Multidisciplinary Approach and Outcomes of Pretreatment Small (cT1a) Renal Mass Biopsy: Single-Center Experience

Abstract

Purpose:

We evaluated our experience of a multidisciplinary approach to renal mass biopsy (RMB) for small renal masses (SRMs) employing in-office ultrasound (US)-guided biopsy by urology (24%), CT, or US biopsy by interventional radiology (IR) (79%), and endoscopic ultrasound (EUS)-guided biopsy by gastroenterology (GI) (4%).

Materials and Methods:

A single-institution retrospective review of patients who underwent RMB for SRM from May 2013 to August 2019 was conducted. Data regarding patient demographics, tumor characteristics, biopsy technique, histopathology, and management were collected. Diagnostic rates, concordance with final pathology, complications, and outcomes were analyzed.

Results:

Of the 192 biopsies reviewed, 63% biopsies were malignant, 20% were benign, and 17% were nondiagnostic. Based on biopsy results, 71 patients (37%) elected active surveillance. Thirty-eight (20%) patients underwent cryoablation, 56 (29%) underwent partial nephrectomy, 14 (7%) underwent radical nephrectomy, and the remaining patients were treated elsewhere. The rate of surgery for benign pathology after pretreatment RMB was 3%. The concordance rate between biopsy and final pathology was 99% for malignancy, 96% for specific pathology subtype, and 85% for renal cell carcinoma grade. Median time from diagnosis to definitive treatment was 97 days (urology: 76, IR: 110 and GI: 54, p = 0.002). Three (1.6%) Clavien I complications were reported.

Conclusion:

Our multidisciplinary approach to RMB for clinical stage T1a demonstrated favorable safety and diagnostic rates, which effectively directed management strategies and minimized surgery for benign disease. Urologist-performed office biopsies significantly shortened the time from diagnosis to definitive treatment. Our experience with GI EUS biopsy has demonstrated feasibility and safety for tumors that were otherwise not accessible percutaneously.

Introduction

In contemporary practice, up to 25% of surgically removed clinical stage T1a (≤4 cm) small renal masses (SRMs) are benign.¹ The absolute number of excised benign tumors has been rising due to increased renal mass detection because of widespread use of CT.² Moreover, up to 60% of malignant SRMs are indolent and may not require immediate surgical therapy.³ Renal mass biopsy (RMB) is a safe, cost-effective, and accurate method to characterize renal masses,⁴ and has been shown to favorably alter patient management.^5,6

Since 2013, our Urology department has employed routine pretreatment RMB for patients presenting with SRMs who are candidates for active treatment (surgery or cryoablation). To our knowledge, routine biopsy of SRMs with a multidisciplinary approach, including urology, interventional radiology (IR), and GI has not previously been reported. In the current study, we evaluate the impact of our institutional practice of a routine, comprehensive, multidisciplinary approach to pretreatment RMB in the management of SRMs.

Materials and Methods

Patient selection

With Institutional Review Board approval, we reviewed a prospectively maintained database of patients who underwent a renal biopsy for a cT1a renal mass at the University of California, Irvine Medical Center from May 2013 to August 2019. Patients were excluded if they had: tumors larger than 4 cm, biopsy performed at the time of an ablative procedure, inaccessible medical records, and/or renal biopsy for other than a renal mass.

Biopsy technique

Our techniques of the CT-guided and office-based, ultrasound (US)-guided RMB have been previously described.^7,8 For SRMs detectable during in-office US with a safe tract for needle deployment, patients are offered in-office biopsy. Tumors that are not visualized well, those without a clear needle trajectory, or patients in which an office procedure is deemed imprudent by the urologist are referred to IR for CT- or US-guided biopsy. For tumors located anteriorly or medially thereby precluding a safe percutaneous access, an endoscopic ultrasound (EUS)-guided biopsy is provided by a gastroenterologist (GI). GI EUS-guided RMBs are performed in an outpatient endoscopy suite under intravenous (IV) sedation or general anesthesia. The patient is placed in a lateral decubitus position and an Olympus GF-UC140P linear EUS endoscope (Olympus Medical Systems Corporation, Tokyo, Japan) is advanced through the patient's mouth into the stomach and duodenum.

