Carcinoma of bladder treated by supervoltage irradiation

CARCINOMA OF BLADDER TREATED SUPERVOLTAGE IRRADIATION

BY

A. H. LAING,* M.R.C.P.(Glas.), M.R.C.P.(E), F.F.R., and K. M. DICKINSON, F.R.C.S. From the Westminster Hospital, London, S. W. 1. THIS paper presents the results and complications of supervoltage radiation in the treatment of carcinoma of the bladder at Westminster Hospital, with special reference to the significance of the dose of radiation employed. Since 1951 supervoltage radiation using either a Van de Graaff 2 MV Generator or a rotating Telecobalt Unit has been used for external radiation treatment of carcinoma of the bladder. Since the introduction of this treatment the policy has been to treat all cases of carcinoma of the bladder by such means with the exceptions of those satisfactorily controlled by endoscopic methods or those having a single pedunculated growth suitable for treatment by excision, with or without interstitial irradiation. Many of the patients were unsuitable for any conventional form of surgery due to age or general condition and unless the patient had widespread disease or was in extremis, radiotherapy was undertaken. All but 8 patients were personally assessed by the same surgeon, both before radiotherapy and throughout the follow-up period. The management of the patients during treatment was undertaken jointly by the urologist and radiotherapist. Routine urological investigations were carried out in all cases and included pyelography, cystography, eystoscopy and biopsy, and examination of the pelvis under anaesthesia. MATERIAL Between 1951 and 1961 138 patients were treated, there being 103 males and 35 females. The average age was 63, the youngest being 33 and the oldest 86 (Fig. 1). Of this series, 57 per cent (79 cases) had supervoltage radiation as the primary method of treatment; 26 per cent (36 cases) had previously been treated by endoscopic methods, but were no longer controlled by such means; and 17 per cent (23 cases), all referred from other hospitals, had had previous bladder surgery with subsequent recurrence of the tumour. An attempt was made to give radical, i.e. curative, radiotherapy to every patient unless the carcinoma had spread beyond the pelvis. Such a course was completed in 122 cases. In 9 cases the planned radical course of treatment was stopped when it

41" 4 3 3 I B B SOLID

MIXED PAPILLARY

C) AGE 3 0 4 0 Z

50

YRS ^

60 7 0 8 0

90

I. AGE AND SEX D I S T R I B U T I O N 2. TYPE OF T U M O U R

FIG. 1 Age, sex and type of tumour.

became obvious that the slight chance of cure did not justify the upset to the patient. In a further 7 cases only palliative radiotherapy was undertaken and in these the distressing pain or haematuria was temporarily relieved (Table 1). It is of interest to note that 7 patients had unrelated malignant tumours occurring at other sites, before or after the onset of carcinoma of the bladder.

TABLE 1 COURSES OF RADIOTHERAPYGIVEN 2MV Radical

_

Palliative

5

Total

35

87

6

Incomplete Radical

Co 60

3 2

i 40

122

]

9 7

_

I

* Now at The Royal Marsden Hospital, London, S.W.3. 154

CARCINOMA

OF B L A D D E R

H.V.L7.4 ram. ~1:~

K v.2000

TREATED

BY S U P E R V O L T A G E

I~D. I 0 0 cm.~

srJ~ DOSE M/+XIMUM I"UMOUR OOSE ~OIIMUM TOMOUX ~

7 6 . "} ~ E OF IIOt

!

IRRADIATION

I00 ~

c t r~t'~e. L

155

d~JL

B ,x ~ - - ~

\

/

liuns

(

..

~e 70 RIGHT

LEFT

pOSTERR fo Fzo. 2 2 MV Isodoso Distribution. K.V. THERATRON FIELDS

(SIZES,¢=¢.)

HV.L. I0.$ tvV~,Pb

4S~"

E$.D 7~ r-r~s )4En[IMUM~ M O U R

BX 12 r-ms.

8OTJ

ROTATIONAL CYCLING

LEFT

RIGor

160 eQ.~_

SO

~O 30

f

A PoETER IOR

FZG. 3 Cobalt Isodose Distribution.

