S U R G I C A L T R E A T M E N T O F BRAIN METASTASES FROM RENAL CELL CARCINOMA ROBERT A. BADALAMENI; M.D. ROBERT W. G L U C K , M.D. G E O R G E Y WONG, PH.D. CLAIRE G N E C C O , M.S.
ERIC KREUTZER, M.D. HARRY W. HERR, M.D. W I L L I A M R. FAIR, M.D. JOSEPH H. G A L I C I C H , M.D.
From the Urology and Neurosurgery Services, Department of Surgery, and the Division of Biostatisties, Memorial Sloan-Kettering Cancer Center, New York, New York
ABSTRACT--Between January 1976 and December 1986, 22 patients with renal c~ underwent surgical resection of brain metastases at Memorial Sloan-Kettering Cance of the patients had metastases limited to the brain and 12 also had extracranial metasa patients' received external radiotherapy. Five had craniotomy after failing radiation th had adjuvant radiotherapy. Two patients died within thirty days following craniotomt survival of the remaining 20 patients was 20.9 + 6.8 months calculated according survival model. Variables examined in relation to survival included absence or presenc nial metastases at time of craniotomy, time interval between nephrectomy and diagno,~ metastases, neurologic status prior to craniotomy, location of the brain tumor, and None of the variables was significant at the 10 percent level by the Weibull analy,~ three favorable prognostic factors, namely metachronous brain metastasis more than nephrectomy, minimal or no neurologic deficit at time of craniotomy, and inJrate~ show a trend toward improved survival with p < 0.20. The data suggest that surgical single and occasionally multiple brain metastases is warranted in selected patients tc carcinoma.
Of the 15,000 eases of renal cell eareinoma diagnosed annually in the United States, approximately one-third will present with metastases and in another one-third subsequent metastases will develop.1 The optimum treatment of metastatie renal eell e a r e i n o m a remains undefined. Therapeutic options including ehemotherapy, 2 radiotherapy, 3 and immunotherapy, 4 have been uniformly disappointing. Surgical resection of metastatic loci in seleeted patients, such as those with solitary lung lesions, has been associated with prolonged survival. ~-s Less is known, however, of the results of surgical treatment of renal cell eareinoma metastatic to the brain. Over a ten-year period, 22 patients with renal cell carcinoma at the Mew-
112
orial Sloan-Kettering Cancer I treated by surgical extirpation ot metastases. The results of this trc reviewed to assess survival and to tors influencing prognosis. Spec variables were examined in relati( and included the absence or pres( cranial metastases at the time ot length of the time interval betw tomy and the diagnosis of brail neurologie status prior to eraniot, of brain lesion, and patient age. Material and Method From January 1976 to Deeembe atively unselected group of 22 t
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!metastases from renal cell carcinoma unALL PATIENTS l 20 PTS. 8 C~NSOREO) ~nt craniotomy and extirpation of tumor TICK MARK t l ) INDICATES LAS~ FOLlOW-uP 0 0 ~morial Sloan-Kettering Cancer Center. !ia for craniotomy consisted of a nonrnorimedical status and one or two surgically iible brain metastases. Eighteen patients c;irnale and 4 were female. The mean age 0 Z ifty-six years (range 31-71 years) . Nineteen i !t~ had a presumed single brain metastapatients, 2 intraeranial tumors were ified. The brain tumors were metachroH~ ents; 4 had synchronous lesions. 0:2o ¸ o turation between nephreetomy 0 c:E osis of brain tumor was thirty EL g 0-120 months). patients u n d e r w e n t radical md renal hilar lymphadeneeo tary neoplasm in the remaining o nreseetable due to advanced lo0 (]0 1 2 O0 24. 00 36 O0 4;3 O0 60. O0 72.00 SURVIVAL IN MONTHS ,~histology of the primary tumor carcinoma in 20 patients and FIGURE 1. Overall survival of patients with surgical treatment of brain metastases from renal cell ~'inoma in 1. Metastases to hilar carcinoma. The term "censored" refers to patients ~re identified in 2 patients, In all who were still alive at last follow-up. istology of the brain metastases ¢ith the primary tumor. The one I not undergo nephreetomy had Statistical "methods Loma in the brain. Owing to the small sample size (n = 20 eval~etastases in all patients were uable patients) and the relatively heavy cenIeurologie symptoms and signs soring (8 patients were still alive at the last ehe (12 patients), hemiparesis follow-up), the usual nonparametric Kaplan;eizures (4), visual field defects Meier method 0 was deemed inappropriate for ~iand cognitive defects (2). Diagnosis was establishing prognostic significance of the variirmed in all patients by eomputerized toables. Instead, a fully parametric survival anal~aphy; 10 patients had additional evaluaysis that afforded much more statistical sensitiv~ by cerebral angiography. F o l l o w i n g ity was c a r r i e d out. Specifically, it was gnosis of intraeranial metastases all patients empirically determined that the survival times ~ evaluated for extent of extraeranial disease of the patients closely followed a Weibull distri~0utine laboratory tests, ehext x-ray film, button, a well-known distribution widely used lli~scan, and either abdominal sonography or J in life-testing problems.20 For each variable, a i ~puterized tomography. 