British Journal qf Urology (l991), 68,349-354 0 1991 British Journal of Urology

Renal Carcinoma with Inferior Vena Cava Malignant Thrombosis

E. PROCA

Department of Urology, Faculty of Medicine, Fundeni Hospital, Bucharest, Romania

Summary-During an 1 1 -year period a total of 3 14 patients underwent surgery for renal carcinoma; 70 had venous extension of the tumour, 31 had extension to the main renal vein and were staged V1 and 39 had involvement of the inferior vena cava and were staged V2.

Special attention was paid to the latter group, which was divided into 2 subgroups: V2a for caval extension without ingrowth and V2b for caval extension with infiltration of the caval wall. Thirty- eight patients with caval involvement underwent surgery, with a 13% post-operative mortality rate.

Most of the patients with malignant caval ingrowth (V2b) had concomitant lymph node and distant metastases. However, some had negative lymph nodes and no metastases at the time of operation.

Perifascial nephrectomy associated with caval tumour removal or lateral subhepatic caval resection for patients staged V2aNOMO significantly increased the survival rate when compared with that of patients with no surgery on the obstructed vena cava.

has limited indications but, in selected cases, may prolong survival.

carcinoma and suggests the splitting of stage V2 into V2a for patients with free-floating caval extension and V2b for caval thrombus with ingrowth and caval wall infiltration.

Total resection of the completely obstructed subhepatic vena cava for patients staged V2bNOMO

This retrospective study supports the reintroduction of indicator V in the TNM staging of renal

Involvement of the inferior vena cava in patients Skinner et al. (1972) felt that survival was related with renal carcinoma is not uncommon (4-10%) more to perinephric invasion, lymph node and (Marshall and Reitz, 1985), but its significance distant metastases than venous involvement, while remains controversial. This complication has al- Cukier and Charbit (1986) considered venous ways been associated with a poor outcome, with involvement to have a better prognosis than lymph the survival rate at 5 years being 25% after node involvement. nephrectomy (Gilloz et al., 1986). However, in Our findings do not contradict these statements, recent years encouraging reports have been pub- but we feel that venous involvement is underesti- lished following radical nephrectomy, caval throm- mated and deserves more consideration as a bectomy or caval resection (Skinner et al., 1972; predictive factor for survival. Several of the above Kearney er al., 198 1). controversies derive from inaccurate staging of

In some cases caval thrombi were extracted from venous extension of renal carcinoma. the right atrium using either cardiopulmonary by- Some clinical classifications disregard the fact pass under cardioplegia and deep hypothermia that main renal vein involvement has a much better (Belis et al., 1989) or a venous by-pass (Atwood et prognosis (30-60% 5-year survival rate) (Gilloz et al., 1988). al., 1986) than caval tumour extension and in the

same stage I11 they include renal vein, caval and Accepted for publication 2 June 1990 nodal invasion (Merrin, 1979).

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350 BRITISH JOURNAL OF UROLOGY

The 1987 TNM classification of genitourinary tumours has omitted indicator V for vascular invasion, which is included as T3b for both renal vein and vena cava (Schroder et al., 1988).

Other classifications are more accurate in staging venous involvement, as main renal vein thrombosis is labelled V1 (stage 11) and caval thrombosis is labelled V2 (stage 111) (UICC, 1974).

On the other hand, clinical data (including our findings) have shown that in many cases caval involvement represents a mere extension of the main renal vein thrombus within the caval lumen without ingrowth, while in other cases-fewer than in the first category-there is malignant invasion of the caval wall.

The significance of these 2 types of caval involvement seems to us to be of practical impor- tance, since a free-floating caval thrombus can be completely extracted using appropriate surgical manoeuvres, with a reasonably good prognosis (Freed, 1980), while invasive caval thrombus, which is commonly accompanied by regional lymph node involvement, requires partial or even total subhepatic caval resection, operations which are both complicated and difficult (Komatsu et al., 1985).

The purpose of this retrospective study was to support the reintroduction of V1 and V2 categories in the TNM staging system of renal carcinoma with venous extension and eventually to suggest the splitting of V2 into V2a for a non-adherent free- floating caval extension and V2b for an invasive intracaval extension.

Patients and Methods

Over the last 11 years (1977-1988) 314 patients underwent surgery for renal carcinoma. There were 196 males (62.4%) and 118 females (37.6%). Their mean age was 56 years (range 21-83).

The tumour was located on the right side in 160 patients (51%) and on the left side in 154 patients

According to the UICC (1987) TNM classifica- tion, 8 patients (2.5%) were staged pT1,57 patients pT2 (18.2%), 184 patients pT3 (58.6%) and 65 patients pT4 (20.7%).

