|Year : 2018 | Volume
| Issue : 1 | Page : 49-54
Long-term outcomes of nephrectomy and inferior vena cava thrombectomy in patients with advanced renal cell carcinoma: A single-center experience
Chi-Chih Lien1, Kao-Lang Liu2, Po-Ming Chou1, Wei-Chou Lin3, Hui-Ching Tai1, Chao-Yuan Huang1, Shuo-Meng Wang1, Kuo-How Huang1, Yeong-Shiau Pu1
1 Department of Urology, National University Hospital, National University, College of Medicine, Taipei, Taiwan
2 Department of Radiology, National University Hospital, National University, College of Medicine, Taipei, Taiwan
3 Department of Pathology, National University Hospital, National University, College of Medicine, Taipei, Taiwan
|Date of Web Publication||23-Feb-2018|
Department of Urology, National Taiwan University Hospital, 7 Chung-Shan South Road, Zhongzheng District, Taipei 100
Source of Support: None, Conflict of Interest: None
Background/Purpose: This study evaluated the long-term outcomes of nephrectomy and inferior vena cava (IVC) thrombectomy in patients with advanced renal cell carcinoma (RCC). Methods: From January 1996 to December 2013, we retrospectively collected the clinical data of 31 patients with pathologically confirmed RCC and IVC tumor thrombus. All patients received nephrectomy and IVC thrombectomy. We examined the clinical outcomes, including cancer-specific survival, progression-free survival, and postoperative complications, during a 90-day period. The associated prognostic factors were also analyzed. This study is registered with the National Taiwan University Hospital Research Ethics Committee (number 201305059RINC). Results: The median follow-up period was 24 months. Of 20 patients with nonmetastatic disease, 15 developed metastases during the study period. The overall 5-year cancer-specific survival rate was 30.8% in the nonmetastatic group versus 12.5% in the metastatic group. The level of IVC thrombus (Levels I–II vs. Levels III–IV) was not significantly associated with the 5-year cancer-specific survival (P = 0.43). The Fuhrman grade and sarcomatoid type were statistically significant predictors of cancer-specific survival (Fuhrman Grades III–IV vs. Grades I–II: Hazard ratio [HR] = 0.11, P = 0.04; sarcomatoid type: HR = 0.136, P = 0.001). Fuhrman grade, capsular invasion, and positive surgical margins were associated with 1-year progression-free survival (Fuhrman Grades III–IV vs. Grades I–II: HR = 0.08, P = 0.04; capsular invasion: HR = 0.15, P = 0.04; positive surgical margins: HR = 0.16, P = 0.05). The most common perioperative complication was massive blood loss. The most common recurrence sites were bones, liver, and lungs. Conclusion: The pathologic Fuhrman grade, sarcomatoid type, positive surgical margins, and capsular invasion were significant predictors of oncological outcomes in patients with advanced RCC and IVC thrombus.
Keywords: Inferior vena cava thrombus, nephrectomy, renal cell carcinoma, thrombectomy
|How to cite this article:|
Lien CC, Liu KL, Chou PM, Lin WC, Tai HC, Huang CY, Wang SM, Huang KH, Pu YS. Long-term outcomes of nephrectomy and inferior vena cava thrombectomy in patients with advanced renal cell carcinoma: A single-center experience. Urol Sci 2018;29:49-54
|How to cite this URL:|
Lien CC, Liu KL, Chou PM, Lin WC, Tai HC, Huang CY, Wang SM, Huang KH, Pu YS. Long-term outcomes of nephrectomy and inferior vena cava thrombectomy in patients with advanced renal cell carcinoma: A single-center experience. Urol Sci [serial online] 2018 [cited 2021 Sep 24];29:49-54. Available from: https://www.e-urol-sci.com/text.asp?2018/29/1/49/226026
| Introduction|| |
Renal cell carcinoma (RCC) accounts for approximately 4% of adult cancers. One of the unique features of RCC is the intraluminal tumor growth into the renal venous circulation, known as a venous tumor thrombus. Approximately 4%–10% of RCC patients have a tumor thrombus involving the inferior vena cava (IVC); moreover, in 1% of cases, the tumor extends into the right atrium. Approximately 45%–70% of patients with RCC and IVC thrombus experience survival benefits from nephrectomy and IVC thrombectomy., Preoperative identification of the tumor thrombus level [Supplementary Table 1], which is associated with the choice of surgical method, is important. Meanwhile, higher-level tumor thrombi tend to be associated with more advanced disease. However, the clinical outcomes of nephrectomy and IVC thrombectomy in patients with advanced RCC have not been reported in Taiwan. In this study, we analyzed the long-term clinical and oncological outcomes in a tertiary referral center in Taiwan.
| Methods|| |
From January 1996 to December 2013, 31 patients (23 men and eight women) received nephrectomy with IVC thrombectomy for advanced RCC with the extension of the tumor thrombus into the IVC (T3b/c, according to the tumor/node/metastasis [TNM] criteria of the American Joint Commission on Cancer [AJCC] 2010) at National Taiwan University Hospital (identifier 201305059RINC). The study closed to accrual in 2013, after review by the independent data-monitoring committee, but data collection continued for 36 months until December 31, 2016. The requirement of informed consent was waived for this study, and patient information was retrospectively reviewed from a prospectively collected database that recorded the hospital chart and complication-related data of all patients treated with nephrectomy. The data of demographics, clinical presentations, preoperative staging, and pathology were collected through chart reviews. Long-term survival data were collected during follow-up visits and additional telephone interviews with the cancer case manager.
