Long-term Results of Resection of Renal Cell Cancer with Extension into Inferior Vena Cava

0022-584'/)87 (i.371-0021 $02.00/0 ,JCURNAL OF UROLOGY

Copyright

1981

The \Villiams & "VVilkins Co.

LONG-TERM RESULTS RESECTION RENAL CELL WITH EXTENSION INTO INFERIOR VENA CAVA JOHN A. LIBERTINO,* LEONARD ZINMAN AND ELTON WATKINS, JR. From the Department of Urology and Sias Surgical Research Unit, Lahey Clinic Medical Center, Burlington, Massachusetts

ABSTRACT

From July 2, 1971 to April 1, 1985, 47 patients (median age 63 years) with renal cell cancer extending into the renal vein or inferior vena cava were evaluated and treated. Two-thirds of the tumors occurred in men and three-fourths were found in the right kidney. Of the 44 patients operated on 35 had no evidence of preoperative metastatic disease at operation. The patients were divided into ideal, favorable and unfavorable subgroups. The adjusted 5 and 10-year survival rates in the former 2 groups (32 patients) were 68.8 and 60.2 per cent, respectively. In contrast, 12 patients with nodal involvement or metastases had an adjusted median survival time of 1.2 years with no survival extending beyond 4.8 years. We believe that an extended operation for renal cell cancer with involvement of the vena cava is warranted and provides reasonable long-term survival in properly selected patients. Procedures currently used for the management of vena caval tumor thrombi include venacavotomy, partial mural venacavectomy, segmental suprarenal venacavectomy and ahiotomy, usually in conjunction with venacavotomy. Venacavotomy, the most widely used method to extract tumor thrombus from the vena cava, consists of extending the vena caval incision from the orifice of the renal vein cephalad and removing the free floating thrombus in continuity with the tumor. Partial mural venacavectomy involves removal of variable lengths of the lateral vena caval wall with thrombus and kidney en bloc followed by vascular reconstruction of the wall of the vena cava with a narrow but patent lumen. In segmental venacavectomy a cylindrical portion of the inferior vena cava is excised when it has been invaded by tumor thrombus. Because renal cell tumor rarely invades the wall of the vein or vena cava, complete cylindrical resection of the vena cava seldom is justified, and a major effort should be made to reconstruct the vena cava after partial venacavectomy. Despite the technical difficulty necessary to manipulate the suprarenal retrohepatic portion of the inferior vena cava, the need for complete removal of associated malignant disease and the imminently life-threatening nature of such occlusions argue for a systematically aggressive ""'""''·'u•n to tumor thrombectomy and reconstruction of the vena cava.

The management of patients with renal cell cancer with extension into the vena cava is controversial and challenging. Variable results that have been reported by different investigators 1- 3 have added to the confusion (see table). Tumor thrombus or complete occlusion of the inferior vena cava poses the potential life-threatening sequela of fatal pulmonary embolus or extension into the hepatic vein with consequent hepatic failure. The complexities of the surgical procedure and conflicting reported results have created confusion and pessimism in the minds of some regarding the value of resection of the vena cava, thrombectomy and vena caval reconstruction. Proper selection of patients and meticulous attention to surgical technique will improve clinical results and make this difficult problem less controversial in the future. Radical management of patients with renal cell cancer involving the vena cava and experience with salvage procedures after chemotherapy for testicular carcinoma have expanded the scope and responsibility of the urologist in operations on the infrahepatic and suprahepatic portions of the inferior vena cava. During the last 2 decades aggressive surgical approaches have been adopted for removal of renal tumor thrombi. With mriro,vemEmt in preoperative methods of am,essrntg the cranial extent of the tumor thrombus in the vena cava, the appropriate surgical procedure for recovery of the venous extension of the can be tumor can be ,rn~u.nv~ and troublesome ~~·""""'°'..:,v prevented. The most common cause of vena caval thrombosis is neoplastic thrombus arising from a renal or adrenal cancer directly into the lumen of the inferior vena cava. Other cancers uterus and retroperitoneal tissues conarising from the stitute the remainder of the nonrenal tumors that can invade the inferior vena cava. Retroperitoneai sarcoma, embryonal ceH cancer, ovarian cancer, congenital webs, Wilms tumor and leiomyosarcoma of the vena cava also can cause vena caval occlusion. Recognition that the inferior vena cava may be involved with a neoplastic tumor process was described as early as 1688 by Blancardus. 4 Early attempts at resection and repair of the vena cava include removal of a renal tumor thrombus from the inferior vena cava by Berg in 1913, 5 partial resection of the vena cava by Rehn in 1922, 6 and extraction of tumor from the atrium by Ardekani and associates in 1971. 7 0

