CARCINOMA OF THE BLADDER

CARCINOMA OF THE BLADDER

By NOEL THOMPSON, F.R.C.S. Formerly Surgical Registrar, Royal Victoria Infirmary,

Newcastle upon Tyrie

THE urinary bladder is a common site of tumour formation, and like the lung shows an increasing incidence of growths. Badenoch (1956) found that bladder growths constituted 10 per cent. of all cases of tumour formation admitted to St Bartholomew’s Hospital in recent years, and Jewett (1956) believes that 3 per cent. of all deaths resulting from malignant disease of all types are due to carcinoma of the bladder.

That the incidence of bladder growths is increasing is shown by Case (1953), who in a statistical analysis of death certificates for males in England and Wales for the period 1921-50. found a rise from fifty-three per million in 1921 to seventy-three per million in 1950; he deduces that even when allowance is made for increased longevity in the population, there remains a real increase in the incidence of bladder growths.

Jn view of the relative frequency with which this condition is encountered it was considered that an analysis of a consecutive series of patients suffering from carcinoma of the bladder, and treated in the general surgical wards of a teaching hospital by a unit working under the personal direction of a general surgeon (Mr John Brumwell) having a special interest in genito-urinary surgery, might prove of some interest.

Materials.-Of the 146 consecutive patients treated for growths of the bladder over a period of ten years (1 947-56), seventy-five suffered from non-infiltrating papillary growths and seventy-one from infiltrating growths. This analysis deals with the seventy-one cases of infiltrating bladder growths, of papillary and non-papillary types.

All patients have been successfully traced. Of the survivors, all but three (4.3 per cent.) have been cystoscoped recently; concerning

these three patients, a statement on their present health has been received in response to a postal questionnaire.

Classification.-The separation of the infiltrating growths reported here, from the non-infiltrating growths (excluded from consideration), was often based upon cystoscopic appearances only, though during the latter years of the survey all growths were in addition submitted to endoscopic biopsy.

The lack of histological data in all cases is not considered of absolute or critical importance : biopsy can prove misleading in as many as 50 per cent. of cases (Orr, 1951) because of the varying histological appearances present in different parts of the tumour. The overi-iding importance of cystoscopic appearances i n the diagnosis of infiltrating growths has been stressed by Band (1950), Riches (1952), and Winsbury-White (1953).

Site Incidence.-Of the seventy-one cases of infiltrating growths of the bladder, fifty (70.4 per cent.) were situated on the base of the bladder and twelve (16.9 per cent.) situated on the lateral wall. The remainder were scattered more or less uniformly elsewhere.

Of the fifty basal growths, fifteen were in immediate relationship to a ureteric orifice. sixteen were on the trigone, and eighteen had spread to involve lateral walls or fundus in addition to the bladder base. I n one case the growth occurred in a sacculus on the base of the bladder.

Survival Rates in Relation to Site of Growth.-There was no significant difference in the survival rates of patients with basal growths when compared with patients having growths

287

288 B R I T I S H J O U R N A L O F U R O L O G Y

elsewhere. Thus of fifty patients with basal growths, 26 per cent. are alive and 74 per cent. are dead, while comparable figures in twenty-one cases of growths involving other regions of the bladder are 29 and 71 per cent.

Thus in twelve cases of growth judged to be beyond any constructive therapy (all dying within fourteen months) the growth was basal in ten cases. Similarly, in twenty cases treated by palliative radiotherapy, the site was basal in fourteen cases (all but three of whom had died within fourteen months).

Age and Sex Incidence (Table ]).-The great majority of patients were males, who accounted for fifty-four (76 per cent.) of the patients treated.

Basal growths, however, predominate in inoperable cases.

TABLE I Age and Sex Incidence

30 to 39 40 to 49 50 to 59 60 to 69 70 to 79 80 to 89

Total . -~

_ _ - - ~

I Male. 1 Female. 1 Total. ,

I 1 I ... I

1 1 6 I9 ' 24 18 1 6

14 6 20

15 5 1 4

71 i 54 1 17

The highest incidence of malignant growths of the bladder occurred in patients 50 to 80 years old. This group included sixty-three (88.7 per cent.) out of the sekenty-one cases. The youngest patient was 35 years and the oldest 82 years old.

