Carcinoma of renal parenchyma, renal pelvis and ureter—radiological diagnosis and treatment planning

Cancer TreatmentRe:4ews (1980) 7, 29-48

Carcinoma of renal parenchyma, renal pelvis and ureter--radlological diagnosis and treatment planning J. A r n r n o n , J. H . K a r s t e n s

Radiology Department~ ~Ied. Fakultiit R11"TH Aachen, Goethestr. 27-29, D-51 Aachen, F.R.G.

G. D u r b e n

lh'ology Department, AIed. Fakult~'t R I I:TH ..lachen, GocthcJtr. 27-29, D-51 Aachen, F.R~.G.

and K. H. Barth

Department of Radiology and Radiological Science. Tt, e Johns Hopkins UniversiO', Baltimore AfD 21205, U.S.A.

I. I n t r o d u c t i o n T u m o r s of~the r e n a l p a r e n c h y m a , t h e renal pelvis a n d the u r e t e r differ c o n s i d e r a b l y a c c o r d i n g to t h e s t r u c t u r e of t h e i r m a t r i x tissue. O v e r 9 0 % o f a d u l t renal t u m o r s are renal cell c a r c i n o m a s (50). R e n a l s a r c o m a s a r e rare entities, they" i n c l u d e liposarcomas, l e i o m y o s a r c o m a s , r h a b d o m y o s a r c o m a s , a n g i o s a r c o m a s , f i b r o s a r c o m a s a n d fibrox a n t h o s a r c o m a s (8). ~Vilms t u m o r s are m o s t f r e q u e n t i n c h i l d h o o d , b u t t h e y are n o t d e a l t with in this review. Finally, m e t a s t a t i c tumocs are c o n s i d e r e d a m o n g the t u m o r s o f the r e n a l p a r e n c h y r n a a n d the renal pelvis. T h e r e exist m a n y classifications o f r e n a l t u m o r s (26, 55). V~'e prefer the simplified classification o f renal t u m o r s o f G l e n n (34), w h i c h is b o t h c o m p l e t e a n d u n c o m p l i c a t e d , e m b r a c i n g all 1;l~e lesions that predispose to r e n a l mass or n e w g r o w t h ( T a b l e 1). A m o n g t u m o r s o f t h e renal pelvis a n d t h e u r e t e r transitional cell c a r c i n o m a s are most c o m m o n . T h e y m a y involve t h e e n t i r e u r o t h e l i u m a priori or by s u b s e q u e n t s p r e a d (91, I02). Because o f the i n t i m a t e a n a t o m i c r e l a t i o n s h i p b e t w e e n r e n a l "pelvis a n d ureter, t u m o r s in b o t h areas are discussed together. 030.5-7372/80/010029q-32 $02.00/0 (~) I980 Academic Pr¢:~ Inc. (London) Ltd. 29

j. AhIXION ETAL.

30

T a b l e 1. S i m p l i f i e d c l a s s i f i c a t i o n o f r e n M t U m O r s f r o m G l e n n (34)]

[adapted

1. Benign tumom Renal capsule RcnM parcnvhyma Vascular tumors CFst~c lmions, dyspl.-~ias, hydronephrosis Heteroplastic, mesenchymal tumors 2.

.

4.

Tumors of renal pelvis Benign papilloma Transitional and squamous cclI carcinomas, adcnocarcinoma.¢ Pararenal tumors Benign Xlalignant Embryonic tumors Nephroblastoma (Wilms' tumor) Embryonic, mesothellomatous tumors Sarcomas

5. Nephrocarclnoma Renal cell carcinoma, adenocarcinoma, "'hype~mphroma" Papillary- cystadenocarclnoma 6.

Other mallgnanclc-'~ Primary: mc..'~enchymal,hemanglopericytoma, mycloma Secondary: metastatic lesions

T u m o r s o f t h e renal p a r e n c h y m a , t h e renal pclvis a n d the u r e t e r arc n o t v e r y sensitive to r a d i a t i o n or c h e m o t h e r a p y . S u r g e r y is t h e r e f o r e t h e p r i m a r y f o r m o1" t r e a t m e n t (I 3, 79, 80). C o m p l e t e resection o f a d v a n c e d t u m o r s m a y h o w e v e r be impossible a n d long t e r m t r e a t m e n t needs to i n c l u d e metastases. T h e r c is thereforc a n e e d for n o n - o p c r a t i v e t r e a t m e n t . Since n e w e r d i a g n o s t i c a n d t h e r a p e u t i c m e a n s b c c o m c available, a revision o f t r e a t m e n t i n d i c a t i o n s for r e n a l a n d u r i n a r y tract n e o p l a s m s has b e c o m e ncccssary. C o m p r e h e n s i v e d i a g n o s t i c c v a h t a t i o n o f the t u m o r is a p r e r e q u i s i t e for p l a n n i n g o f successful t h e r a p y a n d for critical e v a l u a t i o n o f t h e results o f n e w t r e a t m e n t d e v e l o p Irlcrlts. II. C l a s s i f i c a t i o n

1. Renal cell carcinoma T u m o r classification a c c o r d i n g to stages h a s n o t b e e n well a c c e p t e d (28). T h e m o s t f r e q u e n t l y used classification s y s t e m a t p r e s e n t is t h e 1978 TN1VI--System o f t h e U I C C . T h e r e is no essential difference h o w e v e r f r o m file T N M - S y s t e m p u b l i s h e d in 1974. T h i s system considers n o t o n l y t h e categories T , N a n d M b u t also t h e h i s t o p a t h o l o g i c a l gn'ading G a n d v e n o u s i n v o l v e m e n t V. T h e following are t h e m i n i m u m r e q u i r e m e n t s for assessment o f t h e T , N a n d IV[ categories. I f these c a n n o t be m e t t h e s y m b o l T X , N X or M X wilI be used.

T categories: Clinical e x a m i n a t i o n , u r o g r a p h y a n d a r t e r i o g r a p h y p r i o r to definitive t r e a t m e n t . V e n o c a v o g r a p h y is r e c o m m e n d e d . .N'categories: Clinical e x a m i n a t i o n a n d r a d i o g r a p h y i n c l u d i n g l y m p h o g r a p h y a n d urography.

RENAL rUMORS

31

31 categories: Clinical examination a n d radiography. In the more ad,vanced p r i m a r y tumors or w h e n clinical suspicion warrants it, radiographic or i.e,otope studies are r e c o m m e n d e d . T h e following is a sumrnal~" of TNM-classification : T1 T2 T3 T4 N1 N2 N3 N4 V1 V2

Small t u m o r / n o enlargement of kidney. Large tumor]cortex not broken. Perinephrlc or hilar extcnsion. Extension, to neighbourlng organs. Single homolateral regional. Contra- or bilateral/muhiple regional. Fixed regional. Juxta-regional. Renal vein involved. V e n a cava involved.

2. Renal pelvis and ureter T h e r e is no TNN,I-classification for these tumors. J e w e t t and Strong (47) r e c o m m e n d a classification in stages similar to that of bladder carcinomas. T h e following is a proposed classification for transitional cell carcinomas of the renal pelvis and ureter (25) : Stage I Stage II Stage I I I

Stage I V

Non-invaslve tumor. T u m o r with superficial invasion. T u m o r invasion into the muscuIarls of the renal pelvis or into tile renal p a r e n c h y m a for tumors of the renal pelvis or into tile muscular wall for tumors of d~e ureter. T u m o r invasion into neighboring organs or lymph nodes, presence of hematogenous mqtastases.

