Annals of Surgical Oncology 10:705-710 (2003)
© 2003 Society of Surgical Oncology
Hepatic Resection for Metastatic Renal Tumors: Is It Worthwhile?
A. Alves, MD,
R. Adam, MD, PhD,
P. Majno, MD, PhD,
V. Delvart, Biostatistician,
D. Azoulay, MD, PhD,
D. Castaing, MD and
H. Bismuth, MD, FACS
From the Centre Hépato-Biliaire, Hôpital Paul Brousse, Université Paris-Sud, Villejuif, France.
Correspondence: Address correspondence and reprint requests to: René Adam, MD, PhD, Centre Hépato-Biliaire, Hôpital Paul Brousse, Université Paris-Sud 94804, Villejuif, France; Fax: 33-01-45-59-38-57; E-mail: rene.adam{at}pbr.ap-hop-paris.fr
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ABSTRACT
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Background: Liver metastases of malignant renal tumors are regarded as having an ominous prognosis because they are infrequently amenable to radical surgery and respond poorly to chemotherapy. Little is known of the outcome of isolated metastases to the liver for which resection is potentially curative.
Methods: Data on 14 patients with liver metastases from renal tumors who underwent a liver resection in a single center between 1982 and 2001 were analyzed retrospectively.
Results: There was no operative or postoperative mortality. The median survival was 26 months, with a survival rate of 69% at 1 year and 26% at 3 years. The curative pattern of hepatectomy (2-year survival, 69% vs. 0%; P = .001), an interval between the nephrectomy and the diagnosis of liver metastases in excess of 24 months (2-year survival, 71% vs. 25%; P = .05), tumor size <50 mm (2-year survival, 83% vs. 17%; P = .006), and the possibility of achieving a repeat hepatectomy in the case of recurrence (2-year survival, 100% vs. 21%; P = .02) were associated with a better outcome after the liver resection. Four patients were alive without evidence of disease at 6, 12, 26, and 96 months after the first hepatic resection, and one was alive with hepatic recurrence 18 months after resection.
Conclusions: In patients with liver metastases of malignant renal tumors, an aggressive policy for achieving tumor eradication seems to offer a chance for long-term survival, especially after a long disease-free interval from the nephrectomy. However, despite an aggressive policy for achieving tumor eradication, recurrence frequently occurs after liver resection.
Key Words: Liver metastases • Renal tumor • Hepatic resection • Prognosis
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INTRODUCTION
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Metastases occur in 50% of patients with renal tumors, and 20% of these are liver metastases. The prognosis of patients with metastatic renal cancer is poor: most patients die within 4 months, and only 10% are alive at 1 year.1,2 This reflects the lack of effective treatment: the response to chemotherapy is rarely observed or durable, and surgery can remove the disease in only a minority of cases. In 2% to 4% of patients, however, metastases are isolated and are accessible to radical surgery.3 The purpose of this study was to investigate the outcome of resection in patients with liver metastases from renal tumors and to try to identify the indications for liver surgery in these circumstances.
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PATIENTS AND METHODS
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Patients
Between June 1982 and September 2001, 14 patients with metastases from renal tumors were submitted to a liver resection. Hepatic surgery was considered when resection was likely to be curative in the absence of irresectable extrahepatic metastases. Resectable extrahepatic metastases were not considered as a contraindication provided that the overall surgical strategy aimed to be curative. The patients’ characteristics and the features of the tumors are listed in Table 1.
Characteristics of the Renal Disease
The histological type of the tumor was renal cell carcinoma in 10 cases, nephroblastoma in 3 cases, and fibrosarcoma in 1 case. The nephrectomy treating the original tumor had been performed at the referring hospital and had achieved radical removal of the tumor in all cases. During this operation, eight patients had tumor spread outside the perinephric capsule: five into the retroperitoneal fat, one into the diaphragm and the liver, one into the small intestine, and one into the adrenal gland. Six patients had received adjuvant systemic chemotherapy after the nephrectomy: three patients with Wilms’ tumor, one with sarcoma, and two with renal cell carcinoma. One patient had received adjuvant radiotherapy after the nephrectomy. Before the hepatic resection, one patient underwent embolization of the hepatic artery because of a large arterioportal fistula.
Characteristics of the Hepatic Disease
The metastases were metachronous in 12 cases and synchronous in 2 cases. The interval between radical nephrectomy and the diagnosis of liver metastases was 1 to 108 months, with a median of 37 months. In all cases, the liver metastases were discovered on routine ultrasonography or computerized tomography in the absence of symptoms of liver involvement. The metastases were solitary in five patients. The greatest diameter of the lesions ranged from 30 to 210 mm, with a median of 60 mm. The site of the disease was the right lobe of the liver in 11 patients and the left lobe in 1 patient and was bilobar in 2 patients. At the time of hepatic resection, one patient had lung metastases that were resected 1 month after liver surgery.
