Impacts of Complete Endophytic Renal Tumors on Surgical,Functional,and Oncological Outcomes of Robot-Assisted Partial Nephrectomy

Abstract

Objective:

Complete endophytic renal tumors (CERTs) are the most challenging for robot-assisted partial nephrectomy (RAPN). This study aimed to determine the impact of CERT on outcomes of RAPN.

Methods:

All RAPN cases for localized renal tumor undertaken at Yokohama City University Hospital between 2016 and 2023 were enrolled. Tumor characteristics and surgical, functional, and oncologic outcomes of RAPN were compared between CERT and non-CERT groups.

Results:

Consecutive 666 patients were enrolled, and 76 (11.4%) were identified as CERT (3 points of “E” score). CERT showed smaller tumor diameters (p < 0.001), more predominant hilar tumor (p = 0.029), higher “N” scores (p < 0.001) and “L” scores (p = 0.006) than non-CERT. The CERT group showed longer warm ischemia times (p < 0.001), more frequent positive surgical margins (p = 0.028), and relatively lower trifecta achievement rates (p = 0.101) than the non-CERT group. In multivariable analysis, the CERT was an independent predictor for trifecta achievement but not for pentafecta achievement.

Conclusions:

CERT was associated with longer warm ischemia time, positive surgical margin, and lower trifecta achievement, but not with surgical complication and pentafecta achievement in RAPN. This study suggested that CERT had limited influence on long-term renal functional preservation; however, it had strong impacts on short-term surgical outcome.

Introduction

At present, robot-assisted partial nephrectomy (RAPN) is commonly performed for localized cT1 renal tumors,^1
–3 demonstrating higher feasibility, safety, and accuracy of surgical manipulation than open or laparoscopic partial nephrectomy.^4,5 Furthermore, with advances in RAPN techniques, it is being used for larger, more complex, and technically challenging renal tumors.⁶

Complete endophytic renal tumor (CERT), usually scored based on the “E” domain of the RENAL nephrometry score,⁷ characterizing degrees of tumor growth into the normal renal parenchyma, is classified into exophytic, mesophytic, and endophytic tumor groups. It is one of the most challenging tumors for RAPN owing to unclear tumor localization, without visual clues, and the requirement of larger and deeper resection to avoid a positive surgical margin.^8,9 Previous studies have shown that the oncologic and functional outcomes of RAPN for CERT were almost equivalent to that for non-CERT.^10

–13 However, some studies indicate lower trifecta achievement and a higher perioperative complication rate in CERT compared with non-CERT,⁹ whereas others do not¹⁴; hence, the impact of CERT on surgical outcomes including trifecta achievement remains controversial. Furthermore, pentafecta achievement in RAPN for CERT has not been fully investigated.

Therefore, this study aimed to determine the impact of CERT on surgical, functional, and oncologic outcomes of RAPN including trifecta and pentafecta achievement.

Materials and Methods

Patient cohort

Clinical information for analysis was obtained from the institutional medical record database on all consecutive patients who underwent RAPN for localized renal tumor at Yokohama City University Hospital between 2016 and 2023. The study protocol was approved by an Institutional Review Board (F220700047) and the requirement for informed consent was waived owing to the retrospective nature of the study.

Surgical techniques

Four surgeons performed RAPN, and all procedures were performed using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA). RAPN was performed using four da Vinci arms and one or two assistant ports. The choice of approach was based on tumor location. The retroperitoneal approach was chosen for tumors located on the posterior or lateral side of the kidney or in patients having a history of transperitoneal operation. The main renal arteries were clamped with a bulldog clamp using arterial clamping technique. In cases where the tumor was near the hilum of the kidney, the renal vein was clamped. We decided the number of vessel clamps to be clamped by referring to 3D images reconstructed from digital imaging and communications in medicine data of contrast-enhanced CT images using the SYNAPSE VINCENT system (FUJIFILM, Inc., Tokyo, Japan). An ARIETTA 70 probe (Hitachi, Inc., Tokyo, Japan) was used for ultrasound examination to evaluate tumor distribution and plan excision margins. Intravenous mannitol was administered before and after clamping the vessel to protect renal function. After clamping the vessel, tumor excision was performed using cold scissors and a sealing device for thick vessels. After resection, an inner running suture was placed to close the large vessels and collecting system at the tumor base using 3-0 barbed sutures. This was followed by renal parenchymal suturing using 0-barbed sutures. An early unclamping technique was adopted depending on the individual case, such as cases where the ischemia time was prolonged, or if there was a need to confirm bleeding.³

