Running Head: Retroperitoneal partial nephrectomy

Retroperitoneal Nephrometry Scoring System (RETRO) for Minimal-Invasive Partial

Nephrectomy

Sunyi Ye1*, Lixian Zhu2*, Ping Wang1, Xinxing Sun3, Xin Xu1,

Feng Zhao4, Xiaolin Yao1, Qiang Huang5, Yun Dai1, Dan Xia1, Shuo Wang1*

Institutions:

1 Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang

University, Hangzhou, China

2 Department of Thyroid Disease Center, The First Affiliated Hospital, School of Medicine,

Zhejiang University, Hangzhou, China.

3 Department of Operating Center, The First Affiliated Hospital, School of Medicine,

Zhejiang University, Hangzhou, China.

4 Department of Radiation Oncology, The First Affiliated Hospital, School of Medicine,

Zhejiang University, Hangzhou, China.

5 Department of Radiology, The First Affiliated Hospital, School of Medicine, Zhejiang

University, Hangzhou, China.

Authors contribution statement

SYY, LXZ and SW had full aaccess to all the data in the study and takes responsibility

for the integrity of the data and the accuracy of the data analysis.

Study concept and design: SYY, LXZ, PW, SW.

Acquisition of data: LXZ, XXS, XX, FZ, XLY, YD.

Analysis and interpretation of data: SYY, PW, QH, YD, DX.

Drafting of the manuscript: SYY, LXZ, DX.

Critical revision of the manuscript for important intellectual content: XXS, QH, Dai,

DX, SW.

Statistical analysis: LXZ, FZ, XLY.

Obtaining funding: SYY.

Administrative, technical, or material support: YD, DX, SW.

Supervision: DX, SW.

Other (specify): None.

Acknowledgements

None.

Funding statement

This work was supported by National natural science foundation of China (No. 81800558).

Conflict of Interest

The authors declared that there is no conflict of interest.

Ethics statement

The study was obtained local ethic committee approval.

Data sharing statement

We can share our data with the journal for representing analysis and interpretation of the data.

However, we do not want the readers to view or download our data.

Abstract

Purpose: To propose a standardized scoring system of renal tumors suitable for partial

nephrectomy based on mini-invasiveness and retroperitoneal approach.

Materials and Methods: One-hundred and five patients in retroperitoneal group were

prospectively enrolled from January 2017 to December 2018. Perioperative characteristics of

all patients were collected: age, gender, BMI, preoperative blood test and imaging results,

operation time (the time period starts from the skin incision to the final skin closure), estimated

blood lost, clamping time, complications within 30 days, American Society of

Anesthesiologists (ASA) score, pathology. An algorithm was extracted, and it was used to

predict the risk of complications.

Results: Symptoms, ASA score and RETRO score were significantly correlated to

postoperative complications, excluding tumor size, ischemia time and operation time. Adjusted

RETRO points were an independent factor to predict complication rate (p=0.006). Limitation

was that it did not analyze the relationship between the RETRO score and the long-term

outcomes.

Conclusions: The RETRO score simplifies the risk evaluation of partial nephrectomy for

patients with renal tumor, especially benefits those surgeries performed under robot-assisted

laparoscope via retroperitoneal approach. The new RETRO score system that we developed is

a selection criterion to perform surgery via different approach, and an accurate system to

evaluate the complexity during partial nephrectomy.

Key Words: Partial nephrectomy; Retroperitoneal nephrometry; surgical approach; score

system; mini-invasive

Background

Partial nephrectomy (PN) is becoming the standard treatment for patients with low-stage

renal tumor (1). The 2019 updated Guidelines on renal cell carcinoma illustrated that localized

T1 tumors are best managed by partial nephrectomy rather than radical nephrectomy,

irrespective of the surgical approach (LE: 1b). Tan et al. analyzed more than 3000 patients with

low-stage renal cell carcinoma under radical nephrectomy or partial nephrectomy, they found

that the long-term overall survival was similar between radical and partial nephrectomy (2).

While the risk of development of metabolic or cardiovascular disorders is increased after radical

nephrectomy (3). Patients with T2a also received PN, estimated blood lost and perioperative

complications were higher, the all-cause mortality and oncologic outcomes were similar

compared to radical nephrectomy (RN)(4,5).