Liver Resection: Operative Data
The resection performed was a right hepatectomy in 11 cases. This was extended to segment 4 in one patient and to segment 4 and segment 1 in one patient; it was associated with an atypical resection in three patients for whom intraoperative ultrasonography discovered metastases in the left liver and was associated with left lobectomy in one patient. The surgical procedure in the last three patients was a bisegmentectomy, a left lobectomy, and an atypical resection. Clamping of the hepatic pedicle (Pringle’s maneuver) was performed in six cases (15, 19, 28, 30, and 34 minutes). A total vascular exclusion (35–137 minutes) was performed in five cases. Nine patients received an intraoperative blood transfusion (2–42 U of packed red cells; median, 3 U).
Statistical Analysis
Survival was evaluated according to the method of Kaplan and Meier. Prognostic variables related to the primary tumor (histology and tumor extension through the perinephric capsule), to the hepatic metastases (number, size, and time interval from the nephrectomy), and to liver resection (curative patterns and need for a repeat hepatectomy) were evaluated with regard to patient survival. Groups were compared with the log-rank test. P values <.05 were considered statistically significant.
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RESULTS
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Resection
A complete macroscopic and microscopic resection (R0) was achieved in 11 patients. In two patients, tumor tissue was present at the margin of the resection on histological examination of the specimen (R1), and in another patient the resection was complete, but synchronous lung metastases were left in place awaiting further surgery.
Mortality
There were no deaths within 60 days from the operation.
Morbidity
Two patients developed transient hepatic failure. A biliary leak occurred in three patients and resolved spontaneously. Two patients developed pneumonia. One patient required reoperation for bleeding. The median length of hospital stay was 14 days (range, 7–28 days).
Recurence
Recurrent disease developed in 12 patients. In four cases this was in the form of disseminated disease, and the patients died 8, 9, 12, and 15 months after liver resection. Two other patients died of vertebral and cerebral metastases at 29 and 18 months. In the last six patients, recurrence was in the form of isolated hepatic metastases 2 to 28 months after the first hepatectomy. One of these patients, with a positive margin (R1) at the first hepatectomy, died with lung metastases 8 months after surgery. In three patients, a repeat resection on the left lobe was performed after 7, 27, and 28 months from the first hepatic resection. One of these patients underwent five liver resections and one vertebral resection and is presently alive 8 years from the first hepatectomy (Fig. 1). One patient was treated with percutaneous radiofrequency at 20 months from the first hepatectomy. The last patient was alive with hepatic recurrence treated by systemic chemotherapy.
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FIG. 1. Abdominal computed tomographic (CT) scan of a patient with a large renal cell carcinoma (A) resected by a left nephrectomy with lymphadenectomy. Hepatic metastases appeared 44 months thereafter (B) and were treated with a right hepatectomy with partial resection of segments 3 and 4. The first hepatic recurrence occurred 28 months after liver resection (C) and was submitted to a repeat partial resection of segment 3. Two other localized hepatic recurrences were treated by a third and a fourth repeat hepatectomy. An abdominal CT scan at 79 months from the first liver resection did not show further recurrence (D).
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Survival
The median survival was 26 months, with an overall survival rate of 69% at 1 year, 52% at 2 years, and 26% at 3 years (Fig. 2). Whereas the overall survival of the 14 patients was 52% at 2 years, it was 56% at 2 years for the 10 patients with renal cell carcinoma and 38% for the patients with metastases from other renal tumors. At present, four patients are alive without hepatic recurrence at 6, 12, 26, and 96 months.
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FIG. 2. Overall survival of the 14 patients who received resection of liver metastases from a renal tumor.
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Analysis of Factors Associated With Survival
For the overall group of patients, the survival was shorter for patients with invasion through the perinephric capsule as compared with patients with no extension of the primary tumor (2-year survival, 30% vs. 60%), but the difference was not significant (P = .4). The interval between the nephrectomy and the diagnosis of liver metastases affected survival: patients with a disease-free interval of >24 months survived longer as compared with patients in whom the liver metastases were diagnosed within 24 months from the renal operation (2-year survival, 71% vs. 25%; P = .05; Fig. 3). In addition, patients who underwent a curative liver resection survived longer than those with a palliative hepatectomy either because of concomitant lung metastases or because of a positive resection margin (2-year survival, 69% vs. 0%; P = .001).
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FIG. 3. Survival according to the time interval (<24 months or >24 months) between the nephrectomy and the liver resection.
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There was a significantly better survival for patients with a largest lesion of 
50 mm compared with patients with the largest lesion >50 mm (2-year survival, 83% vs. 17%; P = .006). The number of metastases did not affect the outcome. In patients with recurrence, survival was improved when this was localized to the liver and a repeat hepatectomy could be performed (2-year survival, 100% vs. 21%; P = .02).
The histological type of the primary renal tumor did not seem to influence the outcome of liver resection (2-year survival, 33% vs. 53%; P = .7). However, a separate analysis of prognostic factors was made in the subgroup of 10 patients with renal cell carcinoma, with similar results, especially for the two main prognostic factors: size of the largest lesion <50 mm (2-year survival, 80% vs. 25%) and disease-free interval >24 months (2-year survival, 67% vs. 33%).