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CLINICAL EXPERIENCE

From July 2, 1971 to January 1, 47 patients with renal cell cancer extending into the renal vein or inferior vena cava were evaluated and treated at our clinic. Followup extended to 1. Patient age ranged from 45 to 82 years, with a median age of 63 years. Two-thirds of the tumors occurred in men and three-fourths occurred in the right kidney. An operation was performed on 44 of the 47 patients. Of the 44 patients 35 had no preoperative evidence of metastatic disease when operated on, while 9 who were operated on early in our experience had preoperative evidence of metastatic disease. Three patients who had evidence of metastatic disease later in our experience were treated conservatively without an operation. Duration of followup extended from 6 months to 13.7 years. SYMPTOMS AND SIGNS

Most patients present with symptoms and signs typical of renal cell cancer, with hematuria, flank or abdominal pain and a flank or abdominal mass predominating. However, nearly

Accepted for publication August 20, 1986. * Requests for reprints: Department of Urology, Lahey Clinic Medical Center, 41 Mall Rd., Burlington, Massachusetts 01805.

21

LIBERTIN()~

Results Refe~ence

No. Pts.

Obse:-eved 5-Y r. Survival

11

45.0

21

28.5

14.3

24

16.6

4.0

44

44.0

4.5

(%)

Skinner and associates 1 Schefft and associates 2 Kearney and associates 3 Present study

Operative Mortality

' ' ""'"'"'"n,.rn ana' vena cava are c1osect moved from cardiopulmonary

(%)

Not available

Our study was limited to carcinoma with renal vein and vena caval extension. The remaining reports included all patterns of cancer growth.

and the

is re- ·

STATISTICAL METHODS

Data were analyzed for actuarial survival by the KaplanMeier product limit method. Significance of differences in actuarial survival patterns of subgroups was analyzed by the log rank method or by the Lee-Desu modification of the Kruskal- Wallis test with log rank scores. Confidence limits of a survival distribution were calculated by the method of Rothman." SURVIVAL

half of our patients demonstrated signs or symptoms directly referable to involvement of the vena cava. Extension into the vena cava should be suspected when bilateral lower extremity edema, right or left varicocele of recent onset, dilated superficial abdominal wall veins, caput medusae, pulmonary embolus or proteinuria is noted in association with a renal tumor. PREOPERATIVE TESTS

Because renai cell cancer primarily is a radiological diagnosis and because the presence or absence of metastases is paramount in deciding on treatment, all patients should be evaluated with excretory urography (IVP), computerized tomography (CT) of the abdomen, lung tomography, bone scan, liver function tests and selective renal arteriographyo Extension into the vena cava must be considered consequently, inferior venacavography is indicated) when a perihilar mass associated with a nont,Lin,cti.,onmg kidney i.s seen on an IVP, filling defects are noted on the venous phase of arteriography and involvement of the renal vein or vena cava is suspected on CT. Superior venacavography is indicated in the presence of total occlusion of the vena cava or when the uppermost limit of vena caval extension cannot be determined clearly by inferior venacavographyo In addition to superior venacavography, study of the right heart may be warranted in patients who demonstrate complete occlusion ·cf the inferior vena cava. Preoperative studies must delineate the proximal and distal limits of the tumor thrombus so that the appropriate surgical approach can be used. Careful preoperative evaluation of a patient with a tumor thrombus in the vena cava cannot be overemphasized. The presence of nodal involvement as well as distant visceral and metastasis must be excluded for any hope of cure. The level vena caval involvement also must be known so that the surgeon can a safe ,w,,A,·o,tn,,"' approach and maneuvers that may be required any resection.