Using water as an acoustic interface, ultrasonography is performed to visualize the tumor through the gastric wall for left-sided tumors and through the duodenum for right-sided tumors. An EUS fine-needle aspirate (FNA) needle or endoscopic Trucut biopsy needle (Quick-Core; Wilson-Cook Medical, Inc., Winston-Salem, NC) is introduced to obtain either FNA or core biopsies, respectively. Upon completion, the water is aspirated and the patient is transferred to a recovery room and monitored for 2 to 4 hours.

Outcome analyses

Patient demographics, tumor characteristics, biopsy techniques, pathological results, and management strategies were collected. Histopathological results, diagnostic rates, and concordance between biopsy and surgical pathology were also analyzed. Biopsies were classified according to the service (urology, IR, or GI) and further classified according to the imaging modality used (US-guided, CT-guided, or combined CT and US) and technique (core or FNA). Histopathological results were classified into malignant, benign, or nondiagnostic. Nondiagnostic biopsies were further classified as either “indeterminate,” when pathology was insufficient for diagnostic purposes, or “technical failure,” when the tumor was missed by the biopsy needle as corroborated by only normal renal parenchyma or fibroconnective tissue in the biopsy core. Biopsies of a malignant nature were further classified based on histologic subtype and grade. Biopsy-related complications, rate of repeat biopsies, primary management, time from diagnosis to biopsy and treatment, and oncologic outcomes (mortality, recurrence, or distant metastasis) were assessed.

Discrete data points were expressed as number of events and relative percentages; continuous data were expressed as means and standard deviations. Pertinent variables were compared between urology and IR using Chi-square and t-test for categorical and continuous variables, respectively. Statistical analyses were conducted using SPSS v.25 © (IBM Corporation, Armonk, NY).

Results

Subjects

Among 192 patients, 46 (24%) RMB were performed by urology, 139 (72%) RMB were performed by IR, and 7 (4%) RMB were performed by GI (Table 1). The median time from clinical diagnosis (i.e., first office consultation) until RMB was 14 days (IQR 7–28) for urology, 41 days (IQR 22–72) for IR, and 29 days (IQR 12–30) for GI. Overall, median time from clinical diagnosis of renal mass to treatment was 97 days (IQR 69–166), with 76 days for urology, 110 for IR, and 54 days for GI (p = 0.002).

Table 1.

Demographic and Clinical Information

	Uro (n = 46)	IR (n = 139)	GI (n = 7)	All (n = 192)	p ^a
Age, years, mean (%)	65.7 (29–88)	63.7 (21–88)	62.4 (28–75)	64.1 (20–88)	0.37
Gender, no. (%)
Female	22 (48)	53 (38)	3 (43)	78 (40)	0.49
Male	24 (52)	86 (62)	4 (57)	114 (60)	0.49
Body mass index, mean ± SD	26.7 ± 4.42	29.2 ± 7.49	29.4 ± 5.92	28.6 ± 6.83	0.01
Charlson Comorbidity Index, mean ± SD	5.17 ± 2.08	5.18 ± 2.05	5.14 ± 1.86	5.18 ± 2.04	0.98
American Society of Anesthesiologists, mean ± SD	2.68 ± 0.48	2.67 ± 0.59	2.86 ± 0.69	2.68 ± 0.57	0.95
Presenting symptom, no. (%)
Incidental	44 (96)	118 (85)	3 (43)	165 (86)	0.31
Flank pain	2 (4)	11 (8)	2 (29)	15 (8)
Hematuria	0 (0)	4 (3)	1 (14)	5 (2)
Urinary tract Infection	0 (0)	3 (2)	1 (14)	4 (2)
Cancer Surveillance	0 (0)	3 (2)	0 (0)	3 (2)
Days from, median (IQR)
Diagnosis to Biopsy	14 (7–28)	41 (22–72)	29 (12–30)	32 (16–66)	0.19
Biopsy to management decision	7 (7–21)	15 (8–28)	9 (9–16)	13 (7–28)	0.52
Diagnosis to treatment	76 (54–110)	110 (75–187)	54 (33–166)	97 (69–166)	0.002

Bold signifies significance p < 0.05.

p-value comparing Urology and IR only.

GI = gastroenterology; IR = Interventional Radiology

Tumor characteristics

The mean tumor size for RMBs performed in the urology office was 3.09 ± 0.78 cm, which was larger than those performed in IR (2.6 ± 0.80 cm) (p < 0.001). Tumor characteristics, including laterality, size, location, depth, and complexity are summarized in Table 2.

Table 2.