A proposed classification by t u m o r size for carcinomas o{" the renal pelvis is shown in Figure 1. This classification can also be used for tumors of tl~e ureter. Tumors of the renal pelvis a n d ureters have varying degrees of cell differentiation as do transitional cell carcinomas of the bladder an d histopathologic grading is therefore identical: "GO" GI G2 G3 GX

Papilloma, i.e. no evidence of anaplasia. High degre.e of differentiation. M e d i u m degree of differentiation. Low degree of differentiation or undifferentiated. Grade c a n n o t be assessed.

IH. Oncologic c r i t e r i a 1. Renal cell carcinoma T h e classical triad of hematuria, flank pain an d palpable tu mo r exists in only i6~/o of all patients according to Tveter (98). None of these signs is present in about one third of all patients according to Melicow a n d Uson (66). T h e observation .by Ekelund a n d Jonsson (27) that h y p e r n e p h r o m a s are discovered incidentally d u r i n g urographie examination is of increasing importance. A m o n g their 369 patients a renal cell carcin oma was found incidentally in 13°/o.

32

J. AMlkION E T

AL.

O f particular interest are paraneoplastic symptoms (65). Particularly frequent are tkver, hematologic changes and hypertension. Elevated levels of fl-chorio-gonadotropin and renin as well as erythropoe*~n were found in the serum of patients with renal cell carcinomas without correlation to tmnor extent (95). Marshall and Walsh (65) divide patients with extrarenal manifestations into two gwoups, those with systemic symptoms like fever, a n e m i a , gastroin'testinal symptoms, and those with disease entities like amyloidosis, neuromyopathy and thrombosis. Infi'equent are poiycythemia,~ hypercaleenfia, galactorrhea and Cushing's syndrome. O f significance is the decreased activity of y-GT in t h e urine of patients with renal cell carcinoma whicl~ H a u t m a n n , Kisters and Lutzeyer (42) found in all of 16 patients with renal cell carcinoma. ~¢'orth mentioning is the paraneoplastic hepatic abnormalities manifested by an abnormal profllrombin time, elevation of alkaline phosphatase, prolonged br0nasulphthalein retention and changes i n the protein electrophoresis. Hepatomegaly Can be present. These cl!anges are reversible following nephrectomy (32).

taging of Tumors | { ~

~ I .......I{ "

-ill A F-~Z'

l. " ] ":,

Prosposed classificationfor carcinomas of therenal pelvis, modified fi'om that for transitional cell carcinomas of the bladder byJewett and Strong (47) [adapted from Cummings et at. (25)].

Figure 1.

Tumor gwading is of prognostic Significance. Table 2 relates degreesof malignancy to the five-},ear survival rates. Invasion into neighboring structures is typical for the primary tumor With the renal pelvis'and the renal-veins beingaffected first..Tumor thrombi can reach the inferior vena cava ~md extend up the.right atrium. L y m p h nodes are first affected i n t h e region of the renal hilum; then in the contrhlateral para-a0rtic region and l a t e r in tl3e mediastinum. O f particular :therapet~tic interest'is the fact that distant.hen!at0genous metastases are more freqtient than lymph node metastases. The frequency of 0ygan metastases is listed in Table,'3' The following routes o f metastatic spread are known (8) : (a) Lymphogenous s p r e a d to the l y m p h n o d e s o f the renal hilum and less frequently to oilier lumbar a n d me¢li~,stifially.mph nodes. ~This spread'depends on the" size 0f {he primary tumor;and;its degree of ma!ignancy (TabJe.2), (b) Lymphogenotis s p r e a d v i a the th0racic duct. into the venous system resulting in lymphohematogenous seeding,

RENAL T U M O R S

33

T a b l e 2. S i g n ~ c a n c e o f t u m o r g r a d i n g f o r r e n a l cell c a r c i n o m a s : p e r c e n t involvement of renal capsul~ renal veins and regional lymph n o d e s ( u p p e r halt') c o m p a r e d to 5 - y e a r s u r v i v a l r a t e s ( l o w e r h a l l ~) ( a d a p t e d f r o m H e r m a n e k , S i g e l a n d C h l e p a s (48) a n d C h l e p a s , H e r m a n e k a n d Sigel (20)

Involvement

Grade I

Grade II

Grade III

CategoD" pT3, pTac

17

30

54

Venous invasion macroscopic'ally macroscopically or microscopically

I1

41

70

33

73

93

0

8

36

Regional lymph node invasion

Five }'ear survival

Tumor within the renal capsule

Grade I

Grade II

100

68

Tumor extensioa into Iymph nodes or veia

61

T a b l e 3. ]Percent incidence o f l y m p h n o d e a n d carcinoma from autopsy material

Grade II1

35

hernatogenous

metastases

o f renal

cell

Contra-

No. of patients

Lungs

Lymph nodes

Liver

lateral Bone Adremal kidney

523

55

34

33

32

19

11

6

70 181 191 100

64 5ff 67 40

23 37 41 20

23 43 39 16

19 28 39 ~

13 18 17 --

10 I7

14 I0 7

9

11

Braia

Author Bennington and Kradjian (9), Creevy (24), Kozoll et al. (52), Graham (36), Luck6 et al. (63) Walter (103) Ball (7) Riches et al. (78) Hajdu and Thomas (44))

(c) H c m a t o g e n o u s s p r e a d is tile m o s t f i ' e q u e n t f o r m o f s p r e a d , p a r t i c u l a r l y ariel" t u m o r invasion into the inferior v e n a cava. O f particular irrtportance are the p a r a v e r t e b r a l veins ( B a t s o n ' s P l e x u s ) w h i c h a l l o w m e t a s t a s e s to s e e d q u i t e o f t e n d i r e c t l y i n t o n e i g h b o r i n g v e r t e b r a l b o d i e s . T h i s is i l l u s t r a t e d in F i g u r e 9. R e t r o g r a d e s e e d i n g v i a t h e g o n a d a l v e i n s is also possible, a n d m a y r e s u l t in "a v a r i c o c e l e ill t h e testis. T h e h i g h e r f r e q u e n c y o f h e m a t o g e n o u s o v e r l y a n p h o g e n o u s s p r e a d o f m e t a s t a s e s m e a n s fllat w h e n e v e r t h e l a t t e r a r e f o u n d t h e h e m a t o g e n o u s s p r e a d h a v e to b e l o o k e d for. A u n i q u e b e h a v i o r o f r e n a l cell c a r c i n o m a s is s p o n t a n e o u s r e g r e s s i o n o f t h e i r m e t a s t a s e s , w h i c h h a s b e e n r e p o r t e d s e v e r a l times. S i l b e r , C h a n g a n d G o u l d (86)

J. AMMON E T AL.

3-}

collected 41 su~l cases from the literature. This phenomenon, however, needs to be regarded with critical reservation because o£ the lack ofhistoIoglc proof in most o£ the reported cases including one o£ our ow~l experience (PIate 1). 2. Renal pelvis and ureter Most authors regard transitional cell carcinomas as a disease of the entire urothelium (91, 102). T h e etiology of primary transitional ceil carcinoma of the pelvis and ureter is closely related to that of bladder tumors.

® N N z2".d.4 ;,

:y//.~' //Z~

;.~/.4///~

V/. ~//.,-;5.