Preoperatively, all patients underwent routine blood tests, ultrasound, computed tomography or magnetic resonance imaging, and bone scintigraphy. The surgical indications for nephrectomy and IVC thrombectomy are as follows: No evidence of bony, brain, or peritoneal metastases; good Eastern Cooperative Oncology Group performance status (status 0–1); estimated glomerular filtration rate >30 mL/min/1.73 m 2; and surgically resectable visceral metastases. Clinical and pathological staging were performed using the TNM classification provided by the AJCC. The tumor grade was classified according to the Fuhrman grading system.
The IVC thrombus level was graded according to the Mayo classification [Supplementary Table 1]. Among the 31 study participants, 10 (32.3%) had a Level I thrombus, 9 (29%) had Level II, 8 (25.8%) had Level III, and 3 (9.7%) had Level IV [Table 1].
All patients underwent nephrectomy and thrombectomy through the abdominal approach. In four patients (12.9%), combined procedures were performed with a cardiovascular surgeon operating on the IVC thrombus. To approach the tumor thrombus above the diaphragm, sternotomy was performed in three cases. For pulmonary artery thromboembolectomy, extracorporeal circulation with cardiopulmonary bypass was needed in one case. Partial resection and IVC replacement were necessary in two cases (6.5%). Postoperatively, nine patients (29%) received cytokine treatment, and two (6.6%) were treated with multitargeted therapy. No patient was treated with tyrosine kinase inhibitors as neoadjuvant therapy.
Cancer-specific survival and progression-free survival were estimated using the Kaplan–Meier method. Subgroup differences were tested through the log-rank test. The predictive factors for cancer-specific survival were assessed using the Cox proportional hazards regression model. Statistical significance was established for P < 0.05. All statistical analyses were performed using the SPSS statistical package (version 15, SPSS Inc., Headquarters, Chicago, IL, USA).
| Results|| |
During the study period, 31 patients received nephrectomy and IVC thrombectomy. Five patients were excluded due to incomplete data, and the remaining 26 were enrolled in this study. The median age was 65 years (range, 39–79 years); 19 tumors originated from the right side and 11 from the left side. The median tumor size was 9 cm (range, 4–17 cm). Within the study sample, 24 (92.3%) patients were symptomatic, and three (11.5%) were diagnosed based on incidental imaging findings. The most common symptom was gross hematuria (n = 14; 53.8%), followed by flank or abdominal pain (n = 6; 23.1%). In 11 patients (42.3%), distant metastases were diagnosed preoperatively. In four patients, the lung was the most common site of metastases. [Table 1] lists the clinical data of the study population.
The median hospital stay was 21 days (range, 10–58 days). One patient died of sepsis during the 30-day postoperative period, and the operation-related mortality rate was 3.2%. The most common complication was massive blood loss and acute kidney injury (AKI). Five patients (19.2%) required surgical intervention for the management of complications. The perioperative complications were classified using the Clavien system [Table 2].
|Table 2: Complications (grade according to the Clavien classification of surgical complications)|
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Among the RCC patients, pathological examination revealed the clear cell type in 22 (84.6%), papillary type in 4 (15.4%), and sarcomatoid type in 4 (15.4%). Lymph node involvement was noted in 14 patients (53.8%). Positive surgical margins were observed in 11 patients (35.5%).
The median follow-up period was 24 months. During this period, 18 patients died, among whom 16 died of tumor progression. Cancer-specific survival at 1, 3, and 5 years for the whole cohort was 70.4%, 33.3%, and 30.8%, and for the patients without preoperative metastases, it was 77.8%, 38.9%, and 38.9% (median survival, 29 months), respectively. The survival in the metastatic group was 55.6%, 22.2%, and 12.5% (median survival, 18 months) [Figure 1]a at 1, 3, and 5 years, respectively.
|Figure 1: Results of the Kaplan–Meier analysis. (a) Cancer-specific survival classified according to the presence of perioperative metastasis. (b) Cancer-specific survival classified according to the tumor thrombus level (Level I or II vs. III or IV). (c) Cancer-specific survival classified according to the tumor grade (Fuhrman Grade I or II vs. Grade III or IV). (d) Progression-free survival classified according to the presence of positive surgical margins|
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Univariate analysis revealed that the pathologic Fuhrman grade and sarcomatoid type were statistically significant predictors for cancer-specific survival (Fuhrman Grades III–IV vs. Grades I–II: Hazard ratio [HR] = 0.11, P = 0.04; sarcomatoid type: HR = 0.136, P = 0.001) [Table 3]. The Fuhrman grade [Table 1]c, capsular invasion, and positive surgical margins were associated with 1-year progression-free survival (Fuhrman Grades III–IV vs. Grade I–II: HR = 0.08, P = 0.04; capsular invasion: HR = 0.15, P = 0.04; positive surgical margins: HR = 0.16, P = 0.05) [Table 1]d and [Table 4].