With the development of robot-assisted surgical technique, more and more patients received

robot-assisted laparoscopic partial nephrectomy. Off-clamp technique was used in totally

endophytic renal tumors under robotic platform(6). There are different approaches for partial

nephrectomy, transperitoneal way is undertaken by most urologists over the world.

Retroperitoneal approach also has its unique advantages, especially for those tumors located

posterior side of the hilar, the kidney does not need to be mobilized around (7). It saves time and

makes the manipulation much more easily.

The nephrometry scoring system-R.E.N.A.L was reported in 2009 (8). It gave a qualitative

and standardized evaluation system for various tumors. Lots of other nephrometry scoring

systems also emerged, PADUA classification, C-Index method, and NePhRO system et al. (9-11).

However, none of these scoring systems are correlated with different surgical approaches.

Especially for surgeons who are used to perform PN via retroperitoneal way, there is no

evaluation criteria to be used.

The objectives of this study are (1) to propose a standardized scoring system of renal tumors

suitable for partial nephrectomy based on mini-invasiveness and retroperitoneal approach; (2)

to evaluate the effectiveness and predict overall complications after PN according to this

classification system.

Methods

Patients and tumors

We prospectively included 122 patients who underwent Robot-Assisted Laparoscopic Partial

Nephrectomy (RALPN) between January 2017 and December 2018. Inclusion criteria: (1)

clinical stage 1 (cT1) renal tumors; (2) solitary kidney tumor; (3) age<80 years; (4) enhanced

CT was performed in our medical center. Patients with abnormal coagulation function or acute

inflammation (temperature>38.0℃) were excluded. Among these patients, 105 cases received

the operation through retroperitoneal approach, 17 cases were via transperitoneal way. All these

surgeries were performed by one surgeon (Dr. Wang), minimizing the methodological bias. All

included patients received non-invasive renal angiography through computed tomography

(CTA) examination. Three urologists independently read CT images and evaluated these

parameters of each tumor: (1) diameter of the tumor (Radius); (2) Endophytic; (3) relationships

with anterior lip (Transperitoneal/retroperitoneal); (4) relationships with renal vessel trunk

(vessel Rete), vessel trunk includes the first and secondary renal artery/vein, or the diameter of

the artery is larger than 3 mm; (5) relationships with renal polar (Origin). We call it RETRO

nephrometry classification system (Table 1).

When tumors locate in the front lip of the hilum, the manipulation will become difficult via

retroperitoneal approach. The transperitoneal way is recommended. The definition of the “front

lip” is that the space contains in the front side of the hilum, the inner boundary line is the inner

edge of the kidney, the outer boundary is the line links the orifice of the hilum, the upper

boundary is the line links the high point of the orifice and the up corner of the hilum, the inferior

boundary is the line links the lower point to the orifice and the lower corner of the hilum (see

Figure 1a). This space is a “forbidden zone” when the retroperitoneal approach is used. Tumors

in this area are difficult to be handled, and it’s hard for surgeon to do the resection and suture.

Any tumor which “invades” this “forbidden zone” will be recommended to be removed from

transperitoneal group (see Figure 1d). Otherwise, retroperitoneal way is suggested when tumors

locate in other area of the kidney. The first parameter is an impression for the surgeon to judge

which surgical approach is best for the patient.

The maximal diameter of the tumor is also a critical factor affecting the surgical manipulation.

One point is given to tumors that are 2cm or smaller, 2 points are given to tumors between 2-4

cm, 3 points are given to tumors between 4-6 cm, and each 2 cm larger gets another 1 point. No

ceiling of the score is set. The classification is different from the TNM staging system, because

the retroperitoneal cavity is not as large as the peritoneal space, and the diameter plays a more

sensitive role (see Figure 1b).

Another parameter is the percent of the protrusion of tumors. Exophytic masses are easily to

be resected than endophytic one. Totally endophytic tumor is assigned 3 points. Tumors that

are 50% or more endophytic are assigned 2 points. Tumors that are less than 50% endophytic

are assigned 1 point (see Figure 1c).