Product limit analysis of actuarial survival of the over-all group of 44 patients undergoing resection indicated an observed 5-year survival rate of 44.0 ± 9.1 per cent (standard error) and an observed IO-year survival rate of 28.9 ± 11.0 per cent. Observed median survival time was 45.8 months. Data relating to 2 perioperative deaths and 2 deaths of confirmed unrelated disease (7 and 116 months) were censored for calculation of adjusted survival rates. The adjusted 5 and 10-year survival rates were 47.3 ± 9.6 and 41.4 ± 10.0 per cent, respectively. The adjusted median survival time was 57.2 months (fig. 1). Since no detectable difference was seen in survival patterns among patients with regional lymph node involvement and those with distant organ metastasis or contiguous organ invasion, the series was divided into 3 subgroups: 1) an ideal subgroup of 19 patients with disease confined to the kidney and vena cava without manifestations ofperinephric fat extension, rlistant metastasis or contiguous organ involvement, 2) a favorable subgroup of 13 patients without extrarenal extension other than perinephric fat invasion and 3) an unfavorable group of 12 patients with combinations of involvement of regional lymph nodes, contiguous structures and distant metastasis. The ideal and favorable groups showed no significant difference in survival pattern (p = 0.93). For the combination of these groups (32 patients) the adjusted 5 and 10-year survival % Survival

100

OVERALL SERIES (n=44)

[J 95% CL 80

60

CARDIOPULMONARY BYPASS

The presence of tumor within the atrium «,~1mJ'"" the use of ,n1,1vcv1,11v and cardiopulmonary bypass. In select group of patients a chevron incision combined with median sternotomy the best exposure. Cardiopulmonary bypass is not performed until the entire kidney has been mobiattached the renal veino This portion of the lized, procedure must be done systemic heparinization, required for cardiopulmonary bypass, is instituted to avoid excessive bleeding. For cardiopulmonary bypass, the heart is cannulated with the arterial return by means of the ascending aorta, and the venous drainage by means of the superior vena cava and right common femoral vein. Bypass then is instituted, the right atrium is opened and the intra-atrial portion of the tumor is removed. Attention then is directed to the infradiaphragmatic portion of the procedure via the technique described previously. After complete removal of the tumor thrombus, the atriotomy

40

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16

Years FIG. 1. Adjusted survival of 44 patients after resection of renal cell carc\no_ma with vena c!lval ext~nsio? calculated by Kaplan-Meier product h1:111t_method. Median survival time (?J~T) is 57.2 months. Stippled area md1cates 95 per cent confidence hm1ts. Vertical marks indicate censoring at times of living followup.

rates were 68.8 ± 10.l and 60.2 ± 12.0 per cent, wi>,:r,,,,..-i-m11 The median survival time could not be calculated in group at 13.7 years, the longest period of followup. In contrast, the 12 patients with nodal involvement or n1etastatic disease showed an adjusted median survival time of 1.2 years with no survival extending beyond 4.8 years (fig. 2). The difference in survival patterns was highly significant statistically (p = 0.002). Although the survival pattern of 5 patients with regional lymph node involvement did not differ significantly from the pattern in 7 patients with distant metastasis or contiguous organ invasion (p = 0.13), the group with nodal involvement showed an adjusted median and longest survival time of 4.8 years contrasted with equivalent values of 1.2 and 3.8 years in the group with metastasis or invasion. No dominant pattern of distant tumor spread was discernible. Recently, 3 patients with evidence of distant metastasis have not undergone an operation. One patient was alive 4.4 months after diagnosis and 2 are dead with a median survival time of 4.4 months. PERIOPERATIVE DEATH AND MORBIDITY

Two patients (4.5 per cent) died in the perioperative period: 1 of an air embolus and 1 of a myocardial infarction, for a perioperative mortality rate of 4.5 per cent. Of the 44 patients 5 (11 per cent) experienced appreciable morbidity postoperatively. In 1 patient with cirrhosis hemorrhage from esophageal varices was associated with the adult respirntory distress syndrome and acute tubular necrosis. Early in our experience 1 patient had a pulmonary embolus, 1 had duodenal obstruction and 1 had transient encephalopathy owing to hyperammonemia. Permanent renal failure did not develop in any patient. DISCUSSION