Presenting Symptom (Table II).-ln two cases the primary presenting symptom was not recorded; in the residual sixty-nine cases it is shown in Table 11. Of these sixty-nine cases, fifty-five (79.7 per cent.) reported hzmaturia as the presenting symptom, but only two patients failed to develop hzmaturia at some stage before presenting themselves at hospital.

TABLE I1 Presenting Symptom

_ _ - _ _ _ _ ~

Presenting Symptom.

I Number 1 of Cases.

1 Percentage , , of Cases.

1 Hzniaturia . Frequency . 1 Dysuria . Vesical Calculus . Strangury . 1 Pain .

Total i Retention .

Secondary symptoms developed in sixty-two of the sixty-nine cases. The commonest h a s frequency of micturition (sixteen cases, 23.2 per cent.), followed by hzmaturia (twelve cases,

C A R C I N O M A O F T H E B L A D D E R 289

17.4 per cent.); but dysuria (twelve cases, 17.4 per cent.), pain (eleven cases, 15-9 per cent.), loss of weight (eight cases, 11.6 per cent.), and urinary retention (three cases, 4.3 per cent.) also occurred.

The duration of the primary symptom before the patient sought medical advice averaged 8.2 months, the longest being five years and the shortest two days. Of the sixty-nine patients, no less than twenty-one (30 per cent.) had suffered symptoms for one year or more before seeking advice. Basing an assessment of intelligence upon the occupation of the patient, there was no evidence to suggest that the more intelligent sought advice at an earlier stage.

Pain appeared as a symptom in eleven cases, always as a secondary symptom except in one patient with an ulcerating growth of the bladder base who complained of pain in the left groin over a period of eight months as his presenting symptom. In the remaining cases pain appeared due to spread of the growth outside the bladder in trigonal growths, infection, bladder-neck obstruction, and in one case of renal pain to blockage of a ureteric orifice by growth.

Pain was a late symptom and of very bad prognosis. Of the eleven cases, four were considered beyond constructive therapy and six received palliative radiation ; nine of these patients died within a year.

Loss of weight was a very late symptom and indicated a hopeless prognosis. It occurred in eiyht patients, always as a secondary symptom. All were inoperable, and died within fourteen months.

Retention of urine was a late symptom and indicated a hopeless prognosis. It occurred in only three patients, but in only one of these was it a presenting symptom. In all cases it resulted from an extensive trigonal growth, and all were inopcrable. All died within two and a half years.

Survival Rates in Relation to Cystoscopic Appearances.-Gross pathological appearances, as seen through the cystoscope, are of prognostic significance. Thus :

I . Pedunculated growths showed almost double the survival rates of sessile growths (41.7 and 23.7 per cent.).

2. Although there was no significant difference between multiple and single foci of growth i n the case of sessile growths, yet when pedunculated growths are considered, the single tumours shohed a considerably increased survival rate when compared with multiple tumours (50 and 33 per cent. respectively).

3. No pedunculated growth showed ulceration, but of the fifty-nine sessile growths, twelve (20.3 per cent.) were ulcerated. Of these, all but one had died within one year and only two cases were considered to be operable. The sole survivor was a case of ulcerating transitional-cell carcinoma involving fundus and posterior wall of bladder, who is free of recurrence five years after partial cystectomy.

Survival Rates in Relation to Histopathology (Table III).-Detailed histological reports are available on most of the growths treated by surgery (or a combination of surgery with radiotherapy) and endoscopic biopsies have been taken routinely on all cases treated since 1953. In all, forty cases have been reported on by the pathologist.

Of these forty cases, twenty-five (62.5 per cent.) were transitional-cell carcinoinata : as well as being the commonest malignant tumour, it yielded the best survival rate, 52 per cent. being still alive.

The single case of leiomyosarcoma is of interest as representing a very rare tumour. Primary sarcoma occurs i n less than I per cent. of primary bladder tumours, and of these only seventy-five cases have been myosarcomata (Ramey et a/., 1953). The present case occurred in a male aged 73, who presented with a twelve weeks’ history of hrematuria, and was found on cystoscopy to have a massive fungating growth which almost obliterated the bladder lumen. Palliative radiotherapy was used, and the patient died three months later.