The relationship between the tumor and main vessels also affects the surgical manipulation.

Main vessels include the primary or secondary artery/vein, or those with diameter larger than

3mm. The distance that is 0.6cm or larger is assigned 1 point. The distance which is less than

0.6cm is assigned 2 points. If the tumor closely touches or compresses main vessels, or vessels

go through the tumor, 3 points are assigned (see Figure 1e).

It is assigned 1 point if tumors originate from the middle 1/3 portion of the outer boundary

edge. Tumors that originate from the superior or the inferior 1/3 of the outer edge are assigned

2 points. Based on 2 points, tumors which are on the ventral side of kidney are assigned as 3

points (see Figure 1f).

Patients received retroperitoneal RALPN in full flank (decubitus) position. Vessel clamping

was routinely used. All tumors were removed with an adequate margin to make sure the

integrity of pseudo capsule. Clinical features of all patients were collected: age, gender, BMI,

preoperative blood test and imaging results, operation time (the time period starts from the skin

incision to the final skin suture), estimated blood lost, clamping time, complications within 30

days, American Society of Anesthesiologists (ASA) score, pathology. Postoperative

complications were evaluated by the Clavien-Dindo classification system (12,13).

Statistical analysis

The student t test was used for continuous variables, and they were given as the mean plus

standard deviation (The homogeneity of variance of each test has been assessed). The Mann-

Whitney U test was used for non-Normally distributed continuous variables, and they were

given as the median and interquartile range (IQR). The Pearson or Likelihood Ratio χ2 test was

used for categorized variables. Both Logistic regression and ROC curve were used (The

multicollinearity of independent variables has been assessed). Backward: Conditional method

was used in regression analysis. Y was a dependent variable, X1, X2, X3--- were independent

variables, Y= b0+b1X1+b2X2+---+bkXk, probability P=
𝑒𝑌

1+𝑒Y
. A two-sided p<0.05 was considered

statistically significant. All data were analyzed with the Statistical Package for Social Sciences

software, v.20.0 (SPSS Inc., Chicago, IL, USA).

Results

In retroperitoneal group, 63 patients (60.0%) were male and 42 patients (40.0%) were female.

The median age was 54y (IQR: 46-63), and the median BMI was 24.3 (IQR: 22.2-26.3). In

transperitoneal group, 12 patients (70.6%) were male and 5 patients (29.4%) were female. The

median age was 56y (IQR: 53-63), and the median BMI was 22.6 (IQR: 20.8-25.0) (Table 2).

Among the perioperative characteristics, most were comparable between two groups. While

BMI, operation time and overall complication rate were significantly different. Operation time

was a little longer, and overall complication rate was also higher in transperitoneal group. BMI

was higher in retroperitoneal group, that might because we preferred to use retroperitoneal

approach for patients with relatively high BMI. The operation time was longer in

transperitoneal group, that because the time of preparing patients’ position, placement of trocars

and the skin closure were longer. The post-operative complication rate (GradeⅠ) was high in

transperitoneal group, there were 14 cases (82.4%) after operation. The ischemia time was

similar. It was 18 (IQR:15-22.5) minutes in retroperitoneal group, and 17 (IQR:12-27.5)

minutes in transperitoneal group (p=0.891).

In univariate analysis (Table 3), symptoms, ASA score and RETRO score were related to

postoperative complications in retroperitoneal group. The median RETRO score was 7 (IQR:

5-9). And the score of RETRO classification could significantly affected the postoperative

complication rate (p<0.05). The other factors did not impact on complication, even the radius

did not affect the overall complication rate. While in the transperitoneal group, the radius was

the only factor which had a significant impact on complication rate.

In logistic regression analysis, the overall complication rate in retroperitoneal group was

associated with symptoms, ASA score and RETRO score. The algorithm was extracted from

the logistic analysis, Y=-2.413+20.909X1+0.729X2+0.972X3, X1 indicated symptoms, X2

indicated ASA score, and X3 indicated RETRO score. Complication probability P=
𝑒𝑌

1+𝑒Y
.