The reported incidence of renal cell adenocarcinoma in the United States is 3.5 per 100,000 population per year. 9 Although renal cell carcinoma has been reported in patients of all ages %

Survival ,-------------------------, 39

100

26 , 23 111 21 t10

80

NO METASTASIS (n=32)

I

Lg

8

I

1° ---L ,7

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1'/MST

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METASTASIS (n,,, 12)

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1 Numbe,

at Risk

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i

I I I

0 0

2

4

6

8

10

12

14

16

Years FIG. 2. Adjusted survival relative to degree of tumor extension. Tumor extension is limited to subcapsular growth or extension to perinephric fat (solid line indicates ideal and favorable categories). Dashed line (unfavorable category) indicates combination of regional node involvement, distant metastases and contiguous organ invasion. Vertical marks indicate censoring at times of living followup. MST, median survival time.

to old agt\ the 1nedian age at ~,c,,c,L,:vow has "been. bet~Neen 55 and 57 years. numerous

~···~~u,y

single and multidrug chemotherapeutic regimens, radiation therapy and hormonal uuuuµu1m,1u1:1. surgical extirpation remains the mainstay for C'1i-r,a-rrn;o, treatment of renal cell cancer. In a review of 309 patients treated radical nephrectomy between 1935 and 1965 Skinner and associates reported an operative mortality rate of 5 per cent, with an over--all survival rate of 45 per cent at 5 years and 33 per cent at 10 years. 10 Excluding patients who had metastasis when first evaluated the 5 and 10-year survival rates were 57 and 44 per cent: respectively. In an effort to evaluate results of treatment and the prognosis of individual patients better Flocks and Kadesky proposed a pathological staging systemn that subsequently was modified by Robson and associates. 12 · 1., The staging system for renal cell carcinoma that currently is used is stage I-tumor confined within the renal capsule without involvement of the perinephric fat, stage II-tumor invasion of perinephric fat but confined to Gerota's fascia, stage III-tumor involving the renal vein and/or regional nodes with or without involvement of the vena cava or perinephric fat and stage IV-distant metastasis or histological involvement of contiguous visceral structures. When survival rates were assessed according to this staging system Skinner and associates reported 5 and 10-year survival rates of 65 and 56 per cent, respectively, in 102 patients with stage I cancer, 47 and 20 per cent, respectively, in 22 with stage II cancer, 51 and 37 pe1· cent, respectively, in 108 with stage HI cancer, and 8 and '? per cent, respectively, in 77 with stage IV cancer."' A shortcoming of this staging system is apparent when critical analysis of stage III disease is made. Patients with renal vein or vena caval involvement but without nodal or perinephric involvement have had survival rates that are similar to those in patients with stage I disease. 1 • 12 • 14 · 15 Among our 47 patients with extension of renal cell cancer to the vena cava treated by thoracoabdominal radical nephrectomy and partial resection of the vena cava, survival. rates were excellent when involvement of nodes or perinephric fat was absent. Survival rates for these patients exceed reported 5-year survival rates for ,.,_.,-·'"'"Q with stage I renal cancer. Intracaval tumor thrornbus is a manifestation of advanced renal cell carcinoma but occasionally it sociated with Wilms tumor and adrenal carcinoma. mately 5 per cent of the patients undergoing radical rn,r,un,,ctom_y for renal cell carcinoma have extension of tumor bus into the inferior vena cava. The level of extension varies of thrombus at the level of the renal vein from a small atrium, A recent into the the vena cava is classification of extension of the tumor depicted in 3. Among our 44 patients the tumor extended into the vena cava at the level of the renal vein in 16.7 per cent, above the renal veins but infradiaphragmatic in 62.5 per cent, supradiaphragmatic but not into the atrium in 12.5 per cent and into the right atrium in 8.3 per cent. Extended survival was achieved in patients regardless of whether the tumor was supradiaphragmatic or infradiaphragmatic. Chronic renal failure requiring dialysis did not develop in any of our patients. This is in contradistinction to other reported series 2• 3 and may be attributed to meticulous technique, which includes every effort to avoid occlusion of the venous outflow of the contralateral kidney and favors partial rather than complete vena caval resection. Clearly, from our results no benefit is gained by operating on any patient with preoperative evidence of metastasis. Likewise, to proceed with vena caval thrombectomy, resection and reconstruction when intraoperative evidence of liver, nodal, meso-

24

LIBERTINO, ZINMAN AND WATKINS REFERENCES

i

{A·---------------8····------------

2{A····--B----

1.

