Minimally Invasive Partial Nephrectomy in the Era of Robotic Surgery.

OBJECTIVES: The objectives of the study were to compare the operative features, complication rates, functional, and pathological outcomes of laparoscopic partial nephrectomy (LPN) and robotic-assisted partial nephrectomy (RPN).
METHODS: The demographics, perioperative, and follow-up data of patients who underwent partial nephrectomy between January 2007 and April 2020 with minimally invasive methods were retrospectively analyzed. Patients with minimum 3 months follow-up were enrolled in the present study. Perioperative and pathological outcomes were compared between the patients underwent LPN and RPN.
RESULTS: A total of 85 patients (65 LPN and 20 RPN) were included in the present study. The mean patient age at the time of surgery was 56.31±10.48 years. Female-to-male ratio was 30/55. Patients in the RPN group had higher R.E.N.A.L. and PADUA scores (p=0.039 and p=0.030, respectively). Median warm ischemia time, median operation time, median intraoperative estimated blood loss, mean post-operative hemoglobin change, and median hospitalization time were similar between groups (p=0.133, p=0.753, p=0.079, p=0.882, and p=0.473, respectively). Artery-only clamping rate was significantly higher in RPN group (p=0.033). The cost of RPN was significantly greater than LPN (p<0.001). Transfusion rates, post-operative complication rates, percent of estimated glomerular filtration rate change at the last follow-up, and trifecta achievement were similar between the groups (p=0.622, p=0.238, p=0.428, and p=0.349, respectively).
CONCLUSION: In this series, similar perioperative and functional outcomes were achieved by RPN compared to LPN in more complex renal masses. Copyright:

At present, European Association of Urology guidelines strongly recommend partial nephrectomy (PN)[1] for cT1 renal masses.[2] PN can be performed, either with an open, laparoscopic, or robotic-assisted approaches. The basic principles of modern PN were first reported by Vermooten in 1950.[3] Laparoscopic PN (LPN) was first introduced by Winfield et al. in 1993.[4] With the introduction of robotic systems in surgical procedures, Gettman et al. published the first robotic-assisted PN (RPN) series in 2004.[5] The rate of PN for treatment of renal masses has increased over time.[6]

Nowadays, the rate of renal masses incidentally diagnosed constitutes more than half of all renal masses.[7] As a result of this, surgical interventions for small renal masses have increased. This trend was followed by raise of interest in minimally invasive surgery in effort to reduce morbidity and hospitalization time and expedite recovery after surgery.[8] Various studies have been conducted to investigate the impact of different approaches of PN on perioperative outcomes; however, these studies achieved inconclusive results.[1,9-14]

In this study, we present our experience in minimally invasive PN. We reported the operative features, complication rates, functional, and pathological outcomes of LPN and RPN. We hypothesized that implementation of RPN improved the perioperative results after PN.

Methods

This study was performed with the approval of the Local Ethics Committee of Hacettepe University (June 23, 2020/GO 20/584). Since 2007, 104 patients underwent PN by minimally invasive methods (LPN or RPN) due to solitary renal masses in a single institution. Patients converted to open surgery or eventually radical nephrectomy, and those with missing data were excluded from the study. Patients with at least 3 months of follow-up were enrolled in the pre-sent study. In total, the data of 85 consecutive patients were retrospectively analyzed in the present study.

All patients in the study were operated with a transperitoneal approach by three surgeons experienced in minimally invasive surgery depending on initial assignment at referral. Patients were informed in detail about both surgical methods. After then, the patients made their choices about the surgical method. Warm ischemia method and the use of intraoperative ultrasound were determined in accordance with primary surgeon’s discretion.

Patients were divided into two groups according to the surgical method applied, LPN or RPN. Groups were compared in terms of gender, age, body mass index (BMI), lesion side, lesion size, clinical stage, R.E.N.A.L. score,[15] PADUA score,[16] SPARE score,[17] American Society of Anesthesiologists score, Charlson comorbidity index (CCI), operation time (excluding docking time in RPN group) (min), post-operative complications, ischemia type (non-ischemic, hilar clamping, artery only clamping or selective arterial clamping), warm ischemia time (WIT) (min), post-operative estimated glomerular filtration rate (eGFR) change, last follow-up eGFR change, post-operative hemoglobin change, estimated blood loss (EBL) (mL), blood transfusion rates, hospitalization time (days), total cost of surgical procedures, and trifecta achievement. eGFR was estimated using The Modification of Diet in Renal Disease formula.[18] Tumors were categorized according to the 2017 TNM staging system.[19] Post-operative (30-day) complications were compared between the groups with the Clavien–Dindo classification.[20] Post-operative comp-lications were classified as minor (Grade 1-2) and major (≥ Grade 3) complications. Trifecta defined as the combination of negative surgical margins, no intraoperative and 90-day post-operative complications, and WIT <25 min.[21]

Statistical Analysis

All statistical analyses were performed using the Statistical Package for the Social Sciences 24.0 (IBM Corp., Chicago) software for Windows. Kolmogorov–Smirnov test was used to determine the normality of data. For univariate analysis, the Chi-square test was used for nominal data, the Student-t-test was used for parametric variables, and the Mann–Whitney U-test was used for non-parametric variables. Mean±standard deviation is used for parametric variables, while median and interquartile range is used for nonparametric variables. P<0.05 was considered statistically significant.