The regional lymph nodes were found to have been invaded in 84 patients (26.8%) and visceral metastases were present at the time of diagnosis in 51 patients (16.2%).

All patients were operated on by the same surgeon. Preference was given to the anterior

(49%).

lumbar access was used in 35 patients, either because the diagnosis of cancer was uncertain or the patient was in poor condition. In 2 patients thoracophrenolaparotomy was performed.

The tumour-bearing kidney was excised in 91% of cases, 18 laparotomies remained “white” (5.7%); in 4 cases (1.2%) partial nephrectomy was per- formed and surgery was contraindicated in 5 cases

The overall post-operative mortality rate was 6.68% (21 patients). Fifteen of these fatalities occurred in patients with locally advanced disease, when surgery was overestimated and extensive resection of adjacent involved organs was per- formed : pancreatocolectomy (2), partial hepatec- tomy, cholecystectomy and right hemicolectomy (4), lateral excision of duodenum with ileal patch (3) and left hemicolectomy (6).

Special attention was paid to venous involve- ment. Of 3 14 patients, the tumour extension reached but remained confined to the main renal vein in 31 cases (9.8%), while in 39 patients (12.4%) the tumour extended to the inferior vena cava. In this latter group the tumour was right-sided in 27 patients, left-sided in 11 and in 1 instance the inferior vena cava was directly invaded by an upper pole right renal carcinoma.

According to the classification of Kearney et al. (1981), 33 patients had the upper limit of caval thrombus below or not above the posterior edge of the liver; in 5 cases the thrombus was retrohepatic and 1 patient had right atrial extension.

The diagnosis of caval thrombosis was suspected in patients with a non-functioning kidney, recent varicocele, swelling of the lower limbs and cavo-

(1.7%).

Fig. Patient with left renal carcinoma and extension within the intraheuatic vena cava. Free-floatine intracaval thrombus

transperitoneal approach <277 patients), while stage T3NOMOV2a. Y

RENAL CARCINOMA WITH INFERIOR VE!NA CAVA MALIGNANT THROMBOSIS 35 1

caval type subcutaneous venous collateral circula- tion. However, in most cases clinical symptoms were absent. In our experience the urographically silent kidney is highly suggestive of either total parenchymal tumour destruction or caval throm- bus.

Although heavy proteinuria is considered indic- ative of caval obstruction, only 1 patient was admitted with the pseudonephrotic syndrome (gen- eralised oedema and ascites) and this subsided after nephrectomy .

In most patients, the diagnosis of caval throm- bosis was established with reasonably good accu- racy either on computed tomography (CT) (80.4%) or echography (89%).

Venacavography was reserved for patients sus- pected on CT or echography of having caval obstruction.

The diagnosis of caval thrombosis was confirmed by surgery in 38 patients; 1 patient did not undergo surgery.

As mentioned above, according to surgical exploration and pathological examination of the specimen, caval thrombosis was labelled V2a when the thrombus extended from the main renal vein within the caval lumen, whose endothelial lining remained untouched, and V2b in cases of tumour extension with intracaval ingrowth, i.e. with caval wall penetration. Accordingly, 18 patients were staged V2a and 20 patients V2b.

Results

In the group of patients with non-adherent intra- caval thrombus (V2a), all tumours were located on the right side: in most cases there was no local lymph node invasion and no metastases (Table 1).

In 17 patients perifascial nephrectomy and limited pericaval lymphadenectomy associated with thrombus extraction were performed, either by cavotomy or lateral resection of vena cava (Table 1).

There were 2 post-operative deaths, due to myocardial infarction on the seventh day and to pulmonary embolism on the eleventh day.

In 1 patient with caval extension of tumour staged pT3N3V2aMOG3, the vena cava could not be dissected because of lymph node enlargement and only simple nephrectomy was performed. The patient died 10 months post-operatively. The remaining 15 patients were followed up for at least 1 year after surgery (Table 1).

Twenty patients staged V2b had malignant caval thrombosis invading either a limited area of the caval wall (15 patients) or involving most, if not the full length of the abdominal vena cava (5 patients). All bat 2 patients had enlarged pericaval lymph nodes and in 5 cases metastases were present. All patients were surgically explored.