SUPRADIAPHRAGMATIC

A. lntrocardiac 8. lntrapericardial 2. INFRADIAPHRAGMATIC

A. Supra hepatic veins 8. lnfrahepatic veins

FIG. 3. Classification of vena caval (IVC) thrombus extension. Ao, aorta. Reprinted with permission from Libertino, J. A.: Renal cell cancer with extension into vena cava. In: Rob & Smith's Operative Surgery; Urology, 4th ed. Edited by W. S. McDougal. London: Butterworth & Co, p. 127, 1986.

colonic or psoas metastasis is discovered has no merit. On the other hand, excellent survival rates can be expected in patients without evidence of metastatic disease noted preoperatively or intraoperatively, making an aggressive surgical approach reasonable, less controversial and warranted. Gerald J. Heatley provided extensive statistical computations.

1. Skinner, D. G., Pfister, R. F. and Colvin, R.: Extension of renal cell carcinoma into the vena cava: the rationale for aggressive surgical management. J. Urol., 107: 711, 1972. 2. Schefft, P., Novick, A. C., Straffon, R. A. and Stewart, B. H.: Surgery for renal cell carcinoma extending into the inferior vena cava. J. Urol., 120: 28, 1978. 3. Kearney, G. P., Waters, W. B., Klein, L. A., Richie, J. P. and Gittes, R. F.: Results of inferior vena cava resection for renal cell carcinoma. J. Urol., 125: 769, 1981. 4. Blancardus. Cited by Schecter, D. C.: Cardiovascular surgery in the management of exogenous tumors involving the vena cava. In: Surgery of the Veins. Edited by J. J. Bergan and J. S. T. Yao. Orlando: Grune & Stratton, chapt. 28, pp. 393-412, 1985. 5. Berg, A. A.: Malignant hypernephroma of the kidney. Its clinical course and diagnosis, with a description of the author's method of radical operative cure. Surg., Gynec. & Obst., 17: 463, 1913. 6. Rehn, E.: Gefasskomplikationen und ihre Beherrschung bei dem Hypernephrom. Z. Urol. Chir., 10: 326, 1922. 7. Ardekani, R. G., Hunter, J. A. and Thomson, A.: Hidden hypernephroma simulating right atrial tumor. Ann. Thorac. Surg., 11: 371, 1971. 8. Rothman, K. J.: Estimation of confidence limits for the cumulative probability of survival in life table analysis. J. Chron. Dis., 31: 557, 1978. 9. MacDonald, E. J.: Present incidence and survival picture in cancer and promise of improved prognosis. Bull. Amer. Coll. Surg., 33: 75, 1948. 10. Skinner, D. G., Colvin, R. B., Vermillion, C. D., Pfister, R. C. and Leadbetter, W. F.: Diagnosis and management of renal cell carcinoma: a clinical and pathologic study of 309 cases. Cancer, 28: 1165, 1971. 11. Flocks, R. H. and Kadesky, M. C.: Malignant neoplasms of the kidney: an analysis of 353 patients followed five years or more. J. Urol., 79: 196, 1958. 12. Robson, C. J.: Radical nephrectomy for renal cell carcinoma. J. Urol., 89: 37, 1963. 13. Robson, C. J., Churchill, B. M. and Anderson, W.: The results of radical nephrectomy for renal cell carcinoma. J. Urol., 101: 297, 1969. 14. Middleton, R. G. and Presto, A. J., III: Radical thoracoabdominal nephrectomy for renal cell carcinoma. J. Urol., 110: 36, 1973. 15. Ochsner, M. G., Brannan, W., Pond, H. S., III and Goodier, E. H.: Renal cell carcinoma: review of 26 years of experience at the Ochsner Clinic. J. Urol., 110: 643, 1973.