Tumor Characteristics

	Uro (n = 46)	IR (n = 139)	GI (n = 7)	All (n = 192)	p ^a
Laterality, no. (%)
Left	23 (50)	79 (57)	3 (43)	105 (55)	0.40
Right	23 (50)	60 (43)	4 (57)	87 (45)	0.40
Tumor size (cm), mean ± SD	3.09 ± 0.78	2.60 ± 0.80	2.47 ± 1.04	2.72 ± 0.83	<0.001
Tumor description, no. (%)
Solid	45 (98)	134 (96)	7 (100)	186 (97)	0.64
Cystic	1 (2)	5 (4)	0 (0)	6 (3)
Bosniak 3	0 (0)	4 (3)	0 (0)	4 (2)
Bosniak 4	1 (2)	1 (1)	0 (0)	2 (1)
Tumor location, no. (%)
Upper pole	5 (11)	49 (35)	3 (43)	57 (30)	0.001
Interpolar	24 (52)	47 (34)	4 (57)	75 (39)	0.02
Lower pole	17 (37)	43 (31)	0 (0)	60 (31)	0.45
Tumor depth, no. (%)
Endophytic	8 (17)	24 (17)	3 (43)	35 (18)	1
Exophytic	28 (61)	60 (44)	0 (0)	88 (46)	0.03
Mesophytic	6 (13)	45 (32)	4 (57)	55 (29)	0.02
No data	4 (9)	10 (7)	0 (0)	14 (7)
Anterior/posterior, no. (%)
Posterior	35 (76)	76 (54)	0 (0)	111 (58)	0.01
Anterior	6 (13)	43 (31)	4 (57)	53 (27)	0.02
Neither	5 (11)	16 (12)	3 (43)	24 (13)	0.78
No data	0 (0)	4 (3)	0 (0)	4 (2)
Complexity (by RENAL score), no. (%)
Low (4–6)	27 (59)	76 (55)	0 (0)	103 (53)	0.99
Mod (7–9)	17 (37)	48 (35)	6 (86)	71 (38)
High (10–12)	2 (4)	5 (4)	1 (14)	8 (4)
No data	0 (0)	10 (6)	0 (0)	10 (5)
Mean RENAL score, mean (SD)	6.26 ± 1.58	6.38 ± 1.64	8.43 ± 1.13	6.43 ± 1.65	0.67
Hilar, no. (%)
No	44 (96)	118 (85)	4 (57)	166 (86)	0.35
Yes	2 (4)	11 (8)	3 (43)	16 (9)
No data	0 (0)	10 (7)	0 (0)	10 (5)

Bold signifies significance p < 0.05.

p-value comparing Urology and IR only.

Biopsy procedure

All urology office biopsies were performed with US guidance under local anesthesia. Of the IR biopsies, 28 (20%) were performed with only US guidance, 59 (43%) were performed with only CT guidance, and 52 (37%) were performed with combined CT and US guidance. One hundred thirty-five (97%) of the IR-performed biopsies were performed with IV sedation and 4 (3%) were performed with general anesthesia. Five (71%) of the GI EUS biopsies were performed under general anesthesia, whereas 2 (29%) were under IV sedation. Of note, none of the office biopsies required IV sedation.

The overall complication rate was 1.6% (3/192); all in the IR group. All three had a moderately sized perinephric hematoma (maximum diameter 4.3 cm²) noted on immediate postbiopsy imaging (Clavien–Dindo Grade I), all were managed conservatively without hospital admission or transfusion. There were no tumor seeding events observed. Procedural information is summarized in Table 3.

Table 3.

