renal cortical neoplasms, with diagnosis trailing rather than preceding treatment unlike for most other genitourinary tract tumors be they of bladder or prostate origin.

From 2005 to 2010, according to the Surveillance, Epidemiology, and End Results program database there was an 11% increase in partial nephrectomy, and 6% increase in needle ablative therapy. Despite this increase, in 2010, 30% of small renal cancers were still treated with radical nephrectomy. Further epidemiological studies suggest that treatment of small renal masses with radical nephrectomy rather than partial nephrectomy or thermal ablation, results in the deterioration and shortening of patients' lives despite the final diagnosis revealing a renal cancer.¹²

This study was conducted to elucidate the role of pretreatment renal biopsy in the management of small renal masses in the United States in 2017. Prior studies, 2010 and earlier, were markedly limited due to a paucity of responses; indeed, there were only 142 responses from urologists practicing in the United States during a survey period from 2005 to 2010. Moreover, before 2010, data on renal mass biopsy were limited.^{13

–20} The current survey represents a nearly 10-fold increase in U.S. respondents compared to earlier reports; also in this survey nearly half of the respondents noted treating >20 small renal masses a year. It is clear that in the United States of America today, only a minority of urologists routinely perform a renal mass biopsy. Indeed, nearly one-third of urologists never perform biopsy on a small renal mass.

Two-thirds of responders cited that their primary reason not to perform a renal mass biopsy was due to a lack of change in the management plan. However, current data clearly support the contention that when a renal biopsy reveals a benign lesion, the best course of action is cessation of ongoing monitoring or at most annual radiographic surveillance.

While minimally invasive approaches, either laparoscopic/robotic excision or image-guided needle-based thermal ablation, have substantially decreased the morbidity of therapy their cost or rate of complications still outweigh the expense and risks of renal biopsy. The reported rate of major complications secondary to renal mass biopsy is <1%.^5,20,21 A recent meta-analysis by Pierorazio and colleagues similarly demonstrated Clavien II–IV complication rates of 0.2%, 3.9%, and 3.0% for renal mass biopsy, partial nephrectomy, and thermal ablative therapy, respectively.²²

A significant reason many urologists reported not performing a renal mass biopsy is the risk of a false negative result when a needle biopsy misdiagnoses a cancerous lesion as benign. The false negative rate of renal mass biopsy is 3.1%.²³ While this is of concern, it should also be noted that <2% of small renal masses progress to metastatic disease during surveillance.^24,25 A policy of active surveillance should uncover any rapidly growing lesion (i.e., >3–5 mm/year.), which would then stimulate a repeat biopsy.

The concern regarding a false positive biopsy is likely also overemphasized. The risk of this occurring is 4%.²³ Recently, Richard and colleagues evaluated the accuracy of renal mass biopsy in a multi-institutional setting using a Canadian registry from 2011 to 2015; they reported a nondiagnostic rate of 13% that fell to 9% with a repeat biopsy.²⁰ These results are consistent with a recent meta-analysis presented by Marconi and colleagues, which noted a diagnostic rate of 92%; similarly a systematic review by Patel et al. cite a <10% nondiagnostic rate when incorporating a repeat biopsy.^21,23 These studies indicate that biopsies commonly are diagnostic; and when they are not, a repeat biopsy or treatment can be pursued.

There is a distinct heterogeneity of cancer progression in patients diagnosed with renal cell carcinoma depending on their histopathologic subtype. Clear cell when high grade and Type II papillary subtypes are associated with more aggressive features while chromophobe and Type I papillary are more indolent in their nature.³ Richard and colleagues noted that renal mass biopsy histology and grade have been found to be highly concordant with final surgical pathology, 93% and 94%, respectively.^20,26 Of note, most (75.6%) of the small renal masses with biopsy proven renal cancer were found to be low-Fuhrman grade renal cell carcinoma.^20,26 Renal mass biopsy can change patient management among those with a cancer diagnosis to support consideration of active surveillance versus expedient intervention.

We found that respondents' opinions were in line with contemporary literature regarding the possible seeding of the needle tract during biopsy; very few respondents indicated a concern about needle tract seeding. Indeed, it is an exceedingly rare complication with only eight reports of implantation of renal cell carcinoma in percutaneous biopsy tracts over the last four decades.²⁷ This marked decrease in tumor seeding is likely secondary to the increasing use of smaller biopsy needles, better tumor targeting, and the use of a tract protective coaxial sheath, which decreases the direct contact of needle adherent biopsied tissue with the surrounding tissue.

Renal mass biopsy is traditionally performed under CT guidance. As such, not surprisingly, 94% of respondents noted that when a renal biopsy is sought, an interventional radiologist invariably performs the procedure. However, this practice is now slowly beginning to change due to the advent of ultrasound-guided office-based renal mass biopsy. The office approach is reserved for nonhilar, posterior, subcostal tumors; it allows the biopsy to be accomplished free of ionizing radiation, at a third of the cost of a CT-guided hospital-based biopsy, and with a similar diagnostic and complication rate.²⁸ Interest among urologists to learn this technique is evident in that nearly half of the responding urologists (48.3%) reported a desire to learn ultrasound-guided office-based renal biopsy.

The urologist's type of practice influenced their use of small renal mass biopsy. Indeed, while 20% of university urologists reported that they would never perform a biopsy over 33% of nonuniversity urologists would similarly never pursue a pretreatment biopsy. This finding complements the finding that survey participants practicing at academic centers were significantly more likely to change their attitude toward renal biopsy based on recent literature when compared with their nonacademic counterparts.

There are several limitations that we noted in our study. First, our response rate was only 32% among those individuals who received and opened the survey; compared with previous studies not focused on U.S. population, we had anticipated a stronger response rate given our focus on USA-based urologists. However, it is important to note that the total number of responders in this study is nearly ten times larger than the number of USA-based responders from all the previous renal biopsy surveys combined. Given that the average office worker receives 121 emails a day and the average open rate is 31%, one could argue that a new standard for response rate might be considered for web-based surveys.²⁹ Additionally, the responses were self-reported by the person completing the survey. We did not audit nor confirm the responses against the respondents' actual practice records. Lastly, rates of renal mass biopsy might have been higher if respondents were given additional qualifiers such as age and comorbidities of the patient or whether concern for metastatic disease or nonrenal cell carcinoma were included in the differential diagnosis.

Conclusions

Despite recent evidence supporting the cost effective role of renal mass biopsy in the management of small renal masses, 32% of American urologists would never perform a biopsy in a renal mass ≤4 cm because they believe it would not change their management strategy. This nonbiopsy approach to renal mass biopsy is more prevalent among those urologists who see fewer than five small renal mass cases a year who are in a nonacademic setting. Currently, interventional radiologists perform almost all small renal mass biopsies, although nearly half of the respondents expressed an interest in learning office ultrasound-guided renal biopsy of a small renal mass.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Abbreviation Used

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