3

4

8

8

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Cl-~

C~.~

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I_.2

6

T~,-.~

I 88 _ Ts-~

I

8

23

,!9

T~-t~

Ztz -La

L~.5

Sacrum ( centrat )

Figure 2. Incidence of metastatic renal carcinoma in different vertebral bodies. It is obvious that the upper and lower lumber spine are most frequently affected.This distribution correlateswith the extent of BaL~on's venus plexus which allows direct tumor seedinginto adjacent vertebral bodies [adapted from Arkl~-~s(5)].

Coincidental uroepithelial tumors of the ureter a n d pelvis are f o u n d in patients in w h o m industrial'exposure to carcinogens is clearly a fact6r in their bladder cancer (64, 85). According to Statistics by Silverberg (87) 96% o£ all urotheliat tumors are located in the bladder, 2 % in flae rena[pelvis, 1.5 % ! n t h e ureter and 0.5% in the urethra. T h e statistics o£ Silverberg (87) are readily u n d e r s t o o d because o£ tile relative rapid transit of chemical carcinogens through the upper urinary tract and file urethra, c o m p a r e d to the stasis time of urine in the bladder. There are two groups of patients with a specifically higher incidence of tumors of the renal pelvis a n d ureter: (a) p a t i e n t s afflicted w i t h Balkan" nepIaropathy and (b) patients suffering from analgesic nephropathy (phenacetin-containing analgesics) (76). Both diseases are forms o£ interstitial nephritis associated with destx'uctive changes in the renal papillae. T h e tumors are relatively slow-growing aild have multiple loci i n

RENAL TUMORS

35

the urinary tract. Noteworthy is the bilaterality and multiplicity of the tumors. Transitional cell carcinomas are the most frequent (80-90%) ; less frequent are epidermoid carcinomas, undifferentiated carcinomas and adenoearcinomas (10-20%). Sarcomas arc extremely rare. The ureter a n d renal pelvis can also be involved by metastases (8). According to statistics produced by Abeshouse (1) 45 patients who died from carcinoma of the ureter h a d metastases with a frequency of 31% in regional lymph nodes, 27% in bone, 20% in the lung, 11% in inguinal lymph nodes, 2% in the brain and 31°Io diffuse. Due to the thin wall of the ureter even small tumors may cosily infiltrate into neighboring lymph nodes as well as into adjacent vertebral bodies (Plate 2). This has significance for radiation therapy planning. I-Iematuria is present in 75% of patients and usually it is painless. The passage of vermiform or worm-shaped blood clots accompanied by ureteral colic m a y be a severe symptom. A significant proportion of these patients have associated bladder tumors and may also present widl symptoms of fi'eqvency and dysuria in addition to the symptoms of hematurla.

IV. ]Radiologic diagnosis I. Renal cell carcbwma

T h e preoperative diagnostic approach is well cstablished and illustrated in Figure 3. T h e first investigation is usually an excretory urogram with tomograms. I f a space occupying lesion is discovered or suspected, sonography allows dctinition of the solid or cystic nature of the lesion. I f sonography demonstrates an echo-free cystic lesion, cyst puncture and cytologic examination of the aspirate is performed. In e ~ e of a solid lesion angiography may follow immediately. When available, computer tomography should be performed in addition to or in place of sonography as an additional means of defining renal pathology and especially to find additional lesions, define infiltration into adjacent structures and assess lymph node involvement (Plate 3). T u m o r invasion Urogfophy

1

ro.,o

{ Ro.ot ,.oss ]

l _

_

Cyst p u n c t u r e• " - ' - - ' - - t

i

T,p, c o,

--

!I T= mlIo,

]

l....... :'"l - t

I

Arteriog¢ophy

I

Surqery

Surgery

Figure 3. Decision tree for w o r k - n p o f r e n a l mass lesions.

'J

36

J. AM,",ION ET'AL.

of tile inferior vena cava m a y be well seen on contrast e n h a n c e d CT-scans by e n h a n c e m e n t of the vascularity oft.he t u m o r thrombus. C o m p u t e r t o m o g r a p h y has not yet been i n c l u d e d as a test for classification u n d e r thc n e w TNR'i-System. T h e reason is that t r e a t m e n t centers vcithout C T would no longer be able to use this system (82). A n g l o g r a p h y is still the most p e r t i n e n t diagnostic investigation in renal ceil c a r c i n o m a a u d should always i n c l u d e selective a n g i o g r a p h y of both kidneys (11). T h e first task o f a n g i o g r a p h y is usually to confirm the presence of a renal cell c a r c i n o m a . "l'lais can be d o n e with confidence in h y p e r v a s c u l a r tumors. These h y p e r v a s c u l a r tumors comprise b e t w e e n 75 a n d 90/o o~ o f all renal cell carcinomas (22, 29). I n the case of h y p o v a s c u l a r tumors, e p i n e p h r i n e e n h a n c e d angiog r a p h y m a y be helpful "delineating non-constricted t u m o r vessels a n d the n a t u r e of the vascular supply m a y give an indication as to w h e t h e r one is d e a l i n g with a p r i m a r y t u m o r of the renal p a r e n c h y m a or a s e c o n d a r y invasion from a n a d r e n a l t u m o r or even a t u m o r of the renal pelvis (22). Secondly since a n g i o g r a p h y r e m a i n s the most sensitive investigation for venous t u m o r invasion, high dose arteriog'raphy (20-30 rnl contrast) injected selectively with good opacification o f the venous phase as well as inferior v e n a c a v o g r a p h y is essential for c o m p l e t e diagnostic evaluation. Sincc all solid renal tumors u l t i m a t e l y r e q u i r e surgery for definitive tissue diagnosis a n d treatment, the role of a n g i o g r a p h y can be surnnlarlzcd: to define the vascular characteristics of a renal t u m o r w h i c h allows either a confident or m e r e l y suggestive preoperative diagnosis, to delineate the vascular supply route, to d e m o n s t r a t e absence or presence of t u m o r in the c o n t r a l a t e r a l k i d n e y as well as presence or absence of venous invasion. This allows the most a c c u r a t e p l a n n i n g of surgery a n d / o r r a d i a t i o n therapy. T h e rules for classification (100) require tbr the assessment of N- a n d ~{-categories a d d i t i o n a l technics: chest X - r a y a n d u r o g r a p h y . I n the m o r e a d v a n c e d p r i m a r y tumors or w h e n clinical suspicion warrants, a d d i t i o n a l r a d i o g r a p h i c or isotope studies are recommended. C T plays a d o m i n a n t role in follow-up e x a m i n a t i o n s as a non-invasive technique. I t is most suitable for the discovery 9 f local recurrence, r e t r o p e r i t o n e a l l y m p h n o d e i n v o l v e m e n t or liver a n d l u n g metastases. It also can be used to assess effects of t h e r a p y (Plate 4). U l t r a s o u n d serves as a screening test in t u m o r follow-up, but one has to be a w a r e of occasional technical difficulties in e.xamining the a r e a of the left k i d n e y (10). XArhen e x a m i n i n g the t h o r a x for metastases either by conventional tornogTaphy or C T one needs to be a w a r e of the possibility o f l y m p h o g e n o u s metastases s p r e a d i n g t h r o u g h the d i a p h r a g m along the pleural surface (5, 48). This is illustrated in Plate 5. A g a i n C T is superior to conventional t o m o g r a p h y in revealing p l e u r a l metastases (71). 2. Renal pelvis and ureter