/

156

CLINICAL

RADIOLOGY

Therefore, in the period under review there are RADIOTHERAPY TECHNIQUE available for study these dose schedules by fixed or Localising cystograms were taken with anterior rotational techniques. skin and rectal markers. As the patient remained in the supine position throughout treatment, no shift of the bladder occurred and only one set of RATE OF RESPONSE TO R A D I O T H E R A P Y films (antero-posterior and lateral) was required. In the earlier cases of the series the patients were Between 1951 and 1958 the patients were treated cystoscoped at every 2,000r to assess progress. This by the Van de Graaff 2 MV Generator (F.S.D. practice, however, was discontinued when it be100 cm.; H.V.L. 7.4 ram. Pb), one anterior and two came obvious that the initial response of the tumour or more antero-lateral fields being used (Fig. 2). was not necessarily an indication of the outcome of Since 1958 most patients have been treated by the treatment, and moreover that frequency, urgency Cobalt Unit (F.S.D. 75 cm.; H.V.L. 10-5 ram. Pb) and strangury often followed the examination. The with either full rotation or multiple arcs (Fig. 3). present routine is to eystoscope the patient 3 The volume treated varied according to the months after the completion of the radiotherapy clinical estimate of the tumour size, but in all eases and then at regular intervals after that depending on the whole bladder was irradiated. The average the response. At 3 months, 80 per cent of the papiltumour volume treated was 9 × 9 × 10 cm. ; this lary and 30 per cent of the solid type of carcinoma was included in the 80 per cent isodose which was showed definite improvement. About 15 per cent considered to be the minimum tumour dose, the of all groups showed no response and continued to 90 per cent being taken as the maximum, deteriorate; with the remainder the response was Initially, the aim was to give a maximum tumour equivocal. After 3 months the results were easier to dose of 6,000-6,500r over 6-7 weeks. In 1953 a assess; most anaplastic tumours rapidly deteriorated higher dosage of 8,000r was given over 6 weeks in while many of the well differentiated tumours the hope that this would give better results, but as continued to regress. In 4 of these cases the regresthere was a considerable increase in the complication sion continued for a year until the bladder was rate the dose was reduced to the original figure. 'clear. Since 1958 patients treated by the rotation techSURVIVAL RATE nique have been given 6,000-7,000r over 5-6 weeks, depending on the volume to be treated and the Consideration of the 'turnout-free 3-year survival clinical response. rate' can be misleading. A patient followed up In 1950 when the Van de Graaff Generator was carefully and having no sign of recurrence will be installed, the National Physical Laboratory (N.P.L.) classed as a 'tumour-free 3-year survivor', yet may calibrations of dosemeters made with the 2 MV die in the fourth year with uncontrollable, local x-rays were not available. The Physics Department disease, whereas another patient surviving a much of this hospital calibrated the dosemeter by means longer length of time, but requiring periodic treatof standard radium tubes and this calibration was ment for recurrence, cannot be so classed despite used until the end of 1957. During that year the the much better prognosis. In an earlier communidosemeter was compared with those of two other cation (Cox, 1960), the 3-year survival rate for 56 hospitals which had been calibrated by the N.P.L. patients of this series was given, but it will be seen for supervoltage radiation and this led to the dis- that the rate continues to fall appreciably in the covery that the doserneter factor being used was ensuing years (Fig. 4). In spite of such limitations, 15 per cent too low, and thus the dose of radiation crude 3- and 5-year survival rates have been used. received by the patients had been 15 per cent higher The survival rate of those treated with radical radiothan was intended. Since January 1958 the correc- therapy will now be reviewed in relation to: ted factor has been used and regularly checked by (1) Type, stage and histological grade of the the N.P.L. and at the same time a decision was carcinoma. made to continue to use the roentgen as the unit of (2) Urinary tract complications. dose (Wilson, 1959). In terms of the present day (3) Treatment. N.P.L. roentgen, our three maximum tumour (1) Type, Stage and Histological Grade of the dosage schedules, with five treatments per week Carcinoma.--All tumours were typed, staged and have been graded according to the British Institute of Urology (1) 6,900-7,500r in 6-7 weeks. Classification (Pugh, 1957). This assessment, re(2) 9,200r in 6 weeks. gardless of previous treatment, was made just before (3) 6,000-7,000r in 5-6 weeks. t h e start of radiotherapy and where doubt about

CARCINOMA

IOO

OF B L A D D E R

TREATED

BY S U P E R V O L T A G E

==PAP.

~

,,,,-=MIXED

90-I~ "%, %

/

S OLID

I00-

9o ~ $ ~

,o-I % \

,o

,04 \ \ \

,o

v,,,\

o"°

157

IRRADIATION

~

20

-==STAGE 1

E

~ 20 °"P I0. 0

1962 61

0

I

6 0 59

2

58 57

3

4.