Results

A total of 85 patients (65 LPN and 20 RPN) were included in the present study. The mean patient age at the time of surgery and median follow-up period was 56.31±10.48 years and 12 (3.5–34.50) months, respectively. Female-to-male ratio was 30/55.

Patients in the RPN group had larger tumor size, higher cT1b tumor rate, and higher R.E.N.A.L. and PADUA scores (p=0.005, p=0.011, p=0.039, and p=0.030, respectively). The patients’ demographics and preoperative features are summarized in Table 1.

Table 1

Demographics and pre-operative data

	Laparoscopic	Robotic-assisted	p
Patient n (%)	65 (76.5)	20 (23.5)	–
Gender (%)			0.571[c]
Male	63.1	70
Female	36.9	30
Age, year, mean (SD)	56.08 (10.87)	57.05 (9.3)	0.719[t]
BMI, kg/m2, median (IQR)	28.40 (25.35–30.45)	29.82 (27.38–31.94)	0.104[m]
ASA score (%)
1	23.1	15	0.228[c]
2	67.7	85
3	9.2	0
CCI, median (IQR)	0 (0–1)	0 (0–1)	0.447[m]
Surgical side (%)
Left	56.9	55	0.879[c]
Right	43.1	45
Lesion size, mm, median (IQR)	25.50 (20–32)	31.50 (26–46.50)	0.005[m]
Clinical stage (%)
cT1a	93.7	70	0.011[c]
cT1b	6.3	30
R.E.N.A.L. score, median (IQR)	5 (4–6)	7 (5–8)	0.039[m]
PADUA score, median (IQR)	7 (7–8)	8 (7.25–9.75)	0.030[m]
SPARE score, median (IQR)	1.5 (0–2.25)	2 (0.75–4.25)	0.135[m]

: Univariate analysis (Chi-square test);

: Univariate analysis (Mann–Whitney U-test);

: Univariate analysis (Student-t-test); ASA: American Society of Anesthesiologists; BMI: Body mass index; CCI: Charlson comorbidity index; IQR: Interquartile range; SD: Standard deviation.

Median WIT, median operation time, median intraoperative EBL, mean post-operative hemoglobin change, median post-operative eGFR change percent, and median hospita-lization time were similar between groups (p=0.133, p=0.753, p=0.079, p=0.882, p=0.509, and p=0.473, respectively). Artery-only clamping rate was significantly higher in RPN group (80% vs. 43.1%, p=0.033). The cost of RPN procedure was significantly greater than LPN (p<0.001) (Table 2).

Table 2

Comparison of perioperative outcomes between groups

	Laparoscopic	Robotic-assisted	P
Operation time, min, median (IQR)	180 (120–187.5)	175 (145–195)	0.753[m]
Intraoperative EBL, mL, median (IQR)	75 (50–100)	200 (50–250)	0.079[m]
Ischemia type (%)
Non-ischemic	4.6	0	0.033[c]
Hilar clamping	47.7	20
Artery only clamping	43.1	80
Selective arterial clamping	4.6	0
WIT, min, median (IQR)	22 (18–25)	22.5 (20.25–32.25)	0.133[m]
Transfusion rate (%)	6.2	10	0.622[c]
Post-operative complications (%)
Minor	12.3	25	0.238[c]
Major	1.5	5
Post-operative eGFR change, %, mean (SD)	–0.04 (0.17)	–0.07 (0.12)	0.509[t]
Postoperative hemoglobin change, g/dL, median (IQR)	–1.2 ([–0.80]–[–1.70])	–1.25 ([–0.27]–[–2.27])	0.882[m]
Length of hospital stay, day, median (IQR)	3 (2–4)	3 (3–4)	0.473[m]
Total cost of procedure, ?, median (IQR)	4542 (3442–6020)	17626 (9336–22340)	<0.001[m]

: Univariate analysis (Chi-square test);

: Univariate analysis (Mann–Whitney U-test);

: Univariate analysis (Student-t-test); EBL: Estimated blood loss; eGFR: Estimated glomerular filtration rate; IQR: Interquartile range; SD: Standard deviation.

Intraoperative and post-operative transfusion rates were 2.4% and 5.9%, respectively. Transfusion rates were similar between the LPN and RPN groups (p=0.622). The number of patients with Clavien Grades 1, 2 and 3a complications were 5 (5.9%), 8 (9.4%), and 2 (2.4), respectively. Post-operative complication rates were similar between groups (p=0.238) (Table 2).