Diagnostic evaluation also has to consider initial w o r k u p as well as followup studies. I n c l u d e d in the initial vcorkup are a n t e g r a d e a n d r e t r o g r a d e u r o g r a p h y . C 6 r n m o n l y a r a d i o l u c e n t defect in the r e n a l pelvis has to be differentiated further. Tile principle alternatives are an uric acid stone, m a t r i x calculus a n d blood clot; p a r e n c h y m a l tumors o r parapelvic cysts m a y also cause an extrinsic defect. F u r t h e r m o r e vascular impressions, ectopic papillae, pyelitis cystica, leucoplakia, c h o l e s t e a t o m a a n d i n f l a m m a t o r y g r a n u loina a r e o t h e r differential diagnoses (Plate 6) (56). T h e r e t r o g r a d e investigation permits the collection of washings for histology a n d cytology a n d if indicated, r e t r o g r a d e brush Mopsy (31, 101). I f the cytologic findings f r o m the lesions are positive a n d suggest a n anaplastic h i g h g r a d e t u m o r , b r u s h biopsy

RENAL TUMORS

37

is c o n t r a i n d i c a t e d . I f the cytologic findings are negative or show only well-differemiated cells, brush biopsy -;s i n d i c a t e d to provide the information necessary to decide b e t w e e n segmental and r a d i c a l surgery. R e n a l C T a n d s o n o g r a p h y allow evaluation of a non-opaeifying kidney a n d in a d d i t i o n can assess size a n d extent of the p r i m a r y tumors as well as regional l y m p h n o d e metastases. A n g i o g r a p h y has been apptlcd, particularly to assess intrarenal s p r e a d of neoplasms. Since the tumors arc hypovascular, in contrast to most renal cell carcinomas, anglog r a p h i c criteria rely on vascular invasion, e n e a s e m e n t a n d a m p u t a t i o n . Confidence in a n g i o g r a p h i c diagnosis is divided, r a n g i n g between "-13°~,oa n d a m e r e 602,0 a c c u r a c y (21). L y m p h o g r a p h y should be reserved for special indications a n d therc arc ~o guidelines in this respect because of the small n u m b e r of cases w h i c h would require .~uch a study. T h e t u m o r s are llsually t r e a t e d operatively a n d subsequent follow-up studies inch~de X - r a y e x a m l n z t i o n of the thorax, bone a n d liw:r scans, excretory u r o g r a p h y a n d u r i n e cytolog3, a n d cystoscopy. T h e diagnostic studies n e e d to be orientated on clinical s y m p t o m a t o h ) g y as illustrated in Plate 2.

V. T r e a t m e n t

1. Renal cell carcinoma T a b l e 4 gives a syatopsis o f c o m m o n t r e a t m e n t modalities lbr renal cell c a r c i n o m a . (a) Operative procedures. T h e first t u m o r n e p h r e c t o m y was performed by ~,Volcott in 186t (97) (Table 4). In 1869 S i m o n (88) u n d e r t o o k the first p l a n n e d n e p h r e c t o m y a n d laid the foundations for operative t r e a t m e n t . Presently radical n e p h r e e t o m y i n c l u d i n g excision of ipsilateral a n d contralateral lymph nodes d o w n to the aortic bitLtrcation is r e g a r d e d as basic t r e a t m e n t . Even in the presence o f metastasis >,imple n e p h r e c t o m y will g e n e r a l l y be carried out for palliative t r e a t m e n t . Surgery can be c o m b i n e d with preoperative r a d i a t i o n t h e r a p y a n d several modifications h a v e been described (61). Preoperative or palliative renovascular embolization will be dealt with in section (b) " v a s c u l a r embolization t e c h n i q u e s " . Palliative surgery includes n e p h r c c t o m y tbr h e m a t u r i a , pain, fever a n d a n e m i a as i n d i c a t e d previously. Klippel a n d A h w e i n (52) agree that n e p h r e c t o m y will successfiflly eliminate these acute symptoms, h o w e v e r it does not significantly prolong survival. S u r g e r y is also a consideration for local r e c u r r e n c e or solitary metastases. Surgical r e m o v a l o f metastases can be c o m b i n e d with p r e o p e r a t i v e r a d i a t i o n or c h e m o t h e r a p y . E v e n for bilateral t u m o r s or t u m o r in a single "kidney, partial resection with preservation of as m u c h n o r m a l tissue as possible is the t h e r a p y of'choice. (b) Radiation therapy. R a d i a t i o n t h e r a p y has been a d v o c a t e d by several authors as a p r e o p e r a t i v e or postoperative m e a s u r e ; Preoperative r a d i a t i o n is a i m e d at r e d u c t i o n o f t u m o r size, t u m o r cell n u m b e r , t u m o r vitality a n d to avoid intraoperative t u m o r s p r e a d (83). A m o n g the n u m e r o u s studies c o n c e r n i n g the significance of p r e o p e r a t i v e r a d i a t i o n for r e n a l cell c a r c i n o m a s o n l y a few fulfill the criteria necessary for prospective controlled trials. These are the 41 cases r e p o r t e d by van d e r Werf-Messing (104), 88 cases b y J u u s e l a , M a l m i o , A l f t h a n a n d Oravisto (49), 30 cases by yon Lieven (60), 59 cases r e p o r t e d by Paces, Doleekova a n d Z a m e c n i k ( 7 2 ) .

38

J. A M M O N E T AL,

Von Lieven (60) recommends short term radiation therapy for all angiographically docttmentcd renal cell carcinomas with low likelihood of operative complications. For tumors expected to present dlffictdtics during operation such as size, regional invasiotb cxtcn.~ivc parasitic blood supply, long term preoperative radiatioll and postoperative radiation is pretbrred. Von Lieven (60) points out that a deft|rite assessment of the ctTcctivcncss ot" preoperative radiation is only possible by a randotnizcd study with large numl)crs. As a rule proopcrative radiatiort employs 30 Gy, this dose can be given within 2-3 weeks with different moditlcations in the fractionations (61). l'ostopcrative radiation is rccommemled for all less thatt well difrcrentiatcd tumors and for all tumors of" the category pT2-4 and V I - 2 . Postoperative radiation is able to T a b l e 4. S y n o p s i s o f t r e a t m e n t m o d a l l t i e s o f r e n a l inauguration and the year of its introduction

Year 11161 1869 1900

1928 1939 1963 1964 1967 1971 1973

cell

carcinoma

T h e r a p e u t i c technique

First successful planned tzephrectomy Radiation therapy e r a retroperitotical nephrogenic t u m o r Regression or distant metastases following t~ephrectomy Neplwectomy and puhnonary lobectomy for solitary metatasis Radical nephrectomy by thoraco-abdominal a p p r o a c h with removal of adrenal gland, perinephric fat and regional l y m p h nodc.s hlcgavolt therapy Chemotherapy Endocrine therapy (progesteron) for metastatic tumors Traztscatheter embollzatlon or arterial supply to renal cell carcinoma

author

+

after Tinker Simon Cooley

+ --

Bumpus

(+)

Barlmy et al.

(+)

Robson

+

Kuttig et al. Woodruff et ol. Bloom

+ --

(+)

Almgard et d .

