SEARCH

SEARCH BY CITATION

Keywords:

  • renal cell carcinoma;
  • laparoscopic radical nephrectomy;
  • minimally invasive surgery

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

While laparoscopic radical nephrectomy (LRN) has been confirmed in various studies to be at least as efficacious as open radical nephrectomy (ORN) in terms of oncological control and more advantageous from the perspective of minimal invasiveness, very few studies have examined its feasibility and efficacy when applied to renal masses exceeding 7 cm in size, and even fewer involved results obtained from multicentre investigations. The present study retrospectively reviewed the outcome of LRN for masses exceeding 7 cm in size carried out in 26 institutions between 2000 and 2007 and concluded that LRN offers results comparable to ORN in terms of both tumour control and procedure-associated morbidities.  Furthermore, details from the study suggest that while the size of renal mass that can be treated using LRN may not be a necessarily limiting factor, the experience of the laparoscopic surgeon is a primary determinant in the overall outcome.

OBJECTIVE

  • • 
    To assess the feasibility and oncologic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with large renal cell carcinomas (RCCs) >7 cm in size.

PATIENTS AND METHODS

  • • 
    We analysed the data from 255 patients who underwent radical nephrectomies at 26 institutions in Korea between January 2000 and December 2007 for RCCs > 7 cm in size.
  • • 
    Eighty-eight patients who underwent LRNs were compared with 167 patients who underwent ORNs. The patients with tumor thrombi in the renal vein or IVC, and lymph node or distant metastases were excluded.
  • • 
    We compared the operative time, estimated blood loss, complication rates, and 2-year overall and disease-free survival rates between the LRN and ORN groups.

RESULTS

  • • 
    The median duration of postoperative follow-up was 19 months for the LRN group and 25.8 months for the ORN group.
  • • 
    The operative time was significantly longer in the LRN group than in the ORN group (241.5 ± 74.8 min vs 202.7 ±  69.6 min, P < 0.001) and blood loss was significantly lower in the LRN group than in the ORN group (439.8 ± 326.8 mL vs 604.4 ± 531.4 mL, P = 0.006).
  • • 
    No statistically significant difference was found in complication rates, the 2-year overall (92.7% vs 94%, P = 0.586) and disease-specific (90.1% vs 93.7%, P = 0.314) survival rates between the LRN and ORN groups.

CONCLUSIONS

  • • 
    Despite the longer operative time, LRN was an effective and less invasive treatment option for clinical T2 renal tumors. It achieved a degree of cancer control similar to that obtained with ORN.

Abbreviations
BMI

body-mass index

ECOG

Eastern Cooperative Oncology Group

LRN

laparoscopic radical nephrectomy

ORN

open radical nephrectomy.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Since the report of the first laparoscopic nephrectomy by Clayman et al. in 1991 [1], laparoscopic radical nephrectomy (LRN) has become a standard of care for RCC at many centers [2]. Multiple studies have confirmed the oncologic equivalence of LRN to open radical nephrectomy (ORN) [2–8] with clear benefits in terms of minimal invasiveness, such as decreased blood loss, less pain, better cosmesis, shorter hospital stay and faster convalescence [3,5,7,9]. However, most of the current literature has focused on LRN involving masses <7 cm, which are now more often treated with nephron-sparing surgery. While the indications for LRN are being expanded to include masses larger than previously indicated, the literature to date lacks studies regarding the feasibility and efficacy of laparoscopy for masses >7 cm, although several recent publications have reported on surgical outcomes [6,7]. The chief concern regarding the use of LRN for large renal tumors is whether the smaller working space allowed by a large tumor makes dissection more difficult and consequently causes more bleeding or has an adverse impact on oncologic outcomes. The purpose of this study was to evaluate the feasibility of LRN for large renal masses and to compare the operative and oncologic outcomes with ORN.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

We retrospectively reviewed the medical records of all patients who have undergone radical nephrectomy at 26 institutions between January 2000 and December 2007 for renal masses >7 cm. The size of the tumor was determined pathologically. The exclusion criteria for both LRN and ORN were the presence of tumor thrombi involving the renal vein or the inferior vena cava, bulky lymphadenopathy, perirenal extension, and extensive involvement of adjacent structures. Cases meeting any of these criteria were excluded to eliminate the effect of all factors other than tumor size which could affect the surgical and oncological outcome. Lymphadenectomy was not carried out as a routine in those cases where lymph node enlargement was not observable in imaging studies. Cases with lymph node enlargement and thus requiring lymphadenectomy were excluded from the study.