In 5 patients the abdominal vena cava was resected from its origin to the posterior liver edge

Table 1 and Inferior Vena Cava Thrombectomy or Lateral Caval Resection

Survival of Patients with Renal Carcinoma and Inferior Vena Cava Thrombosis Staged V2a. Nephrectomy

Paiients Stage Post-operative survival in months Status

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

pT3pNOMOV2aG2 146 pT2pNOMOV2aG2 48 pT2pNOMOV2aG2 72 pT3pN2MlHep.V2aC3 24 pT3pN2MIHep.VZaG3 6 pT2pNOMOV2aG2 36 pT3pNOMOV2aG3 48 pT3 pN3MIOss.V2aG3 24 pT3pNOMOV2aG2 18 pT3pNOMOV2aC3 12 pT3pNOMOV2aG2 24 pT4pNOMOV2aG2 12 pT3pNOMOVZaG2 20 pT3pNOMOV2aC3 12 pT3pNOMOV2aG2 12 pT3pNOMOV2aG2 - pT3pNOMOV2aC3 - pT3pN3MOV2aG3 10 (no surgery on

vena cava)

~~~~

Alive, free of cancer Alive, free of cancer Natural death Died of cancer Died of cancer Alive, free of cancer Alive, free of cancer Alive, with vertebral metastases Alive, free of cancer Alive, free of cancer Alive, free of cancer Alive, free of cancer Alive, free of cancer Alive, free of cancer Alive, free of cancer Post-operative death-myocardial infarction Post-operative death-pulmonary embolism Died of cancer

352 BRITISH JOURNAL OF UROLOGY

and removed en bloc with the right kidney and lymph nodes. The left main renal vein was resected with preservation of the left spermatic vein and adrenal veins.

Two patients had an uneventful post-operative course, 3 developed acute renal failure and were treated by haemodialysis (2 recovered fully and 1 died of uraemia) (Table 2).

In 2 patients with right renal carcinoma staged NOV2b, perifascial nephrectomy was associated with lateral resection of the subhepatic vena cava and the adherent intracaval thrombus was removed. There was no post-operative renal failure or lower limb oedema (Table 3).

In 10 patients no attempt was made either to relieve the caval obstruction or excise the throm- botic vena cava. Simple nephrectomy was per- formed to alleviate pain and to control haematuria; 2 laparotomies remained “white” (all with sus- pected left kidney tumours) and 1 patient died during surgery (due to inadvertent thrombus frag- mentation and pulmonary embolism) (Table 4).

The overall post-operative mortality rate for patients with malignant thrombosis of the vena cava was 13% (5/38).

To establish whether tumour extension to the vena cava provided independent prognostic infor-

mation as to the presence or absence of lymph node metastasis all patients were divided into 4 groups :

(1) NO/V2a (14 patients) (2) N+/V2a (4) (3) NO/V2b (2) (4) N+/V2b (15)

For each group the probability of survival was calculated according to Chin (1984) for the first 2 post-operative years and the following data were obtained :

(1) NO/V2a: P3=0.88 (2)N+/V2a:P1=0.19 (3) NO/V2b : P4 = 1 (4) N + /V2b : P2 = 0.04 The probability of survival was calculated for the

first 2 years after surgery because the patients staged N+/V2a and N+/V2b were followed up for a maximum of 2 years.

The difference between the 4 probabilities was tested by pairs and was found to be significant (P<O.OOl).

Discussion Perinephric invasion, lymph node involvement and distant metastases are reliable predictors of post-

Table 2 Survival of Patients with Renal Carcinoma and Abdominal Vena Cava Invasion Staged V2b. Nephrectomy and Total Resection of Subhepatic Vena Cava

Patients Stage Operation Post-operative survival in months Status

~~ ~

1 pT4pN2MOV2bG3 Total abdominal caval resection and 20 Died of cancer

2 pT3pN3MlHep.V2bG3 Total abdominal caval resection and 6 Died of cancer

3 pT3pN2MlHep.V2bG3 Total abdominal caval resection and - Post-operative death-uraemia

4 pT4pN2MOV2bC2 Total abdominal caval resection and 16 Alive

5 pT3pN2MOV2bG2 Total abdominal caval resection and 18 Died of cancer

nephrectomy

nephrectomy

nephrectomy

nephrectomy

nephrectomy

Table 3 Lateral Resection of Subhepatic Vena Cava

Patients with Renal Carcinoma and Inferior Vena Cava Thrombosis Staged V2b. Right Nephrectomy and

Patients Staged Operation Post-operative survival in months Status

1 pT3pNOMOV2bG2 Lateral resection of abdominal 48

2 pT3pNOMOV2bG2 Lateral resection of abdominal 13 vena cava and nephrectomy

vena cava and nephrectomy

Alive

Alive

RENAL CARCINOMA WITH INFERIOR VENA CAVA MALIGNANT THROMBOSIS 353

Table 4 Relieve Caval Obstruction. Palliative Simple Nephrectomy

Patients wi th Renal Carc inoma and Abdominal Vena C a v a Thrombosis Staged V2b-No At tempt to

Patients Stuge Post-operative

Operation survival in months Status

I 2 3 4 5 6 7 8

9 10

pT3pN2MOV2bC3 pT4pN3MlHep.Oss.V2bGx pT3pN2M1 Hep.Oss.VZbG3 pT4a + bpN2MOV2bGx pT3pN3MOV2bG3 pT3pN2MOV2bGI pT4bpN2MOV2bG3 pT3pN2M1 Hep.V2bG3

pT3pN2MOV2bG3 pT3pN2MOV2bG3

Nephrectomy Inoperable Nephrectomy Inoperable Nephrectomy Nephrectomy Nephrectomy Nephrectomy