(-I--)

T a b l e 5. I n c i d e n c e o f l o e a I r e c u r r e n c e s i n c l u d i n g t h e result of treatment for surgery alone and surgery combined wlth postoperative radiat i o n [ a d a p t e d f r o m R a f t a (75)]

No. o f patients

No. o r p a t i e n t s with local recurrence

96 94

24 (25%) 7 (7%)

of

Significance

~Volcott, cir.

-- Therapeutic measures no longer i:1 use. (4-) Potential therapeutic regimen. ~" Currettt therapeutic regimen.

Surgery Surgery+radiation

the

Author

Nephrcctomy

T h e r a p e u t i c regimen

wlth

RENAL TUMORS

39

,'educe the rate of local rccut't'ez~ce as indicated in "Fable 5. Localization technique is identical for pro- and postoperative radiation. T h e r a p y planning is facilitated by simulator marking as well as (3"I' scans (Plate 7). High dose tumor radiation became possible after introduction of.~fegavolt therapy. The field of preoperative as well ~ postoperative radiation covers the tttnlor, the rezml pediclc and the regional lyrnphnodes (4). Opinions differ about inclusions of contralatcral lymph nodes into the radlatiot~ field. Presently concemration of postoperative radiation to tlde tumor bed a n d the ipsilateral lymphnodcs are favored for several reasons: tumor inv;tsion into regional lymph nodes carries a high likelihood ofhematogenotts spread. L y m p h node metastases do not generally limit survival, however, hematogcnous metastases do. For this reason radiation to contralatcral lymph nodes appears excessive. Postoperative radiation should deliver 50 Gy to the tumor bed. !,Vith careful fractionatiou (1.5-2.0 Gy it~ individual doses and weekly dose not exceeding I0 Gy) it is possible to avoid undesirable side effects. Radiation treatment of metastases is feasible, however high doses arc required (Plate 8). In general radiation is able to slow down tumor growd! and in addition achieve a certain analgetic effect. There ha\,e been numerous attempts to increase the effectivehess of radiation to metastases by combining it with endocrine therapy or chemotheral~y ; none of these changes has succeeded in clinical practice. T h e low !'adlosensitivity, however justifies such attempts. M a n y authors including Buschke and Parker (16) feci that a'adiation therapy should always be attempted since individual tumor sensitivity varies greatly. In additionl one has to coTasider the little knowda observation ot" deI Regato (77) that rad{ation cft~cts m a y be delayed. (c) Vascular embolization techniques. Preoperative renal vascular embolization was introdueled by Almgard, Fernstr6m, Haverling and Ljungqvist (3) to facilitate surgery through reduction of intraope,'ativc bleeding and demarcation of the isc2~mic tumor against the normal surrounding tissues. Fu,-thi~r advantages i n c l u d e early ligatioza of the renal vein minimizing tide possibility of tumor cell dlsl6dgcment dur'~ng surgery. Subsequently ,aumerous technical improvements of the cmbolization technique have been described with'the largest experience collected by the reiatively~ easy'6mbolizatiou with gelatine sponge (gelfoam) (44). Embolization with wool augme,ttcd steel coils (30, 37) a n d more recently detachable silicone balloons (105) are the most advanced, safest and most selective occhtsion methods in use at present (Plate 9a-c). T h e idea of therapeutic infarction of renal tu,nors by embolic occlusion of their blood" supply was advocated by a n u m b e r of author's, however the long term effectiveness is unproven (14, 38). If the entire vascular bed of a tumor cannot be occludcd~ viable tumor remains and is apt to grow. Furthermore r a p i d colLateralization has been obse~'ed since no cmbolization technique so fat" was able to occlude down to the capillary level. Palliative embolizatio~,for bleeding, on the other hand, has bec~ very successful a n d should be tried before nephrectomy is considered for dais indication (3, 35, 93). Renal vascular embolization is always accompanied by s0#ere paint due to infarction. Fever also occurs frequently. Both pain and fever usually subside within :~-8h. Sepsis has developed in some instances as well as transient hypertension (93).

(d) Endocrine therapy. Hormone dependence of renal cell carcinomas is unclear and primarily supported by epidemiologic data. These in tuft1 are in part contradictory.

J. A/~IMON E T AL.

40

A c c o r d i n g to Benningtott a n d K r a d i j a n (9) r e n a l cell c a r c i n o m a occurs twice as often in m e n than in w o m e n . O n the other h a n d E k e l u n d and Jonsson (27) observed h y p e r n e p h r o m a s m o r e fi'equently in w o m e n thma in m e n in the 30-40 year age group. R e n a l gestagen susceptibility is suggested e x p e r i m e n t a l l y by the presence of renal estrogen receptors in some a n i m a l species (19). T r e a t m e n t with gestagcn h o r m o n e s is based on the original publica~'~ion by Bloom (12). T h i s r e g i m e n has been f o u n d to r e t a r d progression of metastatic d'isease a n d palliate p a i n (58). A useful r e g i m e n is long t e r m t r e a t m e n t with 3 I e d r o x y p r o g e s t e r o n e (18) (Plate I0). O n e should also consider g o n a d r o t r o p i n inhibition by androgens. T h e r e f o r e a n d r o g e n t h e r a p y should be c o n s i d e r e d if gestagens are ineffective. T h e resuhs o f e n d o c r i n e t h e r a p y h a v e been analysed b y Hrushesky a n d ~ u r p h y (45). N i n e studies up to 197I published a success r a t e o f 17°,0. After 1971 the r e p o r t e d results are less favourable. T a b l e 6 is based on the analysis of 502 patients with an overall success r a t e of 1.6%. T a b l e 6. R e s u l t s o f e n d o c r i n e t h e r a p y in p a t i e n t s w i t h m e t a s t a t i c r e n a l ceil c a r c i n o m a [ a d a p t e d frona H r u s h e s k y a n d M u r p h y (45)]

No. o f

patients

Result

98 21 58 73 166 I5 71

7 (7%) I (4%)

502

8

o

o o 0 0 0.6%)

Author Talley (96) Legha, Slavik and Carter (57) Alberto and Senn (2) Lokich and Harrison (62) Hahn and Brodovsky (39) yon Lieven and Hahn (58) Klippel and Ahwein (52) Total

R e c e n t l y , indications for e n d o c r i n e t h e r a p y h a v e become less clear, since a n d r o g e n s did not prove superior to estrogenes in p r o d u c i n g remission. T h e a n a b o l i c effect of a n d r o g e n s h o w e v e r m i g h t be beneficial for r e m i n e r a l i z a t i o n of osteolytic foci. F u r t h e r m o r e a n d r o g e n s h a v e only m i n i m a l side effects. Also if gestagens a p p e a r ineffective, testosterone m a y be a d d e d . T h e r e f o r e indications for a n d r o g e n t h e r a p y m i g h t be i n t e r p r e t e d generously. N e w possibilities m a y be offered b y antiestrogens. A c c o r d i n g to a study by the Eastern C o o p e r a t i v e O n t o l o g y G r o u p as r e p o r t e d by K l i p p e l a n d A l t w e i n (52) a 15% response r a t e was a c h i e v e d with antiestrogens as c o m p a r e d to 5 % response with gestagens. T h e s e results w a r r a n t further trials.