S

56

6

55

1962 61

7

0

YEARS

6 0 59 58 57

I 2 YEARS

Fro. 4

3

4-

S

Fro. 5

FIG. 4 ~ P e r c e n t a g e Survival Rate---all types. FIG. 5--Percentage Survival Rate for Papillary Carcinoma by Stage.

lO0I00"II= ~,i~

9o~\ ,O1%

I00-

,WELL "~--D,FFE,,E,,IA, ED

~.

~'Ik

k -'ANA''AS''c

7

STAGEII~ =in,==

90,. 70.

ll!

,o.

j

i~

J =,WELL DIFFERENTIATED ~ANAPLASTIC "''SQUAMOUS

~_ 60-

~'I e,

b. l '~

90

50. 40.

\ == 2o

o..O20] ~ k

~

6"0 IO,

~ 2o a~ io

IO.

C

~

1962 61 6 0

O

I

2

YEARS

,' 59 SB 5"7

3

4.

S

O

!

w

w

1962

61

O

I

w

6 0 59

2 3 YEARS

I

il

$8 57

4

5

o 1962 61 6 0

0

59 58 57

I 2 3 YEARS

4-

5

FiG. 6 FIG. 7 FIG. 8 Fxo. 6--Percentage Survival Rate for Papillary Carcinoma by Grade. FIG. 7--Percentage Survival Rate for Solid Carcinoma by Stage. FIG. 8--Percentage Survival Rate for Solid Carcinoma by Grade.

some of the earlier cases existed the case notes and biopsy specimen were reviewed. The difference between the papillary and solid type in both behaviour and prognosis is well known. Between these two groups are those in which the

lesion consists of both papillary and solid elements and these have been classed as a mixed group. The papillary group carry the best prognosis and the solid, the worst. At 3- and 5-years the papillary group have an overall survival rate of 56 per cent

158

CLINICAL

RADIOLOGY

TABLE 2 THREE-YEAR SURVIVORS Ana 31astic

Differentiated Type

Stage No. of cases

Survivors

No. of cases

Survivors

I

20

14 (70 %)

5

3

II

4

2

5

0

II

9

4

13

III

2

0

2

II

13

I I I & IV

--

Papillary Mixed papillary and solid

6 (46~)

3 (23 ~ ) 1

16

3 (19%)

13

0

Solid --

Squamous. 5 cases, all stage IL None survived 3 years.

TABLE 3 FIVE-YEAR SURVIVORS Differentiated Type

Anaplastic

Stage No. of cases

Survivors

No. of cases

Survivors

I

12

6 (50 ~ )

5

3

II

~4

0

4

0

II

5

1

11

III

2

0

2

II

13

III & IV

--

Papillary Mixed papillary and solid

3 (23~)

13

2 (18 %) 0 2 (15~)

Solid --

7

0

Adenocarcinoma. 1 case unstaged, surviving 4 years.

and 36 per cent and the solid, 21 per cent and 15 per cent respectively. The survival rate at 3- and 5-years according to the clinical stage and histological grade is shown in Figs. 4-8 and Tables 2 and 3. It is seen that the highest survival rate is in cases of well differentiated, Stage I papillary carcinoma, but in other groups where the tumour has reached Stage II the survival rate is still appreciably high. It is interesting to note that the survival rate of the solid and the mixed groups are practically the same. Only one patient with a tumour beyond Stage I[ survived 3 years; this patient, however, had an early recurrence and one year after the radiotherapy the bladder was opened and the growth treated by interstitial radioactive cobalt. Only one patient with a squamous cell carcinoma survived for more than a year. This patient had a diverticulum removed before radiotherapy; the diverticulum contained a squamous cell carcinoma

which had invaded the perivesical tissues. In another 5 cases where squamous metaplasia was present in otherwise predominantly transitional cell tumour the survival rate was just as poor and all the patients died within a year. There was only one patient with an adenocarcinoma of the bladder treated with a radical dose and this patient remains alive and well at 4 years. The value of radiotherapy in this case is unknown as recurrent growth had been removed by partial cystectomy 3 months before, the original growth having been excised 3 years before this. (2) Urinary Tract Complications.--Uraemia was the chief cause of death, which was not surprising since intravenous pyelography before treatment showed that 47 per cent of patients had either some degree of upper urinary tract obstruction or pyelonephritic changes. Obstruction of a ureter by carcinoma led to hydronephrosis or a non-functioning kidney in 55 per cent of the solid tumour group;

