Robot-assisted laparoscopic partial nephrectomy: Contemporary results over a wide range of tumor complexity

Abstract

Background

Partial nephrectomy (PN) is considered the gold standard surgical treatment for renal masses < 7cm in size (T1 tumors). Since the introduction of the robotic-assisted laparoscopic PN (raPN) in high-volume centers, it has been increasingly adapted and standardized by urologists worldwide. There is growing evidence that the robot-assisted laparoscopic technique is associated with superior outcomes compared to those of open and conventional laparoscopic techniques. This study aimed to summarize the contemporary outcome data of raPN for renal tumors with varying degrees of complexity and to assess whether the outcomes reported from high-volume centers are reproducible in a limited caseload setting.

Materials and methods

This was a retrospective study of a single surgeon's experience, including 123 consecutive patients undergoing raPN at our institution. Ultimately, 110 patients were included in the analysis. Basic characteristics, tumor complexity as described by the RENAL score, complications described by the Clavien-Dindo classification system, and functional and oncological outcomes were assessed and analyzed statistically.

Results

Of the 110 patients, 27 (24%), 61 (55%), and 23 (21%) had low, intermediate, and high degrees of complexity, respectively, according to the RENAL score. A cancer-negative surgical margin was achieved in 108 (97%) patients. A total of 70 (64%) patients had no loss of renal function, while 20 (27%) had minimal loss of renal function. Complications of > 3 Clavien-Dindo classification during the first 30 postoperative days occurred in 5 (5%) patients. The 3 complexity groups were found to have significantly different ischemia time: Low, 8 minutes (interquartile range [IQR], 8–9.5); Intermediate, 12 minutes (IQR, 10–13); and High, 15.5 minutes (IQR, 11.25–18.75) (p < 0.001). There were no significant differences between the groups.

Conclusions

Contemporary standards for raPN are safe and reproducible. Adherence to the technique reported by centers of excellence yielded comparable results with regard to tumor control, preservation of renal function, and complication rates in lower-volume settings.

1. Introduction

Three decades ago, open partial nephrectomy (PN) emerged as an alternative treatment modality to open radical nephrectomy, with the aim of preserving renal tissue, and consequently renal function. Currently, PN is the guideline-recommended gold standard treatment for renal masses <7cm (clinical T1 tumors according to the tumor, node, metastases system),^[1,2] with broad evidence regarding the safety of the procedure and its superiority over radical nephrectomy, mainly due to the preservation of renal function.^[3,4] In recent years, an increasing number of studies have shown not only the feasibility but also the advantageous outcomes of PN, even for renal masses >7cm (clinical T2 tumors).^[5] As described by Cacciamani et al. in two systematic reviews and meta-analyses,^[6,7] it is not primarily the tumor size, but the overall complexity of the renal mass that seems to limit the selection of patients qualifying for nephron-sparing surgery, hence the technical feasibility of PN. Therefore, instruments, such as the RENAL score,^[8] PADUA score,^[9] and C-Index^[10] have been implemented for preinterventional assessment and quantification of the complexity of renal masses, whereby the RENAL score seems to outperform the others.^[11] The achievement of trifecta (negative surgical margins, minimal loss of renal function, and no perioperative complications) as described by Hung et al.^[12] as the final outcome must be the ultimate goal of PN. By the end of the last century, laparoscopic techniques have been used in this field of surgery, and the general advantages of laparoscopy (ie, shorter hospital stay, less postoperative pain, and decreased blood loss) have also been shown in PN.^[13] The addition of robotic assistance helped overcome the disadvantages of conventional laparoscopy and reduce the learning curve for urological surgeons.^[14,15] Since PN is a technically more challenging procedure than RN, the expertise and caseload of the surgeon,^[16] as well as the technical aspects with superiority of the robot-assisted laparoscopic approach compared to those of open^[17] and conventional laparoscopic approaches^[14] are very important. The aim of our study was to present the outcomes of robot-assisted laparoscopic PN (raPN) from a secondary referral hospital in Switzerland and to compare these results with those from international high-volume centers.

