Laparoscopic Radical Versus Laparoscopic Partial Nephrectomy for Clinical T 1b N 0 M 0 Renal Tumors: Comparison of Perioperative,Pathological,and Functional Outcomes

Abstract

Aim:

To compare outcomes in patients treated with laparoscopic partial nephrectomy (LPN) and laparoscopic radical nephrectomy (LRN) for clinical T_1bN₀M₀ renal masses.

Materials and Methods:

Between 2002 and 2008, 33 and 52 consecutive patients who underwent LPN and LRN, respectively, for clinical stage T_1bN₀M₀ tumors were retrospectively identified from a prospectively maintained database of 450 patients undergoing laparoscopic renal surgery. Perioperative, pathological, and postoperative outcomes were compared.

Results:

The two groups of patients were similar in age, sex, and body–mass index. Mean radiographic tumor size was smaller (4.8 vs. 5.2 cm, p = 0.04) in the LPN group. Mean operative time (228 vs. 175 minutes, p < 0.0001) and mean estimated blood loss (233 vs. 112 mL, p = 0.003) were higher in the LPN group. Intraoperative complication rates of 15.2% versus 5.7% (p = 0.28) and postoperative complication rates of 24.2% versus 13.5% (p = 0.20) were observed in the LPN and LRN groups, respectively. Overall median follow-up was 15 and 21 months for the LPN and LRN cohorts, respectively. A 12.5% and 29.3% decline in estimated glomerular filtration rate was observed (p = 0.002), and 30.3% compared with 55.7% of patients developed an estimated creatinine clearance (eCrCl) <60 mL/minutes after treatment (p = 0.04) for LPN and LRN, respectively. There were no differences in pathological stage distribution between the two groups. In the LPN group there were no local or systemic recurrences, and one positive surgical margin was observed. One patient developed metastatic disease in the LRN group.

Conclusions:

LPN for T_1b renal tumors provides superior intermediate-term preservation of renal function compared with LRN. Continued follow-up of these patients is required to evaluate oncological outcomes.

Introduction

N ephron-sparing surgery (NSS) for renal-cell carcinoma (RCC) provides recurrence-free and long-term survival rates similar to those observed in patients treated with radical nephrectomy (RN) for tumors <4 cm.^1

–4 Further, NSS is becoming the standard of care for the treatment of these small renal masses.⁵ The current size cut-off is related to several studies that demonstrated improved survival in patients undergoing partial nephrectomy (PN) for tumors <4 cm compared with tumors >4 cm.^2,3 These studies ultimately formed the basis of 2002 TNM staging classification. By comparing outcomes in patients undergoing RN to PN, equivalent cancer control has been demonstrated with lesions 4 to 7 cm.^6

–10 Further, NSS is associated with improved quality of life, preservation of renal function, and potentially improved overall survival.^11

–14 On the basis of these findings, there is a clear rationale for considering elective NSS in patients with localized T_1b tumors.

The benefits of laparoscopic approaches to RN are well established. Laparoscopic PN (LPN), introduced in 1993, has emerged as a minimally invasive approach to NSS with excellent results.¹⁵ LPN is associated with shorter operative time, less pain, lower hospital costs, and comparable 5-year oncological results compared with open PN.^16,17 With increasing experience, improved techniques, and refined equipment, urologists are performing LPN on larger, more complex lesions. In fact, LPN for tumors >4 cm has previously been demonstrated to be feasible in expert hands.^18,19

The objective of this study was to compare perioperative, pathological, and functional outcomes of patients undergoing laparoscopic RN (LRN) and LPN for T_1bN₀M₀ renal lesions.

Materials and Methods

Patient selection

Institutional review board approval was obtained. A retrospective review of our institution's prospectively maintained database (October 2002–June 2008) of LPN and LRN was performed. All patients with radiographic, clinical stage T_1b enhancing renal lesions treated with LPN and LRN were reviewed. Clinical staging was performed using cross-sectional imaging, which was utilized preoperatively. Patients with clinically node-positive disease or evidence of metastatic disease were excluded from the analysis. A minimum of 6-month follow-up was required for patient inclusion. In addition, patients with solitary kidneys or end-stage renal disease (ESRD) (stage 5, estimated glomerular filtration rate [eGFR] <15 mL/minute/1.73 m²) were excluded. Central tumors were defined as hilar tumors or tumors abutting the pelvicaliceal system or sinus fat.

