Role of the Laparoscopic Approach to Cytoreductive Nephrectomy in Metastatic Renal-Cell Carcinoma: Does Size Matter?

Abstract

Background and Purpose:

Retrospective studies have shown laparoscopic cytoreductive nephrectomy (LCN) to be a safe procedure in selected patients. The objective of this article is to identify characteristics that may predict when a laparoscopic procedure may offer improved postoperative outcome and whether it affects the timing of postoperative systemic therapy compared with open surgery.

Patients and Methods:

A cohort of 43 LCN cases were matched with 43 open cytoreductive nephrectomy (OCN) cases based on both pathologic size of tumor and stage. Eleven cases were laparoscopic converted to open nephrectomy. Cases excluded from the analysis were adjacent organ involvement, inferior vena cava involvement, and bulky lymphadenopathy. Data analysis of 11 variables was performed using the t test, log-rank, and Wilcoxon tests. Significance was at P = 0.05. Survival data were calculated using the Kaplan-Meier estimate.

Results:

Significant differences between LCN vs OCN were estimated blood loss (mean 277 ml vs 816 ml) and length of hospitalization (3.2 days vs 5.1 days). The median size of tumor for LCN cases was 7.5 cm and for OCN, 9.5 cm. The mean size of tumor of LCN vs laparoscopic converted to open cases was 6.8 cm vs 11.2 cm, and this difference was significant. There was no significant difference in postoperative performance status, time to commencement of systemic treatment, or in survival time between both groups. This study provides further evidence that a laparoscopic approach with cytoreductive nephrectomy in metastatic renal-cell carcinoma is a safe option for tumors 10 cm and smaller. The approach (laparoscopic vs open) had no effect on postoperative complications or time to systemic therapy.

Conclusion:

Procedures with tumors larger than 10 cm were more likely to be converted to an open procedure. Tumors larger than 10 cm may be best approached via an open procedure, especially in the presence of involvement of adjacent organs or bulky lymphadenopathy.

Introduction

T reatment guidelines for patients with metastatic renal-cell carcinoma (RCC) are under constant development. Currently, cytoreductive nephrectomy followed by immunotherapy offers the best survival for patients with a good performance status and without significant morbidities.^1,2 High failure rates to complete the postoperative immunotherapy because of rapid progression of disease or postoperative-related morbidity is a concern, however.³

Retrospective studies have shown laparoscopic cytoreductive nephrectomy (LCN) to be a safe procedure in selected patients.^3

–6 The main advantage of LCN in this population would be to decrease the postoperative convalescence period, allowing earlier initiation of immunotherapy. Circumstances in which the laparoscopic approach may not be ideal are tumors that involve neighboring organs, inferior vena cava (IVC) thrombus, or bulky lymphadenopathy.

The objective of this study is to identify characteristics that may predict when a laparoscopic procedure is considered safe and allows faster recovery.

Patients and Methods

Between 1999 and 2008, 139 cytoreductive nephrectomies were performed at our institution by eight surgeons. Of these, 45 were LCN including 12 cases that were laparoscopic converted to open cytoreductive nephrectomy (OCN). A variety of approaches were used for the OCN and LCN procedures. Most OCN cases were performed via subcostal incision; other approaches included a flank approach and thoracoabdominal incision. The laparoscopic approach was transperitoneal and generally performed with four ports consisting of two 12-mm ports (one usually at or lateral to the umbilicus) and two 5-mm ports. Hem-o-lok (Weck, Teleflex Medical, Research Triangle Park, NC) clips were used to ligate the renal artery, and an endovascular stapler was used to ligate the renal vein.

Three surgeons were involved with all the laparoscopic surgeries. The hand-assisted approach as well as the traditional laparoscopic approaches was used based on surgeon preference. The kidney was placed in a 15-mm Endocatch II bag (Autosuture, Covidien Inc, Mansfield, MA) and removed with an incision extending from one of the 12-mm ports, often in the midline.

A pair-matched cohort was created consisting of 43 LCN patients (including 11 laparoscopic converted to open) matched with 43 open cases. All cases were matched based on both pathologic tumor size and stage. Cases excluded from the analysis were those with IVC involvement (six cases) and tumor extending beyond the Gerota fascia (eight cases). Two laparoscopic cases, one with T₁ and the other with T₄ stage disease, were not paired because there was not a comparable match.