Clinical assessment

We analyzed the clinical factors in this study, including surgical parameters (operative duration, console time, warm ischemia time, estimated blood loss, and complications), pathologic parameters (surgical margin and histopathologic diagnosis), postoperative estimated glomerular filtration rate (eGFR), and oncologic outcome (cancer-free survival). Each parameter derived from RENAL nephrometry score including CERT and hilar tumor were defined using preoperative contrast or noncontrast CT imaging. Trifecta was defined as a negative surgical margin, no postoperative complications, and a warm ischemia time of 25 minutes or less. Pentafecta was defined as the absence of an upstage of chronic kidney disease and a minimum of 90% total eGFR preservation, in addition to trifecta achievement. Postoperative complications were categorized according to the Clavien–Dindo classification.

Statistical analyses

Continuous variables were reported as means and standard deviations. Comparisons between the two groups were carried out using Student's t-test or chi-square test. Multivariable binomial logistic regression analysis with stepwise selection was used to evaluate preoperative clinical factors predicting the achievement of trifecta and pentafecta. All statistical analyses were two-sided and a value of p < 0.05 was considered statistically significant. All analyses were conducted using SPSS version 28.0 (IBM Corp., Armonk, NY).

Results

Patient characteristics

A total of 666 consecutive patients were enrolled in this study with 76 (11.4%) identified as CERT (3 points of “E” score; Table 1). The remaining 590 patients consisted of 291 (49.3%) with exophytic (1 point of “E” score) and 299 (50.7%) with mesophytic (2 points of “E” score) tumors, treated as non-CERT in this study (Table 1). Patients with CERT had smaller tumor diameters (p < 0.001), more predominant hilar tumor (p = 0.029), higher “N” scores (p < 0.001), and “L” scores (p = 0.006) than patients with non-CERT. No significant differences were identified between the two groups in terms of sex, age, body mass index, blood test results including preoperative eGFR and medical history.

Table 1.

Comparison of Characteristics Between Patients with Complete Endophytic Renal Tumors and Noncomplete Endophytic Renal Tumors

