|Year : 2021 | Volume
| Issue : 3 | Page : 234-240
Experience with management of renal cell carcinoma with inferior vena cava/right atrial tumor thrombus
Shitangsu Kakoti1, Rahul Jena1, Sanjoy Kumar Sureka1, Aneesh Srivastava1, Anil Mandhani2, Uday Pratap Singh1
1 Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Urology and Renal Transplant, Fortis Memorial Research Institute, Gurugram, Haryana, India
|Date of Submission||07-Jan-2021|
|Date of Decision||04-Apr-2021|
|Date of Acceptance||11-May-2021|
|Date of Web Publication||1-Jul-2021|
Uday Pratap Singh
Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: We aimed to present our experience in managing renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus.
Methods: Records of all patients aged 18 years and older, with a diagnosis of primary renal masses with IVC thrombus, presenting to our institute from January 2012 to August 2020 were retrospectively reviewed. Patients with tumor thrombus limited only to renal vein were excluded from the analysis. Their hospital course and outcomes were recorded and evaluated for predictors of survival.
Results: During the study period, we treated 61 patients with a renal mass and concurrent IVC thrombus and 56 of these underwent surgery. 7 of them had level III and 6 had level IV thrombus. A total of six patients received neoadjuvant tyrosine kinase inhibitor (TKI) therapy and all of them showed a decrease in size and level of tumor thrombus and cardiopulmonary bypass was safely avoided. Fourteen patients had distant metastasis and underwent cytoreductive surgery and of these 12 patients received TKI therapy after surgery with a mean survival of 26.8 months. The overall survival at 2 and 5 years of nonmetastatic group was 81.1% and 47.5% respectively and in metastatic group was 35.1% and 0%, respectively. Poor performance status, distant metastasis, higher T stage, higher thrombus levels, and positive surgical margins were all predictors of decreased survival.
Conclusions: Complete surgical resection in both nonmetastatic and metastatic RCC with IVC thrombus has long-term survival benefits. Neoadjuvant TKI therapy, with adequate preoperative planning, helps in decreasing the size of the thrombus and in safely avoiding bypass in level III and IV IVC thrombi.
|How to cite this article:|
Kakoti S, Jena R, Sureka SK, Srivastava A, Mandhani A, Singh UP. Experience with management of renal cell carcinoma with inferior vena cava/right atrial tumor thrombus. Indian J Urol 2021;37:234-40
|How to cite this URL:|
Kakoti S, Jena R, Sureka SK, Srivastava A, Mandhani A, Singh UP. Experience with management of renal cell carcinoma with inferior vena cava/right atrial tumor thrombus. Indian J Urol [serial online] 2021 [cited 2022 Dec 1];37:234-40. Available from: https://www.indianjurol.com/text.asp?2021/37/3/234/320401
| Introduction|| |
Renal cell carcinoma (RCC) is the third most common malignancy of the genitourinary tract. It is the commonest upper tract tumor showing extension of tumor thrombus into the renal vein and inferior vena cava (IVC). Tumour thrombus is found in about 4%–10% of patients with RCC,, and is more common in right-sided renal masses. The Mayo classification system is commonly used for classifying the level of IVC tumor thrombus. The TNM classification (AJCC 8th Edition; 2017) is generally used for staging and surgical planning. Contrast-enhanced computer tomography (CECT) is the most common radiological investigation performed during the initial evaluation of RCC. However, on the identification of an IVC tumor thrombus, it is prudent to do a magnetic resonance imaging (MRI) preferably with venography, because MRI is the gold standard investigation for identifying any IVC wall invasion by the thrombus which may necessitate a change of surgical planning. A significant proportion of patients present with unresectable or metastatic disease along with IVC thrombus. Among all options for treatment, surgical removal of the kidney along with IVC thrombectomy is the most beneficial, with 5-year survival rates varying from 50% to 65%.,, When nephrectomy without IVC thrombectomy is done, the prognosis is extremely poor. The procedure is technically difficult and requires multidisciplinary management. Even then, mortality has been reported to vary from 3% to 16% and morbidity can be up to 70%.,, In this study, we have reviewed our series of cases and have presented our experience in management and outcomes.