RETRO score was classified into three categories, 4-6 was indicated 1 point, 7-10 was indicated

2 points, and ≥11 was indicated 3 points. If a patient had symptom (X1=1), ASA score was 3

(X2=3), RETRO score was larger than 11 (X3=3), then Y=-

2.413+20.909ⅹ1+0.729ⅹ3+0.972ⅹ3=23.599, P=
𝑒𝑌

1+𝑒Y
≈1. This patient was most probably had a

complication. Another finding from the regression analysis was that patients with RETRO

scored 2 were 1.85-fold higher risk of complication compared to those patients with RETRO

scored 1. The complication risk of patients with RETRO scored 3 points were dramatically

higher compared to those with RETRO scored 1 point.

During the 1-year follow-up, two cases in transperitoneal group relapsed. The pathology is

clear cell renal carcinoma (ccRCC, Fuhrman grade Ⅲ) and papillary renal cell carcinoma

(pRCC). The recurrence rate in transperitoneal group was significantly higher than that in

retroperitoneal group (p=0.008). The 2-year progression-free survival rate in retroperitoneal

group was 99%, while it was 88.2% in transperitoneal group.

Discussion

This study originally proposed a new nephrometry scoring system for PN via retroperitoneal

approach. It was named “RETRO” scoring system. Furthermore, a formula was extracted from

the logistic analysis, which could predict the probability of the post-operative complication rate.

The main factors affecting the complication rate were symptoms, ASA score and RETRO score.

The fat round the kidney, especially the adhesive perinephric fat would bring difficulties during

the surgery (14). The adhesive perinephric fat did have a significant influence during the

laparoscopic single-site donor nephrectomy (15). All patients included in this study received

operations under robot-assisted laparoscope. RALPN had lower morbidity and incidence of

CKD upstaging (16-18). A novel trifecta for RALPN was conceived(19). Off-clamp technique was

recommended since it decreased the probability of severe chronic kidney disease in the long-

term(20).

The “RETRO” classification system includes five major parameters. The “T” indicates the

approach for operation. Tumors those invades “forbidden zone” do not mean that they cannot

be removed through retroperitoneal way. It indicates the manipulation via retroperitoneal cavity

will become very complicated. It needs more operation time and retroperitoneal experience.

The other four parameters are quantitative factors. According to our experience, the nearness

to major vessel is more critical than that to the collecting system. And under the 3D scope, the

collecting system is more easily to be noticed and repaired. On the contrary, the vessel trunks

near the mass should be more taken care of. It was reported that the hemorrhage was among

4%-5% after partial nephrectomy, and they needed invasive treatment instead of blood

transfusion (21,22). Thus, in our series, all cases received robot-assisted laparoscopic

nephrectomy and were performed by the same surgeon. It avoided the heterogeneity caused by

the surgical tools and different manipulation skills. The fourth parameter is the polar location

of the mass. Under retroperitoneal way, it will be easier if the mass nears the renal equator. The

two polar tumors are more difficult to be exposed and make the suture more complicated.

Conclusions

Different renal tumor conditions need individualized treatment strategy. The “RETRO”

scoring system provides an approach selection and evaluation criterion for surgeons, especially

for those used to perform PN via retroperitoneal approach under mini-invasive platform, and

predicts a postoperative complication rate estimation. RETRO nephrometry system is a

beneficial addition to REANL and PADUA scoring systems.

Table 1. The specific score associated with each retroperitoneal anatomical feature included in

RETRO classification.

Table 2. Perioperative characteristics of included patients.

Table 3. Factors related to complications: univariate analysis.

Figure 1. (a) The blue square space is the “front lip”; (b) tumor size classification; (c)

endophytic degree of tumors; (d) if tumor invades the “front lip”, transperitoneal approach is

recommended; (e) The relationship with major vessels; (f) polar location of the tumor.

Figure 2. RETRO score, 2+2+1+1=6; RENAL score, 1+2+1+a+3=7a.

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*Corresponding author: Dr. Sunyi Ye1, Dr. Lixian Zhu2, Dr. Shuo Wang1

Address: 1Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang

University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. 2Department of

Thyroid Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University,

Hangzhou, China.