	Completely endophytic	Noncompletely endophytic	p
Number	76 (11.4%)	590 (88.6%)
Age	62.2 ± 12.8	62.7 ± 12.9	0.749
Sex
Female	13 (17.1%)	178 (30.2%)
BMI	24.5 ± 3.6	24.5 ± 4.3	0.938
ECOG PS
0	72	581	0.117
1	4	8
2	0	1
Blood test
Neutrophil ratio, 10³/μL	3658.0 ± 1417.2	3926.6 ± 3486.0	0.507
Lymphocyte ratio, 10³/μL	1551.9 ± 662.7	1637.1 ± 641.9	0.289
Hemoglobin, g/dL	14.0 ± 1.3	14.1 ± 2.0	0.603
Albumin, g/dL	4.3 ± 0.3	4.3 ± 0.3	0.214
Calcium, mg/dL	9.3 ± 0.3	9.3 ± 0.5	0.602
Creatinine, mg/dL	0.8 ± 0.2	0.9 ± 0.4	0.334
LDH, U/L	179.5 ± 29.5	184.2 ± 36.2	0.279
CRP, mg/dL	0.07 ± 0.07	0.2 ± 0.5	0.186
Medical history
Hypertension	35 (46.1%)	288 (48.8%)	0.650
Diabetes mellitus	10 (13.2%)	105 (17.8%)	0.398
Single kidney	1 (1.3%)	9 (1.5%)	1.000
Tumor size	23.6 ± 8.4	29.3 ± 12.7	<0.001
Clinical T stage
cT1a	73 (96.1%)	468 (79.3%)	<0.001
cT1b	3 (3.9%)	122 (20.7%)
RENAL score
Total	8.9 ± 1.3	6.8 ± 1.7	<0.001
R score
1	73 (96.1%)	467 (79.2%)	<0.001
2	3 (3.9%)	123 (20.8%)
E score
1	0	291 (49.3%)	<0.001
2	0	299 (50.7%)
3	76 (100%)	0
N score
1	8 (10.5%)	182 (30.8%)	<0.001
2	12 (15.8%)	124 (21.0%)
3	56 (73.7%)	284 (48.1%)
A score
A	33 (43.4%)	260 (44.1%)	0.990
P	27 (35.5%)	217 (36.8%)
X	16 (21.1%)	113 (19.2%)
L score
1	21 (27.6%)	258 (43.7%)	0.006
2	19 (25.0%)	152 (25.7%)
3	36 (47.4%)	180 (30.5%)
Hilar tumor	8 (10.5%)	27 (4.6%)	0.029

A = anterior; BMI = body mass index; CRP = C-reactive protein; ECOG PS = Eastern Cooperative Oncology Group Performance Status; LDH = lactate dehydrogenase; P = posterior; X = not clear.

Perioperative oncologic and renal functional outcomes

The CERT group showed longer warm ischemia times (p < 0.001), more frequent positive surgical margins (p = 0.028), and a relatively lower trifecta achievement rate (p = 0.101) than the non-CERT group (Table 2). However, there were no significant differences between the CERT and non-CERT groups in terms of perioperative complication rate (Clavien–Dindo ≥2), change rate of eGFR at 1-year postprocedure, and survival outcomes.

Table 2.

Comparison of Surgical, Functional, and Oncologic Outcomes of Robot-Assisted Partial Nephrectomy Between Complete Endophytic Renal Tumor and Noncomplete Endophytic Renal Tumors Groups

	Completely endophytic	Noncompletely endophytic	p
Number	76 (11.4%)	590 (88.6%)
Surgical approach
Transperitoneal	21 (53.8%)	200 (48.3%)
Retro peritoneal	18 (46.2%)	214 (51.7%)
Clamping
Nonclamp	1 (1.3%)	1 (0.2%)	0.001
A clamp	56 (73.7%)	523 (88.6%)
AV clamp	19 (25.0%)	66 (11.2%)
Operation duration	195.0 ± 35.7	193.4 ± 45.4	0.768
Console time	127.3 ± 39.3	125.8 ± 42.1	0.778
Warm ischemia time	21.3 ± 6.9	18.6 ± 6.6	<0.001
Estimated blood loss, mL	63.5 ± 147.4	68.6 ± 172.1	0.803
Weight of surgical specimen	12.4 ± 9.2	22.9 ± 32.1	0.007
eGFR
Preoperation	71.6 ± 16.2	68.6 ± 19.1	0.229
Postoperative 1 year	61.6 ± 16.2	59.8 ± 16.1	0.522
Perioperative complications
Clavien–Dindo ≥2	1 (1.3%)	15 (2.5%)	0.428
Pseudoaneurysm	0	3	0.856
Conversion to radical nephrectomy	0	4 (0.7%)	1.000
Positive surgical margin	3 (3.9%)	9 (1.5%)	0.028
pTNM
Benign tumor	8 (10.5%)	57 (9.7%)	0.087
pT1a	62 (81.6%)	438 (74.2%)
pT1b	1 (1.3%)	68 (11.5%)
pT2a	0	1 (0.2%)
pT3a	5 (6.6%)	31 (5.3%)
Pathologic findings
Clear cell carcinoma	54 (71.1%)	426 (72.2%)	0.808
Papillary	3 (0.4%)	48 (8.1%)
Chromophobe	6 (7.9%)	37 (6.3%)
Other	13 (17.1%)	79 (13.4%)
Trifecta achievement	48/69 (69.6%)	437/558 (78.3%)	0.101
Pentafecta achievement	12/41 (29.3%)	108/370 (29.2%)	0.992
Follow-up duration, months	12.0 (1–64)^a	12.5 (1–85)^a	0.068
Survival
Cancer-free survival	74 (97.4%)	583 (98.8%)
Survival with cancer	2 (2.6%)	3 (0.5%)
Disease-specific mortality rate	0	2 (0.3%)
Other mortality rate	0	2 (0.3%)