| Materials and Methods|| |
We retrospectively reviewed the records of all patients of RCC at our institute from January 2012 to August 2020. All patients aged 18 years and older, with a diagnosis of primary renal masses with IVC thrombus, were included in the analysis. Patients with tumor thrombus limited only to renal vein were excluded from the analysis. Data were recorded regarding symptoms, clinical findings, preoperative investigations, neoadjuvant therapy, need for added procedures such as angioembolization, intra-operative procedure and findings, tumor pathology, postoperative course, and duration of the last follow-up. The level of thrombus was classified as per the Mayo Clinic classification after evaluation by CECT and/or MRI of the abdomen with Doppler ultrasonography of the IVC in select cases. Complications that occurred during the same hospital stay or within one month of surgery were recorded and graded according to Clavien–Dindo grading. Follow-up time was calculated from the time of surgery until the death of the patient or the time of the last follow-up visit. The comparison of different parameters was done by Chi-square or Fisher's exact tests. Survival analysis was done by the Kaplan–Meier technique with the help of IBM SPSS Statistics for Windows, version 26 (IBM Corp., Armonk, NY, USA).
| Results|| |
During the study, there were 1309 patients presenting to the outpatient department with a diagnosis of renal mass due to RCC. There were 61 patients with concurrent IVC thrombus and 56 of these patients underwent IVC thrombectomy at the time of nephrectomy [Figure 1]. Of the remaining five patients, two were lost to follow up, one patient with a level IV thrombus developed massive pulmonary thromboembolism (PTE) 1 day prior to surgery and died. The remaining two patients were considered to have unresectable primary tumor due to involvement of the head of pancreas and the duodenum and superior mesenteric artery respectively. The baseline characteristics of those that underwent surgery and preoperative parameters are mentioned in [Table 1].
A total of six patients received neoadjuvant tyrosine kinase inhibitor (TKI) therapy. Three patients had level III thrombus and 3 had level IV. Among the level III thrombi, the indication of neoadjuvant therapy was poor performance status in one case and tumor extension into confluence of hepatic veins in 2 cases. The first patient showed improvement in performance status after 3 months of sunitinib therapy and underwent open radical nephrectomy and IVC thrombectomy. The other two patients showed regression of the thrombus from the hepatic vein confluence along with a decrease in the diameter and vascularity of the thrombus as evidenced from the follow-up CECT scans, after 3 months of pazopanib therapy. One of the patients with level IV thrombi had thrombus extending to just below the level of the right atrium with extension into the confluence of the hepatic veins and also the opposite left renal vein. He showed a good response to pazopanib therapy and after 6 months, his thrombus had decreased in size to just above the diaphragm and had regressed from the left renal vein and the hepatic vein confluence. This patient underwent surgery without the need for sternotomy or cardiopulmonary bypass. The remaining 2 level IV thrombi also showed a similar response to TKI therapy with decrease in the level of thrombi and could avoid cardiopulmonary bypass during surgery. The mean duration of TKI therapy was 5.8 months (1–12 months) and three patients suffered from adverse effect in the form of oral ulcerations and gastric intolerance. A total of 14 patients (MSKCC risk classification: Favourable-2, Intermediate-12) had distant metastasis and underwent cytoreductive surgery. Ten patients had pulmonary, two had skeletal and one each had liver with pulmonary and skeletal with pulmonary metastases. Five patients underwent preoperative angioembolization for large vascular primary tumors.
Intraoperative findings are mentioned in [Table 2]. A total of 7 cases required sternotomy. Two of these were in level III thrombi where it was difficult to apply supra-hepatic clamp from the abdominal side due to the large diameter of the distended IVC. IVC wall invasion was seen in 11 patients and 3 of these required repair of the IVC wall using pericardial patch graft. The other 8 were managed by primary closure of the IVC using poly-propylene sutures. Lymphadenopathy was suspected in 19 patients with the help of preoperative imaging. Intraoperatively enlarged and suspicious lymph nodes isolated from the renal mass were found in only 14 patients in whom lymphadenectomy was performed. In the rest, lymphatic tissues were removed in toto with the primary mass. Additional organ resection like distal pancreatectomy with splenectomy, segmental transverse colon resection, and only splenectomy was required in three patients.
Postoperative outcomes have been shown in [Table 3]. The most common postoperative complications were nausea, vomiting, and fever. A total of 28 patients showed 30 complications which were graded as per Clavien Dindo scoring system. Majority of the complications were Grade I. Two patients died in the immediate postoperative period. Of these, one patient had a level III thrombus and had needed extensive liver mobilization and a sternotomy for suprahepatic clamping. He developed diffuse oozing from the liver surface intraoperatively, requiring multiple transfusions and hepatic packing. Postoperatively, he went into shock and could not be revived. The other patient had a level IV thrombus, that was inside the right atrium. A fragment of this thrombus migrated into the pulmonary circulation causing PTE intraoperatively. Postoperatively, this patient could not be extubated and died from complications of PTE. The findings of pathological staging are outlined in [Table 4]. Clear cell RCC was the commonest variety followed by papillary RCC. Three patients had sarcomatoid RCC on the final histopathology. A total of 17 patients received adjuvant TKI therapy after wound healing, of which 12 had preoperatively diagnosed metastatic disease and five patients were deemed to be at high risk of progression based on adrenal involvement and perirenal fat involvement on histopathological examination. Local recurrence in renal fossa and ipsilateral psoas muscle was seen in four patients (7%) during follow-up, which were also treated with TKI therapy.