CARCINOMA

OF B L A D D E R

TREATED

in addition, over a quarter of this group had changes in the other kidney, although prostatic enlargement may have been a causative factor in a few. Pyelonephritic changes were most commonly found in patients with papillary tumours, where repeated cystoscopy and diathermy over many years had exposed them to the risk of infection. In the series as a whole, those cases with renal damage demonstrable by intravenous pyelography had a poorer prognosis (Fig. 9). Radiotherapy in this series gave rise to the following urinary complications: (a) Exacerbations of urinary infection were commonly precipitated and in 3 cases death occurred from acute fulminating ascending infection. (b) Anuria due to obstruction of the only patent ureter by reactionary oedema occurred in one patient. The course of radiotherapy which was almost completed was stopped and urine was passed 2 days later. (c) Acute retention due to general congestion of the bladder and prostate developed in 5 patients necessitating prostatectomy. (3) Treatment.--The 3-year survival rate has been analysed to show the influence of the dose given, the technique used and the effect of any surgery performed before radiotherapy. Two patients, who subsequently had total cystectomy for recurrent carcinoma which occurred within one year of radiotherapy and who survived three years, have not been included in these survival figures (Table 4). The survival rate of patients with papillary tumours was 53 per cent and there was no statistically significant difference in the results according

BY S U P E R V O L T A G E

159

IRRADIATION

IOO. • • [~k,,

mmm= NORMAL

SO" k ~

>

.

m

I.V.P.

ABNORMALI.V.R

\',\ %

2O

O11962

0

I 61

I

; 60

: 59

2

3

: 58

4

; 57

5

YEARS

FI~. 9 Percentage Rate Related to Renal Function.

to dose given or technique used. The survival rate of patients with solid tumours was 19 per cent and here again there was no statistically significant difference in the various groups. It should be noted that there were no survivors with a minimum tumour dose of less than 5,500r, there being no selection of cases within the groups. Before commencing radiotherapy, 47 per cent of the patients with papillary or solid tumours had undergone previous treatment such as partial cystectomy or repeated cystodiathermy. These patients had a lower survival rate than those who were given radiotherapy as the primary method of treat-

TABLE 4 THREE-YEAR SURVIVORS OF TRANSITIONAL CELL CARCINOMA RELATED TO TYPE AND DOSE OF RADIATION

Fixed field Type

Minimum tumour dose

No. of cases

Survivors

Rotation

Total

No. of cases

Survivors

No. of cases

Survivors

5,000-5,500r

5

3

1

0

6

3

5,500-6,000r

5

4

8

5

13

9 (69 ~ )

>6,000r

15

6 (40~)

-

-

15

6 (40~ )

25

13 (52~)

9

5

34

18 (53 ~ )

0

3

0

10

0

Papillary Total 5,000-5,500

7

5,500-6,000r

12

3 (25 ~ )

3

0

15

3 (20~)

< 6,000r

16

5 (31 ~ )

1

0

17

5 (29 ~ )

35

8 (23 ~ )

7

0

42

8 (19 ~ )

Solid Total

160

CLINICAL RADIOLOGY TABLE 5 THEE-YEAR SURVIVAL RELATED TO TYPE AND SURGERY

Type

Surgery before radiotherapy

No surgery before radiotherapy

No. of cases

Survivors

Papillary

15

7 (47 %)

Solid

21

2 (10 %)

ment, but the difference is not statistically significant (Table 5). COMPLICATIONS Although supervoltage radiation compares favourably with orthovoltage radiation it remains a severe form of treatment with respect to immediate reactions and later complications. Immediate Reaetions.--Frequency, strangury, dysuria, diarrhoea, tenesmus or general irradiation effects occurred during radiotherapy in two-thirds of the patients treated. Simple measures were often effective, but in one-third of the number treated the symptoms were severe enough to interrupt treatment. The incidence of bladder symptoms has been less in recent years, since greater attention has been given to the treatment of urinary infection. Skin reactions were negligible. The incidence of immediate reactions was not found to be related to the total maximum dose given (Table 6) nor to the technique used. No patient given a maximum tumour dose of less than 7,000r suffered from general irradiation effects, and the incidence of rectal symptoms, sufficient to interrupt treatment, was the same with either technique. Late Complications.--Complications due to radiotherapy have only been considered in those cases responding well to treatment and after a period of nine months following radiotherapy. Earlier than this period, carcinoma was commonly present and therefore with any arising complication it was impossible to state whether the carcinoma or the radiotherapy was the responsible agent. These late complications have been classified as (1) Persistent frequency of micturition (2) Perineal fibrosis (3) Post-irradiation haemorrhagic cystitis. Patients suffering from early reactions did not necessarily develop later complications and in some cases later complications appeared in patients who had been free from early reactions. The incidence of late complications was related to the total dose given (Fig. 10; Table 6), but not to the technique used. Surgery of the bladder or the prostate performed either in the few months before radiotherapy