Median (minimum–maximum).

eGFR = Estimated glomerular filtration rate.

Predictors of trifecta achievement

In multivariate analysis, CERT (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.06–3.82, p = 0.032), tumor size (OR: 1.06; 95% CI: 1.04–1.08, p < 0.001), age (OR: 1.02; 95% CI: 1.01–1.04, p = 0.009), and “L” score (OR: 1.77; 95% CI: 1.05–3.01, p = 0.034) of the RENAL nephrotomy score were found to be significant predictive factors for trifecta achievement (Table 3).

Table 3.

Multivariable Logistic Regression Model to Predict Trifecta Achievement of Robot-Assisted Partial Nephrectomy

	Initial step				Final step
	p	OR	95% CI of OR		p	OR	95% CI of OR
	p	OR	Lower	Upper	p	OR	Lower	Upper
Age	0.009	1.02	1.01	1.04	0.009	1.02	1.01	1.04
BMI	0.833	1.00	0.95	1.05
Tumor size	<0.001	1.06	1.04	1.09	<0.001	1.06	1.04	1.08
Non-CERT vs CERT	0.035	0.93	0.86	1.00	0.032	2.02	1.06	3.82
“N” score
1 vs 2	0.414	0.72	0.32	1.60	0.422	0.72	0.32	1.60
1 vs 3	0.072	1.82	0.95	3.49	0.058	1.87	0.98	3.58
“L” score
1 vs 2	0.064	1.70	0.97	2.99	0.049	1.75	1.00	3.07
1 vs 3	0.049	1.71	1.00	2.92	0.034	1.77	1.05	3.01
Hilar tumor	0.324	1.15	0.87	1.52

CERT = complete endophytic renal tumor; CI = confidence interval; OR = odds ratio.

Predictors of pentafecta achievement

In multivariate analysis, only tumor size (OR: 1.04; 95% CI: 1.01–1.06, p = 0.003) was significant predictive factor for pentafecta achievement (Table 4).

Table 4.

Multivariable Logistic Regression Model to Predict Pentafecta Achievement of Robot-Assisted Partial Nephrectomy

	Initial step				Final step
	p	OR	95% CI of OR		p	OR	95% CI of OR
	p	OR	Lower	Upper	p	OR	Lower	Upper
Age	0.449	1.01	0.99	1.03
BMI	0.436	0.98	0.92	1.04
Hypertension	0.517	1.18	0.71	1.96
Diabetes mellitus	0.952	1.02	0.56	1.85
Tumor size	0.003	1.04	1.01	1.06	0.003	1.04	1.01	1.06
Non-CERT vs CERT	0.737	1.02	0.93	1.11
“N” score
1 vs 2	0.725	0.90	0.48	1.67	0.684	0.88	0.48	1.63
1 vs 3	0.035	1.94	1.05	3.58	0.052	1.79	1.00	3.21
“L” score
1 vs 2	0.745	0.91	0.51	1.61	0.612	0.86	0.49	1.52
1 vs 3	0.040	1.82	1.03	3.21	0.058	1.71	0.98	2.97
Hilar tumor	0.108	0.76	0.54	1.06