The overall survival (OS) at 2 and 5 years of nonmetastatic group was 81.1% and 47.5% respectively and in metastatic group was 35.1% and 0%, respectively. For nonmetastatic patients who received adjuvant TKI, OS at 2 and 5 years was 50% and 0%, respectively. The predictors of OS are enumerated in [Table 5]. Multivariate cox regression analysis showed significant differences in OS in patients having distant metastases (P = 0.014), margin positivity (P = 0.043), T-staging (P = 0.001) and tumour thrombus levels (P = 0.000) [Table 6].
| Discussion|| |
The presence of tumor thrombus in the IVC in a case of RCC poses a technical challenge to the surgeon. Radical nephrectomy with the removal of the vena caval thrombus is the treatment of choice in both nonmetastatic and metastatic settings, unless there are fitness factors precluding surgery.,, In the metastatic setting, cytoreductive surgery along with targeted therapy improves OS.,,, It also avoids death due to pulmonary embolism that may result from inadvertent migration of the tumor thrombus from the IVC or right atrium into the pulmonary circulation. In our series, we also found improved OS (mean survival of 28.8 months) in12 patients with distant metastasis, who received TKI therapy (sunitinib or pazopanib) after surgery. In a series of 30 patients, cytoreductive nephrectomy and IVC thrombectomy in metastatic RCC achieved an actuarial survival rate of 17% and 80% of patients were able to complete immunotherapy. Zisman et al. in their series of 207 patients of RCC with venous thrombi reported that these patients had similar OS rates irrespective of metastatic status and that cytoreductive nephrectomy with venous thrombus removal resulted in better response to immunotherapy.
The use of neoadjuvant therapy with TKI is still investigational and understudy, especially in patients with IVC tumor thrombus. Shuch et al. stated that the use of neoadjuvant TKI may cause medical infarction of the thrombus due to their mechanism of action which involves inhibition of the VEGF pathway. So theoretically, the vascularity of the thrombus, which is often arterialized with its own independent blood supply, would decrease leading to a decrease in the size and level of the thrombus, which in turn would facilitate easier removal or avoid a sternotomy, thus improving peri and post-operative outcomes. They found reduction in the level of thrombus from level II to level I after sunitinib therapy. However many other authors found no such outcomes in their studies., In our series we used neoadjuvant targeted therapy in six patients. One patient showed an improvement in performance status, making it possible for him to undergo surgery. The rest of the five patients showed a decrease in the level of thrombus along with decrease in diameter and vascularity and could successfully avoid bypass and even sternotomy in some of the cases. Hence, we believe that the use of neoadjuvant TKI does help in decreasing the size of the thrombus and facilitating less blood loss and ease of surgery, in addition to improving the preoperative performance status. However, these findings need to be validated in larger series. Preoperative angioembolization can be helpful when there is a large highly vascularized thrombus with independent supply from the renal artery or aorta, to shrink the thrombus to a more manageable level or to avoid bypass or liver mobilization. In our series five patients with large tumors (>12 cm with > level III thrombi) underwent angioembolization. However, except for decreased intraoperative bleeding during nephrectomy, no other effect on the level of the thrombus was noted. No patients who underwent angioembolisation received any neoadjuvant TKI therapy.