| Discussion|| |
Surgery is the only method for curing patients with advanced RCC., In some circumstances, surgeries in patients with advanced RCC are a challenge for surgeons, especially in those with IVC thrombus. For instance, vascular control of Level III and IV IVC thrombi requires more extensive dissection, venous bypass, or even cardiopulmonary bypass and hypothermic circulatory arrest.,, Previous studies have revealed that in patients with nonmetastatic RCC and IVC involvement, the 5-year survival rate ranges between 40% and 65%; however, the 5-year cancer-specific survival rate for metastatic disease was only 7.4%. In our series, the 5-year cancer-specific survival rates for nonmetastatic and metastatic diseases were 38.9% and 12.5%, respectively. Meanwhile, we also analyzed 56 patients with metastatic RCC who did not meet the protocol for surgery at our hospital. The 5-year cancer-specific survival rate was 0%, and the median survival was 10 months.
Approximately one-third of patients with RCC and associated tumor thrombus also present with distant metastases. In our series, 35.5% of the patients with RCC and IVC thrombus presented with simultaneous metastases. Ali reported a median survival of 5 months and a 5-year survival rate of 0% for this group.
In our analysis, 4 out of 10 patients with metastatic disease died, whereas one patient (follow-up period, 98 months) remained alive. The 3-year survival rate was 22.2%, and the median time to death was 18 months (range 2–98 months). This finding may be due to the younger age of the patients with metastatic disease in our series. The average age was 58.7 years, and seven patients (63.6%) were younger than 60 years. Some authors do not advise radical or cytoreductive surgery for patients with metastatic disease and IVC thrombus , because they believe that the limited chance of longer survival does not justify the morbidity of nephrectomy with IVC thrombectomy. In our study, the metastatic status was not an independent factor for cancer-specific survival (median survival for metastasis disease [18 months] vs. median survival for nonmetastatic disease [24 months]: HR = 0.22, P = 0.20). Although this result may be due to the selection bias introduced by the enrollment criteria for operation, including a good performance status and acceptable laboratory data, it indicated an acceptable outcome for patients in the metastatic group, who could receive extensive surgery followed by metastasectomy.
Many studies have focused on the prognostic factors for patients undergoing IVC thrombectomy with advanced RCC. Ciancio et al. reported that the level of tumor thrombus is not an independent prognostic factor, but distant metastasis at presentation, higher nuclear grade, and nonclear cell histology are significant prognostic factors influencing cancer-specific survival. Our result also indicates that the thrombus level cannot be an independent prognostic factor (Levels I–II [37 months] vs. Levels III–IV [34 months]: HR = 2, P = 0.42). Even Level III of the Mayo classification cannot predict a poor prognosis. Mandhani et al. presented a new classification for IVC thrombi: Level I is described as a thrombus located caudal to the hepatic vein; Level II includes all retrohepatic, suprahepatic, infradiaphragmatic, and supradiaphragmatic thrombi reaching up to the right atrium; and Level III comprises atrial thrombi. Only Level III thrombi require cardiopulmonary bypass. Despite not being an independent predictor of survival in our study [Table 1]b, shorter survival (in months) was observed in the patients with Level III–IV thrombi. This may be due to the relatively small sample size in our study. Therefore, additional prospective studies on the new classification system or Mayo system are needed to determine if the thrombus level could be an independent prognostic factor. The only four patients with sarcomatoid-type RCC had very poor outcomes and only survived for 2, 4, 10, and 18 months.
Similar to most retrospective studies, the most common complication in our series was massive blood loss. However, the second type of complication was AKI. Shin et al. reported that intraoperative management seems to influence the risk of AKI after surgery; in particular, the longer the IVC clamping time is, the higher the risk of postoperative AKI is. However, additional information, including the clamping site of the IVC and adjacent branch, clamping time, and presentation of possible hypotension during clamping, is required for determining the cause of AKI. Furthermore, chronic kidney disease after IVC thrombectomy with postoperative AKI should be followed up.
The present study was a retrospective review of a single-institution experience and is accordingly limited by inherent biases. Therefore, the perioperative and complication data might have been limited by the information available in the patients' charts. This study was not limited to a single-surgeon; therefore, the bias from different surgeons should be considered, and the value of multivariate analyses is limited by the sample size.
| Conclusion|| |
The pathologic Fuhrman grade, sarcomatoid type, positive surgical margins, and capsular invasion were significant predictors of oncological outcomes in patients with advanced RCC and IVC thrombus.
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[Table 1], [Table 2], [Table 3], [Table 4]