Of the four cases of anaplastic carcinoma simplex, one patient (a female, aged 72, with a


sessile growth of 2 cm. diameter on the lateral wall of the bladder) is still alive five years after undergoing partial cystectomy.

All cases in the present series suffered from primary bladder growths, except in the single case of an angio-endothelioma probably originating in the peritoneal endothelium and secondarily spreading into the bladder and rectus sheath, The patient was a male aged 50, whose bladder growth melted away under conventional deep X-ray therapy, the bladder remaining free of growth eight years later. Recurrence in the rectus muscle sheath was excised in 1953 but has since reappeared.

TABLE 111

Relation of Histopathological Appearances to Clinical Prognosis

I Histology. ' Average 1 1 1 Average I I Per 1 Survival 1 1 Per I Survival I

I I

I Num- I Per ~ Num- I

1 ber. I cent. 1 ber. cent. , Per,od, I ber. I cent. 1 Period. ~

Villous carcinoma . . I 3 ~ 7.5 Squamous-cell carcinoma . I 4 ~ 10.0 Anaplastic carcinoma . I 4 1 10.0 Adenocarcinoma . . 2 I 5.0 Leiomyosarcoma . . ! 1 i 2.3 Angio-endothelioina . . ~ I I 2.3

I Total . , 40 I ...

1 33 3 I 41 months 1 ' 25 0 I 96 months I 25 0 I 60months 0 0 0 I Omonths 0 0 0 1 Onionths I I 1000 1 84months

17 ... ...

2 I 66 6 1 17months ~

3 I 7 5 0 ' l7months 1 3 I 75 0 ' 3 months 1 2 1 1000 I24months 1 1 1000 3 months 0 I 0 0 Omonths I

I I 23 ... 1 ... 1

Depth of penetration of the growth into the bladder wall has been established by Jewett (1952 a) as the most significant single factor affecting prognosis after operation. This gains support from the findings in this series ; thus of two cases of total cystectoniy in which the growth had penetrated more than halfway through the bladder muscularis, both died within a year. In seven cases of partial cystectomy where the relevant data are recorded, it was found that where the growth had passed more than halfway through the muscle coat, four out of five cases had died i n an average period of fourteen and a half months; but in two cases where penetration was less than halfway through the muscle coat, both patients still survive after periods of eight years and five years respectively.

THERAPY OF CARCINOMA OF THE BLADDER

Of the seventy-one cases here considered, all were primary bladder growths except one (the peritoneal endothelioma considered above). Of the seventy cases of primary growth, fourteen were treated by surgery alone, twenty-one were treated by radiotherapy alone, twenty-one were treated by a combination of surgery with radiotherapy, and fourteen were judged as being too advanced for any therapy except the administration of suitable analgesics.

Cases treated by Surgery (Fig. ]).-These numbered fourteen (20 per cent.) of the total of

Only three patients (21.4 per cent.) of the fourteen so treated still survive, with an average

Only two out of eleven patients treated more than five years ago still survive, giving a

seventy patients.

survival period of 5.8 years.

five-year survival figure of 18.2 per cent.

C A R C I N O M A O F THE B L A D D E R 29 1

Out of twelve patients, four have survived three years (i.e., 33.3 per cent.); and of the fourteen patients, six (42.8 per cent.) have survived one year (see Fig. 4).

Of nine cases treated by partial cystectoniy two (22 per cent.) survived five years and four (44 per cent.) survived three years, while of four cases treated by total cystectomy and ureterocolic anastomosis, two died in the immediate post-operative period (one of cerebral thrombosis and one of intestinal obstruction) and the remaining two cases died within thirteen months.

One patient only was treated by diathermic excision at open operation, and died four days post-operatively of renal failure.

Frc;. 1

Trea tment b y surgery only.

Cases treated by Radiotherapy (Fig. 2).-These numbered twenty-one (30 per cent.) of the total of seventy patients.

All were considered surgically inoperable following assessment based upon cystoscopic appearances, bimanual palpation, and (in seven cases) endoscopic biopsy. In all cases, however. the general condition of the patient allowed palliative radiotherapy.