No. of cases

Survivors

19

11 (58 ~)

21

6 (29 ~ )

i

or in the follow-up period led to a higher incidence of complications (Fig. 10: Table 7). One patient who received a m a x i m u m dose of 9,300r later developed necrosis of the rectosigrnoid colon, for which partial colectomy was necessary. This patient previously had exploration of the bladder and it was noted at the partial colectomy that the colon was firmly adherent to the bladder.

Persistent Frequency of Micturition.--Persistent troublesome frequency of micturition was a disturbing feature in 13 patients, of whom 4 later developed systolic bladders with capacities reduced to less than 3 oz. These patients with systolic bladders all had a m a x i m u m tumour dose of more than 7,000r. All the 13 patients had urinary infection during the time of radiotherapy and even if the infection was later cleared, the frequency persisted. Eleven of these cases received radiotherapy during the early years of the survey when the importance of prompt treatment of a concurrent urinary infection was not fully appreciated. TABLE 6 COMPLICATIONS RELATED TO TOTAL DOSE OF RADIOTHERAPY

Maximum tumour dose

No. treated

< 7,000r

63

29 ~

15

> 7,000r

59

36 ~

42

122

32 ~

28

Total

Immediate reactions

Late complications

TABLE7 PERCENTAGE COMPLICATIONS RELATED TO MAXIMUM DOSE AND SURGERY

Max. tumour dose With surgery

No surgery

Total

< 7,000r

22~

4~

15

> 7,000r

60 ~

24 ~

42

Total

39 ~

14~

28

CARCINOMA

OF

BLADDER

TREATED

BY S U P E R V O L T A G E

161

IRRADIATION

O]o / NO SURGERY

6

SURGERY

60 50 40 30

m

%

,o i

COMPLICATION SURGERY

D 20 I0

3YR. SURVIVORS

COMPLICATION NO SURGERY

LA

<6000 6 0 0 0 6500 7 0 0 0 >7500 6500 7 0 0 0 7 5 0 0

5000-

.)(.MAX TUMOUR DOSE NO, OF CASES TREATED

SSO0--

<6000

5SO0

6000 MIN. TUMOUR DOSE

FIG. 10

FIG. 11

Percentage C o m p l i c a t i o n Rate Related to M a x i m u m T u m o u r Dose. P e r c e n t a g e Survival a n d Complication Rates Related to M i n i m u m T u m o u r Dose.

TABLE 8 COMPLICATIONS RELATED TO SURGERY AND DOSAGE OF RADIATION

! N o surgery

Sur :ery

Total

i Max. t u m o u r dose

< 7,000r

> 7,000r

< 7,000r

> 7,000r

27

29

36

30

122

1

4

2

8

15

Frequency

0

3

5

5

13

Perineal fibrosis

0

1

2

8

11

Total number of case treated Haemorrhage

1 t I

Perineal Fibros&.--In this condition the perineum becomes fibrosed and indurated and the passage of instrument per urethra is often impossible. Its incidence in this series was low, apart from the group who both underwent surgery and were treated to a maximum tumour dose of more than 7,000r (Table 8). The difference in the incidence between this group and those who did not undergo surgery is statistically significant (P<0.05). Post-Irradiation Haemorrhage.--In 15 patients (12 per cent) bleeding, considered to be due to radiation treatment and not tumour, was sufficiently severe to necessitate admission of the patient to hospital. Haemorrhage resulting from treatment probably occurred in others, but as tumour was also present the source of bleeding could not be ascertained. Haemorrhage occurred in a further patient and it was thought to be due to tumour, but subsequent events showed that it may have been a result o f treatment+ " WherL-bleeding did occur, the outcome was unpredictable and the management

empirical. The time interval between radiotherapy and the first occurrence of bleeding varied considerably; most cases commenced within a year, but in 2 cases the bleeding did not occur until the sixth year. In some cases the bleeding settled with conservative treatment, whereas in others, massive +b l o o ~ transfusions .were necessary. Conservative treatment included wash out with silver nitrate, light endoscopic diathermy and direct electrical current stimulation. All were commonly tried, but usually with little or only temporary success. In one patient, ligation of the internal iliac arteries was performed, but without any helpful results. In 4 patients, where bleeding persisted despite massive blood transfusion, total cystectomy was carried out as the only means of saving the patients' lives. In addition there was a further case where cystectomy was done in the belief that bleedwas due to recurrent tumour (Table 9). T h e last Case shown in the table is most instructive. Originally a large ulcerating solid tumour of