'Fen patients had Weibull survival curve was fitted to each of the i iase limited to the brain, and 12 patients two categories of the variable. The method of ~tastatie sites which included maximum likelihood was used to estimate the bone (4), liver (1), adrenal unknown parameters. Since the Weibull distri9dominal wall (1), and ovary bution is skewed to the left, median survival times were calculated instead of mean survival ived corticosteroid therapy at time to characterize average patient survival. ~rior to elective eraniotomy. The usual likelihood ratio test was used to de:d failed whole b r a i n ratermine prognostic significance of the variables. undergoing surgery. Fifteen i . . . . adjuvant whole brain raResults ~fherapy (2,000-4,000 rad in fractionated ~ses> following eraniotom~: Steroids w e r e ta%vo patients died within thirty days of surgied and discontinued postoperatively in all eal resection of brain metastases, resulting in an ~t 9. patients, who required chronic therapy operative mortality of 9 percent (2/22). Of i ~eoncurrent spinal cord compression ripest, 1 patient with synchronous renal and . . . . .
AUGUST 1990
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VOLUME XXXVi, NUMBEI/ 2 113
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F[OURE 2. Survival of patients w i t h onset of cerebral metastases < one year after nephrectomy versus survival of patients w i t h onset of cerebral metastases >_ one year after nephrectomy. D
MILD OR NO DEFICIT
( 10 PTS
4 CENSORED/
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FIGURE 3. Surviva ! of patient w i t h mild or no neurologic deficit versus survival of patients w i t h moderate or severe neurologic deficit at presentation of cerebral metastases. brain tumors had a fatal spontaneous intra-abdominal hemorrhage from a nonreseetable primary tumor after eraniotomy; the other, with a metachronous brain tumor, continued to deteriorate neurologically following resection of the
114
brain tumor. Both were excluded lowing survival analysis. Of the 20 evaluable patients, th viral was 20.9 _+_ 6.8 months months) (Fig. 1). Twelve patient: ease, 6 are alive but have had sub, tion of systemic metastatic loci, 1 ease three months after eranio patient died in an auto accident dence of disease four months f{ niotomy. In the 6 patients alive moral of subsequent metastatic fo removal included lung (4), adr( bone (1). Three of the 6 patients h dered clinically free of disease (m~ by the resection of additional met Eight patients had cerebral n~ relapse. Tumor recurred at the op 3 patients. In 5 patients distant ce tases were detected at varying i craniotomy. Thus, local control o brain tumor(s) was achieved in 8[ 20). All 8 patients with central n. relapse had concurrent systemie the time of recurrent brain diseas, tients; renal fossa, 2; bone, 1; live these 8 patients had a second neur, eedure. Two had presumed coml~ of the recurrent brain tumors an, temie metastases within two mont 2 had ventrieuloperitoneal shunts twelve and fifteen months followi procedure. The onset of cerebral metastasi following nephreetomy showed a better survival (p = 0.16) (Fig. 2, tients with an interval between and brain metastasis > one year t of 30 + 12.3 months, and those < + 3.9 months. Neurologic grade at time ot niotomy as defined by Karnofs cheva111 was found to influence s 0.19) (Fig. 3, Table I). Patients w: neurologic deficit (Karnofsky seer, had a median survival of 29.6 _+ Those patients with a Karnofsky s 70, i.e., readily apparent hemip~ eal signs of raised intracranial pi median survival of 13.1 _+ 5.5 m The location of the brain met~ tentorial versus supratentorial, w; feet survival (p = 0.19) (Fig. 4, T~ the 20 patients had lesions in b were excluded from this analysis
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for the 6 patients w i t h infratentorial leas 28.0 + 14.6 months c o m p a r e d w i t h 3.9 months for the 12 patients with su?rial lesions. median survival for patients with solifin metastases was 33.1 + 18.1 months 5.1 - 6.1 months for patients w i t h conbrain and systemic metastases. The meivival of patients age forty-five to sixtyt more t h a n sixty-five w a s 22.4 + 10.2 and 19.3 _ 8.9 months, respectively. these dichotomized variables w e r e nonmt (Table I).