Among the 255 patients with T2 stage RCC examined in the present study, 88 patients were treated by LRN, and 167 patients were treated by ORN. The decision to perform either LRN or ORN was made preoperatively according to the surgeon’s or patient’s preference and based on patient characteristics. Only surgeons with significant laparoscopic experience carried out laparoscopic procedures, while all surgeons performed open surgery. LRN was performed transperitoneally (63.6%), retroperitoneally (11.4%) or using the hand-assistance technique (25%), depending on the surgeon’s preference.

Intraoperative complications included those necessitating immediate treatment, such as injury of major vasculature, organs, or bowels. Postoperative complications included major problems such as prolonged ileus and pulmonary insufficiency. Clinical problems that did not necessitate medical care, such as temporary azotemia and drug fevers, were not included.

After approval by the Institutional Review Board at Seoul National University Bundang Hospital, Korea (B-0801-053-105), general and clinical/pathologic data from the eligible patients were retrieved from medical records and reviewed retrospectively. The authors used the database of the Korea National Statistical Office to determine patient survival if the patient was lost during follow-up. The Medical Research Collaboration Center at Seoul National University Hospital was consulted regarding survival analysis. Differences in demographics and clinical and pathological factors were evaluated using the Student t-test and χ2 test for continuous and categorical variables, respectively. Survival curves were estimated using the Kaplan–Meier method and compared using the log-rank test. All P values were two-sided and P < 0.05 was considered to indicate statistical significance.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The patient and tumor characteristics are presented in Table 1. The mean patient age in the LRN and ORN groups was 57.8 years and 55.1 years, respectively, and the mean body-mass index (BMI) was 23.7 and 23.8, respectively. Patients in both groups were similar in Eastern Cooperative Oncology Group (ECOG) performance status. The mean tumor size was also comparable between the LRN and ORN groups (9.2 cm and 9.8 cm, respectively, P = 0.07). The operative time was significantly longer in the LRN group than in the ORN group (241.5 ± 74.8 min vs 202.7 ± 69.6 min, P < 0.001), and blood loss was significantly lower in the LRN group than in the ORN group (439.8 ± 326.8 mL vs 604.4 ± 531.4 mL, P = 0.006).

Table 1.  Demographic data and preoperative tumor characteristics
 LRNORNP
  1. LRN, laparoscopic radical nephrectomy; ORN, open radical nephrectomy; ECOG, Eastern Cooperative Oncology Group (ECOG); BMI, body-mass index; Rt, Right; Lt, Left.

Number of patients88167
Gender (%)  0.66
 Male58 (65.9)104 (62.3) 
 Female30 (34.1) 63 (37.7) 
Age, mean ± SD, years57.8 ± 12.4 55.1 ± 13.20.11
ECOG performance status (%)  0.07
 063 (71.6) 96 (57.5) 
 115 (17.0) 51 (30.5) 
 2 1 (1.1%)  3 (1.8) 
 3 0  2 (1.2) 
BMI, mean ± SD, kg/m2)23.7 ± 2.8 23.8 ± 3.70.89
Tumor laterality, n (%)  0.07
 Rt37 (42) 88 (52.7) 
 Lt51 (58) 79 (47.3) 
Tumor size (range, cm) 9.2 (7.2–16)  9.8 (7.3–22)0.07

Four cases in the LRN group involved conversion to open procedures, three as a result of vascular injury and one because of mechanical trouble with the CO2 gas insufflator. Table 2 lists the intraoperative and postoperative complications. Two cases with bowel injury were noted in the LRN group; they were managed by intracorporeal suturing. The difference in incidence of intraoperative complications between the LRN and ORN groups was not of statistical significance (10.2% vs 14.4%, P = 0.349). The incidence of postoperative complications was also similar in both groups (17% vs 12.6%, P = 0.330). Most of the postsurgical complications, such as prolonged ileus and respiratory complications, were managed conservatively; however, repair was carried out for incisional hernia (one case in each group) and wound dehiscence (three cases in the ORN group) (Table 2).