2. Materials and methods

This retrospective study included 123 consecutive patients undergoing raPN using the technique described previously in high-volume centers^[13–15] between December 2012 and May 2019 by a single experienced surgeon. Regardless of the degree of the complexity of tumor, a patient was deemed eligible if clinically meaningful preservation of the renal tissue of the affected kidney was possible. Regarding follow-up, patients visited the outpatient clinic regularly for 6 weeks and 6 months after the operation, and thereafter at yearly intervals. For the analysis, 13 patients were excluded due to missing or refusal to provide informed consent. A patient with metastatic adrenal gland tumor remained in the study and analysis, since the primary outcomes focused on perioperative rather than long-term results. All included patients provided written permission for further use of their medical data, and the Ethical Committee of the Canton of Zurich approved the study.

Reporting was performed according to STROBE guidelines.^[18] Accordingly, we defined the following outcomes of interest: perioperative performance outcomes, oncological outcomes (survival and status of the surgical margin), complications assessed using the system described by Clavien-Dindo^[19] and renal function, and renal function deterioration after surgery. Furthermore, the impact of the degree of complexity of the RENAL score on the above-mentioned outcomes was examined.

For descriptive analyses, mean and standard deviation were used to summarize approximately normal continuous variables, while median and interquartile range were used for ordinal and skewed continuous variables. Frequency and percentage were used to summarize categorical variables.

For the statistical inference of the outcome variables, means or medians with 95% confidence intervals (CI) for variables with a skewed distribution or with a cut-off threshold were reported. A 95% CI was used for binary variables.

The outcomes were compared among the 3 complexity groups, namely low, medium, and high degrees based on the RENAL score. Non-normal continuous variables were compared using the Kruskal-Wallis test, categorical variables were compared using Fisher’s exact test, and the resulting p-values were considered exploratory. No subgroup or sensitivity analyses were performed, and due to the low number of events, no adjustment for confounding factors could be done. No additional statistical methods were used to address missing values.

To assess the change in renal function due to the operation, we further categorized the glomerular filtration rate (GFR) into groups G1-G5 according to the chronic kidney disease (CKD) classification, and compared pre- and postoperative values up to the time of the first regular outpatient control at approximately 6 weeks postoperatively. The GFR was classified as G1 ≥90 mL/ min/1.73m² (normal to high function), G2 = 60–89 mL/min/1.73m² (mild insufficiency), G3a = 45–59 mL/min/1.73m² (mild to moderate insufficiency), G3b = 40–44 mL/min/1.73m² (moderate to severe insufficiency), G4 = 15–29 mL/min/1.73m² (severe insufficiency), or G5 <15 mL/min/1.73m² (kidney failure). Since our laboratory sets a threshold at GFR >60 mL/min/1.73m², we combined G1 and G2 into one group. In cases of missing data concerning renal function, we proceeded as follows: preoperative values were assumed normal (G1/G2) if the values during hospitalization or at the first follow-up were normal (G1/G2). If the values at the time point of the first follow-up were missing, the values of the last measurement during hospitalization were used. All analyses were conducted with R 3.6.2, R Core Team (2019).

3. Results

Tables 1–5 summarized the characteristics of the patients and tumors (Table 1), characteristics described by the RENAL score and the corresponding degree of complexity (Table 2), perioperative data (Table 3), trifecta data (Table 4), and the impact of the degree of RENAL score complexity on various outcomes (Table 5), respectively. More than 97% of patients achieved an optimal oncological outcome 30 days after the operation. Almost 95% of patients had no or minor complications. During the first 30 days after surgery, a total of six complications ≥3 using the Clavien-Dindo classification system were observed in 5 patients: pulmonary embolism (n = 2), septic shock (n = 1), trocar hernia (n = 1), and pulmonary embolism and urinary leakage with superinfection (n = 1). The vast majority of patients did not suffer any (65%) or only a minor (27%) deterioration of renal function at 30 days postoperatively, as assessed by the CKD classification system. None of the patients developed severe renal insufficiency nor required transient or permanent hemodialysis.

Table 1.

Study population characteristics.

