Long-term experience with management of renal cell carcinoma involving the inferior vena cava
Article Outline
Abstract
Objectives
To evaluate the long-term outcome and prognosis and influence of patient and tumor characteristics and therapeutic interventions on patients with renal cell carcinoma (RCC) extending to the inferior vena cava (IVC).
Methods
The data of 75 patients (51 men and 24 women; age range 27 to 92 years) with RCC and involvement of the IVC, including 49 without and 26 with metastatic disease, treated between July 1973 and December 1998 were reviewed. The clinical presentation, laboratory and imaging investigations, extent and level of caval involvement, operative details, and estimated blood loss, as well as the postoperative course, morbidity, and actuarial and disease-free survival were analyzed.
Results
Seventy-five patients between 27 and 92 years old with RCC involving the IVC were studied. Of the 54 operative patients, 48 had no metastasis and 6 had metastatic disease; 32 had IVC tumor extension to the infrahepatic or low retrohepatic IVC, 7 had high intrahepatic IVC extension, and 15 had right atrial extension. In 7 patients, tumor had invaded the IVC wall. Partial IVC wall excision was done in 4 patients and resection of a complete segment of the IVC in 3 patients. Tube graft to replace a segment of the IVC was used in 2 patients. Patients with intracardiac extension were initially treated with cardiopulmonary bypass. Subsequently, profound hypothermia and circulatory arrest were also used. Three patients died in the postoperative period: two with and one without metastatic disease. The follow-up period ranged between 25 and 144 months. Of the 48 patients without evidence of metastasis at surgery, the perioperative mortality rate was 2%. Twenty-two patients (47%) were alive without evidence of metastases, 4% developed solitary metastasis, and 36% eventually developed multiple metastases.
Conclusions
Our long-term experience confirms that of other investigators that nonmetastatic RCC with extension into the IVC is a potentially curable condition provided complete removal can be achieved. The level of extension of the tumor thrombus dictates the surgical techniques used for successful removal of the tumor thrombus. The treatment of patients with caval involvement and metastatic disease at presentation needs to be carefully individualized. Those with extensive multiorgan metastases continued to do poorly irrespective of the therapeutic approach chosen.
The incidence of involvement of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC) is reported to be between 4% and 10%.1, 2 Tumor thrombi may extend as far as the right atrium in 1% of patients with RCC.3 The tumor thrombus occasionally extends to the infrarenal IVC. Tumor thrombi may also invade and adhere to the IVC wall. The management of RCC with tumor thrombus extending to the subhepatic IVC is not usually difficult.4 Extension of the tumor to the right atrium, high retrohepatic or suprahepatic (intrahepatic), IVC requires careful planning.5 A thoracoabdominal approach, median sternotomy, cardiopulmonary bypass with profound hypothermia, and circulatory arrest have been used in patients with intracardiac tumor extension and electively in patients with intrahepatic or IVC extension. This allows the IVC to be opened both below and above the liver so that the tumor thrombus is removed as effectively as possible in a bloodless field.6, 7, 8, 9, 10 Resection and reconstruction of the IVC are occasionally necessary when the tumor directly invades the IVC or the tumor thrombus is large and adherent to the caval wall. A pericardial patch may be used for reconstruction of the IVC.10, 11 Total replacement of the IVC using an expanded polytetrafluoroethylene tubular graft seems to provide feasible, good, long-term patency rates.12 We discuss our experience from 1973 to 1999 in treating 75 patients with RCC invading the IVC.
Material and methods
The data of 75 patients (51 men [28 white, 17 black, and 6 other] and 24 women [16 white, 5 black, and 3 other]; age range 27 to 92 years) with RCC and involvement of the IVC treated between July 1973 and December 1999 were reviewed. The clinical presentation, laboratory and imaging findings, extent and level of caval involvement, operative findings and technical details, estimated blood loss, postoperative course, and actuarial and disease-free survival were calculated.
Staging relied on preoperative imaging studies with reliance on chest X-ray, abdominal computed tomography (CT) with selective use of magnetic resonance imaging, chest CT, echocardiography, ultrasonography, and bone scanning.
The level of caval involvement was determined in almost all the surgical patients preoperatively by imaging studies. This included findings on CT, ultrasonography of the IVC, and magnetic resonance imaging. Echocardiography was valuable in patients with suspected intracardiac tumor extension. Inferior venacavography was used earlier in the series but was used in only 3 patients in the past 15 years.
Renal artery embolization was performed 1 day before nephrectomy in 11 patients and on the morning of nephrectomy in 3 patients. Regional lymphadenectomy was not used in most patients (only 6 patients underwent lymphadenectomy). Most patients (n = 46) underwent ipsilateral adrenalectomy.