Malign pathology was detected in 65 (76.5%) patients. The most common types of malign pathology were clear cell carcinoma (n=44, 51.8%), papillary carcinoma (n=13, 15.3%), and chromophobe carcinoma (n=4, 4.7%). Pathological outcomes were similar between groups (Table 3).

Table 3

Pathological and functional outcomes of patients

Parameters	Laparoscopic	Robotic-Assisted	p
Malign pathology (%)	76.9	75	0.859c
Nuclear grade (%)*
1	6.7	0	0.473c
2	80	76.9
3	13.3	23.1
Positive Surgical Margin (%)	10.9	20	0.284c
Last Follow-up eGFR Change, %, Mean (SD)	-0.07 (0.21)	-0.03 (0.16)	0.428t
Trifecta Achievement (%)	56.9	45	0.349c

c: univariate analysis (Chi-square test); t: univariate analysis (Student-t test); eGFR: Estimated glomerular filtration rate; SD: Standard deviation;

For patients with malign pathology.

Functional outcomes are summarized in Table 3. Percent of eGFR change at the last follow-up was similar between groups (p=0.428). The trifecta rate was 54.1% and there was no diffe-rence between two groups for trifecta achievement (p=0.349).

Discussion

Closely following recent advancements in medical technology, important changes occur in field of contemporary surgical practice. Adaptation of robotic systems to surgical procedures has widened the domain of minimally invasive surgery.[8] With the spread of robotic systems, the rate of RPN increased significantly.[22] Consistently, the rate of minimally invasive PN has increased over the years.[6] In this study, we aimed to evaluate our minimally invasive PN experience since introduction of robotic surgery system in our institution.

One of the most important concerns about PN is renal isc-hemia. Renal ischemia was shown to be one of the most important and modifiable parameter in the preservation of kidney function after PN.[23] Cao et al. reported in their meta-analysis that arterial-only clamping provided better results in preserving long-term kidney function than hilar clamping.[24] In our study, the rate of arterial-only ischemia was significantly higher in the RPN group compared to LPN group; however, there was no difference between groups in long-term eGFR change. We believe that limited number of patients in the RPN group affected this result. Robotic surgery offers superior dexterity compared to laparoscopic instruments when achieving selective renal ischemia, with the advantages of magnified 3D vision, flexibility of the instruments, and elimination of tremor.[25] From this aspect, RPN may be of advantage in preserving long-term kidney function.

The current literature has inconsistencies regarding the effect of RPN on perioperative outcomes after PN. Leow et al. and Wu et al. stated that RPN provide superior perioperative outcomes; while Alimi et al. and Aboumarzouk et al. reported comparable perioperative outcomes between RPN and LPN.[1,12-14] In our study, similar perioperative outcomes were determined between the two groups. The factors res-ponsible for discrepancy between studies were thought to be the heterogeneity in study populations as well as different levels of experience in minimally invasive surgery. A randomized prospective multicentric study seems to the best method to address these issues.

Another discussion topic regarding robotic surgery is the financial cost. Mir et al.[26] showed that, RPN had the heaviest financial burden for procedure while the most cost-effective method was LPN. Similarly, Laydner et al.[27] reported that RPN was the most expensive method for PN due to the cost of instruments and necessary supplies. In consistent with the literature, the cost of RPN was found to be significantly higher than LPN in our study. For robotic-assisted surgery to become the standard minimally invasive procedure in PN, it is vital for the system to evolve in much sustainable direction. Further modification, not ne-cessarily simplification, in operating process will hopefully resolve the problem of maintenance cost without dimi-nishing practical convenience of the robotic system.

The short learning curve is one of the most important advantages of RPN compared to LPN.[28] It has been shown that transitioning from LPN to RPN had even shorter learning curve.[29] In our study, all surgeons had enough experience in laparoscopic surgery at the time they made their transition from laparoscopic to robotic surgery. In accordance with the literature, surgeons in our study reached similar proficiency level in robotic-assisted approach with fewer cases, keeping in mind their familiarity with laparoscopy. In addition, the patients who underwent RPN in our institution had tendency to have more complex and lar-ger renal masses. We might speculate that the reasonable learning curve of RPN may have played a role in achieving perioperative outcomes similar to LPN while operating more complex renal masses.

The main limitations of our study are the single-center data, retrospective design, and limited follow-up period. Second, our study includes a limited number of patients. Third, the patients in our study were operated by three different surgeons. This situation may be considered as another limitation. Finally, in our study, the mean tumor size is <3 cm. As the tumor size increases, there may be diffe-rences between the groups in terms of complication rates. This situation was considered as an another limitation of our study. However, the high experience of these surgeons in minimally invasive surgery (>100 cases) minimizes the impact of this limitation.

Conclusion

In this series, the RPN facilitated a minimally invasive app-roach in the treatment of more complex renal masses with similar complication and success rates. The RPN provides the feasibility of artery-only ischemia more successfully than LPN. However, the high financial cost of RPN should be kept in mind during the selection of treatment method.