Biopsy Procedure

	Uro (n = 46)	IR (n = 139)	GI (n = 7)	All (n = 192)
Imaging, no. (%)
CT	0 (0)	59 (42)	0 (0)	59 (31)
CT and US	0 (0)	52 (38)	0 (0)	52 (27)
US	46 (100)	28 (20)	7 (100)	81 (42)
Anesthesia, no. (%)
General	0 (0)	4 (3)	5 (71)	9 (5)
Local	46 (100)	0 (0)	0 (0)	46 (24)
Sedation	0 (0)	135 (97)	2 (29)	137 (71)
Needle type, no. (%)
Both	0 (0)	1 (1)	0 (0)	1 (1)
Core	46 (100)	137 (98)	5 (71)	188 (97)
FNA	0 (0)	1 (1)	2 (29)	3 (2)
Needle size, no. (%)
18-gauge	46 (100)	127 (91)	0 (0)	173 (90)
19-gauge	0 (0)	0 (0)	2 (29)	2 (1)
20-gauge	0 (0)	11 (8)	3 (42)	14 (7)
4F	0 (0)	1 (1)	0 (0)	1 (1)
EUS FNA	0 (0)	0 (0)	2 (29)	2 (1)
Samples taken, no. (%)
Core
1–2	1 (2)	25 (18)	5 (100)	31 (16)
3–4	27 (59)	88 (63)	0 (0)	115 (55)
5–6	10 (22)	17 (12)	0 (0)	27 (14)
>6	2 (4)	7 (5)	0 (0)	9 (5)
Not specified	6 (13)	1 (1)	0 (0)	7 (4)
FNA
1	0 (0)	1 (100)	1 (50)	2 (67)
3	0 (0)	0 (0)	1 (50)	1 (33)
Biopsy-related complications, no. (%)
Clavien I	0 (0)	3 (2)	0 (0)	3 (2)
No complications	46 (100)	136 (98)	7 (100)	189 (98)

EUS = endoscopic ultrasound; FNA = fine-needle aspirate.

Initial histopathology

Overall, 121 (63%) biopsies yielded a diagnosis of malignancy, 38 (20%) were benign, and 33 (17%) were nondiagnostic (Table 4). The nondiagnostic rate for urology, IR, and GI biopsies was 33%, 11%, and 43%, respectively. Of the nondiagnostic biopsies, 11 (33%) were due to indeterminate pathology, whereas 22 (67%) were due to technical failure. Of the Urology office-based biopsies, the overall nondiagnostic rate during the study period was 33%, with 3 (20%) due to indeterminate pathology and 12 (80%) due to technical failure (Table 4). The nondiagnostic rate dropped from 56% during the initial 2 years of office-based biopsy, to 20% in subsequent 4 years (p = 0.01) (Fig. 1). Further breakdown of the IR nondiagnostic rate based on the imaging modality used was 5% for CT only, 7% for US only, and 19% when CT and US were employed. The GI nondiagnostic biopsy rate was 43% (3/7), with one failure associated with FNA of a solid tumor.

FIG. 1.

Diagnostic rate of Urology office biopsies.

Table 4.

Histopathology

	Uro (n = 46)	IR (n = 139)	GI (n = 7)	Total (n = 192)	p ^a
Diagnostic, no. (%)	31 (67)	124 (89)	4 (57)	159 (83)	0.001
Malignant	23 (74)	95 (77)	3 (75)	121 (76)
Adenocarcinoma	1 (4)	0 (0)	0 (0)	1 (1)
B cell lymphoma	0 (0)	1 (1)	0 (0)	1 (1)
Metastatic	0 (0)	1 (1)	0 (0)	1 (1)
RCC	22 (96)	93 (98)	3 (100)	118 (97)
Clear cell	18 (82)	69 (74)	3 (100)	90 (76)
Low grade (1–2)	12 (67)	54 (77)	5 (100)	69 (77)
High grade (3–4)	2 (11)	7 (10)	0 (0)	9 (10)
Grade not specified	4 (22)	8 (11)	0 (0)	12 (13)
Papillary	4 (18)	17 (18)	0 (0)	21 (18)
Type 1	2 (50)	12 (70)	0 (0)	14 (67)
Type 2	0 (0)	2 (12)	0 (0)	2 (9)
Not specified	2 (50)	3 (18)	0 (0)	5 (24)
Chromophobe	0 (0)	6 (6)	0 (0)	6 (5)
Clear cell papillary (tubulopapillary)	0 (0)	1 (1)	0 (0)	1 (1)
Benign, no. (%)	8 (26)	29 (23)	1 (25)	38 (24)
Oncocytoma	4 (50)	19 (66)	0 (0)	23 (60)
Angiomyolipoma	4 (50)	6 (21)	1 (100)	11 (29)
Fat-poor	1 (25)	2 (33)	0 (0)	3 (27)
Fat-rich	1 (25)	0 (0)	0 (0)	1 (1)
Not specified	1 (25)	4 (67)	1 (100)	6 (54)
Fat-average	1 (25)	0 (0)	0 (0)	1 (1)
Cyst	0 (0)	3 (10)	0 (0)	3 (8)
Papillary adenoma	0 (0)	1 (3)	0 (0)	1 (3)
Nondiagnostic, no. (%)	15 (33)	15 (11)	3 (43)	33 (17)	0.001
Indeterminate pathology	3 (20)	6 (40)	2 (67)	11 (33)	0.43
Technical failure	12 (80)	9 (60)	1 (33)	22 (67)	0.43
Repeat biopsy done
No (subsequent management)	6 (40)	12 (80)	3 (100)	21 (64)
Active surveillance	4 (66)	10 (83)	2 (67)	16 (76)
Cryoablation	1 (17)	2 (17)	0 (0)	3 (14)
Surgery	1 (17)	0 (0)	1 (33)	2 (10)
Yes (repeat biopsy result)	9 (60)	3 (20)	0 (0)	12 (36)
Benign	3 (33)	1 (33)	0 (0)	4 (33)
Malignant	6 (67)	1 (33)	0 (0)	7 (58)
Nondiagnostic	0 (0)	1 (33)	0 (0)	1 (8)