[]]
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( 12 PTS.
3 CENSORED)
X
INFRATENTORIAL
(
3 CENSORED)
TICK MARK ( I )
6 PTS
INDZCATES LAST FOLLOW-UP
o o
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La >6-
55, O n_ O c12 o_ o
Comment
6-
~ie have been f e w series reviewing the i1 history of renal eell e a r e i n o m a meta}0 the brain. Left untreated, Decker et ~monstrated a m e a n survival of t h r e e IS. Larger series of other p r i m a r y tumors intreated b r a i n metastases have r e p o r t e d survivals of three to six months, ta'14 Exr a d i o t h e r a p y and eortieosteroids have videly used for palliation. In 29. patients m m a r y renal tumors, D e e k e r et al. 12 re[a m e a n survival of eight months followdiotherapy. Although there are no con[ studies to d e m o n s t r a t e the superiority of rm of t r e a t m e n t over another, surgical exis thought to offer p r o l o n g e d survival as is the potential for cure in seleeted pa-
o 6
T
0. 00
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r 24. 00
~a 36. 00
I 72, 00
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60. 00
SURVIVAL IN MONTHS
FIouRE 4. Survival oJ patients with in]ratentorial versus supratentorial brain metastases. Two patients with simultaneous in]ratentorial and supratentorial lesions were excluded ]rom analysis. Additionally, metastatic intraeranial t u m o r s from renal cell origin a p p e a r to have a m o r e f a v o r a b l e response to surgical t h e r a p y t h a n o t h e r p r i m a r y t u m o r s . 16 S t o r t e b e c k e r ~7 rep o r t e d a m e a n survival of 17.2 months following c r a n i o t o m y and extirpation of t u m o r in 9.7 patients w i t h p r i m a r y renal cell eareinomas. H o w e v e r , 5 of the 27 patients died w i t h i n
TABLE I. Surgical treatment o] brain metastases Jrom renal cell carcinoma: median survival time ± standard error and significance levels (Weibull survival model) Variable
No.
Median Survival Time + Standard Error (mos)
p Value
20
20.9 _+ 6.8
..
10 10
30.3 + 12.3 9.4 _+_ 3.9
0.16
10 10
29.6 +_ 12.4 13.1 _+_ 5.5
0.19
6 12
28.0 ± 14.6 12.9 + 3.9
0.19
9 11
33.1 +_ 18.1 15.1 __+ 6.1
0.23
11 9
22.4 _+ 10.2 19.3 ± 9.0
0.82
metastases after nephrectomy logic deficit fl or none ]erate to severe [on of brain lesion* atentorial ratentorial i of metastases in only in plus other sites
~esars)
5 or >65
h a d both infratentorial a n d supratentorial t u m o r s a n d were excluded from this analysLs,
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V O L U M E XXXVI, N U M B E R 2
115
t w e n t y days of surgery. O'Dea et al.8 describe i m p r o v e d survival with sm'gieal therapy in patients with metastatie renal tumors. Eight patients with single m e t a c h r o n o u s brain metastases h a d a m e d i a n survival of 27.5 months (range 0 to 57 months) c o m p a r e d with seven m o n t h s (range 5-204 months) for 6 patients with solitary synchronous intraeranial lesions. Although the present study includes 3 patients with two brain metastases and 12 patients with e o m e o m i t a n t intraeraniat and extraeranial lesions, a m e d i a n survival of 20.9 + 6.8 m o n t h s was obtained. In this study, the survival of a relatvely unseleeted group of patients compares favorably with previously reported series selected for solitary intraeranial lesions (brain is only known site of metastatie disease). This m a y reflect technologic advances in diagnostic imaging. The ease and lack of risk of computerized t o m o g r a p h y and magnetic resonance imaging, as opposed to angiography, not only tends to result in earlier diagnosis b u t also is superior to the latter in identifying multiple lesions and defining their operability. Patients presenting with cerebral metastases > one year after n e p h r e e t o m y appeared to have a survival advantage. This latent period m a y correlate with the biologic aggressiveness of the t u m o r (which, in the ease of renal cell eareinoma is highly variable) and/or m a y refleet individual variation in the i m m u n o l o g i c response to the neoplasm. 16 This hypothesis is supported by other studies w h i c h correlate improved survival of metaehronous over synehronous intraeranial metastases in patients with renal cell carcinoma. 