World over, there is an increasing body of literature on the use of minimally invasive techniques (robotic, laparoscopic) for radical nephrectomy and IVC thrombectomy. Some studies reported that laparoscopy can be an alternative to open surgery for level ≤ II thrombi and laparoscopic nephrectomy with open venotomy can be a safe option for level III/IV thrombi., In our series, one patient underwent a total laparoscopic procedure for right-sided RCC with level II IVC thrombus, and another two patients underwent laparoscopic-assisted open technique for level II and level III thrombus. Robotic surgery services were unavailable in our institute during the study period. Bypass procedures, either cardiopulmonary or venovenous, are an integral part of any procedure for level III/IV procedures. However, for thrombus causing complete IVC obstruction with extensive collateralization, not extending into the right atrium or having IVC wall invasion, bypass procedure may not be needed. Sequential clamping of caudal IVC first, followed by contralateral renal vein, hepatic artery, portal vein, and lastly, cephalad IVC may be sufficient. Liver mobilization may be necessary for suprahepatic IVC clamping. Even patients with non-obstructive IVC thrombus tolerate suprahepatic clamping quite well. Immediately after removal of the thrombus, suprahepatic clamp can be replaced with infrahepatic clamp, and Pringle maneuver can be released to further lower down liver ischemia times. In our series, only three patients underwent cardiopulmonary bypass for level IV thrombus extending into the right atrium which was successfully removed. In comparison to a previous study done from our institute a decade before, which utilized venovenous bypass for most of the cases of level II/III thrombus, the present series managed to avoid it safely. The mean operating time found in our study was 214 min and average blood loss was 765 ml, which are comparable to the other similar series. The OS improves after radical nephrectomy and IVC thrombectomy. Many studies reported a 5-year OS rate varying from 30% to 63%.,, In our series, the 2-year and 5-year OS was 69.7% and 38.7% respectively. All the negative predictors of survival namely poor performance status, higher T stage, distant metastases and positive surgical margins found in our study correspond to those reported in other studies. Our study found the level of thrombus to be a significant predictor of survival. This is probably due to the smaller number of level III/IV thrombi. Literature also supports lymph nodes positivity, distant metastases, higher Fuhrman's grade, and variant histology as predictors of poor prognosis, which are reflected in our study.,
The limitations of our study are that it is a retrospective study with a small sample size. Hence, some of the findings such as, response to neoadjuvant TKI therapy and cytoreductive nephrectomy and IVC thrombectomy, need to be validated in larger series. However recent large trials like the CARMENA trial, did not mention any subset analysis on these groups of patients., Maybe because, enrolling a large number of patients with RCC with IVC thrombus and metastases, fit enough to undergo cytoreductive nephrectomy followed by TKI therapy in a prospective study is a difficult task.
| Conclusion|| |
Almost 50% of patients with nonmetastatic RCC and IVC thrombus survive five years following surgery. Cytoreductive nephrectomy with IVC thrombectomy followed by TKI therapy in metastatic RCC with venous tumor thrombi also provides acceptable OS. The use of neoadjuvant TKI may help in decreasing the size of the thrombus facilitating easier surgical excision. Bypass procedures can be safely avoided for most level III thrombi with adequate preoperative planning.
Financial support and sponsorship: Nil.
Conflicts of interest: There are no conflicts of interest.
| References|| |
da Costa WH, Moniz RR, da Cunha IW, Fonseca FP, Guimaraes GC, de Cássio Zequi S. Impact of renal vein invasion and fat invasion in pT3a renal cell carcinoma. BJU Int 2012;109:544-8.
Mootha RK, Butler R, Laucirica R, Scardino PT, Lerner SP. Renal cell carcinoma with an infrarenal vena caval tumor thrombus. Urology 1999;54:561.
Nesbitt JC, Soltero ER, Dinney CP, Walsh GL, Schrump DS, Swanson DA, et al
. Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus. Ann Thorac Surg 1997;63:1592-600.
Neves RJ, Zincke H. Surgical treatment of renal cancer with vena cava extension. Br J Urol 1987;59:390-5.
Kallman DA, King BF, Hattery RR, Charboneau JW, Ehman RL, Guthman DA, et al
. Renal vein and inferior vena cava tumor thrombus in renal cell carcinoma: CT, US, MRI and venacavography. J Comput Assist Tomogr 1992;16:240-7.
Haferkamp A, Bastian PJ, Jakobi H, Pritsch M, Pfitzenmaier J, Albers P, et al
. Renal cell carcinoma with tumor thrombus extension into the vena cava: Prospective long-term followup. J Urol 2007;177:1703-8.
Skinner DG, Pritchett TR, Lieskovsky G, Boyd SD, Stiles QR. Vena caval involvement by renal cell carcinoma. Surgical resection provides meaningful long-term survival. Ann Surg 1989;210:387-92.
Ljungberg B, Stenling R, Osterdahl B, Farrelly E, Aberg T, Roos G. Vein invasion in renal cell carcinoma: Impact on metastatic behavior and survival. J Urol 1995;154:1681-4.
Sosa RE, Muecke EC, Vaughan ED Jr., McCarron JP Jr. Renal cell carcinoma extending into the inferior vena cava: The prognostic significance of the level of vena caval involvement. J Urol 1984;132:1097-100.