p-value comparing urology and IR only.

RCC = renal cell carcinoma.

The most common malignant diagnosis was renal cell carcinoma (RCC) (97%): 90 (76%) clear cell, 21 (18%) papillary (Type 1: 14, Type 2: 2, not specified: 5), 6 (5%) chromophobe, and 1 (1%) clear cell papillary (tubulopapillary). Other malignant diagnoses included metastatic parotid gland adenocarcinoma, B cell lymphoma, and metastatic adenoid cystic carcinoma. The most common benign diagnosis was oncocytoma 23 (60%), followed by angiomyolipoma 11 (29%). Three (8%) tumors were diagnosed to be renal cysts (by corresponding decrease in size upon aspiration with no malignant cells noted in the fluid and epithelial lining) and one (3%) tumor was a papillary adenoma.

Of the 33 patients who had a nondiagnostic biopsy, 12 (34%) had a repeat biopsy, all performed by IR under CT guidance. Eleven (92%) had a diagnostic result on the repeat biopsy, including seven malignancies (six low-grade and one high-grade clear cell renal cell carcinoma [ccRCC]), and four benign tumors (oncocytoma). None of the GI EUS biopsies underwent a repeat biopsy procedure. Histopathology results are summarized in Table 4.

Management and final pathology

Based on biopsy-directed treatment strategy, 71 (37%) patients elected for active surveillance (AS), 38 (20%) underwent cryoablation, 56 (29%) underwent partial nephrectomy (PN), and 14 (7%) had a radical nephrectomy (RN); 1 patient who was diagnosed with B cell lymphoma underwent systemic chemotherapy. Twelve patients had their subsequent care at outside institutions from which we were unable to secure follow-up information. Among the 71 patients managed with AS, 35 (49%) had a benign biopsy, 19 (27%) had a malignant diagnosis (11 low-grade ccRCC, 5 papillary type 1, 1 chromophobe, 1 metastatic, and 1 adenocarcinoma), and 17 (24%) had a nondiagnostic biopsy and declined a repeat biospy (Table 5).

Table 5.

Management

Primary treatment	Uro (n = 46), no. (%)	IR (n = 139), no. (%)	GI (n = 7), no. (%)	Total (n = 192), no. (%)
Active surveillance	18 (39)	49 (35)	4 (57)	71 (37)
Benign	7 (39)	27 (55)	1 (25)	35 (49)
Malignant	4 (22)	14 (29)	1 (25)	19 (27)
Nondiagnostic	7 (39)	8 (16)	2 (50)	17 (24)
Cryoablation	4 (9)	34 (25)	0 (0)	38 (20)
Percutaneous	4 (100)	32 (94)	0 (0)	36 (95)
Laparoscopic	0 (0)	2 (6)	0 (0)	2 (5)
Partial nephrectomy	19 (41)	35 (25)	2 (29)	56 (29)
Laparoscopic	15 (68)	27 (60)	2 (67)	44 (63)
Open	1 (5)	4 (9)	0 (0)	5 (7)
Robot-assisted	3 (14)	4 (9)	0 (0)	7 (10)
Radical nephrectomy	3 (7)	10 (7)	1 (14)	14 (7)
Laparoscopic	3 (14)	8 (18)	1 (33)	12 (17)
Open	0 (0)	1 (2)	0 (0)	1 (1)
Robot-assisted	0 (0)	1 (2)	0 (0)	1 (1)
Subsequent care performed at outside institution	2 (4)	10 (7)	0 (0)	12 (6)
Chemotherapy	0 (0)	1 (1)	0 (0)	1 (1)