Nephrectomy Nephrectomy

12 4 3 2 3

Not k 12 -

14 .-

Died of cancer Died of cancer Died of cancer Died of cancer Right colon invasion and obstruction

Died of cancer Died of pulmonary embolism on 1 l th post- operative day Vertebral metastases and paraplegia Intraoperative death-pulmonary embolism

- nown

operative survival in patients with renal carcinoma. However, progression of a malignant thrombus within the abdominal vena cava could significantly alter both staging and prognosis and should be assessed before surgery.

Current imaging methods (CT, echography, vena cavography) delineate an intracaval thrombus accurately and prepare the surgeon for an adequate management protocol.

Horan et al. (1989) emphasised the accuracy of the combination of vena cavography and magnetic resonance imaging for identification of venous extension of renal carcinoma.

It is surprising that some clinical classifications of renal carcinoma pay little attention to venous involvement and make no prognostic distinction between a non-adherent intracaval thrombus and one with ingrowth. This difference is convincingly demonstrated by our data, since most patients with invasive caval thrombus had positive lymph nodes (1 5 / 17) and 5 also had distant metastases.

In 5 of these patients perifascial nephrectomy and total resection of the subhepatic vena cava was tried “as a desperate appliance to relieve a desperate grown disease” (Hamlet, act IV, scene 3), with little benefit. Nevertheless, survival in this group was significantly longer than in patients treated by palliative nephrectomy.

The patients with non-invasive intracaval throm- bus had a better survival rate because most of them had negative lymph nodes, no metastases and the intracaval thrombus could be completely extracted in all cases.

Patients living for many years after nephrectomy and caval thrombectomy (12 years in 1 case) (Table 1) are a stimulus for the accurate staging of renal

carcinoma, including venous involvement, on which to base surgery.

Our data support the view that caval extension of renal carcinoma could occur independently of either lymph node involvement or metastases and so should form a separate category in the TNM classification, i.e. V1 for thrombosis of the main renal vein and V2 for abdominal caval involvement.

Our experience suggests that splitting the V2 category into 2 subgroups, namely V2a for non- adherent intracaval thrombus and V2b for invasive caval thrombosis, would increase the accuracy of staging and promote better management. In the present study, patients staged NOMOV2a had a better survival rate than those staged NOMOV2b.

In conclusion, we feel that no patient with renal carcinoma and vena caval extension should be denied surgery, provided the lymph nodes are negative and metastases absent.

Statistical analysis of our data demonstrated that a patient staged N +/V2a (P1=0.19) has a proba- bility of post-operative survival almost 5 times longer than a patient staged N + /V2b (P2 = 0.04) and this supports our proposal to split V2 into 2 subgroups, respectively V2a and V2b even for patients with lymph node invasion.

Our clinical analysis confirms the value of nodal metastasis as a prognostic indicator, since patients staged NO/V2a may live 4.5 times longer than patients staged N + /V2a and 22 times longer than patients staged N + /V2b.

The group of patients staged NO/V2b is too small (only 2 cases) to permit valid conclusions, but more such patients, followed up for longer time periods, would encourage a more aggressive approach in cases of renal carcinoma with caval ingrowth. Pre-

3 54 BRITISH JOURNAL OF UROLOGY

operative documentation of the presence and extent of vena cava involvement (CT, echography, vena cavography) is mandatory in all patients before surgical exploration.

For patients staged V2a, the non-adherent throm- bus could be extracted by appropriate surgical manoeuvres, including co-operation with a cardio- vascular surgical team.

Total resection of subhepatic vena cava for V2b staged patients has limited indications and should be reserved for selected NOMO patients with right renal carcinoma. Whenever possible, lateral resec- tion of this vein should be preferred.

All of our patients with left renal carcinoma staged V2b were surgical failures because of concomitant positive lymph nodes and distant metastases.

To date, we have not recorded spontaneous regression of metastases after nephrectomy for renal carcinoma.

Acknowledgement I thank Dr T. Ionescu for his help in statistical analysis.

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The Author E. Proca, MD, Professor of Urological Surgery, Faculty of

Medicine, Urological Department, Fundeni Hospital, Sos. Fundeni nr. 258, sector 2, Bucharest, Romania.