8'~8 The influence of neurologie status at time of eraniotomy on survival has been observed in other series of patients following resection of metastatic brain tumors. 1415 This p h e n o m e n o n most likely reflects the fact that it is easier to preserve normal neurologie function that reverse major deficit. This observation also has been deseribed in patients with p r i m a r y lung cancers metastatic to the brain. 19 T h e distribution of intraeranial metastases from nonrenal p r i m a r y tumors appears to correlate with the relative infratentorial and supratentorial volumes. Thus, approximately 15 percent of metastases are infratentorial and 85 percent are supratentorial, t~ White, Fleming, and L a w ~6 have demonstrated a predilection for renal cell eareinoma to metastasize to infratentorial sites, and the observed rate of infratentorial renal metastases in their series (33 %,
116
6/18) supports their observatio advantage of patients with infr: posed to supratentorial lesions iJ fers from series of nonrenal br~ This finding m a y reflect the sn In contrast to reports in pati static nonrenal p r i m a r y cane brain metastases were not assoe: vival advantage over those witl traeranial disease. This suggesl tients with solitary brain metasl systemic metastases and is con low cure rate following surgiea m a y reflect either low staging a patients or small sample size. In summary, the data suppor gieal reseetion in selected pati cell eareinoma metastatic to ideal candidate w o u l d present n e p h r e e t o m y with a lesion th~ m i n i m a l or no neurologie de these guidelines should be inter 1 tion since signifieant palliation in patients with less favorable eators. The possible contribut: whole brain radiation therapy t patients in this series cannot lc recognized relative radioinsen~ cell carcinoma and the ease of majority of brain metastases [ fact that they are well demareal r o u n d i n g brain p a r e n e h y m a , ra of the necessity of postoperati~ At present, patients in w h o m 1 from renal cell carcinoma arq single intact specimen are not radiotherapy. The Ohi( Di
456 l Colun (DR. References 1. Skinner DG, and DeKernion JB: C and treatment of renal parenehymal tum( Cancer, Philadelphia, WB Saunders Co, 1
133.
2. Bloom HJG: Adjuvant therapy for a kidney: present position and prospects, Br 3. Riehes E: The plaee of radiotherapy parenehymal carcinoma of the kidney, J U 4. Morales A, and Eidinger D: Bacillus ( treatment of adenoeareinoma of the kid
(1976).
5. Golimbu M, et al: Renal cell careinor nostic factors, Urology 27:291 (1986).
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VOI,UME
Surgery for metastatic renal cell carcinoma,
).
Whitmore WF Jr: Solitary metastasis from , J Urol 114:836 (1975). tke H, Utz DC, and Bernatz PE: The treatrcinoma with solitary metastasis, J Urol 120: ld Meier P: Nonparametric estimation from Lons, J Am Stat Assoc 53:457 (1958), ]tatistical models and methods for lifetime n Wiley & Sons, 1982. ~, and Bureheval JH: The clinical evaluation agents in cancer, in Maeleod CM (Ed): Evalrapeutie Agents, New York, Columbia Uni}p 191-205. eroniea L, Herskovie A, and Cummings GD: atients with renal cell carcinoima, prognosis n Oneol 2:169 (1984).
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AUGUST 1990
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VOLUME XXXVI, NUMBER 2
13. Markesberg SR, Brooks Wlt, Gupta G, and Young B: Treatment of patients with cerebral metastasis, Arch Neurol 35: 754 (1978). 14. Zimm S, et al: Intracerebral metastasis in solid tumor patients, Cancer 48:384 (1981). 15. Galicieh J, et al: Surgical treatment of single brain metastasis, factors associated with survival, Cancer 45:381 (1980), 16. White KT, Fleming TR, and Law EK: Single metastasis to the brain, Mayo Clin Proc 56:424 (1981). 17. Stortebecker TP: Metastatic tumors of the brain from a neurosurgical point of view: a follow-up study of 158 eases, J Neurosurg l h 84 (1984). 18. DeKernion JB, l:~aming KP, and Smith RB: The natural history of metastasis renal cell carcinoma, a computer analysis, J Urol 120:22 (1978). 19. Sundarensan N, Galieieh J, and Beattie E: Surgical treatment of brain metastasis from lung cancer, ] Neurosurg 58:666
(1983).
117
ERIC KREUTZER, M.D. HARRY W. HERR, M.D. W I L L I A M R. FAIR, M.D. JOSEPH H. G A L I C I C H , M.D.