All 14 patients who underwent RN had confirmed malignancy on final biopsy result: 8 low-grade ccRCC, 5 high-grade ccRCC, and 1 papillary type 2 RCC. Two (4%) PN yielded a benign diagnosis on final histopathology: angiomyolipoma and oncocytoma. Biopsy pathology for the angiomyolipoma demonstrated only fibroconnective tissue, whereas the biopsy pathology for the oncocytoma was initially suggestive of chromophobe RCC. The remaining PN patients yielded a final histopathology of RCC. The overall rate for benign histopathology after extirpative surgery for patients who underwent pretreatment RMB was 3% (Table 6).

Table 6.

Final Pathology

Final pathology	Uro (n = 22), no. (%)	IR (n = 45), no. (%)	GI (n = 3), no. (%)	Total (n = 70), no. (%)
Partial nephrectomy	(n = 19)	(n = 35)	(n = 2)	(n = 56)
Angiomyolipoma	0 (0)	1 (3)	0 (0)	1 (2)
Oncocytoma	1 (5)	0 (0)	0 (0)	1 (2)
RCC	18 (95)	34 (97)	2 (100)	54 (96)
Chromophobe	0 (0)	4 (12)	0 (0)	4 (7)
Clear cell	17 (94)	24 (71)	1 (50)	42 (78)
Low grade (1–2)	15 (88)	19 (79)	1 (100)	35 (83)
High grade (3–4)	2 (12)	5 (21)	0 (0)	7 (17)
Papillary	1 (6)	5 (15)	1 (50)	7 (13)
Type 1	1 (100)	4 (80)	1 (100)	6 (86)
Type 2	0 (0)	1 (20)	0 (0)	1 (14)
Clear cell papillary (tubulopapillary)	0 (0)	1 (3)	0 (0)	1 (2)
Radical nephrectomy	(n = 3)	(n = 10)	(n = 1)	(n = 14)
RCC	3 (—)	10 (—)	1 (—)	14 (—)
Chromophobe	0 (0)	0 (0)	0 (0)	0 (0)
Clear cell	3 (100)	9 (90)	1 (100)	13 (93)
Low grade (1–2)	2 (67)	6 (67)	0 (0)	8 (62)
High grade (3–4)	1 (33)	3 (33)	1 (100)	5 (38)
Papillary type 1	0 (0)	0 (0)	0 (0)	0 (0)
Papillary type 2	0 (0)	1 (10)	0 (0)	1 (7)
Concordance for malignancy	(n = 22)	(n = 45)	(n = 2)	(n = 69)
Yes	21 (95)	45 (100)	2 (100)	68 (99)
No	1 (5)	0 (0)	0 (0)	1 (1
Concordance by malignant subtype	(n = 21)	(n = 45)	(n = 2)	(n = 68)
Yes	21 (100)	43 (96)	1 (50)	65 (96)
No	0 (0)	2 (4)	1 (50)	3 (4)
Concordance by grade (for ccRCC)	(n = 12)	(n = 33)	(n = 1)	(n = 46)
Yes	9 (75)	30 (91)	0 (0)	39 (85)
No	3 (25)	3 (9)	1 (100)	7 (15)
Final grade is higher	2 (67)	3 (100)	1 (100)	6 (86)
Final grade is lower	1 (33)	0 (0)	0 (0)	1 (14)

ccRCC, clear cell renal cell carcinoma.

For the patients who underwent surgery after an initial diagnostic biopsy, the overall concordance rate for general pathology (benign vs malignant) was 99%. One pretreatment biopsy was suggestive of chromophobe RCC but on final pathology was an oncocytoma. The concordance for RCC histological subtype was 96% (70/73). For ccRCC, concordance by grade (high vs low) was 85% (39/46). Of the seven ccRCC with grade discordance, six (13% overall) had a higher grade on final pathology, whereas only one (2% overall) had a lower grade on the surgical specimen (Table 6).