162

CLINICAL

RADIOLOGY

TABLE 9 TOTAL CYSTECTOMYFOR POST-IRRADIATIONHAEMORRHAGE Effect of radiotherapy on carcinoma

Pathology of removed bladder

Time of operation after radiotherapy

Papillary

Valuable. Sporadic papillomata occasionally appeared.

Gross radiotherapy changes. One tiny papilloma present.

3 years

Alive and well 2 years.

Mixed solid and papillary

Cured.

Gross radiotherapy change. No carcinoma.

4 years 6 months

Died of coronary thrombosis 2 months after operation.

Solid

Cured.

Gross radiotherapy change. No carcinoma.

4 years

Died as result of operation.

Solid

Bladder appeared clear.

Gross radiotherapy changes. Small islets of carcinoma found deep in fibrous wall.

1 year 4 m o n t h s

Died 2 months later from renal failure.

Solid

Persistent ulcer remained and was thought to be due to tumour.

Gross radiotherapy changes. Small islets of carcinoma found deep in fibrous wall.

1 year

Died 6 months later from coronary thrombosis.

Patient

i

Type S.J. 65

the bladder was present, but within 6 months of radiotherapy this tumour had largely disappeared, there being only a shallow ulcer remaining at the site. Elsewhere the bladder mucosa showed telangiectatie changes. Following radiotherapy there was frequent haematuria and the source was considered to be the ulcer. No further regression occurred and at ten months the ulcer was lightly diathermised. The bleeding continued and when the bladder was examined 6 weeks later the ulcer was seen to be twice the previous size and appeared characteristically malignant. On pelvic examination a hard mobile mass, the size of a walnut was present. Therefore, no further time was lost and total cystectomy was carried out. The removed bladder showed generalised post-radiation changes, most marked at the site of the ulcer; the latter was turnout free although viable carcinomatous cells were found elsewhere in the thick fibrous bladder wall. The pelvic mass consisted mainly of indurated tissue. The bleeding which necessitated total cystectomy resulted from treatment and not from carcinoma as originally thought. Diathermy undoubtedly made the ulcer worse. This case illustrates the difficulty which can be encountered in differentiating a malignant lesion from one following treatment. Biopsy may give useful information and in some cases may influence the surgeon not to use diathermy. In the present case, however, diathermy was used in an attempt to stop bleeding and would probably have been used in this attempt irrespective of the histology.

Results

TABLE 10 POST-RADIATIONHAEMORRHAGERELATED TO DOSAGE OF RADIOTHERAPY

Minimum dose

N o . o f cases

< 6,500r

32

1

3~

6,500-7,000r

31

2

6~

7,000-7,500r

15

2

13~

>7,500r

44

10

23

122

15

12~

Total

Haemorrhage due to radiotherapy

Post-radiation haemorrhage was found to be directly related to the dose given (Table 10) but to no other factor. E N L A R G E D PROSTATE During radiotherapy, 5 patients developed acute retention of urine. The radiotherapy was temporarily stopped and after an unsuccessful trial period of catherisation prostatectomy was carried out. Two of these patients, however, had such severe urinary symptoms that they were unable to continue with the radiotherapy and so were unable to complete their full course. Of the 3 patients who completed their treatment, 2 suffered from severe cystitis, grossly contracted bladder and perineal fibrosis, and in one patient a suprapubic urinary fistula never healed.

CARCINOMA

OF B L A D D E R

TREATED

Of 4 patients who had prostatectomy just before radiotherapy, 2 developed contracted bladders and perineal fibrosis, another was unable to complete the full course of treatment due to severe symptoms, and the fourth patient died shortly after.

T O T A L CYSTECTOMY W H E R E R A D I O T H E R A P Y HAS F A I L E D Total cystectomy has to be considered in cases in which radiotherapy has failed to control the disease. Such patients, however, are often unfit for surgery, or the disease may be too extensive. In this series, 8 patients had total cystectomy following recurrence or persistent tumour after radiotherapy (Table 11), in addition to the case previously described. Radiotherapy had no effect on 4 patients who were suffering from local recurrence following total cystectomy as the primary treatment. All were given a palliative course, but survival in all these cases was only a few months.