Patients were followed up at 6 to 12-month intervals postoperatively. At each visit, patients underwent complete blood count, serum chemistry panel, and chest X-rays. Abdominal CT was obtained at intervals of 12 to 24 months. Cancer-free status was determined by negative findings on these studies. Survival was calculated to the last follow-up visit for surviving patients or to death.
Results
Seventy-five patients between 27 and 92 years old (mean age 59.5) with RCC involving the IVC who had a minimum follow-up of 2 years were treated during the study period. More men were affected than women (51 versus 24; 68% versus 32%, respectively). Forty-nine patients had no evidence of metastatic disease. Metastatic disease was found in 26 patients. Fifty-four patients underwent surgical resection (48 patients with no metastases and 6 with metastases). Pathologic examination confirmed the diagnosis of RCC in all 54 surgical patients, as well in 8 of the nonsurgical patients. In the 54 surgical patients, 32 had no capsular penetration and 24 had perinephric fat involvement. Of the 6 patients who underwent regional lymphadenectomy, 2 had positive nodes. The tumor size ranged from 4.5 to 21 cm. Of the 54 operative patients, 32 had IVC tumor extension to the infrahepatic or low retrohepatic level (below the major hepatic veins), 7 had intrahepatic extension (posterior to, or beyond, the major hepatic veins), and 15 had right atrial extension. In 7 patients, tumor had invaded the IVC wall. Partial IVC wall excision was performed in 4 patients, and a complete segment of IVC was resected in 3 patients. A pericardial patch graft was used to reconstruct the IVC in 3 patients, and a tube graft to replace a segment of the IVC was used in 2 patients. Patients with intrahepatic or suprahepatic extension were initially treated by thoracoabdominal exposure, as well as reflection of the liver away from the diaphragm by dividing the right coronary and triangular ligaments and controlling the hepatic circulation with the Pringle maneuver (ie, application of a soft bladed occlusive clamp across the porta hepatis).1 The estimated blood loss was between 400 and 8000 mL. Patients with intracardiac extension were initially treated by cardiopulmonary bypass for removal of the intra-atrial extension. Subsequently, cardiopulmonary bypass, profound hypothermia, and circulatory arrest were used for patients with intrahepatic and intracardiac tumor extension. Three patients died in the postoperative period: two with extensive multiorgan metastases and one without metastatic disease. The cause of death in the 2 patients with metastatic disease was severe coagulopathy. The cause of death in the patient without metastasis was myocardial infarction 3 days postoperatively. Other postoperative complications included brief pulmonary complications (atelectasis) in most patients and temporary renal insufficiency in 28 patients (mild in 20 and moderate to severe in 8, 3 of whom required temporary dialysis).
The follow-up ranged from 25 to 144 months. Of 47 surviving patients without metastases, 22 (47%) were alive without evidence of metastasis at their last follow-up visit. These included 14 (52%) of 27 patients with infrahepatic, 3 (43%) of 7 with intrahepatic, and 5 (38%) of 13 patients with intracardiac tumor extension (no statistically significant differences). Three patients (6%) developed a solitary metastasis that was resected with no recurrence in two and with subsequent development of multiple metastases in one. Seventeen patients (36%) developed multiple metastases. Nineteen patients died during the follow-up period. Of these, six (13%) died of intercurrent disease without evidence of metastases. Thirteen patients died of metastatic disease (including one who had undergone two prior resections of solitary metastatic disease). Four patients were alive with multiple metastases at last follow-up. The actuarial and disease-specific survival rate for the patients with no metastases at surgery was 61% and 67%, respectively at 3 years and 43% and 58%, respectively at 5 years. Of the 6 patients with metastatic disease at surgery, 2 had perioperative mortality (both of the 4 patients with multiorgan metastases). One of the four surviving patients lived for 3 years. The 21 nonsurgical patients included 20 with metastases and 1 without metastases at presentation. The patient without metastases who refused surgical intervention lived for 3 years with slow progression and eventually died after intracardiac extension. All 20 nonsurgical patients with metastases at presentation died within 2 years. The pathologic finding was RCC in the 54 surgical patients and 8 nonoperative, biopsied patients; clear cell type was the most common.