Outcomes

Of the patients on AS, two (3%) patients (one with a nondiagnostic biopsy and the other with low-grade ccRCC), converted to PN due to SRM growth of 2.9 cm over 4 years and 0.4 cm over 9 months, respectively. Histopathology revealed papillary type 2 RCC for the first patient and confirmed low-grade ccRCC for the second patient. With follow-up of 25 and 23 months, respectively, both patients remain with no evidence of disease. Of the 11 patients with low-grade ccRCC, 1 had progression to surgery with mean follow-up of 18 months (range 2–38 months). Of the remaining AS cases, the average growth rate was 1.49 mm/year for those with a malignant SRM (ccRCC: 1.53 mm/year; papillary: 0.88 mm/year, chromophobe: 3.6 mm/year), 1.14 mm/year for those with a benign SRM, and 1.92 mm/year for patients with a nondiagnostic biopsy. AS-specific outcomes are summarized in Table 7.

Table 7.

Active Surveillance Outcomes Based on Pretreatment Biopsy Results

	Uro	IR	GI^a	Total
Active surveillance, no. (%)	n = 18	n = 49	n = 4	n = 71
Progression to surgery	1 (6)	1 (2)	0 (0)	2 (3)
No progression to surgery	17 (94)	48 (98)	4 (100)	69 (97)
Malignant, mean ± SD	n = 4^b	n = 14^c	n = 1	n = 19
Clear cell RCC (low grade)				n = 11
Average tumor growth (mm)	13	5.10 ± 7.6	N/A	2.29 ± 4.43
Follow-up duration (months)	22.6	17.4 ± 11.3	N/A	18.3 ± 10.5
Papillary RCC (type 1)				n = 5
Average tumor growth (mm)	9.0	1.25 ± 2.17	N/A	2.80 ± 3.66
Follow-up duration (months)	83	27.0 ± 20.4	N/A	38.2 ± 28.9
Chromophobe RCC				n = 1
Average tumor growth (mm)	N/A	3.0	N/A	3.0
Follow-up duration (months)	N/A	10.3	N/A	10.3
Benign, mean ± SD	n = 7	n = 27	n = 1	n = 35
Average tumor growth (mm)	3.40 ± 2.89	1.63 ± 4.39	N/A	1.91 ± 4.26
Follow-up duration (months)	35.4 ± 15.1	17.3 ± 13.8	N/A	20.8 ± 17.2
Nondiagnostic, mean ± SD	n = 7	n = 8	n = 2	n = 17
Average tumor growth (mm)	8.0	16 ± 6.96	N/A	4.0 ± 1.33
Follow-up duration (months)	28.3 ± 31.2	25.1 ± 22.5	N/A	23.3 ± 26.6

GI biopsies were all done only recently, with very limited follow-up to adequately assess growth rate.

One patient with adenocarcinoma was not included in this table.

One patient with diagnosis of metastatic adenoma cystic carcinoma was not included in this table.

N/A.

With a mean follow-up time of 26 months (range: 1–70 months), 4 patients (10.5%) among the 38 who underwent cryoablation had a local tumor recurrence; among these 4 patients, 1 underwent a PN and 3 had a repeat cryoablation. Pathology after PN revealed grade 3 ccRCC, which was concordant with initial pathology. The remaining three patients who underwent repeat cryoablation did not have evidence of recurrence on follow-up imaging. One patient with high-grade RCC who underwent PN developed liver metastasis. Five patients (7%) in the AS group and five patients (5%) in the treatment group (1 RN, 2 PN, 2 cryoablation) died within the follow-up period, however, all deaths were due to causes other than cancer recurrence or metastasis (Table 8).

Table 8.

Outcomes

Primary treatment	Total, no. (%)	Metastasis, no. (%)	Tumor recurrence, no. (%)	Mortality, no. (%)
Active surveillance	71 (37)	0 (0)	0 (0)	5 (7)
Benign pathology	35 (49)	0 (0)	0 (0)	0 (0)
Malignant pathology	19 (27)	0 (0)	0 (0)	2 (11)
Nondiagnostic pathology	17 (24)	0 (0)	0 (0)	3 (18)
Cryoablation	38 (20)	0 (0)	4 (11)	2 (5)
Partial nephrectomy	56 (29)	1 (2)	0 (0)	2 (4)
Radical nephrectomy	14 (7)	0 (0)	0 (0)	1 (7)
Subsequent care performed at an outside institution	12 6	—	—	—
Chemotherapy (non-RCC)	1 (1)	—	—	—

Discussion

For renal cortical neoplasms, the traditional standard of extirpative surgery without confirmation of a malignant diagnosis was historically reasonable, as the majority of masses were larger than 4 cm, often presented with symptoms, and were typically aggressive maliganancies.^9
–11 With the CT-driven rise in incidentally detected SRM and with advances in biopsy techniques, RMB has gained an important role in the management of renal tumors.⁹ While the performance of RMB has typically been assigned to IR, we believe that a multidisciplinary approach provides a more comprehensive approach. In this regard, to the best of our knowledge, this is the first report of a routine pretreatment biopsy of SRM that involves three services: Urology, IR, and Gastroenterology.