The two groups were compared for age, operative time, estimated blood loss (EBL), length of hospitalization (LOH), tumor size and pathologic stage, Eastern Cooperative Oncology Group performance status preoperatively and postoperatively (at 2–5 mos), preoperative hemoglobin, calcium, and creatinine levels, as well as time to systemic therapy. Statistical analysis was performed using the nonparametric tests, the t test and Wilcoxon rank tests. Significance was at P = 0.05. Survival data were calculated using the Kaplan-Meier estimate.

Results

This is the largest study of LCN cases to date. Significant differences between LCN vs OCN were EBL (mean 277 ml vs 816 ml) and LOH (3.2 d vs 5.1 d), favoring LCN cases (Table 1). Approximately 70% of tumors of both groups were pathologic T_3a and T_3b (Table 2). The median size of tumor for LCN was 7.5 cm and for OCN, 9.5 cm. Mean follow-up was 21.1 months, and median follow-up was 14 months (range 2–84 mos).

Table 1.

Difference Between Open Cytoreductive Nephrectomy and Laparoscopic Cytoreductive Nephrectomy

Variable	Mean (OCN-LCN)	P value
Preoperative creatinine	−0.065	0.327
Preoperative hemoglobin	−1.219	0.029
PS preoperative	0.000	0.940
Preoperative calcium	−0.809	0.708
Preoperative alkaline phosphatase	20.810	0.702
Months to systemic treatment	4.375	1.000
Operative time	−297.875	0.742
EBL	710.524	<0.001
LOH	1.821	0.001
PS 2–5 months postoperative	0.381	0.098

OCN = open cytoreductive nephrectomy; LCN = laparoscopic cytoreductive nephrectomy; PS = performance status; EBL = estimated blood loss; LOH = length of hospitalization.

Table 2.

Stage Distribution of Laparoscopic and Open Cytoreductive Nephrectomy

	LCN		OCN
T	Frequency	Percent	Frequency	Percent
T₁	1	2.38	–	–
T_1a	3	7.14	0	0
T_1b	2	4.76	2	4.65
T₂	5	11.90	7	16.28
T_3a	22	52.38	24	55.81
T_3b	8	19.05	10	23.26
T_3c	1	2.38	0	0

LCN = laparoscopic cytoreductive nephrectomy; OCN = open cytoreductive nephrectomy.

There were 11 cases in the LCN cohort that were laparoscopic converted to OCN, a 25.6% conversion rate. Table 3 describes the characteristics and reason for conversion of these 11 cases. The significant finding between the two groups is the mean tumor size—6.8 cm (range 2.7–12.7 cm) in the LCN group vs 11.2 cm (range 6–20 cm) in the laparoscopic converted to open group. The average EBL was 627 ml, and LOH was 4.6 days for the laparoscopic converted to open cases.

Table 3.

Laparoscopic Converted to Open Cytoreductive Nephrectomy

	Tumor size (cm)	T stage	Operative Time (minutes)	EBL	LOH	Time to systemic therapy (months)	Survival (months)	Reason for conversion
1	6	T3a	x	400	4	N/A^a	57	Difficulty gaining access to renal hilum
2	10.5	T3b	289	1000	4	1.7	10.8	Tumor fixed to liver, difficult dissection
3	13.5	T3b		369	4	none	7	Tumor crossed midline
4	7.2	T3b	×	600	2	none	13.5	Unable to visualize renal vein and renal vein thrombus
5	7.5	T3b	207	500	4	19.0	43	Right adrenal vein bleed, previous laparotomy for right colonic polyp
6	15	T3b	282	700	5	3.0	15	Difficult dissection, renal vein thrombus
7	15	T2	221	350	6	none	1.6	Avulsed renal vein
8	20	T3a	×	1250	7	4.0	27.5	Large tumor size
9	8.5	T3a	×	800	6	none	5.9	Unable to expose renal artery (previous cholecystectomy/abscess)
10	10	T3a	×	×	5	2.0	20.6	Bowel, mesentery adhered to tumor
11	10	T3b	188	300	4	none	2.1	Thrombus into IVC

EBL = estimated blood loss; LOH = length of hospitalization; IVC = inferior vena cava.

Received high-dose interleukin-2 before nephrectomy; did not receive immunotherapy postoperatively.