Characteristics	Values
Age, yr, mean (SD)	62 (11.7)
BMI, kg/m2, mean (SD)	26.7 (4.7)
Laterality, n (%)
Left side	43 (39.1)
Right side	59 (53.6)
Both sides	8(7.3)
Staging, n (%)
Localized disease	107 (97)
Advanced disease (cN1 and/or cM1)	3 (3)
Renal function
Creatinine, umol/L, median (IQR)	78 (66–87)
MDRD, mL/min/1.73m2, median (IQR)	61 (61–61)

BMI = body mass index; IQR = interquartile range; MDRD = modification of diet in renal disease; SD = standard deviation.

Table 5.

Outcome variables stratified by the degree of RENAL score complexity.

	RENAL score degree of complexity
Variables	Low (4–6)	Medium (7–9)	High (10–12)	p
Perioperative performance
Operation time median, min, (IQR)	185 (150–210)	182.5 (165–220)	210 (177.5–255)	0.064*
Blood loss median, mL, (IQR)	150 (50–287.5)	100 (49–250)	100 (49–337.5)	0.585*
Ischemia time median, min, (IQR)	8 (8, 9)	12 (10, 13)	15.5 (11.25, 18.75)	<0.001*
Conversion rate, n (%)	0 (0)	3 (5)	1 (4.3)	0.651‡
Hosp. time median, d, (IQR)	4 (4–5)	4 (3–5)	4 (3–4)	0.362*
Oncological
Surgical margin, n (%)
R0 (no tumor at surgical margin)	27 (100)	58 (96.7)	22 (95.7)	0.777‡
R1 (microscopic tumor at surgical margin	0	2 (3.3)	1 (4.3)
Complications
Intra-operatively, n (%)	0 (0)	4 (6.7)	1 (4.3)	0.405‡
Until 30 days postoperative CD ≥ 3, n (%)	0 (0)	2 (3.5)	3 (13.6)	0.08‡
Renal function
Mean increase creatine, %, mean (SD)	21.4 (28.9)	31.2 (38.4)	23.8 (42.3)	0.528*
Pre-op vs. Post-op
CKD group deterioration, n (%)
0 level
1 level	19 (82.6)	35 (58.3)	14 (63.6)	0.253‡
>1 level	3 (13.6)	21 (35)	5 (2.7)
≥ G4 (GFR <30 mL/min/1.73m2)	1 (4.3)	4 (6.7)	3 (13.6)
	00	0

CD = Clavien-Dindo classification; CKD = chronic kidney disease; GFR = glomerular filtration rate; IQR = interquartile range; SD = standard deviation.

* Kruskal-Wallis Rank Sum Test.

^† Conversion from robot-assisted laparoscopic partial nephrectomy to robot-assisted laparoscopic radical nephrectomy.

^‡ Fisher Exact Test.

Table 2.

RENAL score and degree of complexity.

RENAL score, n (%)		Degree of complexity, n (%)
4	5 (~5)	Low	27 (24.5)
5	3 (3)
6	19 (17)
7	19 (17)	Medium	60 (54.5)
8	21 (19)
9	20 (18)
10	18 (16)	High	23 (21)
11	4 (~4)
12	1 (~1)

Table 3.

Perioperative data.

Intraoperative performance values
Operation time, min, median (IQR)	187.5 (165–225)
Warm ischemia time, min, median (IQR)	11 (8–14)
Blood loss, mL, median (IQR)	100 (<50–300)
Conversion, n (%)	3 (~3)
Partial to total nephrectomy	3
Hilus control insufficient for PN	1
Renal reconstruction not feasible	2
Laparoscopic to open procedure	0
Intraoperative complications, n (%)	5 (4.5)
Surgical	3 (2.7)
Increased blood loss	1
Renal vein lesion	1
Ureter lesion	1
No surgical	2 (1.8)
Anaphylactic shock due to medication	1
Transient paresis of the foot (by pressure)	1
Surgical margin, n (%)
R0 (no tumor at surgical margin)	107 (97.2)
R1 (microscopic tumor at surgical margin)	3 (2.8)
R2 (macroscopic tumor at surgical margin)	0
Histopathological results
Benign renal tumor, n (%)	25 (23)
Oncocytoma	12 (10.8)
Angiomyolipoma	6 (5.4)
Renal cyst	2 (1.8)
Other	5 (4.5)
Malignant renal tumor, n (%)	85 (77)
Renal cell carcinoma	83 (75.4)
pT1a	61
pT1b	16
pT2a	1
pT3a	5
Other	1 (0.8)
Metastasis	1 (0.8)
Hospitalization
Length of stay, d, median (IQR)	4 (3–5)

IQR = interquartile range; PN = partial nephrectomy.