From the Urology and Neurosurgery Services, Department of Surgery, and the Division of Biostatisties, Memorial Sloan-Kettering Cancer Center, New York, New York
ABSTRACT--Between January 1976 and December 1986, 22 patients with renal c~ underwent surgical resection of brain metastases at Memorial Sloan-Kettering Cance of the patients had metastases limited to the brain and 12 also had extracranial metasa patients' received external radiotherapy. Five had craniotomy after failing radiation th had adjuvant radiotherapy. Two patients died within thirty days following craniotomt survival of the remaining 20 patients was 20.9 + 6.8 months calculated according survival model. Variables examined in relation to survival included absence or presenc nial metastases at time of craniotomy, time interval between nephrectomy and diagno,~ metastases, neurologic status prior to craniotomy, location of the brain tumor, and None of the variables was significant at the 10 percent level by the Weibull analy,~ three favorable prognostic factors, namely metachronous brain metastasis more than nephrectomy, minimal or no neurologic deficit at time of craniotomy, and inJrate~ show a trend toward improved survival with p < 0.20. The data suggest that surgical single and occasionally multiple brain metastases is warranted in selected patients tc carcinoma.
Of the 15,000 eases of renal cell eareinoma diagnosed annually in the United States, approximately one-third will present with metastases and in another one-third subsequent metastases will develop.1 The optimum treatment of metastatie renal eell e a r e i n o m a remains undefined. Therapeutic options including ehemotherapy, 2 radiotherapy, 3 and immunotherapy, 4 have been uniformly disappointing. Surgical resection of metastatic loci in seleeted patients, such as those with solitary lung lesions, has been associated with prolonged survival. ~-s Less is known, however, of the results of surgical treatment of renal cell eareinoma metastatic to the brain. Over a ten-year period, 22 patients with renal cell carcinoma at the Mew-
112
orial Sloan-Kettering Cancer I treated by surgical extirpation ot metastases. The results of this trc reviewed to assess survival and to tors influencing prognosis. Spec variables were examined in relati( and included the absence or pres( cranial metastases at the time ot length of the time interval betw tomy and the diagnosis of brail neurologie status prior to eraniot, of brain lesion, and patient age. Material and Method From January 1976 to Deeembe atively unselected group of 22 t
UROLOGY
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A U G U S T 1990
/
V O L U M E XN
!metastases from renal cell carcinoma unALL PATIENTS l 20 PTS. 8 C~NSOREO) ~nt craniotomy and extirpation of tumor TICK MARK t l ) INDICATES LAS~ FOLlOW-uP 0 0 ~morial Sloan-Kettering Cancer Center. !ia for craniotomy consisted of a nonrnorimedical status and one or two surgically iible brain metastases. Eighteen patients c;irnale and 4 were female. The mean age 0 Z ifty-six years (range 31-71 years) . Nineteen i !t~ had a presumed single brain metastapatients, 2 intraeranial tumors were ified. The brain tumors were metachroH~ ents; 4 had synchronous lesions. 0:2o ¸ o turation between nephreetomy 0 c:E osis of brain tumor was thirty EL g 0-120 months). patients u n d e r w e n t radical md renal hilar lymphadeneeo tary neoplasm in the remaining o nreseetable due to advanced lo0 (]0 1 2 O0 24. 00 36 O0 4;3 O0 60. O0 72.00 SURVIVAL IN MONTHS ,~histology of the primary tumor carcinoma in 20 patients and FIGURE 1. Overall survival of patients with surgical treatment of brain metastases from renal cell ~'inoma in 1. Metastases to hilar carcinoma. The term "censored" refers to patients ~re identified in 2 patients, In all who were still alive at last follow-up. istology of the brain metastases ¢ith the primary tumor. The one I not undergo nephreetomy had Statistical "methods Loma in the brain. Owing to the small sample size (n = 20 eval~etastases in all patients were uable patients) and the relatively heavy cenIeurologie symptoms and signs soring (8 patients were still alive at the last ehe (12 patients), hemiparesis follow-up), the usual nonparametric Kaplan;eizures (4), visual field defects Meier method 0 was deemed inappropriate for ~iand cognitive defects (2). Diagnosis was establishing prognostic significance of the variirmed in all patients by eomputerized toables. Instead, a fully parametric survival anal~aphy; 10 patients had additional evaluaysis that afforded much more statistical sensitiv~ by cerebral angiography. F o l l o w i n g ity was c a r r i e d out. Specifically, it was gnosis of intraeranial metastases all patients empirically determined that the survival times ~ evaluated for extent of extraeranial disease of the patients closely followed a Weibull distri~0utine laboratory tests, ehext x-ray film, button, a well-known distribution widely used lli~scan, and either abdominal sonography or J in life-testing problems.20 For each variable, a i ~puterized tomography. 'Fen patients had Weibull survival curve was fitted to each of the i iase limited to the brain, and 12 patients two categories of the variable. The method of ~tastatie sites which included maximum likelihood was used to estimate the bone (4), liver (1), adrenal unknown parameters. Since the Weibull distri9dominal wall (1), and ovary bution is skewed to the left, median survival times were calculated instead of mean survival ived corticosteroid therapy at time to characterize average patient survival. ~rior to elective eraniotomy. The usual likelihood ratio test was used to de:d failed whole b r a i n ratermine prognostic significance of the variables. undergoing surgery. Fifteen i . . . . adjuvant whole brain raResults ~fherapy (2,000-4,000 rad in fractionated ~ses> following eraniotom~: Steroids w e r e ta%vo patients died within thirty days of surgied and discontinued postoperatively in all eal resection of brain metastases, resulting in an ~t 9. patients, who required chronic therapy operative mortality of 9 percent (2/22). Of i ~eoncurrent spinal cord compression ripest, 1 patient with synchronous renal and . . . . .