Surgical technique and outcome assessment

The techniques for performing LRN and LPN are detailed in a previous publication from our institution.²⁰ All procedures were performed by a single surgeon (A.L.S.). In brief, dissection is preformed primarily with ultrasonic shears and a suction device. The kidney is completely mobilized within Gerota's fascia. The renal vein and artery are dissected. During LRN, hilar vessels are controlled with the endovascular stapler or Hem-O-lock clips. In patients undergoing LPN, the perinephric fat is dissected off the kidney at the level of the renal capsule, leaving only the fat overlying the tumor. A laparoscopic ultrasound probe is used to confirm tumor location, and delineate the extent and depth of the tumor. Different methods of hilar clamping were applied including artery only and artery and vein separately using bulldog clamps, and en-block vascular pedicle clamping using a laparoscopic Satinsky clamp (Aesculap). Hilar control technique was left to surgeon discretion. Mannitol 12.5 g is administered routinely. Excision of the tumor is performed using cold 10-mm large Metzenbaum scissors. After tumor excision and argon beam coagulation, the deep tumor bed (collecting system and open-ended vessels) is closed using 3-0 Vicryl sutures, and the parenchyma is approximated using 2-0 Vicryl sutures. All sutures are end-loaded with LapraTy clips (Ethicon Endosurgery). FloSeal (Fusion Medical Technologies) is applied routinely to the exposed defect before suture closure. Finally, the tumor and any detached perinephric fat are removed using an Endo-Catch bag (United States Surgical) through the 12-mm port site, extending the incision as needed. A 5-mm Blake^® drain is placed thorough the lateral 5-mm port.

The clinicopathological characteristics, operative results, and outcomes were retrospectively analyzed for the entire cohort. Renal function was measured using serum creatinine (sCr) and eGFR, which was calculated using the Cockcroft–Gault equation. Comorbidities were grouped into three categories: hypertension, diabetes, and coronary artery disease. Complications were classified as intraoperative or postoperative, and further stratified into medical and surgical complications. Intraoperative complications were categorized into three groups: vascular injury (a major blood vessel injury necessitating suturing), adjacent organ injury, and hemorrhage (>800-mL blood loss or a need for blood transfusion).

Follow-up

Pathological specimens were reviewed by uropathologists at our institution. Follow-up assessments included evaluation of pathological specimens by uropathologists at our institution, physical examination, sCr and eGFR, chest radiography, and cross-sectional imaging at 6 months. The frequency of clinical and radiographic follow-up thereafter was dependent on pathological stage and grade of the tumor.

Statistical analysis

Commercially available statistical software was used (STATA SE 10). Preoperative, operative, functional, and pathological outcomes were compared using Student's t-test or rank test and chi-square test or Fischer's exact test, with p < 0.05 considered statistically significant.

Results

Between 2002 and 2008, a total of 184 and 266 patients underwent LPN and LRN, respectively. Sixty patients underwent LRN and 33 patients underwent LPN for tumors between 4 and 7 cm. Six patients in the LRN group were excluded because of the presence of preoperative ESRD, one for evidence of distant metastasis, and one because of the presence of loco-regional disease. No patients were excluded from the LPN group. After applying all exclusion criteria, a total of 33 and 52 patients who underwent LPN and LRN, respectively, were reviewed. Patient demographic data and tumor characteristics are detailed in Table 1. The mean age, sex, body–mass index, preoperative comorbidity, and preoperative estimated creatinine clearance (eCrCl) were similar between the two groups. Of note, mean radiographic tumor size was smaller in the LPN group than in the LRN group (4.8 vs. 5.2 cm, p = 0.04). LPN was associated with longer operative time (228 vs. 175 minutes, p < 0.01) and greater mean estimated blood loss (EBL) (233 vs. 112 cc; p < 0.003). Intraoperative complications occurred in 15.2% versus 5.7% (p = 0.8) of the patients in the LPN and LRN groups, respectively. Postoperative complications occurred in 24.2% versus 13.5% (p = 0.20) of patients, respectively. Length of stay was similar between the two groups (2.1 days LPN vs. 2.0 days LRN, p = 0.8). With respect to LPN, mean warm ischemia time (WIT) was 34 minutes (interquartile range [IQR] 28.7–38.2 minutes) and 29 patients (88%) sustained entry into the collecting system during tumor resection that required closure.