Table 4.

Trifecta 30 days after operation.

Characteristics values
Oncological
Overall survival, n (%)	100 (100)
R0 (no tumor at surgical specimen border), n (%)	107 (97.2)
Complications
Complications by CD
None or minor (CD grade <3), n (%)	104 (94.5)
CD = 0	82 (74.5)
CD = 1	12 (10.9)
CD = 2	10 (9.1)
CD grade ≥3, n (%)	6 (5.5)
CD = 3a	1 (~1)
CD = 3b	2 (~2)
CD = 4a	2 (~2)
CD = 4b	1 (~1)
CD = 5	0
Renal function
Creatinine mean, umol/L, mean (SD)	102 (27)
Mean percentage increase compared to preoperative,  %, mean (SD)	27.1 (36.4)
MDRD median, mL/min/1.73m2, (IQR)	61 (50–61)
Level of deterioration by CKD classification, %, (95% CI)
No deterioration	64.76 (56.19–74.24)
Deterioration 1 level	26.67 (18.1–36.15)
Deterioration 2 levels	8.57 (0–18.05)
Deterioration to severe insufficiency or renal failure	0
Need of transient or permanent hemodialysis	0

CD = Clavien-Dindo classification; CI = confidence interval; CKD = chronic kidney disease; IQR = interquartile range; SD = standard deviation; MDRD.

4. Discussion

The aim of our study was to assess the contemporary outcomes of raPN in patients with various degrees of renal tumor complexity in a secondary referral hospital in Switzerland, and to compare these results with the outcomes reported by high-volume centers. Our results show that the current raPN technique that has been developed in high-volume centers is equally efficient and safely adaptable in lower-volume centers. Accordingly, the results obtained in this setting are comparable to the results reported by centers of excellence, which demonstrates the quality and reproducibility of the technique.

With regard to the surgical margin, we observed 3 cases with microscopic tumor at the surgical margin (R1). It is important to note that in 1 case, as histologically described, the tumor surface showed a tear, which occurred during sample recovery. Hence, probably only 2 of these 3 cases had true surgical positive margins, representing only 2% of all cases. Furthermore, the oncological relevance of R1 status, a microscopic positive surgical margin, is debatable. Concerning the length of hospitalization, it must be mentioned that patients in Switzerland are required to stay in the hospital for at least 3 days due to the reimbursement system. The median length of stay is 72 hours, since patients leave the hospital on the morning of the fourth day. Regarding the RENAL score, we found that in almost 75% of cases, there was a higher degree of complexity (54% medium and 21% high), whereas only 25% were of low complexity. This finding is remarkable and clearly represents the contemporary nature of our cohort. With regard to long-term outcomes, the follow-up in our cohort was too short to perform a meaningful analysis; however, at a median follow-up of 1.01 years (95% CI, 0.67–1.5), 100% of patients survived, no case of recurrence occurred, and no late complications or deterioration to severe renal insufficiency or even the need for hemodialysis have been reported. Renal function, especially the assessment of “minor deterioration in renal function,” seems to be controversial, as it may be performed in different ways, as the above-mentioned studies show impressively.

Hung et al.^[12] reported a renal function decrease of greater than 10% in the actual versus volume-predicted postoperative estimated GFR. However, this definition appears to be very technical. From a clinical point of view, in our cohort, almost 92% of patients suffered no clinically relevant deterioration of renal function, defined as the deterioration of one CKD group in maximum, with no deterioration to severe renal insufficiency and no need for transient or permanent hemodialysis.

The fact that approximately 75% patients in our cohort had medium or high tumor complexity according to the RENAL score emphasizes the validity of our conclusion, since historic PN cohorts often included patients with tumors of a low degree of complexity.

Even in the high degree of complexity group (RENAL Score 10–12), negative surgical margins were achieved in almost 96% of patients. The rate of relevant complications (defined as CD ≥3) was below 6% and significant loss of renal function (>1 CKD group) was below 10%, whereas no patient had severe renal insufficiency or required hemodialysis.