AUGUST 1990
/
~
. . . . . . .
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VOLUME XXXVi, NUMBEI/ 2 113
X
< I YEAR
( 10 P78.
4 CENSORED)
> OR = I ' f E A R
{
4 CENSORED}
TICK MARK { I )
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SURVIVAL IN MONTHS
F[OURE 2. Survival of patients w i t h onset of cerebral metastases < one year after nephrectomy versus survival of patients w i t h onset of cerebral metastases >_ one year after nephrectomy. D
MILD OR NO DEFICIT
( 10 PTS
4 CENSORED/
X
MODERATE TO SEVERE DEFICIT
( l0 PTS
~ CENSORED]
TICK MARK ( I )
INDICATES LAST FOLLOW-UP
3
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SURVIVAL IN ~ONTHS
FIGURE 3. Surviva ! of patient w i t h mild or no neurologic deficit versus survival of patients w i t h moderate or severe neurologic deficit at presentation of cerebral metastases. brain tumors had a fatal spontaneous intra-abdominal hemorrhage from a nonreseetable primary tumor after eraniotomy; the other, with a metachronous brain tumor, continued to deteriorate neurologically following resection of the
114
brain tumor. Both were excluded lowing survival analysis. Of the 20 evaluable patients, th viral was 20.9 _+_ 6.8 months months) (Fig. 1). Twelve patient: ease, 6 are alive but have had sub, tion of systemic metastatic loci, 1 ease three months after eranio patient died in an auto accident dence of disease four months f{ niotomy. In the 6 patients alive moral of subsequent metastatic fo removal included lung (4), adr( bone (1). Three of the 6 patients h dered clinically free of disease (m~ by the resection of additional met Eight patients had cerebral n~ relapse. Tumor recurred at the op 3 patients. In 5 patients distant ce tases were detected at varying i craniotomy. Thus, local control o brain tumor(s) was achieved in 8[ 20). All 8 patients with central n. relapse had concurrent systemie the time of recurrent brain diseas, tients; renal fossa, 2; bone, 1; live these 8 patients had a second neur, eedure. Two had presumed coml~ of the recurrent brain tumors an, temie metastases within two mont 2 had ventrieuloperitoneal shunts twelve and fifteen months followi procedure. The onset of cerebral metastasi following nephreetomy showed a better survival (p = 0.16) (Fig. 2, tients with an interval between and brain metastasis > one year t of 30 + 12.3 months, and those < + 3.9 months. Neurologic grade at time ot niotomy as defined by Karnofs cheva111 was found to influence s 0.19) (Fig. 3, Table I). Patients w: neurologic deficit (Karnofsky seer, had a median survival of 29.6 _+ Those patients with a Karnofsky s 70, i.e., readily apparent hemip~ eal signs of raised intracranial pi median survival of 13.1 _+ 5.5 m The location of the brain met~ tentorial versus supratentorial, w; feet survival (p = 0.19) (Fig. 4, T~ the 20 patients had lesions in b were excluded from this analysis
UROLOGY
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A U G U S T 1990
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V O L U M E X]
for the 6 patients w i t h infratentorial leas 28.0 + 14.6 months c o m p a r e d w i t h 3.9 months for the 12 patients with su?rial lesions. median survival for patients with solifin metastases was 33.1 + 18.1 months 5.1 - 6.1 months for patients w i t h conbrain and systemic metastases. The meivival of patients age forty-five to sixtyt more t h a n sixty-five w a s 22.4 + 10.2 and 19.3 _ 8.9 months, respectively. these dichotomized variables w e r e nonmt (Table I).