Table 1.

Demographic, Tumor Characteristics, and Perioperative Outcomes

	LPN	LRN	p-Value
Mean tumor size (cm, range)	4.8 (4.1–7)	5.2 (4.1–7)	0.04
n	33	52
Age, mean (range)	59.6 (23–83)	64.4 (27–85)	0.12
% male	69.7	53.9	0.15
Mean BMI (range)	29.0 (18.2–40.3)	30.0 (28.9–52.0)	0.45
% smoker	33	46	0.25
n, Comorbidities (%)
Hypertension	17 (55)	26 (50)	0.89
Diabetes	7 (21.2)	8 (15.4)	0.49
Ischemic heart Disease	5 (15.1)	9 (17.3)	0.79
Preoperative eCrCl (mL/minute) mean (standard deviation)	87.4 (39.4)	101.4 (41.8)	0.13
% Preoperative eCrCl <60 mL/minute	18	25	0.60
Tumor location (n)			0.71
Lower	17	22
Middle	7	11
Upper	9	18
% central tumor	69.7	74.5	0.63
OR time (minutes)	228	175	p < 0.0001
EBL (mL)	233	112	0.003
Transfusion rate	9.1	5.8	0.56
Conversion (number)	3	1	0.13
Length of stay (days)	2.12	2.02	0.80

BMI = body–mass index; eCrCl = estimated creatinine clearance; OR = operative time; EBL = estimated blood loss; LPN = laparoscopic partial nephrectomy; LRN = laparoscopic radical nephrectomy.

Table 2 summarizes perioperative complications encountered in the groups. In the LRN group, one patient had a delayed postoperative bleed necessitating transfusion of 2 units of packed red blood cells. The patient's condition stabilized with conservative measures. One patient had a severe burn at the diathermy pad site necessitating skin grafting. In the LPN group, one patient developed a urine leak, which was managed conservatively and completely resolved. There was no perioperative death in either group.

Table 2.

Operative and Postoperative Complications

	LPN	LRN	p-Value
Intraoperative complication rate (%)	15.2	5.7	0.28
Bleeding (>800 mL), n	2	0
Bowel injury, n	0	1
Liver/splenic injury, n	3	1
Vascular injury, n	0	1
Postoperative complication rate (%)	24.2	13.5	0.20
Surgical	12.1	5.7
Bleeding, n	2	1
Ileus, n	1	2
Urine leak, n	1	0
Medical	12.1	7.7
Postoperative delirium, n	0	1
Cardiovascular, n	1	1
Other, n	3	2

Table 3 illustrates renal functional outcomes. Preoperative eGFR was not statistically different between the groups (87.39 mL/minute LPN vs. 101.35 mL/minute LRN, p = 0.13). A significant decrease in eGFR was observed in both groups at postoperative day (POD) #1, which was more pronounced in the LRN group (47 vs. 10 mL/minute; p < 0.01). The LPN group did recover renal function with time, but eGFR did not reach baseline levels. At last follow-up, the percent decline in eGFR was 12.5% (median follow-up 15 months) in the LPN group and 29.3% (median follow-up 21 months) in the LRN group, respectively. About 30.3% and 55.7% of patients developed stage 3 chronic kidney disease (eGFR < 60 mL/minute) after being treated with LPN and LRN, respectively (p = 0.04). Further, 0 and 1 patient in the LPN and LRN groups, respectively, developed ESRD requiring maintenance hemodialysis.

Table 3.