Hatakeyama S, Yoneyama T, Hamano I, Murasawa H, Narita T, Oikawa M, et al
. Prognostic benefit of surgical management in renal cell carcinoma patients with thrombus extending to the renal vein and inferior vena cava: 17-year experience at a single center. BMC Urol 2013;13:47.
Singh V, Zaman W, Kumar A, Kapoor R, Srivastava A. Renal cell carcinoma with tumor thrombus extension to inferior vena cava: SGPGIMS experience. Indian J Urol 2004;20:90. [Full text]
Russo P. Multi-modal treatment for metastatic renal cancer: The role of surgery. World J Urol 2010;28:295-301.
Lenis AT, Burton CS, Golla V, Pooli A, Faiena I, Johnson DC,et al
. Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma and venous thrombus—Trends and effect on overall survival.Urol Oncol. 2019 Sep; 37 (9):577.
Manso M, Pacheco-Figueiredo L, Santos-Silva A, Silva J, Silva C, Cruz F. Renal cell carcinoma with venous thrombus: Should surgery be offered when metastasis is present at diagnosis? Urol Int 2018;101:387-90.
Kirkali Z, Van Poppel H. A critical analysis of surgery for kidney cancer with vena cava invasion. Eur Urol 2007;52:658-62.
Naitoh J, Kaplan A, Dorey F, Figlin R, Belldegrun A. Metastatic renal cell carcinoma with concurrent inferior vena caval invasion: Long-term survival after combination therapy with radical nephrectomy, vena caval thrombectomy and postoperative immunotherapy. J Urol 1999;162:46-50.
Zisman A, Wieder JA, Pantuck AJ, Chao DH, Dorey F, Said JW, et al
. Renal cell carcinoma with tumor thrombus extension: Biology, role of nephrectomy and response to immunotherapy. J Urol 2003;169:909-16.
Shuch B, Riggs SB, LaRochelle JC, Kabbinavar FF, Avakian R, Pantuck AJ, et al
. Neoadjuvant targeted therapy and advanced kidney cancer: Observations and implications for a new treatment paradigm. BJU Int 2008;102:692-6.
Cost NG, Delacroix SE Jr, Sleeper JP, Smith PJ, Youssef RF, Chapin BF, et al
. The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus. Eur Urol 2011;59:912-8.
Fukuda H, Kondo T, Omae K, Kobayashi H, Iizuka J, Tanabe K. MP57-06 Limited benefit of targeted therapies on IVC thrombus in renal cell carcinoma. J Urol 2014;191:e643.
Shao P, Li J, Qin C, Lv Q, Ju X, Li P, et al
. Laparoscopic Radical Nephrectomy and Inferior Vena Cava Thrombectomy in the Treatment of Renal Cell Carcinoma. Eur Urol 2015;68:115-22.
Hoang AN, Vaporcyian AA, Matin SF. Laparoscopy-assisted radical nephrectomy with inferior vena caval thrombectomy for level II to III tumor thrombus: A single-institution experience and review of the literature. J Endourol 2010;24:1005-12.
Mandhani A, Patidar N, Aga P, Pande S, Tewari P. A new classification of inferior vena cava thrombus in renal cell carcinoma could define the need for cardiopulmonary or venovenous bypass. Indian J Urol 2015;31:327-32.
] [Full text]
Topaktaş R, Ürkmez A, Tokuç E, Kayar R, Kanberoğlu H, Öztürk Mİ. Surgical management of renal cell carcinoma with associated tumor thrombus extending into the inferior vena cava: A 10-year single-center experience. Turk J Urol 2019;45:345-50.
Tang Q, Song Y, Li X, Meng M, Zhang Q, Wang J, et al
. Prognostic outcomes and risk factors for patients with renal cell carcinoma and venous tumor thrombus after radical nephrectomy and thrombectomy: The prognostic significance of venous tumor thrombus level. Biomed Res Int 2015;2015:163423.
Kulkarni J, Jadhav Y, Valsangkar RS. IVC thrombectomy in renal cell carcinoma-analysis of out come data of 100 patients and review of literature. Indian J Surg Oncol 2012 Jun; 3 (2):107-13.
Wagner B, Patard JJ, Méjean A, Bensalah K, Verhoest G, Zigeuner R, et al
. Prognostic value of renal vein and inferior vena cava involvement in renal cell carcinoma. Eur Urol 2009;55 (2):452-59.
Lien CC, Liu KL, Chou PM, Lin WC, Tai HC, Huang CY, et al
. 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. [Full text]
Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, et al
. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med 2018;379:417-27.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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