Comment
In patients with nonmetastatic RCC and inferior vena caval involvement, the 5-year survival rates range between 18% and 68% after complete surgical resection.1, 5, 6, 7, 8, 9, 10 The presence or absence of perinephric fat involvement, lymph node involvement, or distant metastases are important prognostic factors. The presence of these adverse prognostic findings diminishes survival. There is controversy concerning the prognostic significance of the tumor thrombus level in the IVC.5, 6, 7, 8, 9, 10, 13 Some studies suggest that the risk of metastases and early death is increased with a more cephalad extent of IVC thrombi. Sosa et al.13 reported a 2-year survival rate of 80% in patients with infrahepatic IVC tumor thrombi compared with only 21% in those with suprahepatic thrombi. They found that patients with suprahepatic caval extension were more likely to have perinephric fat and regional lymph node involvement. Skinner et al.8 reported a 5-year survival rate of 35% after surgical treatment for patients with RCC and a subhepatic IVC thrombus, 18% for those with intrahepatic, and 0% for those with atrial tumor thrombi. Others found that in the absence of other adverse prognostic factors, the cephalad extension of IVC involvement did not appear to be prognostically important.5, 7 Likewise, of our patients with infrahepatic, intrahepatic, and intracardiac tumor extension, 52%, 43%, and 38%, respectively, were alive with no evidence of disease (no statistically significant difference).
In patients with extensive caval extension, preoperative renal arteriography and renal artery embolization can be useful with acceptable morbidity.6, 7
The presence of direct caval involvement or dense adherence of the tumor thrombus to part of the caval wall may necessitate caval wall resection. If a major part of the circumference of the IVC is involved, a segment of the IVC can be removed. In the past, this required clamping of the uninvolved renal vein (usually the left). Fortunately, most patients requiring caval resection have tumors on the right side. Prior obstruction of the IVC at the level of the left renal vein encourages collateral venous flow by way of the left adrenal, gonadal, and lumbar veins, which are available for collateral drainage of the left renal vein.14, 15 If the left renal vein and IVC require resection for a left renal carcinoma, a right renal vein-portal vein anastomosis can provide feasible venous drainage for the right kidney. More recently, reconstruction of the IVC has been performed. When partial resection of the IVC is needed, the defect can be repaired by a pericardial or synthetic graft.10, 11 We used a pericardiac patch graft in three of our patients.
Sarti16 first reported total prosthetic replacement of the IVC in 1970 using a tubular polytetrafluoroethylene graft in a patient with advanced Wilm’s tumor. This was also used as an alternative method for IVC reconstruction after trauma.17 Katz et al.15 used this procedure for suprarenal inferior vena caval replacement in RCC with good prosthetic patency 9 months postoperatively. Okada et al.12 reported on long-term patency after IVC replacement with an expanded polytetrafluoroethylene tubular graft in 4 patients with tumor thrombi from RCC. Likewise two of our patients were successfully treated with a tube graft.
For patients with a high retrohepatic and suprahepatic caval thrombus, a thoracoabdominal approach is necessary. Currently, two alternatives are available. One is to control the hepatic circulation by the Pringle maneuver. The liver can withstand 30 minutes of warm ischemia without functional impairment.1, 10, 18, 19 The other alternative is to use cardiopulmonary bypass with deep hypothermic circulatory arrest.6, 7, 9 Cardiopulmonary bypass with deep hypothermic circulatory arrest significantly decreased the morbidity and mortality associated with resection of RCC extending into the right atrium or the IVC at or above the hepatic veins.9 The central nervous system is the organ most sensitive to circulatory arrest, and, at body temperature, it tolerates no more than a few minutes of ischemia. For each 5° of cooling, the tolerated ischemic time doubles. At 18°C, 45 to 60 minutes of ischemia time are well tolerated; 45 to 60 minutes are the upper limits permitted for circulatory arrest and are more than adequate in well-planned procedures. This involves adequate exposure of all surgical areas and full mobilization of the kidney before circulatory arrest to minimize the ischemic time.
Our experience with surgical management of metastatic RCC involving the IVC has been disappointing, especially in patients with extensive multiple organ metastases. High perioperative mortality was noted in this group (33% versus 2% in the patients without metastases). Both deaths were in patients with extensive multiple organ metastases. Of the 4 surviving patients who underwent radical nephrectomy, the 3-year survival rate was 25% (1 patient who had limited pulmonary metastases). This underlies the importance of careful patient selection in this subgroup of patients. Others have demonstrated that long-term disease-free survival can be achieved by the combination of radical nephrectomy, cava thrombectomy, and postoperative immunotherapy in selected patients with metastatic RCC.20 An actuarial overall 5-year survival rate of 17% was achieved. Those with isolated pulmonary metastases and low-grade disease had a 5-year survival rate of 43% and 52%, respectively.20, 21
Conclusions
This long-term experience confirms that nonmetastatic RCC with extension into the IVC is a potentially curable condition provided complete removal can be achieved. The level of extension of the tumor thrombus dictates the surgical approach and technical details. Patients with RCC extending into the IVC and metastatic disease at presentation continue to be challenging. However, selected patients, especially those with limited pulmonary metastases and those with low-grade tumors, may benefit from surgical management before immunotherapy.
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