Renal Functional Outcomes

	LPN	LRN	p-Value
Preoperative eCrCl (mL/minute)	87.4	101.4	0.13
POD #1 eCrCl (mL/minute)	77.3	60.8	0.001
Last eCrCl (mL/minute)	85.8	62.3	0.002
% change of eCrCl (mL/minute)	12.5	29.3	0.002
% postoperative eCrCl <60 mL/minute	30.3	55.7	0.04

POD = postoperative day.

Table 4 summarizes the pathological outcomes. Overall, 11% of lesions were benign. There was a trend toward more benign lesions in the LPN group (p = 0.055); however, there was no difference in the rate of pathological upstaging between the two groups (p = 0.19). One microscopic positive surgical margin was confirmed in the LPN group. There were no local or systemic recurrences observed in the LPN group. One patient in the LRN group developed confirmed metastatic RCC and has been treated with systemic therapy.

Table 4.

Pathological Data (p < 0.05)

	LPN	LRN
Benign lesion	8	5
Infection/cyst	4	1
Angiomyolipoma	2	0
Oncocytoma	2	4
Malignant lesions^a	25	47
Clear cell	13	35
Chromophobe	3	3
Papillary	9	9
Grade
1	1	3
2	11	33
3	8	11
4	1	0
Stage^b
pT_1a	8	6
pT_1b	12	31
pT₂	2	1
pT_3a	3	8
pT_3b	0	1

p = 0.055.

p = 0.19.

Discussion

At present, the optimal treatment for T_1bN₀M₀ renal lesions is controversial. Proponents of NSS quote the established benefits of preservation of renal function. Chronic renal insufficiency is a well-established risk factor for the development of anemia, hypertension, malnutrition, and neuropathy.^11

–14 It is associated with poorer quality of life,^21,22 increased risk of hospitalization, cardiovascular events, and death.¹⁴ Further, Thompson and colleagues¹³ from the Mayo Clinic compared patients with small renal masses treated with PN or RN; RN was associated with decreased overall survival. Further, in a large, multicenter review of 1454 patients undergoing PN or RN for T₁ tumors, no significant difference in the rate of cancer-specific deaths between patients undergoing either treatment was observed.⁵ Leibovich et al⁶ similarly demonstrated that there were no differences in cancer-specific survival and distant metastasis-free survival between patients treated with NSS and RN for 4- to 7-cm RCC after adjusting for pathological features.

Although NSS is clearly an option, it is at present underutilized. A retrospective review of over 10,000 patients treated with PN or RN between 1991 and 2002 has shown that only 2.6% of T_1b lesions were treated with NSS. Of note, patients were treated from 1991 to 2002 and there has likely been some change in practice patterns with increased use of NSS. We are encouraged by the findings from a recent single institution study indicating that in 2007 90% of T_1a and 60% of T_1b lesions were treated with NSS. However, these statistics are from a highly specialized, tertiary care cancer center.²³

The current study is unique in that we chose to compare outcomes in patients undergoing LRN and LPN. There are two key publications addressing LPN for lesions >4 cm, both of which compared outcomes to LPN for smaller lesions. In one study, the Cleveland Clinic group reviewed 425 patients stratified into groups based on tumor size of <2, 2 to 4, and >4 cm. Fifty-eight patients had lesions >4 cm. Mean operative time, EBL, and length of stay were equivalent between the groups. The >4 cm group was not at increased risk for positive tumor margin; however, it was associated with a longer WIT. Of note, their intraoperative complication rate was 14% and postoperative complication rate was 24%, which are comparable to our results.¹⁸ In the second study, the Johns Hopkins and North Shore–Long Island Jewish Health System groups demonstrated a higher complication rate (37%) and longer length of hospitalization in patients undergoing LPN for tumors >4 cm compared with smaller tumors.¹⁹ No other differences were observed between the groups. The authors concluded that LPN is an oncologically feasible option for tumors >4 cm. In our study, comparing LRN to LPN for T_1b tumors, there was a longer operative time and higher EBL in the LPN group, but not a statistically significant difference in operative or postoperative complication rate. Collectively, when interpreting the perioperative data of these studies, LPN for T_1b can be viewed as a feasible option when performed by surgeons with advanced laparoscopic skills.