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DISCUSSION
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Liver metastases occur in 20% of patients with renal carcinoma and are less frequent than metastases to other sites, such as the lung (70%), lymph nodes (50%), or bone (40%).4 Metastases to the liver have a particularly poor prognosis that is worse than that of patients with pulmonary, cerebral, or skeletal involvement.1,2,5,6 In fact, although the aggressive surgical treatment of solitary pulmonary metastases is associated with a 5-year survival of 35% to 50%,7–9 the occurrence of liver metastases is constantly regarded as an ominous prognostic feature. The results of treatment are disappointing.10 The tumor is relatively radioresistant, and there is no indication for radiotherapy apart from the palliative treatment of symptomatic bone metastases. Systemic chemotherapy is not effective, with the possible exception of floxuridine, for which a response rate of 15% to 20% has been reported.6 In a recent study, immunotherapy was not more effective: interleukin-2 had a 20% to 30% response rate, and the addition of interferon alfa did not improve the results. Patients with liver metastases had a much poorer response rate compared with metastases to the lungs and lymph nodes.11
The poor outcome of liver metastases from renal carcinoma is partly explained by the fact that, in most cases, liver metastases are multiple and occur in association with metastases to other sites, in accordance with the pattern of hematogenous dissemination of the tumor.12 Indeed, liver metastases of renal tumors are solitary or localized in only 2% to 4% of cases.3 Although resection has been performed in these circumstances, there are only anecdotal reports on the results of liver surgery. Some series of noncolorectal liver metastases include some patients with lesions of renal origin, but information concerning these patients is difficult to extract.13–16 Publications specifically concerning liver resection for metastases of renal tumors are limited to 2 case reports on 2 and 3 patients17,18 and to 2 series of 4 and 13 patients12,19 (Table 2). The high perioperative mortality of the last study (31%) restricts evaluation of the potential benefit of surgical treatment of this condition.19
Our study has evaluated the outcome of 14 patients who underwent resection of metastases from renal tumors that were isolated or predominantly localized to the liver. There was no mortality within 60 days from the operation. The survival was 69% at 1 year and 26% at 3 years. The most important feature to consider, however, is the chance of long-term survival. Accordingly, 5 patients out of 14 in our series are alive, and 4 are disease free at 6, 12, 26, and 96 months. In the review of the 46 patients of previous reports,12–23 6 patients (13%) survived longer than 5 years. Obviously, only radical excision of the metastases can offer this chance of long-term survival, despite the high incidence of recurrence. An analysis of the factors of prognostic significance in the resection of liver metastases from renal tumors has not been performed previously. In this study, these factors have been assessed. In our experience, an interval of >24 months between the nephrectomy and the diagnosis of liver metastases was found to have a positive effect on survival, in accordance with the data on metastases of renal carcinoma to other organs.23 The histological type of the primary tumor was assumed to have an important prognostic influence on the outcome. Accordingly, outcomes for Wilms’ tumor and renal sarcoma are usually better than those for renal cell carcinoma.14,20 However, in our study, no difference was observed in survival between the 10 patients with liver metastases of renal cell carcinoma (56% at 2 years) and the patients with metastases from other renal tumors (38% at 2 years). Extension of primary disease and the number and histological type of the metastases did not seem to have an influence, although this should be taken with caution because of the limited number of patients. Liver metastases >50 mm were associated with a significantly poorer survival, as previously reported for colorectal liver metastases.24
As expected, the absence of adequate safe margins at the hepatectomy and the presence of lung metastases, even if secondarily resected, were associated with a poorer outcome. Faced with the constant tumor recurrence observed after liver resection in our patients, an aggressive policy to treat hepatic recurrence was associated with a prolonged survival, as demonstrated by the better outcome of patients who where submitted to a repeat hepatectomy.
In summary, the absence of alternative treatments of demonstrated efficacy and the poor natural prognosis of liver metastases from renal cell carcinoma advocate surgical treatment in patients for whom radical resection may be achieved. However, a tumor recurrence occurred in most patients despite the attempt at radical resection. Repeat hepatic resection is able to prolong remission when the tumor recurrence is limited to the liver and still resectable. Adjuvant therapies (i.e., chemotherapy, immunotherapy, or both) would be helpful in the future to prevent tumoral recurrence and to improve patient outcome.
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ACKNOWLEDGMENTS
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The authors thank Henri Bensadoun, Service d’Urologie, Center Hospitalier de Caen, France, for helpful criticism and review of the manuscript.
The acknowledgments are available online at www.annalssurgicaloncology.org.
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FOOTNOTES
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When potentially curative, resection of liver metastases from renal tumors is able to offer a chance of prolonged survival, but recurrence frequently occurs.
Received for publication July 25, 2002.
Accepted for publication April 8, 2003.
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ABSTRACT
INTRODUCTION