Urologist-performed office-based RMB is performed under local anesthesia, without the use of ionizing radiation, and with greater patient convenience.^12,13 It is less expensive compared with IR-performed biopsy due to significantly lower direct and indirect facility costs.⁸ The current article is also the first to demonstrate that Urology office-based RMB expedites care by shortening the time from clinical diagnosis to definitive treatment by 34 days.

While office-based RMB provides many advantages, it remains limited due to the complexity or location of the SRM; hence, the important role for both IR-based CT/US RMB as well as GI-directed RMB. Also, it is clear that office-based RMB has a definite learning curve. Our nondiagnostic rate was 56% and 57% in the first 2 years of our experience, respectively. With greater experience, this subsequently dropped to 22% by year three (Fig. 1).

While our diagnostic rates are consistent with reports from other centers,^14,15 careful patient selection is key for selecting the appropriate imaging modality and hence venue. Our early experience with GI EUS core biopsy has value in distinguishing benign from malignant with a moderate diagnostic rate. While percutaneous biopsy of hilar tumors is feasible, it carries a high risk for postprocedural bleeding.¹⁶ This complication did not occur in any of our cases as we were able to send those patients for GI EUS biopsies; the EUS biopsy enables the physician to clearly delineate, and thus avoid, the hilar vessels. Currently, this modality is best reserved for tumors that are not amenable to either office- or IR-based biopsy.

Among initial nondiagnostic biopsies, 92% of repeat biopsies yielded a diagnosis, among which, 64% were malignant. This highlights the utility of a repeat biopsy after an initial nondiagnostic biopsy, as more than half may be harboring malignant disease. The overall complication rate was 2%, all perinephric hematomas that resolved with conservative management, which is lower than the literature-reported incidence of 5% to 40%.¹⁷ Our experience demonstrates the safety of RMB with only rare minor complications (i.e., Clavien 1). While the coaxial technique has previously been credited for eliminating any potential risk of tumor seeding from percutaneous biopsy,^18,19 it is important to note that in our experience, we had no incidence of tumor seeding despite GI and Urology biopsies not routinely using coaxial sheaths.

Current clinical practice guidelines fail to provide clear recommendations on routine RMB for SRM considered for AS^20,21; as such, RMB has not become a standard of practice for the majority of urologists.²² Our experience demonstrates that knowledge of tumor histopathology informs decision making; as such, following diagnostic RMB, a majority (57%) of patients elected to undergo AS (37%) or thermal ablation (20%). Most importantly, our experience with pretreatment biopsy yielded an overall rate of surgery for benign histopathology of only 3%, which is far lower than the 20% to 25% rate noted in centers where biopsy is not routinely performed.^1,23

–26 Outcomes of AS, ablation, and surgery have likewise been favorable. There is one caveat: while the concordance rate for malignant pathology is 99%, the initial biopsy tended to underestimate the pathological grade for 13% of patients undergoing surgery for RCC.

There are several limitations in our study. The retrospective nature of our study meant that some patients had incomplete chart data, inaccessible imaging studies, and/or a lack of follow-up data. In addition, the use of pre- and postbiopsy quesstionaires would have provided additional data regarding medical decision making to determine whether biopsy results influenced a patient's likelihood of pursuing surgery or preferring AS. Also, not all urologists perform RMB at our institution, and thus some patients were referred directly to IR regardless of the lesion's location. Our experience with GI EUS-guided RMB is limited as it was only employed for renal tumors otherwise inaccessible to a percutaneous approach in the Urology office or in the IR suite.

Conclusion

Our initial experience with a comprehensive, multidisciplinary approach to pretreatment RMB for SRM has demonstrated excellent safety and favorable outcomes be it performed in the Urology office, IR suite, or GI procedure suite. Pretreatment RMB-guided management strategies reduced surgery for benign disease to only 3%. This approach is in line with the maxim for approaching the vast majority of human solid malignancies: a definitive diagnosis preceeds a definitive therapy.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received.

Abbreviations Used

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