Most importantly, the data presented clearly indicate that LPN for T_1b renal tumors provides better intermediate-term preservation of renal function in comparison to LRN. At maximal follow-up, LPN was associated with eGFR of 85.8 mL/minute, correlating to a decline of only 12.5% compared with an eGFR of 62.3 mL/minute (an ∼30% decline) in the LRN group. To the best of our knowledge, only one previous study has demonstrated this finding specifically for patients with renal lesions >4 cm undergoing laparoscopic surgery. Simmons et al²⁴ recently compared patients treated with LRN (n = 75) or LPN (n = 35) for T_1b-T₃ renal lesions. Similar to our results, the postoperative decrease in the eGFR was less in the LPN group than in the LRN group at 13 and 24 mL/minute, respectively. Since these are larger lesions, it can be assumed that a longer WIT will be required, as ice-cooling is more difficult to perform during laparoscopic surgery than during open surgery. Moreover, a longer WIT may potentially offset the advantages of NSS. However, the current study clearly demonstrates that despite these concerns LPN is associated with the preservation of renal function in this patient population. With a mean age of 59.6 and 64.4, these patients have significant life expectancy. As such, every effort must be made to prevent the development of renal insufficiency given its potential consequences.

LPN, which mimics the principles of the open approach, has been demonstrated to have comparable oncological outcomes to open PN at 5 years.^16,17 In our study, with limited follow-up, no local or systemic recurrences were observed in the LPN group. One patient in the LRN with biopsy-confirmed pulmonary metastases has been treated with systemic therapy. In addition, no difference in the rate of pathological upstaging or grade of tumor was observed. In the LPN group there were no local or systemic recurrences demonstrated, and one positive surgical margin (PSM) was observed in the LPN group. This patient has been followed with no evidence of clinical recurrence at 12.3-month follow-up. Given the findings of the studies that have evaluated outcomes in open partial nephrectomy (OPN) for T_1b lesions, we are encouraged by our short-term results. However, longer follow-up and corroborating studies are required to ensure the oncological efficacy of this procedure in this patient population.

The current study has several limitations. It is retrospective and from a single institution, which introduces significant patient-selection bias. Clearly, lesion size and location are not identical, and these as well as patient-related factors influenced operative planning. In addition, the method used for assessing renal function, sCr, and eGFR would ideally be replaced by 24-hour urine collections for creatinine clearance. Further, this study is also limited by a relatively small number of patients. This is of particular importance when comparing the complication data. The fact that a single surgeon with vast experience performed all of the PNs may have also influenced the results. Finally, this study is limited by the short follow-up period. To make meaningful oncological conclusions, 5- and 10-year survival data are necessary.

Conclusions

There is a lack of consensus for the optimal treatment for localized renal masses 4 to 7 cm; however, NSS is growing in popularity. As demonstrated in this study, LPN is an approach to NSS that is feasible and is associated with the preservation of intermediate-term renal function compared with LRN. Longer follow-up is necessary to evaluate oncological outcomes. In this setting, surgeon's expertise and a fully informed patient should dictate which option is ideal for a given clinical scenario.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

References

Belldegrun

, Tsui

, deKernion

, Smith

. Efficacy of nephron-sparing surgery for renal cell carcinoma: Analysis based on the new 1997 tumor-node-metastasis staging system. J Clin Oncol, 1999; 17:2868–2875.

Lerner

, Hawkins

, Blute

et al. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. J Urol, 1996; 155:1868–1873.

Hafez

, Fergany

, Novick

. Nephron sparing surgery of localized renal cell carcinoma: Impact of tumor size on patient survival, tumor recurrence and TNM staging. J Urol, 1999; 162:1930–1933.

Ljungberg

, Hanbury

, Kuczyk

, Merseburger

, Mulders

, Patard

, Sinescu

. European Association of Urology Guideline Group for renal cell carcinoma. Guidelines on Renal Cell Carcinoma. Eur Urol, 2007; 51:1502–1510.

Patard

, Shvarts

, Lam

et al. Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience. J Urol, 2004; 171,6 Pt 1:2181–2185.

Leibovich

, Blute

, Cheville

, Lohse

, Weaver

, Zincke

. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol, 2004; 171:1066–1070.

Dash

, Vickers

, Schachter

, Bach

, Snyder

, Russo

. Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4–7 cm. BJU Int, 2006; 97:939–945.

Becker

, Siemer

, Hack

, Humke

, Ziegler

, Stöckle

. Excellent long-term cancer control with elective nephron-sparing surgery for selected renal cell carcinomas measuring more than 4 cm. Eur Urol, 2006; 49:1058–1063.

Pahernik

, Roos

, Röhrig

, Wiesner

, Thüroff

. Elective nephron sparing surgery for renal cell carcinoma larger than 4 cm. J Urol, 2008; 179:71–74.

10.

Mitchell

, Gilbert

, Murphy

, Olsson

, Benson

, McKiernan

. Partial nephrectomy and radical nephrectomy offer similar cancer outcomes in renal cortical tumors 4 cm or larger. Urology, 2006; 67:260–264.

11.

Huang

, Levey

, Serio

, Snyder

, Vickers

, Raj

, Scardino

, Russo

. Chronic kidney disease after nephrectomy in patients with renal cortical tumors: A retrospective cohort study. Lancet Oncol, 2006; 7:735–740.

12.

Miller

, Schonlau

, Litwin

, Lai

, Saigal

. Urologic diseases in America Project. Renal and cardiovascular morbidity after partial or radical nephrectomy. Cancer, 2008; 112:511–520.

13.

Thompson

, Boorjian

, Lohse

, Leibovich

, Kwon

, Cheville

, Blute

. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol, 2008; 179:468–471.

14.

, Chertow

, Fan

, McCulloch

, Hsu

. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med, 2004; 351:1296–1305.

15.

Janetschek

. Laparoscopic partial nephrectomy: How far have we gone? Curr Opin Urol, 2007; 17:316–321.

16.

Lane

, Gill

. 5-Year outcomes of laparoscopic partial nephrectomy. J Urol, 2007; 177:70–74.

17.

Permpongkosol

, Bagga

, Romero

, Sroka

, Jarrett

, Kavoussi

. Laparoscopic versus open partial nephrectomy for the treatment of pathological T1N0M0 renal cell carcinoma: A 5-year survival rate. J Urol, 2006; 176:1984–1988.

18.

Simmons

, Chung

, Gill

. Perioperative efficacy of laparoscopic partial nephrectomy for tumors larger than 4 cm. Eur Urol, 2009; 55:199–208.

19.

Rais-Bahrami

, Romero

, Lima

, Kohanim

, Permpongkosol

, Trock

, Jarrett

, Kavoussi

. Elective laparoscopic partial nephrectomy in patients with tumors >4 cm. Urology, 2008; 72:580–583.

20.

Zorn

, Gong

, Orvieto

, Gofrit

, Mikhail

, Msezane

, Shalhav

. Comparison of laparoscopic radical and partial nephrectomy: Effects on long-term serum creatinine. Urology, 2007; 69:1035–1040.

21.

Lau

, Blute

, Weaver

, Torres

, Zincke

. Matched comparison of radical nephrectomy vs. nephron sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc, 2000; 75:1236–1242.

22.

Clark

, Schover

, Uzzo

, Hafez

, Rybicki

, Novick

. Quality of life and psychological adaption after surgical treatment for localized renal cell carcinoma: Impact of the amount of remaining renal tissue. Urology, 2001; 57:252–256.

23.

Thompson

, Kaag

, Vickers

et al. Contemporary use of partial nephrectomy at a Tertiary Care Center in the United States. J Urol, 2009; 81:993–997.

24.

Simmons

, Weight

, Gill

. Laparoscopic radical versus partial nephrectomy for tumors >4 cm: Intermediate-term oncologic and functional outcomes. Urology, 2009; 73:1077–1082.