Table 2.  Complications
 LRN (%)ORN (%)P
  1. LRN, laparoscopic radical nephrectomy; ORN, open radical nephrectomy.

Number of patients88167
Intraoperative   
 Vascular/hemorrhage 6 (6.8) 18 (10.8) 
 Bowel 2 (2.3)  3 (1.8) 
 Spleen, liver 1 (1.1)  2 (1.2) 
 Other 0  1 (0.6) 
 Total 9 (10.2) 24 (14.4)0.349
Postoperative   
 Delayed bleeding 5 (5.7)  9 (5.4) 
 Ileus 3 (3.4)  2 (1.2) 
 Respiratory 2 (2.3)  3 (1.8) 
 Cardiac 0  2 (1.2) 
 Incisional hernia 1 (1.1)  1 (0.6) 
 Wound dehiscence 0  3 (1.8) 
 Other 4 (4.5)  1 (0.6) 
 Total15 (17) 21 (12.6)0.330

Table 3 lists the pathologic results. Clear cell-type RCC was confirmed in 88.6% and 79.6% of the patients in the LRN and ORN groups, respectively. The pathological tumor grades were similar in the LRN and ORN groups. The median duration of postoperative follow-up was 19 months for the LRN group and 25.8 months for the ORN group. Local recurrence or distant metastasis occurred in eight patients in the LRN group and 15 patients in the ORN group (P = 0.997). Seven patients in the LRN group and 14 patients in the ORN group died during the follow-up period (P = 0.906). Figures 1 and 2 show the Kaplan–Meier curves for overall survival and disease-free survival, respectively. No statistically significant difference was found in the overall and disease-free survival rates between the LRN and ORN groups. (92.7% vs 94% in 2-year overall survival rate; 90.1% vs 93.7% in 2-year disease-specific survival rate).

Table 3.  Pathologic findings
 LRNORNP
  1. LRN, laparoscopic radical nephrectomy; ORN, open radical nephrectomy.

Number of patients88167
RCC subtype, n (%)  0.069
 Clear cell78 (88.6)133 (79.6) 
 Papillary 1 (1.1)  11 (6.6) 
 Chromophobe 9 (10.2) 17 (10.2) 
 Collecting duct 0  1 (0.6) 
 Unclassified 0  5 (3) 
Fuhrman’s nuclear grade (%)  0.218
 1 6 (6.8)  11 (6.6) 
 244 (50) 76 (45.5) 
 332 (36.4) 70 (41.9) 
 4 6 (6.8) 10 (6) 
image

Figure 1. Kaplan–Meier curve for overall survival according to the surgical method. The Cox proportional hazard ratio is 0.645 (95% CI, 0.267–1.557).

Download figure to PowerPoint

image

Figure 2. Kaplan–Meier curve for recurrence-free survival according to the surgical method. The Cox proportional hazard ratio is 0.785 (95% CI, 0.315–1.955).