Tel:+86-571-87236833;E-mail:yesy@zju.edu.cn; 10918188@zju.edu.cn;

shuowang11@zju.edu.cn.

mailto:shuowang11@zju.edu.cn

Table 1 The specific score associated with each retroperitoneal anatomical feature

included in RETRO classification.

Retroperitoneal anatomical features Score
*

Radius (R)

≤2cm 1

2-4cm 2

4-6cm 3

6-8cm 4

… …

Endophytic (E)

≤50% 1

50-100% 2

100% 3

Trans-anterior lip (T)

Not involved Retroperitoneal approach

Involved Transperitoneal approach

Relationship with renal vessel trunk (R)

≥0.6cm 1

0-0.6cm 2

0 3

Originate from (O)

Middle 1/3 part 1

Upper or lower 1/3 part 2

Ventral side plus upper or lower 1/3

part

* Easy: 4-6 points; Moderate: 7-10 points; Difficult: ≥11 points.

Table 2 Perioperative characteristics of included patients

Retroperitoneal

（n=105）

Transperitoneal

(n=17)

p value

Sex 0.405

Male 63 (60%) 12 (70.6%)

Female 42 (40%) 5 (29.4%)

Age 0.427

Median 54 56

IQR 46-63 53-63

BMI 0.039

Median 24.3 22.6

IQR 22.2-26.3 20.8-25.0

Charlson score 0.691

≤1 82 14

>1 23 3

Symptoms 0.358

Yes 5 0

No 100 17

ASA score 0.929

1 56 9

2 34 5

3 15 3

Location 0.684

Left 50 9

Right 55 8

Size 0.146

Median 3.3 3.6

IQR 2.3-4.1 2.8-4.9

Endophytic 0.958

≤50% 58 9

>50% 37 6

=100% 10 2

Operation time 0.010

Median 90 111

IQR 75-109 97.5-136

Ischemia time 0.891

Median 18 17

IQR 15-22.5 12-27.5

Clavien-Dindo

classification

60 (57.1%) 14 (82.4%) 0.048

Grade Ⅰ 55 14

Grade Ⅱ 5 0

Pathology

ccRCC (Fuhrman

grade)

Ⅰ 12 1

Ⅱ 53 8

Ⅲ 9 1

Ⅳ 1 1

Papillary RCC 6 1

Chromophobe

carcinoma

3 1

Oncocytoma 5 0

Angiomyolipoma 11 2

others 5 2

Table 3 Factors related to complications: univariate analysis

Surgical

approaches

Retroperitoneal（n=105） Transperitoneal (n=17)

Present Absent P value Present Absent P value

Sex 0.421 0.218

Male 34

(32.4%)

(27.6%)

(53.0%)

(17.6%)

Female 26

(24.8%)

(15.2%)

(29.4%)

0 (0%)

Age (yr) 0.285 0.761

≤60 42 27 8 2

>60 18 18 6 1

BMI 0.687 0.659

≤25 35 28 11 2

>25 25 17 3 1

Charlson score 0.376 0.432

≤1 45 37 12 2

>1 15 8 2 1

Symptoms 0.047 -

Yes 5 0 0 0

No 55 45 14 3

ASA score 0.049 0.673

1 26 30 8 1

2 21 13 4 1

3 12 3 2 1

Location 0.310 0.761

Left 26 24 8 1

Right 34 21 6 2

Radius (cm) 0.074 0.043

≤4 40 37 9 0

>4 20 8 5 3

Endophytic 0.921 0.755

≤50% 33 25 7 2

>50% 20 16 5 1

=100% 5 5 2 0

Vessel Rete (cm) 0.643 0.659

≥0.6 36 29 3 1

<0.6 24 16 11 2

Origin 0.08 0.633

Not polar 18 21 1 0

Polar or ventral

hilum side

42 24 13 3

Operation time

(min)

0.080 0.377

≤90 27 28 3 0

>90 33 17 11 3

Ischemia time

(min)

0.071 0.29

≤25 53 44 10 3

>25 7 1 4 0

RETRO score 0.031 0.523

4-6 21 22 2 0

7-10 34 23 11 3

≥11 5 0 1 0

Recurrence 1 104 0.008
*
2 15 /

*
comparison between retro and transperitoneal group.