BY S U P E R V O L T A G E

IRRADIATION

163

CONCLUSIONS The results of treatment of carcinoma of the bladder by supervoltage radiation in this series closely compare with those of other series (Finney and Jones, 1962; Wallace and Payne, 1963). It is seen that patients with well differentiated and noninfiltrating tumours have the best prognosis, and patients with anaplastic and infiltrating tumours less good; the squamous cell type having the worst. The results suggest that for solid tumours a minimum tumour dose of 5,500r in 6 weeks is necessary and that raising the dose above 6,000r not only does not improve results but is associated with a higher complication rate (Fig. 11). With the papillary turnouts the dosage does not appear to be so critical, there being survivors with a minimum tumour dose of 5,000r. The complication rate in certain groups of this series was high but in future this should be reduced if: (i) unnecessary endoscopic and surgical trauma is avoided, (ii) maximum doses in excess of 6,500r in 6 weeks after previous surgery or 7,000r in six

TABLE 11 TOTAL CYSTECTOMYFOLLOWING FAILED RADIOTHERAPY r

'Patient age

Type of tumour

Value of radiotherapy

Spread of tumour

Operation time after radiotherapy

J.F. 71

Papillary

Doubtful. Repeated diathermy performed trying to control disease.

Perivesical spread

18months

Well for 2½ years. Following perforated D.U. he rapidly deteriorated from widespread bladder secondaries.

W.R. 42

Mixed solid/ papillary

Doubtful. Initial improvement. Repeated diathermy performed trying to control disease.

Submucosal spread

1 year

Well for 4 years, then died from local recurrence

R.B. 68

Mixed solid/ papillary

Doubtful. Initial improvement. Repeated diathermy performed trying to control disease.

Perivesical spread

20months

Died 4 months later from widespread disease.

H.T. 69

Mixed solid/papillary

None

Perivesical spread

5 months

Died 2 months later from local recurrence.

L.D. 53

Solid

Initial improvement only.

Perivesical spread

5 months

Died from post-operative pneumonia.

F.E. 51

Solid

None

Breaking through muscle at one very small area.

6 months

Alive and well 2 years.

L.E. 57

Solid

Initial improvement only.

Bladder wall

1 year

Alive and well 3 years.

U.S. 44

Solid

None

Perivesical spread

6 months

Died 6 months later from widespread metastases.

Events following operation

164

CLINICAL

weeks w i t h o u t s u r g e r y are a v o i d e d , (iii) v i g o r o u s m e a s u r e s are t a k e n to e r a d i c a t e u r i n a r y infection. I f p r o s t a t e c t o m y is essential j u s t before, d u r i n g o r i m m e d i a t e l y after a c o u r s e o f r a d i o t h e r a p y to the b l a d d e r the risk o f e n s u i n g severe c o m p l i c a t i o n s m u s t l~e accepted. SUMMARY A series o f 138 p a t i e n t s w i t h c a r c i n o m a o f the b l a d d e r t r e a t e d b y s u p e r v o l t a g e i r r a d i a t i o n is described. R e f e r e n c e is m a d e to the results a n d c o m p l i c a t i o n s o f t r e a t m e n t w i t h special reference to the r a d i a t i o n d o s a g e e m p l o y e d .

RADIOLOGY

Acknowledgements. We wish to thank Mr. Robert Cox, Mr. T. M. Prossor and Dr. K. A. Newton for permission to review this series of cases and for their encouragement and advice; the Photographic and Physics Departments of Westminster Hospital and Mrs. M. Chatfield for secretarial assistance.

REFERENCES Cox, R. (1960). Brit. J. RadioL, 33, 480. FINNEY, R. & JONES, H. C. (1962). Lancet, ii, 580. PUGH, R. C. B. (1957). Brit. J. UroL, 29, 222. WALLACE, D. M. & PAYNE, P. M. (1963). Tumours o f the Urinary Bladder 1950-1959. Institute of Urology and Royal Marsden Hospital Report, South Metropolitan Cancer Registry. WILSON, C. W. (1959). Brit. J. Radiol., 32, 584.