Download figure to PowerPoint

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The utilization of LRN for treatment of small renal masses has diminished because of the emergence of nephron-sparing procedures with comparable outcomes, such as partial nephrectomy, thermal ablation, and cryotherapy [10,11]. Moreover, owing to dramatic improvements in laparoscopic techniques, the indications of LRN have expanded to include larger, more complex masses, as well as cytoreduction [12–14]. However, the increase in applicable tumor size has posed several technical and oncological problems for laparoscopic procedures. An increase in the size of the specimen makes the working space smaller and, as nodal disease is more likely in larger lesions, approach to the renal hilum becomes more difficult, with a correspondingly greater possibility of severe bleeding because of the abundance of parasitic vessels and increased chance of oncological violation by inevitable tumor manipulation [15]. For these reasons, LRN for large renal masses is a technically challenging procedure, even for experienced surgeons. In this study, the average tumor size of the LRN group was about 9.2 cm in diameter, and the largest tumor was 16 cm in diameter. All tumors were successfully extirpated laparoscopically, with the exception of four cases involving conversion to open procedures. The majority of the cases of the LRN group were operated on by surgeons who were highly experienced in laparoscopic surgery: 79 out of the 88 cases performed laparoscopically were operated on by the 10 most experienced surgeons. Despite the considerable numbers of institutions and surgeons participating in this study, most of the surgeries were performed by several major centers: 194 out of the 255 cases examined in the study were operated on by the 10 busiest institutions, to each of whom two or three surgeons are affiliated.

The upper limit of tumor size amenable to direct laparoscopic removal remains to be determined. Dunn et al. [7] found that tumors up to 10 cm in diameter were appropriate. However, Steinberg et al. [16] reported similar perioperative and postoperative outcomes for tumors 7–10 cm in size and tumors >10 cm in size. Thus, tumor size itself does not seem to be a major factor involved in the decision on the treatment modality; the experience of the individual laparoscopic surgeon appears to be the preceding determining factor. The data presented in this study indicated that patients undergoing LRN had a longer operative time and less blood loss than patients undergoing ORN. The significantly lower blood loss in the LRN group compared with the ORN group suggests that the benefits of minimal invasiveness could be retained in T2 lesions, in concordance to other reports [16–18].

The exclusion criteria employed in the present study for both LRN and ORN were the presence of tumor thrombi involving the renal vein or the inferior vena cava, bulky lymphadenopathy, perirenal extension, and extensive involvement of adjacent structures. Although LRN for T3a and T3b lesions or cytoreductive surgery appear to be both feasible and safe, the authors excluded these cases to eliminate all factors other than tumor size which could affect the surgical and oncologic outcome. Several recent reports have evaluated the employment of LRN for T3b disease or cytoreduction [12–14,19]; these studies involved small, highly select subject series and would have benefited from longer follow-up periods. However, the early results indicate that LRN can be performed for large or complex masses, such as those involving renal vein tumor thrombi, without increased perioperative morbidity.

The oncologic outcome of LRN for tumors >7 cm in size appears to be as good as that of ORN. In the present study, the 2-year survival in the two groups was similar. The present results are similar to those of other investigations pertaining to stage T2 tumors [2,6,17,20–22]. Although the follow-up period in this study was not sufficiently long to allow determination of the exact long-term survival, the current study is one of the largest series to present comparative findings for LRN and ORN for renal tumors >7 cm in size.

The major limitation of the current study was that the sample was not randomized and that the data were collected retrospectively. In addition, the criteria for choosing between open and laparoscopic approaches were arbitrary. However, the characteristics of the renal tumor lesions themselves differed little between the two groups, alleviating the possible subjective bias imposed by the surgeons. Another potential limitation was that the median follow-up period in this study was too short for the evaluation of long-term oncologic outcomes of LRN for T2 stage RCC. Yet another crucial limitation of the present study was that owing to several other limitations, such as the mean follow-up period and the number of subjects remaining at the end of the maximal follow-up period, multivariate analysis of sufficient statistical vigor could not be carried out to adjust for various baseline characteristics. Lastly, the standardization of surgical techniques was impossible because of the multi-institutional and retrospective design of the study.

In conclusion, the data presented in this study have shown that larger renal tumors (greater than 7 cm) can be safely resected laparoscopically with less blood loss than open radical nephrectomy, with comparable outcomes, both surgically and oncologically. On short-term follow-up, LRN achieved a degree of cancer control similar to that obtained with ORN. Subsequent studies with longer follow-up periods appears to be necessary for further validation of these findings

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

This research was supported by the Research Foundation Grant funded by the Korean Urological Association (KUA-2007-Byun).

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES