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Prognostic significance of tumor extension into venous system in patients undergoing surgical treatment for renal cell carcinoma with venous tumor thrombus
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EJSO 38 (2012) 630e636
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Prognostic significance of tumor extension into venous system in patients undergoing surgical treatment for renal cell carcinoma with venous tumor thrombus H. Miyake*, T. Terakawa, J. Furukawa, M. Muramaki, M. Fujisawa Division of Urology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan Accepted 26 March 2012 Available online 10 April 2012
Abstract Aims: The objective of this study was to evaluate the prognostic significance of the extent of a tumor thrombus in renal cell carcinoma (RCC) involving the venous system. Methods: This study included 135 consecutive RCC patients with a venous tumor thrombus undergoing radical nephrectomy and tumor thrombectomy between 1985 and 2009. These patients were classified based on the maximal level of the tumor thrombus extending into the venous system, as follows: group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic. Results: Of the 135 patients, 65, 49 and 21 were classified into groups 1, 2 and 3, respectively. The 1, 3 and 5-year cancer-specific survival (CSS) rates in these 135 patients were 89.2, 56.9 and 49.2%, respectively. Among several factors examined, tumor size, tumor grade, perirenal fat invasion and presence of metastasis, but not extent of tumor thrombus, were significantly associated with CSS on univariate analysis. Of these significant factors, only tumor size and presence of metastasis appeared to be independently related to CSS on multivariate analysis. When the patients without metastasis were analyzed separately, CSS in groups 2 and 3 was significantly poorer than that in group 1. Conclusions: These findings suggest the absence of a significant prognostic impact of the level of the tumor thrombus in a complete cohort of RCC patients with a venous tumor thrombus; however, it is warranted to determine whether the level of the tumor thrombus has different effects on the prognosis according to the presence of metastatic diseases. Ó 2012 Elsevier Ltd. All rights reserved. Keywords: Renal cell carcinoma; Venous tumor thrombus; Surgical therapy; Prognosis
Introduction One of the most unique characteristics in renal cell carcinoma (RCC) is its propensity to extend to the venous system. In fact, the incidence of involvement of the renal vein and/or inferior vena cava (IVC) has been reported to range between 4 and 15%.1e8 Due to improved surgical techniques as well as perioperative care, surgical removal of the kidney with the attached tumor thrombus can be performed relatively safely; therefore, surgical treatment remains the mainstay of management for RCC with a venous tumor thrombus.9 However, the prognosis of patients with RCC involving the venous system is generally poor despite aggressive surgical resection of RCC and the tumor thrombus.1e8 For example, Lambert et al reported
* Corresponding author. Tel.: þ81 78 382 6155; fax: þ81 78 382 6169. E-mail address: [email protected] (H. Miyake). 0748-7983/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejso.2012.03.006
that the 5-year overall survival rate in 118 patients with pT3b or pT3c RCC was 40.7%4, while our previous data from 55 RCC patients with tumor thrombus extending into the IVC revealed a 5-year cancer-specific survival rate of 30.3%.6 Collectively, these findings suggest that it would be important to predict the prognosis of such patients in order to determine tailored postoperative surveillance protocols and therapeutic strategies. To date, several studies have identified potential factors significantly associated with the prognosis of RCC patients with a venous tumor thrombus, such as presence of metastatic disease, tumor size, tumor grade, sarcomatoid features and perinephric fat invasion.1e8 However, it remains controversial whether the extent of a venous thrombus could be used as a prognostic predictor in patients with RCC and a venous tumor thrombus; that is, some studies have demonstrated survival differences according to the tumor thrombus level,6,8 whereas other series have shown no significant effect of the level of the tumor thrombus
H. Miyake et al. / EJSO 38 (2012) 630e636
on survival in patients with RCC.1,2,4,5,7 Considering these findings, we retrospectively reviewed the clinical outcomes of RCC patients with a venous tumor thrombus undergoing radical nephrectomy and tumor thrombectomy in a single institution of Japan in order to clarify the prognostic significance of the extent of the tumor thrombus in the venous system. Patients and methods At our institution, a total of 138 consecutive patients underwent radical nephrectomy and tumor thrombectomy without any neoadjuvant therapies and were pathologically diagnosed as having RCC between 1989 and 2009. Of these 138, this study included 135 patients after excluding 3 who died in the perioperative period, consisting of 2 who died of pulmonary embolism and 1 who died of multiple organ failure caused by massive intraoperative bleeding. Informed consent to this study was obtained from each patient, and the study design was approved by the Research Ethics Committee of our institution. All of the 135 patients preoperatively underwent routine blood tests, brain, chest and abdominal computed tomography (CT), abdominal magnetic resonance imaging (MRI) and/or bone scintigraphy. Gross extension of the tumor thrombus into the venous system was detected by preoperative radiological examinations, including contrastenhanced CT, sagittal view of MRI and/or venacavography, and confirmed by intraoperative findings in these 135 patients. In this series, patients were classified based on the maximal level of the tumor thrombus extending into the venous system, as follows: group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic. The surgical procedures performed in this series were previously described in detail.10 Complication data were confirmed via careful review of all patient charts, and complications greater than grade 3 are considered major complications. All pathological examinations were performed by a single pathologist according to the 2009 UICC/American Joint Committee on Cancer TNM system. Information on the clinicopathological characteristics of the included patients was retrieved from their medical records. Generally, all patients were followed by laboratory as well as radiological examinations every 3 months for the first 2 years and every 6 months thereafter to monitor recurrence and metastasis. In the absence of a relapse of RCC 5 years after surgery, the interval between re-examinations was increased. Informed consent for performing this study was obtained from all of these patients, and the study design was approved by the Research Ethics Committee of our institution. The cancer-specific survival rates of included patients were calculated employing the KaplaneMeier method, and the differences were determined by the log-rank test. The prognostic significance of certain factors was assessed using the Cox proportional hazards regression
631
model. All statistical analyses were performed using Statview 5.0 software (Abacus Concepts, Inc., Berkeley, CA, USA), and p values less than 0.05 were considered significant. Results All of the 135 patients included in this study underwent radical nephrectomy and tumor thrombectomy, and were pathologically diagnosed as having RCC. In these 135 patients, the venous tumor thrombus maximally extended to the renal vein in 65 (group 1, 48.1%), infradiaphragmatic IVC in 49 (group 2, 36.3%), and supradiaphragmatic IVC in 21 (group 3, 15.6%), of which 8 extended to the right atrium. Cardiopulmonary bypass was used in 15 patients in group 3, including all 8 who had intracardiac thrombus extension. Postoperative complications were noted in 59 patients (43.7%); however, major complications developed only in 12 (8.9%), including ileus in 5, pulmonary embolism in 2, pulmonary edema in 2, acute renal failure in 2 and myocardial infarction in 1. Following surgery, cytokine therapy using interferona either alone or in combination with low-dose interleukin-2 was performed in a total of 85 patients, consisting of 59 who presented with metastatic disease and 26 who originally presented without metastatic disease and then experienced postoperative recurrence. In addition, 21 patients were treated with molecular-targeted agents, including sorafenib, sunitinib and axitinib, after the failure of cytokine therapy. Table 1 presents detailed clinicopathological characteristics in the 135 patients according to the maximal level of the tumor thrombus; however, there were no significant differences in several parameters examined, except for tumor location, among these three groups. During the observation period of this study (mean, 32.7 months; range, 4e98 months), 56 patients (41.5%) died of RCC progression, and the 1, 3 and 5-year cancer-specific survival (CSS) rates were 89.2, 56.9 and 49.2%, respectively (Fig. 1A). In addition, 23 (35.4%), 22 (44.9%) and 11 (52.4%) patients died of disease progression in groups 1, 2 and 3, respectively, and there were no significant differences in CSS among these three groups (Fig. 1B) as well as between group 1 versus groups 2 and 3 (Fig. 1C). Of several factors examined, preoperative value of C-reactive protein (CRP), tumor size, tumor grade, perinephric fat invasion and presence of metastasis were significantly associated with CSS on univariate analysis; however, there was no significant impact of the extent of the venous tumor thrombus on CSS. Of these significant factors, only preoperative CRP value, tumor size and presence of metastasis appeared to be independently related to CSS on multivariate analysis (Table 2). CSS curves according to preoperative CRP value, tumor size and presence of metastasis are presented in Fig. 2. There were significant differences in CSS with respect to all three factors.
632
H. Miyake et al. / EJSO 38 (2012) 630e636
Table 1 Patient characteristics according to the level of the venous tumor thrombus. Total (n ¼ 135) Age (%) Younger than 60 years 60 years or older Gender (%) Male Female Tumor location (%) Right Left Clinical symptom (%) Yes No C-reactive protein (%) Normal Abnormal Histological category (%) Clear cell carcinoma Others Tumor size (%) Less than 10 cm 10 cm or greater Grade (%) 1 or 2 3 Perinephric fat invasion (%) Yes No Metastasis (%) Yes No
Group 1 (n ¼ 65)
Group 2 (n ¼ 49)
Group 3 (n ¼ 21)
55 (40.7) 80 (59.3)
25 (38.5) 40 (61.5)
22 (44.9) 27 (55.1)
8 (38.1) 13 (61.9)
99 (7.3) 36 (26.7)
50 (76.9) 15 (23.1)
35 (71.4) 14 (28.6)
14 (66.7) 7 (33.3)
80 (59.3) 55 (40.7)
30 (46.2) 35 (53.8)
34 (69.4) 15 (30.6)
16 (76.2) 5 (23.8)
44 (32.6) 91 (67.4)
20 (30.8) 45 (69.2)
17 (34.7) 32 (65.3)
7 (33.3) 14 (66.7)
96 (71.1) 39 (28.9)
47 (72.3) 18 (27.7)
33 (67.3) 16 (32.7)
16 (76.2) 5 (33.8)
125 (92.6) 10 (7.4)
61 (93.8) 4 (6.2)
45 (91.8) 4 (8.2)
19 (90.5) 2 (9.5)
99 (73.3) 36 (26.7)
50 (76.9) 15 (23.1)
35 (71.4) 14 (28.6)
14 (66.7) 7 (33.3)
94 (69.6) 41 (30.4)
46 (70.8) 19 (29.2)
32 (65.3) 17 (34.7)
16 (76.2) 5 (23.8)
53 (39.3) 82 (60.7)
25 (38.5) 40 (61.5)
20 (40.8) 29 (59.2)
8 (38.1) 13 (61.9)
59 (43.7) 76 (56.3)
27 (41.5) 38 (58.5)
22 (44.9) 27 (55.1)
10 (47.6) 11 (52.4)
p value 0.76
0.61
0.010
0.90
0.72
0.85
0.61
0.64
0.96
0.87
In this series, 76 (56.3%) of the 135 patients presented without metastatic disease. When these 76 patients without metastasis were analyzed separately, 38 (50.0%), 27 (35.5%) and 11 (14.5%) were classified into groups 1, 2 and 3, respectively. Cancer-specific death occurred in 19 (25.0%) of the 76 patients, including 5 (13.2%), 10 (37.0%) and 4 (36.4%) in groups 1, 2 and 3, respectively. Of the 76 patients without metastasis, despite the lack of significant differences in CSS among these three groups (Fig. 3A), CSS in groups 2 and 3 was significantly poorer than that in group 1 (Fig. 3B). Furthermore, the extent of the venous tumor thrombus (group 1 versus groups 2 and 3) was identified as a significant predictor of CSS on univariate analysis; however, multivariate analysis showed no independent association between the extent of the venous tumor thrombus and CSS (Table 2). Discussion A tendency to extend into the renal vein, IVC and right atrium is observed in up to approximately 10% of patients with RCC.1e8 Despite being one of the most challenging surgeries for urologists, radical nephrectomy and tumor
thrombectomy can be performed comparatively safely because of the recent advances in perioperative intensive monitoring, surgical procedures and prudent use of vascular bypass techniques9; hence, this type of aggressive surgery is still regarded as the standard treatment for patients with RCC involving the venous system. To date, a number of investigators have reported the outcomes of surgical management for patients with RCC and venous tumor thrombus; however, the prognoses of such patients are generally poor,1e8 and the prognostic stratification of such patients remains controversial. In this study, therefore, we retrospectively reviewed surgical treatment for 135 patients with RCC involving the venous system at a single institution in Japan in order to characterize the clinicopathological features of these patients. The maximal level of the venous tumor thrombus in the 135 patients included in this study was as follows: renal vein in 65, infradiaphragmatic IVC in 49 and supradiaphragmatic IVC in 21. The proportion of right-sided RCC in cases with an IVC thrombus was significantly higher than that in those with a tumor thrombus within the renal vein; however, there were no significant differences in the remaining clinicopathological factors examined in this
H. Miyake et al. / EJSO 38 (2012) 630e636
C 100
Cancer-specific survival (%)
Cancer-specific survival (%)
A
633
80 60 40 20
100 80
Group 1 (n=65)
60 40
Groups 2 and 3 (n=70)
20 p = 0.40
0
0 0
20 40 60 80 Time after surgery (months)
100
0
20 40 60 80 Time after surgery (months)
100
Cancer-specific survival (%)
B 100 80
Group 1 (n=65)
60
Group 2 (n=49) Group 3 (n=21)
40 20
p = 0.66
0 0
20 40 60 80 Time after surgery (months)
100
Figure 1. (A) Cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC) extending into the venous system who underwent radical nephrectomy and tumor thrombectomy. (B) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic). (C) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; groups 2 and 3, inferior vena cava).
study according to the level of the venous tumor thrombus. These findings are consistent with those in previous studies.4,5,7,8 For example, Klatte et al reported that tumors with extension into the IVC or atrium were predominant on the right side, despite the absence of significant differences in other parameters according to the thrombus level.5 These findings suggest that RCC extension into the venous
system may not reflect the biological aggressiveness of primary RCC, considering the equivalent characteristics of RCC patients with venous tumor thrombus irrespective of its level. The 5-year CSS in the 135 patients with RCC and a venous tumor thrombus following surgical treatment was 49.2%, which was similar or even superior to those reported
Table 2 Univariate and multivariate Cox analyses of cancer-specific survival. All patients (n ¼ 135)
Age (years) (Younger than 60 vs 60 or older) Gender (Male vs Female) Tumor location (Right vs Left) Clinical symptom (Yes vs No) C-reactive protein (Normal vs. Abnormal) Histological category (Clear cell carcinoma vs Others) Tumor size (cm) (Less than 10 vs 10 or greater) Grade (1 or 2 vs. 3) Perinephric fat invasion (Yes vs No) Metastasis (Yes vs No) Level of tumor thrombus (Group 1 vs Groups 2 and 3)
Patients without metastasis (n ¼ 76)
Univariate analysis
Multivariate analysis
Univariate analysis
Multivariate analysis
Hazard ratio
Hazard ratio
p value
Hazard ratio
Hazard ratio
p value
e
e
2.34
0.19
e
e
e e e 3.94 e
e e e 0.014 e
1.49 2.04 1.30 5.87 2.11
0.41 0.34 0.53 <0.001 0.18
e e e 4.07 e
e e e 0.011 e
p value
2.12
0.12
1.34 2.22 1.22 5.31 2.07
0.47 0.19 0.58 <0.001 0.17
p value
3.97
0.0024
2.80
0.031
4.16
0.0069
3.55
0.037
3.34 2.52 7.82 1.33
0.0078 0.024 <0.001 0.23
1.10 1.22 5.33 e
0.72 0.65 0.0014 e
3.77 3.01 e 3.29
0.012 0.046
1.56 1.52 e 1.79
0.62 0.67 e 0.46
e 0.037
A
C
100 80 Normal CRP (n=96) 60 40
Abnormal CRP (n=39)
20 p = 0.0019
0
B
Cancer-specific survival (%)
0
20 40 60 80 Time after surgery (months)
100
Cancer-specific survival (%)
H. Miyake et al. / EJSO 38 (2012) 630e636
Cancer-specific survival (%)
634
100 80
Without metastasis (n=76)
60 40 With metastasis (n=59) 20 p < 0.001
0 0
20 40 60 80 Time after surgery (months)
100
100 80 Tumor size < 10 cm (n=99) 60 40
Tumor size ≥ 10 cm (n=36)
20 p = 0.020
0 0
20
40
60
80
100
Time after surgery (months)
Figure 2. (A) Cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC) extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the preoperative serum value of C-reactive protein (CRP). (B) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the tumor size. (C) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the metastatic status.
in previous studies.3e5,7,8 Although predicting the prognosis after surgical treatment facilitates appropriate surveillance protocols and tailored postoperative treatment, there has not been any reliable system closely associated with the prognosis of patients with RCC who underwent radical nephrectomy and tumor thrombectomy. However, previous studies have identified several clinicopathological parameters as prognostic indicators, including tumor size, grade, perinephric fat invasion and sarcomatoid features.4e8 In this series as well, among several factors examined, preoperative CRP value, tumor size and presence of metastasis were identified as independent predictors of CSS, whereas there appeared to be no significant impact of the extent of the venous tumor thrombus on CSS. The prognostic role of tumor extension into the venous system has been examined in several studies. Indeed, the outcomes were not consistent, but large series revealed no difference in survival among the different IVC thrombus levels1,2,4,11e15 or between renal vein and IVC involvement.1,2,4,5,7 Even if the level of the tumor thrombus itself is not prognostically relevant, it would, at least, be crucial for the surgical strategy because of its close association with perioperative morbidity and mortality.5,9 Accordingly, various classification systems for thrombus levels,16,17 which have been proposed to date, remain valuable from the viewpoint of surgical issues. It has been well characterized that the natural history of metastatic RCC with a concurrent thrombus extending into the venous system, particularly into the IVC, is rapidly
progressive. In fact, Lambert et al analyzed the postoperative prognosis of RCC patients with venous tumor thrombus, and reported a 5-year CSS rate of 60.3% in those without and 10.0% in those with metastasis.4 Similarly, in this as well as several previous studies, the presence of metastasis was shown to be the strongest independent prognostic factor in patients with RCC involving the venous system.5,7 Therefore, it would be of interest to evaluate the prognostic significance of the level of the tumor thrombus after excluding patients with metastatic disease. In this series, when 76 patients who presented without metastatic disease were analyzed separately. Although there was no independent impact of the extent of the tumor thrombus on CSS, CSS in patients with an IVC thrombus appeared to be significantly unfavorable compared with that in those with a thrombus within the renal vein. However, some groups reported conflicting outcomes regarding this point; that is, CSS in patients without metastasis was not affected by whether or not the venous tumor thrombus extended beyond the renal vein.2,4,8 It would be difficult to clearly explain this discrepancy; however, several factors could possibly be involved in these outcomes, such as therapeutic options against recurrent disease, postoperative follow-up schedules and different biological features of RCC between Japanese and Western populations. Since RCC patients with a venous tumor thrombus are characterized by high incidences of metastasis at presentation as well as postoperative disease recurrence, it is crucial
H. Miyake et al. / EJSO 38 (2012) 630e636
100
Cancer-specific survival (%)
A
Group 1 (n=38) 80 Group 2 (n=27)
60
Group 3 (n=11)
40 20
p = 0.12
0 0
100
100
Cancer-specific survival (%)
B
20 40 60 80 Time after surgery (months)
Group 1 (n=38) 80 60 Groups 2 and 3 (n=38)
40
635
operators, which could possibly influence the presented outcomes. In addition, several recent studies have reported promising markers which could more precisely predict the prognosis of patients following radical nephrectomy and tumor thrombectomy than conventional parameters examined in this study.20,21 For example, Coons et al reported that the presence of macroscopic necrosis was independently associated with overall survival in patients with RCC and IVC thrombus,20 while Bertini et al identified the presence of a friable thrombus as an independent predictor of CSS based on data from 174 RCC patients with venous tumor thrombus.21 Finally, this study simultaneously included patients having heterogeneous characteristics, because of several changes in therapeutic approaches with time at our institution, particularly that in systemic therapy against metastatic disease. This viewpoint will become more important considering recent complicated therapeutic strategies using molecular targeted agents, including the use of these agents in the preoperative and/or postoperative settings. Conclusions
20 p = 0.020
0 0
20 40 60 80 Time after surgery (months)
100
Figure 3. (A) Cancer-specific survival (CSS) in patients with nonmetastatic renal cell carcinoma (RCC) extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic). (B) CSS in patients with non-metastatic RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; groups 2 and 3, inferior vena cava).
to provide optimal systemic therapy. The better prognostic outcome in this series than those in previous studies3e5,7,8 could be partially explained by the favorable response of advanced RCC to cytokine therapy performed at our institution.18 Currently available findings, including ours, on the prognosis of RCC patients with a thrombus extending into the venous system are based on data from the “cytokine therapy era”; therefore, considering the recent introduction of molecular-targeted agents against advanced RCC into clinical practice,19 the issues associated with the prognosis after radical nephrectomy and tumor thrombectomy should be re-evaluated based on data from the “target agent era” in order to draw definitive conclusion on the prognostic significance of the extent of the tumor thrombus in patients with RCC. Here, we would like to emphasize the limitations of this study. Despite it containing one of the largest numbers of patients with RCC and a venous tumor thrombus from a single institution compared with those in previous studies, this is a retrospective study involving multiple surgeons as
Our present series represents one of the largest series containing 135 patients with RCC and a venous tumor thrombus who underwent surgical treatment at a single institution. The outcomes of this study demonstrate that the level of extension of the tumor thrombus into the venous system had no significant impact on the prognosis in the total cohort of patients included in this study. However, after excluding patients with metastatic disease, which was shown to be the most powerful indicator of a poor prognosis in these 135 patients, there appears to be a significant difference in CSS between patients with a tumor thrombus extending into the IVC and those with a thrombus within the renal vein. Collectively, these findings suggest the different prognostic impact of the level of the venous tumor thrombus in patients with RCC according to the metastatic status. Conflict of interest The authors state no conflict of interest.
References 1. Blute ML, Leibovich BC, Lohse CM, Cheville JC, Zincke H. The Mayo Clinic experience with surgical management, complications and outcome for patients with renal cell carcinoma and venous tumour thrombus. BJU Int 2004;94:33–41. 2. Kim HL, Zisman A, Han KR, Figlin RA, Belldegrun AS. Prognostic significance of venous thrombus in renal cell carcinoma. Are renal vein and inferior vena cava involvement different? J Urol 2004;171: 588–91. 3. Parekh DJ, Cookson MS, Chapman W, et al. Renal cell carcinoma with renal vein and inferior vena caval involvement:
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H. Miyake et al. / EJSO 38 (2012) 630e636 clinicopathological features, surgical techniques and outcomes. J Urol 2005;173:1897–902. Lambert EH, Pierorazio PM, Shabsigh A, Olsson CA, Benson MC, McKiernan JM. Prognostic risk stratification and clinical outcomes in patients undergoing surgical treatment for renal cell carcinoma with vascular tumor thrombus. Urology 2007;69:1054–8. Klatte T, Pantuck AJ, Riggs SB, et al. Prognostic factors for renal cell carcinoma with tumor thrombus extension. J Urol 2007;178:1189–95. Terakawa T, Miyake H, Takenaka A, Hara I, Fujisawa M. Clinical outcome of surgical management for patients with renal cell carcinoma involving the inferior vena cava. Int J Urol 2007;14:781–4. Wagner B, Patard JJ, Mejean A, et al. Prognostic value of renal vein and inferior vena cava involvement in renal cell carcinoma. Eur Urol 2009;55:452–9. Martınez-Salamanca JI, Huang WC, Millan I, et al. Prognostic impact of the 2009 UICC/AJCC TNM staging system for renal cell carcinoma with venous extension. Eur Urol 2011;59:120–7. Whitson JM, Reese AC, Meng MV. Factors associated with surgery in patients with renal cell carcinoma and venous tumor thrombus. BJU Int 2011;107:729–34. Tsuji Y, Goto A, Hara I, et al. Renal cell carcinoma with extension of tumor thrombus into the vena cava: surgical strategy and prognosis. J Vasc Surg 2001;33:789–96. Glazer AA, Novick AC. Long-term followup after surgical treatment for renal cell carcinoma extending into the right atrium. J Urol 1996;155:448–50. Parra J, Drouin SJ, Hupertan V, Comperat E, Bitker MO, Roupr^et M. Oncological outcomes in patients undergoing radical nephrectomy and
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vena cava thrombectomy for renal cell carcinoma with venous extension: a single-centre experience. Eur J Surg Oncol 2011;37:422–8. Kaag MG, Toyen C, Russo P, et al. Radical nephrectomy with vena caval thrombectomy: a contemporary experience. BJU Int 2011;107: 1386–93. Libertino JA, Zinman L, Watkins Jr E. Long-term results of resection of renal cell cancer with extension into inferior vena cava. J Urol 1987;137:21–4. Moinzadeh A, Libertino JA. Prognostic significance of tumor thrombus level in patients with renal cell carcinoma and venous tumor thrombus extension. Is all T3b the same? J Urol 2004;171: 598–601. Neves RJ, Zincke H. Surgical treatment of renal cancer with vena cava extension. Br J Urol 1987;59:390–5. Leibovich BC, Cheville JC, Lohse CM, et al. Cancer specific survival for patients with pT3 renal cell carcinoma-can the 2002 primary tumor classification be improved? J Urol 2005;173:716–9. Miyake H, Kurahashi T, Takenaka A, Inoue TA, Fujisawa M. Clinical outcome of combined immunotherapy with interferon-alpha and lowdose interleukine-2 for Japanese patients with metastatic renal cell carcinoma. Urol Oncol 2009;27:598–603. Lane BR, Rini BI, Novick AC, Campbell SC. Targeted molecular therapy for renal cell carcinoma. Urology 2007;69:3–10. Coons BJ, Stec AA, Stratton KL, et al. Prognostic factors in T3b renal cell carcinoma. World J Urol 2009;27:75–9. Bertini R, Roscigno M, Freschi M, et al. Impact of venous tumour thrombus consistency (solid vs friable) on cancer-specific survival in patients with renal cell carcinoma. Eur Urol 2011;60:358–65.
EJSO 38 (2012) 630e636
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Prognostic significance of tumor extension into venous system in patients undergoing surgical treatment for renal cell carcinoma with venous tumor thrombus H. Miyake*, T. Terakawa, J. Furukawa, M. Muramaki, M. Fujisawa Division of Urology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan Accepted 26 March 2012 Available online 10 April 2012
Abstract Aims: The objective of this study was to evaluate the prognostic significance of the extent of a tumor thrombus in renal cell carcinoma (RCC) involving the venous system. Methods: This study included 135 consecutive RCC patients with a venous tumor thrombus undergoing radical nephrectomy and tumor thrombectomy between 1985 and 2009. These patients were classified based on the maximal level of the tumor thrombus extending into the venous system, as follows: group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic. Results: Of the 135 patients, 65, 49 and 21 were classified into groups 1, 2 and 3, respectively. The 1, 3 and 5-year cancer-specific survival (CSS) rates in these 135 patients were 89.2, 56.9 and 49.2%, respectively. Among several factors examined, tumor size, tumor grade, perirenal fat invasion and presence of metastasis, but not extent of tumor thrombus, were significantly associated with CSS on univariate analysis. Of these significant factors, only tumor size and presence of metastasis appeared to be independently related to CSS on multivariate analysis. When the patients without metastasis were analyzed separately, CSS in groups 2 and 3 was significantly poorer than that in group 1. Conclusions: These findings suggest the absence of a significant prognostic impact of the level of the tumor thrombus in a complete cohort of RCC patients with a venous tumor thrombus; however, it is warranted to determine whether the level of the tumor thrombus has different effects on the prognosis according to the presence of metastatic diseases. Ó 2012 Elsevier Ltd. All rights reserved. Keywords: Renal cell carcinoma; Venous tumor thrombus; Surgical therapy; Prognosis
Introduction One of the most unique characteristics in renal cell carcinoma (RCC) is its propensity to extend to the venous system. In fact, the incidence of involvement of the renal vein and/or inferior vena cava (IVC) has been reported to range between 4 and 15%.1e8 Due to improved surgical techniques as well as perioperative care, surgical removal of the kidney with the attached tumor thrombus can be performed relatively safely; therefore, surgical treatment remains the mainstay of management for RCC with a venous tumor thrombus.9 However, the prognosis of patients with RCC involving the venous system is generally poor despite aggressive surgical resection of RCC and the tumor thrombus.1e8 For example, Lambert et al reported
* Corresponding author. Tel.: þ81 78 382 6155; fax: þ81 78 382 6169. E-mail address: [email protected] (H. Miyake). 0748-7983/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejso.2012.03.006
that the 5-year overall survival rate in 118 patients with pT3b or pT3c RCC was 40.7%4, while our previous data from 55 RCC patients with tumor thrombus extending into the IVC revealed a 5-year cancer-specific survival rate of 30.3%.6 Collectively, these findings suggest that it would be important to predict the prognosis of such patients in order to determine tailored postoperative surveillance protocols and therapeutic strategies. To date, several studies have identified potential factors significantly associated with the prognosis of RCC patients with a venous tumor thrombus, such as presence of metastatic disease, tumor size, tumor grade, sarcomatoid features and perinephric fat invasion.1e8 However, it remains controversial whether the extent of a venous thrombus could be used as a prognostic predictor in patients with RCC and a venous tumor thrombus; that is, some studies have demonstrated survival differences according to the tumor thrombus level,6,8 whereas other series have shown no significant effect of the level of the tumor thrombus
H. Miyake et al. / EJSO 38 (2012) 630e636
on survival in patients with RCC.1,2,4,5,7 Considering these findings, we retrospectively reviewed the clinical outcomes of RCC patients with a venous tumor thrombus undergoing radical nephrectomy and tumor thrombectomy in a single institution of Japan in order to clarify the prognostic significance of the extent of the tumor thrombus in the venous system. Patients and methods At our institution, a total of 138 consecutive patients underwent radical nephrectomy and tumor thrombectomy without any neoadjuvant therapies and were pathologically diagnosed as having RCC between 1989 and 2009. Of these 138, this study included 135 patients after excluding 3 who died in the perioperative period, consisting of 2 who died of pulmonary embolism and 1 who died of multiple organ failure caused by massive intraoperative bleeding. Informed consent to this study was obtained from each patient, and the study design was approved by the Research Ethics Committee of our institution. All of the 135 patients preoperatively underwent routine blood tests, brain, chest and abdominal computed tomography (CT), abdominal magnetic resonance imaging (MRI) and/or bone scintigraphy. Gross extension of the tumor thrombus into the venous system was detected by preoperative radiological examinations, including contrastenhanced CT, sagittal view of MRI and/or venacavography, and confirmed by intraoperative findings in these 135 patients. In this series, patients were classified based on the maximal level of the tumor thrombus extending into the venous system, as follows: group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic. The surgical procedures performed in this series were previously described in detail.10 Complication data were confirmed via careful review of all patient charts, and complications greater than grade 3 are considered major complications. All pathological examinations were performed by a single pathologist according to the 2009 UICC/American Joint Committee on Cancer TNM system. Information on the clinicopathological characteristics of the included patients was retrieved from their medical records. Generally, all patients were followed by laboratory as well as radiological examinations every 3 months for the first 2 years and every 6 months thereafter to monitor recurrence and metastasis. In the absence of a relapse of RCC 5 years after surgery, the interval between re-examinations was increased. Informed consent for performing this study was obtained from all of these patients, and the study design was approved by the Research Ethics Committee of our institution. The cancer-specific survival rates of included patients were calculated employing the KaplaneMeier method, and the differences were determined by the log-rank test. The prognostic significance of certain factors was assessed using the Cox proportional hazards regression
631
model. All statistical analyses were performed using Statview 5.0 software (Abacus Concepts, Inc., Berkeley, CA, USA), and p values less than 0.05 were considered significant. Results All of the 135 patients included in this study underwent radical nephrectomy and tumor thrombectomy, and were pathologically diagnosed as having RCC. In these 135 patients, the venous tumor thrombus maximally extended to the renal vein in 65 (group 1, 48.1%), infradiaphragmatic IVC in 49 (group 2, 36.3%), and supradiaphragmatic IVC in 21 (group 3, 15.6%), of which 8 extended to the right atrium. Cardiopulmonary bypass was used in 15 patients in group 3, including all 8 who had intracardiac thrombus extension. Postoperative complications were noted in 59 patients (43.7%); however, major complications developed only in 12 (8.9%), including ileus in 5, pulmonary embolism in 2, pulmonary edema in 2, acute renal failure in 2 and myocardial infarction in 1. Following surgery, cytokine therapy using interferona either alone or in combination with low-dose interleukin-2 was performed in a total of 85 patients, consisting of 59 who presented with metastatic disease and 26 who originally presented without metastatic disease and then experienced postoperative recurrence. In addition, 21 patients were treated with molecular-targeted agents, including sorafenib, sunitinib and axitinib, after the failure of cytokine therapy. Table 1 presents detailed clinicopathological characteristics in the 135 patients according to the maximal level of the tumor thrombus; however, there were no significant differences in several parameters examined, except for tumor location, among these three groups. During the observation period of this study (mean, 32.7 months; range, 4e98 months), 56 patients (41.5%) died of RCC progression, and the 1, 3 and 5-year cancer-specific survival (CSS) rates were 89.2, 56.9 and 49.2%, respectively (Fig. 1A). In addition, 23 (35.4%), 22 (44.9%) and 11 (52.4%) patients died of disease progression in groups 1, 2 and 3, respectively, and there were no significant differences in CSS among these three groups (Fig. 1B) as well as between group 1 versus groups 2 and 3 (Fig. 1C). Of several factors examined, preoperative value of C-reactive protein (CRP), tumor size, tumor grade, perinephric fat invasion and presence of metastasis were significantly associated with CSS on univariate analysis; however, there was no significant impact of the extent of the venous tumor thrombus on CSS. Of these significant factors, only preoperative CRP value, tumor size and presence of metastasis appeared to be independently related to CSS on multivariate analysis (Table 2). CSS curves according to preoperative CRP value, tumor size and presence of metastasis are presented in Fig. 2. There were significant differences in CSS with respect to all three factors.
632
H. Miyake et al. / EJSO 38 (2012) 630e636
Table 1 Patient characteristics according to the level of the venous tumor thrombus. Total (n ¼ 135) Age (%) Younger than 60 years 60 years or older Gender (%) Male Female Tumor location (%) Right Left Clinical symptom (%) Yes No C-reactive protein (%) Normal Abnormal Histological category (%) Clear cell carcinoma Others Tumor size (%) Less than 10 cm 10 cm or greater Grade (%) 1 or 2 3 Perinephric fat invasion (%) Yes No Metastasis (%) Yes No
Group 1 (n ¼ 65)
Group 2 (n ¼ 49)
Group 3 (n ¼ 21)
55 (40.7) 80 (59.3)
25 (38.5) 40 (61.5)
22 (44.9) 27 (55.1)
8 (38.1) 13 (61.9)
99 (7.3) 36 (26.7)
50 (76.9) 15 (23.1)
35 (71.4) 14 (28.6)
14 (66.7) 7 (33.3)
80 (59.3) 55 (40.7)
30 (46.2) 35 (53.8)
34 (69.4) 15 (30.6)
16 (76.2) 5 (23.8)
44 (32.6) 91 (67.4)
20 (30.8) 45 (69.2)
17 (34.7) 32 (65.3)
7 (33.3) 14 (66.7)
96 (71.1) 39 (28.9)
47 (72.3) 18 (27.7)
33 (67.3) 16 (32.7)
16 (76.2) 5 (33.8)
125 (92.6) 10 (7.4)
61 (93.8) 4 (6.2)
45 (91.8) 4 (8.2)
19 (90.5) 2 (9.5)
99 (73.3) 36 (26.7)
50 (76.9) 15 (23.1)
35 (71.4) 14 (28.6)
14 (66.7) 7 (33.3)
94 (69.6) 41 (30.4)
46 (70.8) 19 (29.2)
32 (65.3) 17 (34.7)
16 (76.2) 5 (23.8)
53 (39.3) 82 (60.7)
25 (38.5) 40 (61.5)
20 (40.8) 29 (59.2)
8 (38.1) 13 (61.9)
59 (43.7) 76 (56.3)
27 (41.5) 38 (58.5)
22 (44.9) 27 (55.1)
10 (47.6) 11 (52.4)
p value 0.76
0.61
0.010
0.90
0.72
0.85
0.61
0.64
0.96
0.87
In this series, 76 (56.3%) of the 135 patients presented without metastatic disease. When these 76 patients without metastasis were analyzed separately, 38 (50.0%), 27 (35.5%) and 11 (14.5%) were classified into groups 1, 2 and 3, respectively. Cancer-specific death occurred in 19 (25.0%) of the 76 patients, including 5 (13.2%), 10 (37.0%) and 4 (36.4%) in groups 1, 2 and 3, respectively. Of the 76 patients without metastasis, despite the lack of significant differences in CSS among these three groups (Fig. 3A), CSS in groups 2 and 3 was significantly poorer than that in group 1 (Fig. 3B). Furthermore, the extent of the venous tumor thrombus (group 1 versus groups 2 and 3) was identified as a significant predictor of CSS on univariate analysis; however, multivariate analysis showed no independent association between the extent of the venous tumor thrombus and CSS (Table 2). Discussion A tendency to extend into the renal vein, IVC and right atrium is observed in up to approximately 10% of patients with RCC.1e8 Despite being one of the most challenging surgeries for urologists, radical nephrectomy and tumor
thrombectomy can be performed comparatively safely because of the recent advances in perioperative intensive monitoring, surgical procedures and prudent use of vascular bypass techniques9; hence, this type of aggressive surgery is still regarded as the standard treatment for patients with RCC involving the venous system. To date, a number of investigators have reported the outcomes of surgical management for patients with RCC and venous tumor thrombus; however, the prognoses of such patients are generally poor,1e8 and the prognostic stratification of such patients remains controversial. In this study, therefore, we retrospectively reviewed surgical treatment for 135 patients with RCC involving the venous system at a single institution in Japan in order to characterize the clinicopathological features of these patients. The maximal level of the venous tumor thrombus in the 135 patients included in this study was as follows: renal vein in 65, infradiaphragmatic IVC in 49 and supradiaphragmatic IVC in 21. The proportion of right-sided RCC in cases with an IVC thrombus was significantly higher than that in those with a tumor thrombus within the renal vein; however, there were no significant differences in the remaining clinicopathological factors examined in this
H. Miyake et al. / EJSO 38 (2012) 630e636
C 100
Cancer-specific survival (%)
Cancer-specific survival (%)
A
633
80 60 40 20
100 80
Group 1 (n=65)
60 40
Groups 2 and 3 (n=70)
20 p = 0.40
0
0 0
20 40 60 80 Time after surgery (months)
100
0
20 40 60 80 Time after surgery (months)
100
Cancer-specific survival (%)
B 100 80
Group 1 (n=65)
60
Group 2 (n=49) Group 3 (n=21)
40 20
p = 0.66
0 0
20 40 60 80 Time after surgery (months)
100
Figure 1. (A) Cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC) extending into the venous system who underwent radical nephrectomy and tumor thrombectomy. (B) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic). (C) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; groups 2 and 3, inferior vena cava).
study according to the level of the venous tumor thrombus. These findings are consistent with those in previous studies.4,5,7,8 For example, Klatte et al reported that tumors with extension into the IVC or atrium were predominant on the right side, despite the absence of significant differences in other parameters according to the thrombus level.5 These findings suggest that RCC extension into the venous
system may not reflect the biological aggressiveness of primary RCC, considering the equivalent characteristics of RCC patients with venous tumor thrombus irrespective of its level. The 5-year CSS in the 135 patients with RCC and a venous tumor thrombus following surgical treatment was 49.2%, which was similar or even superior to those reported
Table 2 Univariate and multivariate Cox analyses of cancer-specific survival. All patients (n ¼ 135)
Age (years) (Younger than 60 vs 60 or older) Gender (Male vs Female) Tumor location (Right vs Left) Clinical symptom (Yes vs No) C-reactive protein (Normal vs. Abnormal) Histological category (Clear cell carcinoma vs Others) Tumor size (cm) (Less than 10 vs 10 or greater) Grade (1 or 2 vs. 3) Perinephric fat invasion (Yes vs No) Metastasis (Yes vs No) Level of tumor thrombus (Group 1 vs Groups 2 and 3)
Patients without metastasis (n ¼ 76)
Univariate analysis
Multivariate analysis
Univariate analysis
Multivariate analysis
Hazard ratio
Hazard ratio
p value
Hazard ratio
Hazard ratio
p value
e
e
2.34
0.19
e
e
e e e 3.94 e
e e e 0.014 e
1.49 2.04 1.30 5.87 2.11
0.41 0.34 0.53 <0.001 0.18
e e e 4.07 e
e e e 0.011 e
p value
2.12
0.12
1.34 2.22 1.22 5.31 2.07
0.47 0.19 0.58 <0.001 0.17
p value
3.97
0.0024
2.80
0.031
4.16
0.0069
3.55
0.037
3.34 2.52 7.82 1.33
0.0078 0.024 <0.001 0.23
1.10 1.22 5.33 e
0.72 0.65 0.0014 e
3.77 3.01 e 3.29
0.012 0.046
1.56 1.52 e 1.79
0.62 0.67 e 0.46
e 0.037
A
C
100 80 Normal CRP (n=96) 60 40
Abnormal CRP (n=39)
20 p = 0.0019
0
B
Cancer-specific survival (%)
0
20 40 60 80 Time after surgery (months)
100
Cancer-specific survival (%)
H. Miyake et al. / EJSO 38 (2012) 630e636
Cancer-specific survival (%)
634
100 80
Without metastasis (n=76)
60 40 With metastasis (n=59) 20 p < 0.001
0 0
20 40 60 80 Time after surgery (months)
100
100 80 Tumor size < 10 cm (n=99) 60 40
Tumor size ≥ 10 cm (n=36)
20 p = 0.020
0 0
20
40
60
80
100
Time after surgery (months)
Figure 2. (A) Cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC) extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the preoperative serum value of C-reactive protein (CRP). (B) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the tumor size. (C) CSS in patients with RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the metastatic status.
in previous studies.3e5,7,8 Although predicting the prognosis after surgical treatment facilitates appropriate surveillance protocols and tailored postoperative treatment, there has not been any reliable system closely associated with the prognosis of patients with RCC who underwent radical nephrectomy and tumor thrombectomy. However, previous studies have identified several clinicopathological parameters as prognostic indicators, including tumor size, grade, perinephric fat invasion and sarcomatoid features.4e8 In this series as well, among several factors examined, preoperative CRP value, tumor size and presence of metastasis were identified as independent predictors of CSS, whereas there appeared to be no significant impact of the extent of the venous tumor thrombus on CSS. The prognostic role of tumor extension into the venous system has been examined in several studies. Indeed, the outcomes were not consistent, but large series revealed no difference in survival among the different IVC thrombus levels1,2,4,11e15 or between renal vein and IVC involvement.1,2,4,5,7 Even if the level of the tumor thrombus itself is not prognostically relevant, it would, at least, be crucial for the surgical strategy because of its close association with perioperative morbidity and mortality.5,9 Accordingly, various classification systems for thrombus levels,16,17 which have been proposed to date, remain valuable from the viewpoint of surgical issues. It has been well characterized that the natural history of metastatic RCC with a concurrent thrombus extending into the venous system, particularly into the IVC, is rapidly
progressive. In fact, Lambert et al analyzed the postoperative prognosis of RCC patients with venous tumor thrombus, and reported a 5-year CSS rate of 60.3% in those without and 10.0% in those with metastasis.4 Similarly, in this as well as several previous studies, the presence of metastasis was shown to be the strongest independent prognostic factor in patients with RCC involving the venous system.5,7 Therefore, it would be of interest to evaluate the prognostic significance of the level of the tumor thrombus after excluding patients with metastatic disease. In this series, when 76 patients who presented without metastatic disease were analyzed separately. Although there was no independent impact of the extent of the tumor thrombus on CSS, CSS in patients with an IVC thrombus appeared to be significantly unfavorable compared with that in those with a thrombus within the renal vein. However, some groups reported conflicting outcomes regarding this point; that is, CSS in patients without metastasis was not affected by whether or not the venous tumor thrombus extended beyond the renal vein.2,4,8 It would be difficult to clearly explain this discrepancy; however, several factors could possibly be involved in these outcomes, such as therapeutic options against recurrent disease, postoperative follow-up schedules and different biological features of RCC between Japanese and Western populations. Since RCC patients with a venous tumor thrombus are characterized by high incidences of metastasis at presentation as well as postoperative disease recurrence, it is crucial
H. Miyake et al. / EJSO 38 (2012) 630e636
100
Cancer-specific survival (%)
A
Group 1 (n=38) 80 Group 2 (n=27)
60
Group 3 (n=11)
40 20
p = 0.12
0 0
100
100
Cancer-specific survival (%)
B
20 40 60 80 Time after surgery (months)
Group 1 (n=38) 80 60 Groups 2 and 3 (n=38)
40
635
operators, which could possibly influence the presented outcomes. In addition, several recent studies have reported promising markers which could more precisely predict the prognosis of patients following radical nephrectomy and tumor thrombectomy than conventional parameters examined in this study.20,21 For example, Coons et al reported that the presence of macroscopic necrosis was independently associated with overall survival in patients with RCC and IVC thrombus,20 while Bertini et al identified the presence of a friable thrombus as an independent predictor of CSS based on data from 174 RCC patients with venous tumor thrombus.21 Finally, this study simultaneously included patients having heterogeneous characteristics, because of several changes in therapeutic approaches with time at our institution, particularly that in systemic therapy against metastatic disease. This viewpoint will become more important considering recent complicated therapeutic strategies using molecular targeted agents, including the use of these agents in the preoperative and/or postoperative settings. Conclusions
20 p = 0.020
0 0
20 40 60 80 Time after surgery (months)
100
Figure 3. (A) Cancer-specific survival (CSS) in patients with nonmetastatic renal cell carcinoma (RCC) extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic). (B) CSS in patients with non-metastatic RCC extending into the venous system who underwent radical nephrectomy and tumor thrombectomy according to the maximal level of the tumor thrombus (group 1, renal vein; groups 2 and 3, inferior vena cava).
to provide optimal systemic therapy. The better prognostic outcome in this series than those in previous studies3e5,7,8 could be partially explained by the favorable response of advanced RCC to cytokine therapy performed at our institution.18 Currently available findings, including ours, on the prognosis of RCC patients with a thrombus extending into the venous system are based on data from the “cytokine therapy era”; therefore, considering the recent introduction of molecular-targeted agents against advanced RCC into clinical practice,19 the issues associated with the prognosis after radical nephrectomy and tumor thrombectomy should be re-evaluated based on data from the “target agent era” in order to draw definitive conclusion on the prognostic significance of the extent of the tumor thrombus in patients with RCC. Here, we would like to emphasize the limitations of this study. Despite it containing one of the largest numbers of patients with RCC and a venous tumor thrombus from a single institution compared with those in previous studies, this is a retrospective study involving multiple surgeons as
Our present series represents one of the largest series containing 135 patients with RCC and a venous tumor thrombus who underwent surgical treatment at a single institution. The outcomes of this study demonstrate that the level of extension of the tumor thrombus into the venous system had no significant impact on the prognosis in the total cohort of patients included in this study. However, after excluding patients with metastatic disease, which was shown to be the most powerful indicator of a poor prognosis in these 135 patients, there appears to be a significant difference in CSS between patients with a tumor thrombus extending into the IVC and those with a thrombus within the renal vein. Collectively, these findings suggest the different prognostic impact of the level of the venous tumor thrombus in patients with RCC according to the metastatic status. Conflict of interest The authors state no conflict of interest.
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