BOOK REVIEW Neoplastic Disease at Various Sites. Volume V. Tumours of these investigations outweigh their practical value and in a the Kidney and Ureter. Edited by SIR ERIC RICHES. lethal disease of this nature, treatment should not be delayed Pp. 432. Edinburgh: Livingstone. Price, £4 10s. unduly for their performance'. The use of exfoliative cytology and needle biopsy of the kidney is well described Tumours of the Kidney and Ureter is the fifth volume in and discussed. The radiological chapter is particularly the series 'Neoplastic Disease in Various Sites' edited by interesting with a section by Dr. Emmett on nephrotomoProfessor Smithers and is another comprehensive, stimulatgraphy. ing, and beautifully produced monograph, well up to the Nephroblastorna is next described as seen and treated high standard of the four earlier volumes. The main at Great Ormond Street (w~th radiotherapy at St. contributor is the editor, Sir Eric Riches. There are also Bartholomew's Hospital). The urgency of treatment is major sections from Dr. R. A. M. Case and Dr. Cuthbert stressed; the usual practice being to perform nephrectomy Dukes, who have already added to the value of earlier within 48 hours, followed by radiotherapy and administration monographs. of Actinomycin-D. The old argument as to the merits of Sir Eric Riches starts with brief historical notes and pre- or post-operative radiotherapy seems resolved and the remarks on classification. He reminds us that Grawitz did reasons for adopting the present plan are well developed not describe what most people think of as 'Grawitz turnouts' both by Mr. D. Innes and Dr. I. G. Williams. The value of and suggests that adenocareinoma of the kidney and nephroActinomycin-D is considered as yet unproved. In 1963, 19 blastoma are the best names for the common tumours of of 38 cases were surviving from 1952-9 inclusive, compared adults and children. Dr. Case begins the main part with an with 9 of 35 from 1945-51 and only 5 of 36 seen in 1925-44. illuminating section on Mortality. The common criticisms Two patients have survived 5 and 4 years after surgical made of statistical mortality analysis are disarmed in advance removal of solitary lung metastases, but no patient with in the chapter on methods and materials. The available recognisable spread (outside the kidney) at the time of facts are elegantly displayed in many coloured graphs and operation has survived. diagrams, with the expected emphasis on cohort analysis and The treatment of renal tumours in adults is discussed the relative importance of death from renal cancer is clearly mainly by Sir Eric Riches and Sir Brian Windeyer. It is demonstrated. He gives much supplementary information in suggested that the value of supplementary x-ray therapy an appendix, of great value to all interested in analysis of should be accepted, but the main evidence quoted for this vital statistics, starting by an analogy with a coffin maker is the collected results of the British Association of Urological who wishes to know how much work he will have (presumSurgeons published in 1951, with a persuasive recent paper ably the National Coffin Manufacture Board with a from Bratherton (1963). Pre-operative treatment to a dose monopoly in the whole of England and Wales). Dr. Cuthbert of 3,000 R in three weeks is advocated in tumours of high Dukes reviews the experimental, geographic and occupational grade, nephrectomy being done after a further three weeks aspects of tumour production. He draws attention to the interval. Post-operative x-ray therapy to a dose of 6,000 R carcinogenic action of plastic film (cellophane), also to or more is suggested when there is lymphatic invasion, leukaemia-indueing viruses which tend to cause renal perinephric spread, or obvious residual tumour. Unfortuntumours in very young chicks and hamsters. In man dye- ately very few details of techniques are given and usually only the tumour dose is quoted without mention of fractionastuffs, textile and rubber processes remain of importance; heredity and geography are so far not known to be of great tion and overall time. Brief hut interesting reviews of the value of chemotherapy relevance. Drs. A. C. Thackray and A. D. Thomson describe the and hormone treatment are given by Drs. Jelliffe and Bloom. Finally Mr. I. H. Griffiths attempts to review the literature pathology of adult renal tumours with assistance from Mr. Turner Warwick and with an interesting chapter on natural regarding prognosis and Sir Eric Riches analyses his personal history by the editor. Diagnosis is then dealt with by Sir series. The whole volume abounds with tables, diagrams and Eric Riches himself except for a chapter on ra-diological illustrations, some in colour and there is a full bibliography diagnosis by Drs. Whiteside and Emmett. Sir Eric reviews and index. Anyone considering treatment of renal tumours the value of such esoteric methods as estimation of C. will need this book, for although one may disagree with Reactive Protein in serum and of urine lactic dehydrogenase, individual points of view, the facts presented are invaluable. K. E. HALNAN hut concludes very sensibly that 'The interest of some of