There were six postoperative complications—three in the LCN and three in the OCN groups—making the overall complication rate 7.0%. In the LCN group, one patient had a pneumothorax, necessitating a chest tube for 1 day. Prolonged return of bowel function that resolved with conservative management was the second complication in the LCN group. In the laparoscopic converted to open group, the syndrome of inappropriate antidiuretic hormone hypersecretion developed in one patient; it was managed medically.

The OCN group had one patient with a pancreatic and splenic injury necessitating splenectomy. Another complication was a retroperitoneal bleed that occurred after atrial fibrillation necessitating cardioversion and a heparin drip developed in the patient. The bleed resolved with expectant management. The third complication was development of delerium tremens that was managed medically.

There was no significant difference in postoperative performance status, time to commencement of immunotherapy (5 vs 9 mos), or overall survival time between the LCN and OCN groups. Median survival (time from surgery to when 50% of patients die) was 20.6 months for the LCN and 14.5 months for OCN patients. This difference was not significant (Fig. 1).

FIG. 1.

Kaplan-Meier survival estimate.

Discussion

Previous studies use 15 cm as the upper limit when considering a laparoscopic approach; however, with the conversion rate and significant difference in size of tumor between the laparoscopic converted to open and LCN cases, we cannot recommend this.^7,8 Defining a tumor size that dictates whether an open or laparoscopic approach is appropriate is difficult to standardize. Factors such as thrombus extent, degree of adenopathy, and skill of the surgeon have to be taken into account.⁹ Hand-assisted laparoscopy may help the surgeon tackle the more difficult cases without converting to an open approach. Hand assistance is also useful in the occasional patient when significant bleeding during renal hilar dissection could be initially managed with direct digital tamponade.

Hallmark randomized studies have demonstrated a significant improvement in overall survival and delay in progression of disease for those undergoing a cytoreductive nephrectomy before interferon-alpha immunotherapy.^1,2 Since then, different forms of medical treatment, such as tyrosine kinase inhibitors, have undergone investigation and shown survival benefits as well.³ Although this study shows no significant difference in time to commencement of immunotherapy between the LCN and OCN groups (5 vs 9 mos, respectively), previous studies have demonstrated a significant difference, with LCN patients starting therapy earlier.^4,6

This study does show a significant difference in shorter LOH for those undergoing LCN, but whether a shorter hospital stay indicates a quicker recovery time to tolerate immunotherapy is not evident. The difference was most likely not significant because of the relatively small patient numbers. Those who undergo LCN may need less pain medication postoperatively and, thereby, recover faster. Bachman and associates,¹⁰ in a retrospective study, demonstrated a decrease in the amount of pain medication needed by those undergoing either a laparoscopic retroperitoneal or hand-assisted donor nephrectomy vs open donor nephrectomy. Future studies that evaluate the amount of medication necessary and its affect on length of recovery of those undergoing a laparoscopic vs open cytoreductive nephrectomy may be helpful. With the advent of newer forms of systemic therapy, surgery that will provide patients with the speediest recovery to initiate treatment may become an advantage.

The limitations of this study begin with the design. This study is retrospective and, although pairs were matched according to potential confounding factors such as pathologic size and stage, there is still a selection bias in the formation of these groups. Ideally, a randomized controlled study may help delineate what tumor size is safe when taking the laparoscopic approach. Although this is the largest study of LCN cases to date, the number is still small, indicating future studies are needed to analyze larger groups and to derive significant conclusions.

Conclusion

LCN for metastatic RCC, in experienced hands, is a safe option for tumors 10 cm and smaller, without adjacent organ involvement, IVC involvement, or bulky lymphadenopathy. According to our data, procedures in which tumors were larger than 10 cm were more likely to be converted to open procedures. Tumor size alone, however, cannot be considered in isolation during decision making regarding the approach in a patient. Apart from tumor characteristics, such as adjacent organ involvement and lymphadenopathy, the surgeon's laparoscopic experience with large tumors must also be considered. The approach (laparoscopic vs open) had no significant effect on postoperative complications or time to systemic therapy.

Footnotes

Acknowledgments

The authors would like to thank staff, including Dr. Stephen Beck, Dr. Richard Bihrle, Dr. Michael Koch, and Dr. Richard Foster, who performed the open surgeries.

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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