Discussion

This study was the largest retrospective single-center study including 76 CERTs (tumors with 3 points of “N” score) and comparing the perioperative, functional, and oncologic outcomes between CERT and non-CERT, and first revealing the impact of CERT on pentafecta achievement of RAPN. The CERT group showed smaller tumor diameters, more predominant hilar tumor (p = 0.029), higher “N” and “L” scores, longer warm ischemia times, more frequent positive surgical margins, and a relatively lower trifecta achievement rate than the non-CERT group. In addition, we found that the CERT was a significant independent predictor for trifecta achievement but not for pentafecta achievement. Meanwhile, there was no difference in surgical complication, conversion to radical nephrectomy, and survival outcome between CERT and non-CERT.

This study first showed that CERT did not contribute to the pentafecta achievement of RAPN with the rate of 29.3% in the CERT and 29.2% in the non-CERT. In the meantime, we found that CERTs were independent and significant predictors of trifecta outcome, although the impact of “E” score on trifecta outcome is controversial, with most studies suggesting that the “E” score does not have a strong effect on trifecta.^9,11,14 Those key findings of this article suggested that CERT had limited influence on long-term renal functional preservation; however, it had strong impacts on short-term surgical outcome with longer warm ischemia time and higher incidence of surgical margin positive. In this study, the trifecta achievement rate was 69.6% in the CERT group, being relatively <78.3% in the non-CERT. Previously, the trifecta achievement of RAPN for CERT varied widely from 37.8% to 88.5%,^8,9,11,14 indicating surgical quality in the previous articles may have huge variation.

This study revealed that CERTs have smaller tumor diameters, higher “N” scores, and relatively higher “L” scores than non-CERTs. They were all reasonable and acceptable in considering CERT as a whole entirely inner renal tumor. Longer warm ischemia times, more frequent positive surgical margins, and relatively lower trifecta achievement rates in the CERT group compared with the non-CERT group were understandable as they are difficult to observe and therefore need extra care with tumor detection, incision, and enucleation. RAPN for CERT exclusively requires a wider and deeper view of the renal sinus fat to observe the tumor base. The procedural solution in our institution is to start the incision with a slightly larger margin, dissect as circumferentially as possible between the cortical medulla and the tumor, and obtain a view of the area where the renal sinus fat meets the tumor.

The “L” score was a significant independent predictor of trifecta achievement in this study, and “N” score relatively was. A high “N” score has already been reported as a risk factor for postoperative complications after RAPN because of a high risk for the openness of the collection system and main artery causing bleeding.¹⁵ The “L” score was reported to contribute to surgical decision making.^16,17

The limitations of this study were that it was a retrospective, single-center study with a small number of patients with CERT compared with non-CERT. However, CERT is relatively rare, hence, previous reports on CERT also enrolled only a small number of cases^8,9,11,14 and we believe the number of CERT cases in this study was adequate. Patients with positive surgical margin and pT3a were closely followed with CT imaging without immediate reintervention in our hospital. To confirm the long-term oncologic outcome of RAPN, further study is warranted.

Conclusions

CERT was associated with smaller tumor diameters, more predominant hilar tumor (p = 0.029), higher “N” and “L” scores, longer warm ischemia times, more frequent positive surgical margins, and relatively lower trifecta achievement rates than non-CERT. Furthermore, CERT was a significant independent predictor for trifecta achievement but not for pentafecta achievement. Finally, there was no difference in surgical complication, conversion to radical nephrectomy, and survival outcome between CERT and non-CERT. This study suggested that CERT had limited influence on long-term renal functional preservation; however, it had strong impacts on short-term surgical outcome.

Footnotes

Authors' Contributions

H.I.: Conceptualization; formal analysis; project administration; and writing—original draft. K.U., M.I., R.J., Takuya Kondo, T.T., Takashi Kawahara, M.K., Y.I., K.M.: Data curation and investigation. H.H., K.M.: Conceptualization; resources; and writing—review and editing.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Abbreviations Used

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