(e) Chemotherahy. Various cytostatic agents ( T a b l e 7) h a v e been a n a l y z e d in a s t u d y by tlle N a t i o n a l C a n c e r Institute for flmir effectiveness (45). T h e statistics o f this study, h a v e h o w e v e r to be v i e w e d critically since T a l l e y (96) a n d Lokich a n d Hm'rison (62) f o u n d little effectiveness for the same c h e m o t h e r a p e u t i c agents. V i n b l a s t i n e a p p a r e n t l y seems to be one of the m o r e potent substances if single d r u g Omrapy is chosen: 135 patients s h o w e d a 250/o remission r a t e (33 patients). M e C C N U p r o d u c e d remission in seven out of 79 patients. All o t h e r substances showed either m i n i m a l or no effectiveness

RENAL TUMORS

41

(45). Ifos£amid was proposed by Bt'iihl, Scheef, Albert a n d Biicheler ( 1 3 ) w i t h 13 remissions a m o n g 27 patients with metastatic renal cell carcinoma. Unusually thvorable results were r e p o r t e d by Ishmael, Burpo a n d Bottbmtey (46) for in~munotherapy c o m b i n e d with a d r i a m y c i n a n d rincristine witJl remissions in a third of the patients. T h e Swiss S t u d y G r o u p for Clinical C a n c e r Research, is evaluating ehemo0aerapy in metastatic h y p e r n e p h r o m a s a n d in tlteir p r e l i m i n a r y report found no evidence of remission following d l e m o t h e r a p y in all 60 cases of metastatic renal cell c a r c i n o m a (92). O n e m a y specttlate about difficulties in assessing the effect of c h e m o t h e r a p y considering th~ possibility of spontaneous remission (Plate l 1). T a b l e 7. R e s u l t s o f c o m b i n a t i o n d r u g t h e r a p y f o r m e t a s t a t i c r e n a l c e l l c a r c i n o m a . It is e v i d e n t t h a t no c u r e , o n l y remissions could be o b t a i n e d . T h e m o s t f a v o r a b l e r e s u l t s a r e t h o s e o f I s h m a e l c t aL (48) f o r a c o m b i n a t i o n o f hormonal therapy, immunotherapy and chemotherapy

~ o . of

Combination

patients

Remis.sions

Author

Velbe + M c G C N U Velbe + CC.N'U Velbe+ Bleo.+ Cis Plat. I fosfamide+ Vincristinc

6 4 11

2

Vincristinc+Hydroxyurea

15

--

Johnson et

~ledroxyprogeste.ronc, BCG + Adriamyein+ Vincristine

31

10

Ishmael et el. (46)

CCN U + Bleomycin CCNU + Bleom. + Plat. + Mcthotrexate

l0 12

"--}

Cannon

Gestagen+ or Androgen+ Velbc+SFU

20

15

5FU + Mitom./Adriarnycin+ DTI G

3

Adriamycln+ Vincristine+ Cyclophospharrdde + Prcdnisone I fosfanfidc+ Vinc-ristlnc

5 5

}

Merrin et al. (67) Samson et at. (8I) Hartwich et al. (41) at.

et al.

(48)

(l 7)

Alberto and Senn 1.okich a ll)

M.

(2)

(62)

Dept. R.,diology, R ~,VTH Aachen

I n essence the effectiveness of c h e m o t h e r a p y in m o n o - or combination d r u g regimens is unproven. I n some selected cases, palliative t r e a t m e n t with c h e m o t h e r a p y is w a r r a n t e d , particularly for pain relief f r o m osteolytic metastases. For this purpose H a r t w i c h , Neidahardt a n d Lutz (41) found a c o m b i n a t i o n of ifosphamide a n d vincristine effective. W e achieved regression of metastases in some eases with a combination o f a d r i a m y c i n a n d c y c l o p h o s p h a m i d ( P l a t e 4). This, however should not be interpreted as general r e c o m m e n d a t i o n for this type of d r u g combination. (f) l m m u n o t h e r a p y . Presently there are no results widl large series e m p l o y i n g i m m u n o t h e r a p y as a postoperative form of t r e a t m e n t or for a d v a n c e d tumors, but large scale evaluations m a y very well be u n d e r t a k e n in the n e a r future. Particularly e n c o u r a g i n g appears the work of M i n t o n , Pennline, Nawrocki, K i b b e y and D o d d (68). These authors injected a non-specific adjuvant, BCG, weekly into n i n e patients with metastatic

42

J. AMMON E T AL.

t u m o r a n d observed c o m p l e t e remission in one case a n d stabilization of the metastatic process in three. O n e p a t i e n t remains in c o m p l e t e remission for 4 years. (Of r e l a t e d interest is the a l r e a d y cited w o r k of Ishmael et al. (46), w h o c o m b i n e d i m m u n o d w r a p y , c h e m o t h e r a p y a n d e n d o c r i n e t h e r a p y . A synopsis of present results o f i m m u n o t h e r a p y is given in T a b l e 8. A c c o r d i n g to all authors, i m m u n o t h e r a p y seems to be m o r e effective the m o r e t u m o r was surgically r e m o v e d , but a n y conclusions as to indications a n d effectiveness of i m m u n o d ~ e r a p y are impossible to m a k e at the present time. 2. T u m o r s o f the renal pelvis and ureter

(a) Operative treatment. N e p h r o u r e t e r e c t o m y w i t h a b l a d d e r c u f f is the classical surgical technique, because tumors o f the renal pelvis i m p l a n t themselves into the ipsilateral ureter a n d into the b l a d d e r n e a r the ureteral orifice (94). h i the case o f a solitary k i d n e y or bilateral ttunors, segmental surgery of r e n a l pelvis a n d u r e t e r is indicated. This decision should be related to the gn'ading. L o w g r a d i n g indicates segmental, high g r a d i n g radical surgery, if dialysis is available to the patient. I n patients w i t h a k n o w n high incidence o f m u l t i p l e tumors as in Balkan nephritis or analgesic nephritis, segmental surgery m a y be the p r i m a r y t r e a t m e n t in low g r a d e tumor. I n c r e a s e d a c c u r a c y of p r e o p e r a t i v e diagnosis especially by u r i n a r y cytology a n d brush biopsy a n d a carelhl follow-up i n c l u d i n g u r i n a r y eytolog,y are the a r g u m e n t s for dfis t h e r a p e u t i c p r o c e d u r e (74, 76). T h e results of surgical t h e r a p y are listed in T a b l e 9. T a b l e 8. R e s u l t s o f i m m u a a o t h e r a p y f o r m e t a s t a t i c r e n a l cell c a r c i n o m a , a d a p t e d f r o m K H p p e l a n d A l t w e i n (5~)

Author

Method

Results

Skinner et al. (90)

Xenogcnic immune-RNS

~forale~ and Edinger (70)

BCG

Tykk/i et al. (99)

Active autologous tumor cells Transfer factor

"Stationary metastases" during 18 months follow-up 25% regression of metast,'tses during 12 months follow-up 25% regression of metastases during 9 month follow-up About 50% "'stabilization of m e t a s t ~ " during 6 month follow-up

iXfontie et al. (69)

T a b l e 9. Y i v e . y e a r s u r v i v a l i n p a t i e n t s f r e e o f tumor ~fter surgery for transitlonaI cell t u m o r s o f t h e u r e t e r o r p e l v i s [ a d a p t e d f r o m G i t t e s (33)]

Stage

Ureter

Pelvis

O-A B C-D

8/8 (100%) 3/7 (43%) 2/21 (10%)

17/24 (71%) 4/9 (44%) 1/20 ( S % )

RENAL TU,~IORS

43

S p r e a d into perihilar a n d p e r i u r e t c r i c l y m p h nodes is m o r e likely in less d i f f e r e n t i a t e d tumors. Infiltration o f these l y m p h nodes q u i c k l y leads to seeding inlo a d j a c e n t rctrop e r i t o n e a l l y m p h nodes a n d sometimes to h e m a t o g e n o u s metastases. This seems to w a r r a n t extensive r e t r o p e r l t o n e a l l y m p h n o d e dissection w h i c h is h o w e v e r , not d o n e routinely, but o n l y if suspiciolm nodes are f o u n d d u r i n g surge1T. (b))[on-operative t r e a t m e n t . N o n - o p e r a t i v e t h e r a p y comprises r a d i a t i o n a n d chenv~t h e r a p y . I m m u n o t h e r a p y as well as a n d r o g e n t h e r a p y has not been e m p l o y e d yet. Success o f r a d i a t i o n d l e r a p y a n d c h e m o t h e r a p y is not v e r y e n c o u r a g i n g , so d m t all a u t h o r s r e g a r d the indications with g r e a t sceptick~m, C o m p a r a t i v e e v a l u a t i o n s are c e r t a i n l y difficult because o f t h e i n f r e q u e n c y o f these tumors. T a b l e 10. F i v e a n d lO-year s u r v i v a l r a t e s o f l a r g e r s e r i e s o f p a t i e n t s w i t h r e n a l ceLl c a r c i n o m a according to therapeutic regimen. The size of the primary tumor was usually not indicated by the authors

Nephrectomy alone No. of pts.

398 96 70 164 175 232

No. of pt.~.

105/345 271 56 40[ 70 50/ 96 351 94 1091190

Ncphrcctomy-+radiation

$/a

No. of pts.

%

30 48 57 52 37 57

5-year sur',-ival rates 26/53 49 21/40 52 ~ ~ 17168 25 46/81 56 9118 50

Totals No. of pts.

°,0

Author

113/398 ~lBJ 96 401 70 671164 811175 1181208

33 50 57 40 46 57

Riches d al. (78) Flocks¢t al. (28) Robson et at. (80) Peeling et al. (73) Rafla (75) Skinner et al. (89)

341192 18/ 66 181 34

17 27 53

29/115 6t[139

25 44

Riches t t at. (78~ Flocks et d . (28) Robson et al. (80} Peeling ¢t a l . (73) Rafla (75) Skinner et at. ~(89)

I 0-year survival rat~

398 96 70 I64 175 232

30/177 91 39 181 34 . 131 68 61[139

17 23 53 .

. 19 44

4/15 9/'27 ~ . 16147 ~

27 33 ~ . 34 ~

.

R e c e n t l y a d a p t a t i o n to t h e t r e a t m e n t o f a d v a n c e d b l a d d e r c a r c i n o m a s has b e e n p r o p o s e d since the f r e q u e n c y o f these l~istologic~ly relat~:d tumors has a l l o w e d ;t~vatm e n t e ' ~ i u a t i o n with p a r t i c u l a r respect to t u m o r gr~/ding ( 5 t ) . Postoperative r a d i a t i o n O l e r a p y is not used r o u t i n e l y , b u t o n l y i f the t u m o r could n o t be r e m o v e d c o m p l e t e l y o r if the p a t i e n t is not a c a n d i d a t e for s u r g e r y (Plates 12, ]3). I n o u r j u d g e m e n t c o m p l e t e l y r e t n o v e d p | ' i m a r y tumor5 a n d those w i t h o u t in trao p e r a t i v e e v i d e n c e o f l y m p h n o d e involvcrtient should n o t receive postoperative r a d i a t i o n . I f l y m p h n o d e metastases w e r e f o u h d o r s u r g e r y d i d n o t r e m o v e the t u m o r c o m p l e t e l y , postoperative r a d i a t i o n is i n d i c a t e d . T h e r a d i a t i o n field Should include the a r e a o f the p r i m a r y t u m o r as well as the ips'ilateral'lymph ~nodes (Plate 13). I f t u m o r iidiltration into a d j a c e n t l u m b a r v e r t e b r a l bodies is found, this a r e a c e r t a i n l y will also h a v e to be i n c l u d e d into the field o f radiation. R a d i a t i o n is g e n e r a l l y c a r r i e d out wide p h o t o n b e a m s o f accelerators all6wing m a . ' ~ m u m d e p t h dose with m i n i m a | dose to

44

J. AMb.ION E T A L .

adjacent tissues. I f C o b a h - 6 0 is used more complex techniques have to be used suclt as rotational therapy. Average total doses are between 50 a n d 60 Gy. Single doses range between 1.5 azad 2 Gy. T h e weekly dose should not exceed 9-10 Gy. Only careful fractionation allows high tumor doses without the risk of radiation damage to the intestines. Only a few communications on the merits of chemotherapy are available. In general, these cases are included in treatment statistics of bladder carcinoma (107). Yagoda et aL (107) report 42 patients with advanced tumors of the urinary tract including one patient with a transitional cell carcinoma of the renal pelvis. A 14°/o initial palliative response was found after treatment with adriamycin. These response rates really only represent transitional ceil carcinomas of the bladder, however, due to similar histology it appears reasonable to extrapolate them to tumors of the renal pelvis and ureter.

VI. S u m m a r y Tumors of the renal parenehyma, the renal pelvis and the ureter are regarded a.~ only poorly sensitive to radiation and chemotherapy. Therefore operative removal of tile tumor remains th.e primary treatment. Postoperative radiation, commonly applied to other tumors, is of questionable value in renal cell carcinomas (Table 10). Non-operative techniques should be applied to palliate metastases and rectnwences. Their effectiveness alone or in combination remains to a great extent unproven, since even patients with advanced primary, tumors may survive several years. However, the basis of the present review was the fact that recent advances in diagnosis allow better evaluation of non-surgical treatment results some of which indeed appear promising. O f particular value in the diagnostic work-up of the postoperative patient are CT and ultrasound, two non-invasive, techniques w h i c h allow repeated assessment of the effects of radiation therapy, chemotherapy, i m m u n o t h e r a p y and also embolization therapy. Based on the TNM-classifieation system (UICG, 1978) an attempt was made to establish the usefulness of the newer diagnostic and therapeutic modalities for xdlieh the following considerations are pertinent: (a) GT and Ultrasound provide considerable i m p l o v e m e n t in pre-operative evaluation of the suspected renal cell carcinoma and allow exact prc-operative staging. The postoperative follow-~lp has been improved. CT especially allows control of effectiveness of non-operatlve procedures. (b) Surget', is still die treatment of choicc for renal cell carcinomas, carcinomas of the renal pelvis and the ureter. Nephrectomy i n the presence of metastases, however, is only indicated i f h e m a t u r i a , local pain, tumor debulking or treatment ofparaneoplastic symptoms is necessary. T h e possibility of spontaneous remission of metastases does not in itself justify an aggressive surgical regimen. (c) Pre-operative embolization is primarily desigr~ed to facilitate surgical removal, however, palliative tuxnor embolization appears to be a worthwhile method particularly for massive or recurrent hematuria. (d) For metastatic tumors endocrine therapy, chemotherapy a n d immunothcrapy are avaJla.ble. Endocrine therapy m a y become more important with the availability o f antiestrogenes. T h e effectiveness of chemotherapy m a y be increased by drug combinations a n d also by combination of chemotherapy and immunotherapy.

RENAL T U M O R S

(e)

45

C a r c i n o m a s o f the renal pelvis a n d u r e t e r are r a r e entities. Surgery, e i t h e r r a d i c a l o r s e g m e n t a l is still t h e t r e a t m e n t o f c h o i c e . T h e i n f r e q u e n c y o f t h e s e t u m o r s , d o e s n o t a l l o w s u f f i c i e n t e x p e r i e n c e w i t h n o n - o p e r a t i v e t r e a t m e n t fo r a p e r t i n e n t r e c o m m e n d a t i o n a t this t i m e . E x t r a p o l a t i o n o f r e s u h s w i t h t r a n s i t i o t m l cell c a r c i n o m a o f dee b l a d d e r a p p e a r s j u s t i f i a b l e , e s p e c i a l l y r e g a r d i n g gn-ading.

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RENAL TUMORS

47

55. Lakey, r~V. I-l'. (1975) T u m o r s of the kidney. In Urology (Karafin, L. & Kendall, A. R., ed~). H a r p e r & Row, Hagerstown/kid., Vol. 2. 56. Laval, K. U. & Bigalke~ K. H . {197B) Pseudotumor den .~ierenbeckerd dutch ein uttspezifischentzfindliches Granulom. Urologe .4 17: 50. 57. Legha, S. S., Slavik, l~I. & Carter, S. K. (1976) Nafo×i,line, an antloestrogen for tile treatment ,=f breast cancer. Lamer .'t8: I535. 58. Lieven, H. van & i-lab.n, D. (1977) Die Behandluzag des metastasierten hypernephroiden Nierenkarzinoms mit b,tedroxy-progesteronazetat (Clinovlr). !tlu neh. ,~fed. lVJrhr. 110: I089. 59. Lieven, I-L van & Lissner, J . (1977) StrahIentherapie beina Adenokarz.inom dee Niere. Strahlenthercpk 1.~3: 245. 60. Lieven, H. yon (19713) Kllnische Ergelmisse der pr/ioperativen Be~trahhmg l~:im Adenokarzinom der Niere. Strahlentherap;e 154: 1. 61. Lieven, H. yon, Trott, K. R. & Sintermann, R. (1978) Experimentelle Ergebnisse der pr~ioperatlven B~trahlung des renalen Adenokarzin~rn~. Strahlentheraple 154: 299. 62. Loklch, J..J. & Harrison, J. H. (I975) Renal cell carcinoma: Natural history, anti chemotherapeutic experience..7. UroL I 14 : 37 I. 63. Luck6, R. & Schlumberger, H. B. (1957) Tumors o f the kidney, renal pelvis and ureter. Alias of Tumor Patholo~., fascicle 30. Armed Force~ lnstin~te o f Patholog'y, Washington D.O. 64. ~facalpine, J. B. (1947) Papillomatous disease of the renal pelvis. Brit..7. UroL 3~: 113. 65. lXfarsh:,ll, F. F. & ~,Valsh. P. C. f1977) Extr~renal manifestations ofrenal carclnoma.ft. UroL 117" 439. 66. /~,felirow, ~f. M. & Uson, A. C. (1960) Non-urologic syrnptomx in patients wlth renal cancer. 07.A.2tLA. 172: I46. 67. /~Ierrln, C., /~,lqttelman, A., FanotJs, N., ~,V:tjsman, Z. & ,Nturphy, G. P. (1975) Chemotherapy of advanced renal cell carcinoma whh xqnblastlne and C C N U . 07. UroL i ! 3 : 2t. 68. ,Xlinton, J. P., pennline, K.~ Nawrocki,J. F., Kibbey, XV. E. & Dodd, .~L C. (1976) Immunotherapy o f h u m a n kidney cancer. Dear. Am. ~|ssot. Cancer Bee. and Am. Xoc. Clln. OneoL 1'7: 301. 69. /~fontie, J . E., llukowski, g . tkI., Deodhar, S. O., Hewlett, J. S., Stewart, B. H . & Straffon, R. A(1977) I m m u n o t h e r a p y ofdlssemlnated renal cell carcinoma with transfer factor, ft. Urol. 117: 553. 70. l~loral~% A. & Edlnger, D. (1976) Bacillus Calmette-Gu6rln in the treatment o f a d e n o e a r c l n o m a of the kidney..7- Urol. 115: 397. 71. lktultm, J . R., Brown. L. R. & Crow, J. K. (1977) Detectlatt of pulmonary n o d n l ~ b y computed t omogra phy...Ira. 07. Roentgenal. 128: 267. 72. Pa~t..~, V., Dol6ckova, V. & ZAmecnik. J . (1978) Preoperative irradiation of renal carcinoma in adults. (Controlled clinical trial), Int. Urol. jVep,~ol. 10: 77. 73. Peeling, XV. B., Nlantell, B. S. & Shepheard, IL G. F. (1969) l'~o~t-operative irradiation in the treatment o f r e n a l cell carcinoma. Brit. 07. UroL 41: 23. 74. Petkovie, S. (I972) Conservation of the kidney in operations for tumour~ o f the rena! pelvis and calyces: a report oi"26 c~'Ises. Brit. 07. Urol. 4,t: I. 75- Rafla, S. (1970) Renal cell carcinoma. Natural history .~nd results of'treatment. Career 25: 2G. 75. Rathert, P., ~{elchior, I"[. & Lutzeyer, XV. (1975) Phenacctin: a carcinogen for the urinary tract? ft. Oral. 1 1 3 : 653. 77. Regato, J. A. del (1974) Radiotherapy of tumors of the urinary tract. Am ft. l~atnlgertel. 121 : 467. 78. Riches, E. W., Grifflths, I. H. & Thackray, A. (2; (1951) New growthn of the kldney and ureter. Brit...7. &real 23: 297. 79. Robson, C . J . (1963) Radical nepbrectomy for renal cell carcinoma.ft. UroL 80: 37. 80. Robson, C . J . , Churchill, B. M. & Ande~on, ~,V. (1969) T h e remllts o f radlca! neplweetomy for renal cell carcinoma. 07. Urol. 101 : 297. 81. Samson, 2kf. K.~ Baker, L. H., Devo% J./~.I., Bttroker, T. R., Izhicki, R. M. & Vaitkeviciu.% %'. K. (1976) Phase I clinicfil trial of combined therapy with vinblastine (NSC,-49842), bleomycln ( N C S 125066) and Cisdicldorodlamine-platlnum (II) (NCS-1 t987.5). Cancer Treatment Reports 60: 91. 82- Schelbe, O. (1979) "I'NNI-S~tem. ~led. Klin. 74: 331. 83. Schnepper, E. (1976) Tfimoren der Niercn t a d Harnlelter. In Stm.hlentherapie (Scherer, E., ed.). Springer-Verlag, Bcrtln, Heidelberg, New York. 84". Schulze, ~'~,'."(1973) Ge~chwiilste dee Bronchien, Lungen und Pleura (c). In Itandbuch tier l~'edizinlschen RaJiologle (Diethelm, L., Olsson, O., Strand, F., "Vieten, ]~I. & Zuppbtger, A., ~_ln). Sprlnger-Ver|ag, Berlln, Heidelberg, New York, Vol. IX, no. 4e. 85. Scott, %V. XV. & B o y d , . H . L . (1953) A study of carcinogenic beta-naphthylarnlne on normal and substituted isolated slgmo~d bladder o f the dog..7. Urol. 70: 914.

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.I. AMMON ET AL.

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