[]]
SUPRATENTORIAL
( 12 PTS.
3 CENSORED)
X
INFRATENTORIAL
(
3 CENSORED)
TICK MARK ( I )
6 PTS
INDZCATES LAST FOLLOW-UP
o o
6
La >6-
55, O n_ O c12 o_ o
Comment
6-
~ie have been f e w series reviewing the i1 history of renal eell e a r e i n o m a meta}0 the brain. Left untreated, Decker et ~monstrated a m e a n survival of t h r e e IS. Larger series of other p r i m a r y tumors intreated b r a i n metastases have r e p o r t e d survivals of three to six months, ta'14 Exr a d i o t h e r a p y and eortieosteroids have videly used for palliation. In 29. patients m m a r y renal tumors, D e e k e r et al. 12 re[a m e a n survival of eight months followdiotherapy. Although there are no con[ studies to d e m o n s t r a t e the superiority of rm of t r e a t m e n t over another, surgical exis thought to offer p r o l o n g e d survival as is the potential for cure in seleeted pa-
o 6
T
0. 00
I~. 0O
r 24. 00
~a 36. 00
I 72, 00
r
4P8. 00
60. 00
SURVIVAL IN MONTHS
FIouRE 4. Survival oJ patients with in]ratentorial versus supratentorial brain metastases. Two patients with simultaneous in]ratentorial and supratentorial lesions were excluded ]rom analysis. Additionally, metastatic intraeranial t u m o r s from renal cell origin a p p e a r to have a m o r e f a v o r a b l e response to surgical t h e r a p y t h a n o t h e r p r i m a r y t u m o r s . 16 S t o r t e b e c k e r ~7 rep o r t e d a m e a n survival of 17.2 months following c r a n i o t o m y and extirpation of t u m o r in 9.7 patients w i t h p r i m a r y renal cell eareinomas. H o w e v e r , 5 of the 27 patients died w i t h i n
TABLE I. Surgical treatment o] brain metastases Jrom renal cell carcinoma: median survival time ± standard error and significance levels (Weibull survival model) Variable
No.
Median Survival Time + Standard Error (mos)
p Value
20
20.9 _+ 6.8
..
10 10
30.3 + 12.3 9.4 _+_ 3.9
0.16
10 10
29.6 +_ 12.4 13.1 _+_ 5.5
0.19
6 12
28.0 ± 14.6 12.9 + 3.9
0.19
9 11
33.1 +_ 18.1 15.1 __+ 6.1
0.23
11 9
22.4 _+ 10.2 19.3 ± 9.0
0.82
metastases after nephrectomy logic deficit fl or none ]erate to severe [on of brain lesion* atentorial ratentorial i of metastases in only in plus other sites
~esars)
5 or >65
h a d both infratentorial a n d supratentorial t u m o r s a n d were excluded from this analysLs,
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A U G U S T 1990
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V O L U M E XXXVI, N U M B E R 2
115
t w e n t y days of surgery. O'Dea et al.8 describe i m p r o v e d survival with sm'gieal therapy in patients with metastatie renal tumors. Eight patients with single m e t a c h r o n o u s brain metastases h a d a m e d i a n survival of 27.5 months (range 0 to 57 months) c o m p a r e d with seven m o n t h s (range 5-204 months) for 6 patients with solitary synchronous intraeranial lesions. Although the present study includes 3 patients with two brain metastases and 12 patients with e o m e o m i t a n t intraeraniat and extraeranial lesions, a m e d i a n survival of 20.9 + 6.8 m o n t h s was obtained. In this study, the survival of a relatvely unseleeted group of patients compares favorably with previously reported series selected for solitary intraeranial lesions (brain is only known site of metastatie disease). This m a y reflect technologic advances in diagnostic imaging. The ease and lack of risk of computerized t o m o g r a p h y and magnetic resonance imaging, as opposed to angiography, not only tends to result in earlier diagnosis b u t also is superior to the latter in identifying multiple lesions and defining their operability. Patients presenting with cerebral metastases > one year after n e p h r e e t o m y appeared to have a survival advantage. This latent period m a y correlate with the biologic aggressiveness of the t u m o r (which, in the ease of renal cell eareinoma is highly variable) and/or m a y refleet individual variation in the i m m u n o l o g i c response to the neoplasm. 16 This hypothesis is supported by other studies w h i c h correlate improved survival of metaehronous over synehronous intraeranial metastases in patients with renal cell carcinoma. 8'~8 The influence of neurologie status at time of eraniotomy on survival has been observed in other series of patients following resection of metastatic brain tumors. 