4.1. Our results in the light of existing evidence

Our results compare favorably with those of existing literature,^[4,20-24] and thus add to the overall body of evidence for raPN. Although the evidence for favorable outcomes of raPN is broad and well known for smaller renal masses (<4cm), our results highlight the reproducibility of such favorable results in more complex tumors.

In patients with a low degree of tumor complexity, we achieved trifecta in all but one case, with the exception of a patient who had a deteriorated renal function in two CKD groups. In a systematic review of 154 patients and meta-analysis focusing on raPN of renal tumors >4cm, the following outcomes were reported: conversion rate to open PN in almost 5%, positive margins in 3.5%, and intraoperative and postoperative complications of 7% and 9.8%, respectively. In our cohort, no patient required conversion to open PN, while rate of positive margin, intraoperative complications and postoperative complication was each found to be 4.5%. However, a direct comparison is difficult because the crude tumor size indication does not sufficiently describe the overall tumor complexity. Hence, the average tumor size within our subgroup reached almost 60 mm, and over 45% of the patients belonged to the highest degree of complexity group. In contrast, almost 60% of tumors <4cm (n = 66) belonged to the medium degree of complexity group. In our overall cohort, the corresponding rates of conversion to open PN, positive margin, intraoperative complications and postoperative complications were 0%, 3.6%, 6%, and 5%, respectively. Our results compare favorably to those of a multi-center study including 886 patients with a mean RENAL score of 6.9 focusing on complications during and after raPN,^[21] even though our patients had tumors with a mean RENAL score of 8. A study focusing on renal tumors of exclusively high complexity^[23] showed a median operation time of 120 minutes, median blood loss of 150mL and median ischemia time of 16 minutes. Complications during the operation occurred in 4.5%, and postoperative complications of higher CD grade occurred in 9.1%. A positive surgical margin occurred in 4.5% of patients. Except for a longer operation time, our results are at the eye level. In a recent study by Wurnschimmel et al.^[24] comparing conventional versus raPN in a randomized study in 115 patients, a mean warm ischemia time of 19.6 minutes, a positive surgical margin rate of 4.9%, a mean operation time of 230.2 minutes and a transfusion rate of 11% was reported in the robotic arm. In this case, our results compare very favorably with 11 minutes, 2.8%, 187.5 minutes and <1%, respectively.

4.2. Our results compared to ablation techniques

Patient and tumor characteristics are crucial factors when the outcomes are compared between different institutions and treatment modalities. Patients qualifying for ablative techniques (ie, cryoablation and radiofrequency ablation) usually harbor kidney tumors of low complexity.^[25,26] The efficacy of renal tumor ablation in these patients is reported to be 90%–95% with complication rates of 6%–7%,^[26] whereas in our cohort in the low tumor complexity group, we achieved oncological efficacy in 100% of patients, and no patient experienced complications.

4.3. Strengths and limitations

The strengths of the study are the consecutive nature of the study cohort, yielding real-life data, and reporting in accordance with the STROBE guidelines.^[18]

As expected, a retrospective design has inherent limitations. Owing to denied or missing informed consent, we had a dropout rate of almost 10% of the original cohort. Although the caseload per clinic is not high, that of the surgeon in this single-surgeon cohort is well within the range of the experience of some surgeons in international high-volume centers, which certainly plays a crucial role in obtaining these favorable results. Another limitation is the limited number of patients in the subgroup analyses as well as missing follow-up data. The reason for this is that many of our patients were followed-up at our institution. The results from these follow-up visits are not always accessible to us. However, we are confident that we did not miss any severely unfavorable outcomes. Due to the limited follow-up with a mean of approximately 1 year, we cannot make any assertions regarding long-term follow-up. For the same reason, however, it is conceivable that we overestimated the negative impact of our operation on renal function, since renal function often recovers over the first weeks of follow-up.

5. Conclusions

In conclusion, the contemporary standard of raPN is safe and reproducible. Adherence to the technique reported by highvolume centers of excellence yields comparable results with regard to tumor control, preservation of renal function, and complication rates even in lower-volume settings.

Conflict of interest statement

The authors have no conflicts of interest to declare.