1415 This p h e n o m e n o n most likely reflects the fact that it is easier to preserve normal neurologie function that reverse major deficit. This observation also has been deseribed in patients with p r i m a r y lung cancers metastatic to the brain. 19 T h e distribution of intraeranial metastases from nonrenal p r i m a r y tumors appears to correlate with the relative infratentorial and supratentorial volumes. Thus, approximately 15 percent of metastases are infratentorial and 85 percent are supratentorial, t~ White, Fleming, and L a w ~6 have demonstrated a predilection for renal cell eareinoma to metastasize to infratentorial sites, and the observed rate of infratentorial renal metastases in their series (33 %,
116
6/18) supports their observatio advantage of patients with infr: posed to supratentorial lesions iJ fers from series of nonrenal br~ This finding m a y reflect the sn In contrast to reports in pati static nonrenal p r i m a r y cane brain metastases were not assoe: vival advantage over those witl traeranial disease. This suggesl tients with solitary brain metasl systemic metastases and is con low cure rate following surgiea m a y reflect either low staging a patients or small sample size. In summary, the data suppor gieal reseetion in selected pati cell eareinoma metastatic to ideal candidate w o u l d present n e p h r e e t o m y with a lesion th~ m i n i m a l or no neurologie de these guidelines should be inter 1 tion since signifieant palliation in patients with less favorable eators. The possible contribut: whole brain radiation therapy t patients in this series cannot lc recognized relative radioinsen~ cell carcinoma and the ease of majority of brain metastases [ fact that they are well demareal r o u n d i n g brain p a r e n e h y m a , ra of the necessity of postoperati~ At present, patients in w h o m 1 from renal cell carcinoma arq single intact specimen are not radiotherapy. The Ohi( Di
456 l Colun (DR. References 1. Skinner DG, and DeKernion JB: C and treatment of renal parenehymal tum( Cancer, Philadelphia, WB Saunders Co, 1
133.
2. Bloom HJG: Adjuvant therapy for a kidney: present position and prospects, Br 3. Riehes E: The plaee of radiotherapy parenehymal carcinoma of the kidney, J U 4. Morales A, and Eidinger D: Bacillus ( treatment of adenoeareinoma of the kid
(1976).
5. Golimbu M, et al: Renal cell careinor nostic factors, Urology 27:291 (1986).
UROLOGY
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AUGUST 1990
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VOI,UME
Surgery for metastatic renal cell carcinoma,
).
Whitmore WF Jr: Solitary metastasis from , J Urol 114:836 (1975). tke H, Utz DC, and Bernatz PE: The treatrcinoma with solitary metastasis, J Urol 120: ld Meier P: Nonparametric estimation from Lons, J Am Stat Assoc 53:457 (1958), ]tatistical models and methods for lifetime n Wiley & Sons, 1982. ~, and Bureheval JH: The clinical evaluation agents in cancer, in Maeleod CM (Ed): Evalrapeutie Agents, New York, Columbia Uni}p 191-205. eroniea L, Herskovie A, and Cummings GD: atients with renal cell carcinoima, prognosis n Oneol 2:169 (1984).
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AUGUST 1990
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VOLUME XXXVI, NUMBER 2
13. Markesberg SR, Brooks Wlt, Gupta G, and Young B: Treatment of patients with cerebral metastasis, Arch Neurol 35: 754 (1978). 14. Zimm S, et al: Intracerebral metastasis in solid tumor patients, Cancer 48:384 (1981). 15. Galicieh J, et al: Surgical treatment of single brain metastasis, factors associated with survival, Cancer 45:381 (1980), 16. White KT, Fleming TR, and Law EK: Single metastasis to the brain, Mayo Clin Proc 56:424 (1981). 17. Stortebecker TP: Metastatic tumors of the brain from a neurosurgical point of view: a follow-up study of 158 eases, J Neurosurg l h 84 (1984). 18. DeKernion JB, l:~aming KP, and Smith RB: The natural history of metastasis renal cell carcinoma, a computer analysis, J Urol 120:22 (1978). 19. Sundarensan N, Galieieh J, and Beattie E: Surgical treatment of brain metastasis from lung cancer, ] Neurosurg 58:666
(1983).
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