Of the twenty-one cases, five (23.8 per cent.) are still alive after periods of one to three and a quarter years. There are no five-year survivals, but the three-year survival rate is one case out of eleven (9 per cent.), and of the twenty-one cases nine survived one year (42.9 per cent.).

The form of radiotherapy used has varied as follows : 1. Local Radizm-Used in four cases (19.1 per cent.), in three of these being combined with

conventional deep X-ray therapy or radioactive isotopic cobalt. It has afforded the most impressive palliation in this group ; of the cases, three (75 per cent.) survived two years, and one (25 per cent.) survived three years. I t was used usually in massive but localised, sessile, fixed growths of the bladder base.

2. Conventional Deep X-ray Therapy.-Used in thirteen (61.9 per cent.) of this group of twenty-one cases. Of these, two cases (15.4 per cent.) are alive after two years and five cases (38.5 per cent.) survived one year.


It was the most commonly applied form of therapy to diffuse inoperable growths, but since I954 has tended to be replaced by megavoltage deep X-ray therapy, produced by a 4-million-volt linear accelerator.

3. Megavoltage Deep X-ray Therapy.-Used in only three (14.3 per- cent.) of the twenty-one cases in this group. Of these, only one case (33.3 per cent.) has survived one year, in this patient cystoscopic appearances being now normal.

39

% -

53

3 0 - ' 27 3 3 't4;

2 21 a

5 18 a -I 15

12 s 5 9 :

3 :

d m

G -

CASES

I-

-

/ -

-

;

- 1 2 3

0

-n 8

ALIVE

DEAD

FIG. 2 Treatment by radiotheraphy alone.

4. Radioactive Isotopic Cobalt.-Was used alone in a single case of leiomyosarcoma, involving This it almost the whole bladder, as a means of halting severe and continuous hrematuria.

succeeded in doing, the patient dying three months later.

Cases treated by Combined Surgery and Radiotherapy (Fig. 3).-These numbered twenty-one (30 per cent.) of the total of seventy patients.

Of the twenty-one cases, nine (42.9 per cent.) are still alive after periods varying from eight months to four years (average two years), but three of these show recurrence of growth in the bladder.

Only two out of eight patients (25 per cent.) have survived five years, seven out of thirteen patients (53.9 per cent.) survived three years, and eighteen out of twenty-one patients (85.7 per cent.) survived one year (Fig. 4).

cl

d l G500r 7 h s 1

r

0 1 ;FI

i! 0 z 1

0 w

+3 I rn m r

c

P


Biopsy reports were available in seventeen patients ; of these one was a villous carcinoma (surviving three years) and one was an adenocarcinoma (surviving three years) ; the remainder were transitional-cell carcinomata.

The combinations of therapy used have varied greatly, but may be summarised as follows :

1 . Open Diathermic Excision plus Deep X-ray Therapy.-In five patients the growth was diathermically excised through a suprapubic cystotomy, but subsequently recurred, the recurrence being then treated by deep X-ray therapy.

All received conventional deep X-ray therapy except one who received megavoltage irradiation (5,000 r in nineteen days) and still survives after four years.

Of the five patients, two (40 per cent.) survived five years and four (80 per cent.) survived three years.

2. Palliative Transplantation of Urerers into Colon, plus Deep X-ray Therapy.-Was used in three patients, where the growth was judged beyond surgical cure and was obstructing one or both ureteric orifices. In one case, megavoltage irradiation was used, the patient still surviving six months later. Both the other patients received conventional irradiation only.

There are no five-year survivors, but one patient (33.3 per cent.) survived three years. 3. Open Diathermic Excision plus Radium-Was used in two cases of localised sessile growths

(transitional-cell carcinomata) of the bladder base. Both continue to survive after a period of three years, without any evidence of recurrence on cystoscopy.

4. Open Diathermic Excision plus Radon Implantation.-In six patients, following diathermic excision of the growth, radon seeds were implanted into the diathermised base of the tumour.

Of these only two patients (33.3 per cent.) survive after periods of two and a quarter and one year, both without evidence of recurrence of growth.

Of the six patients, four (66.6 per cent.) survived two years, and five (83.3 per cent.) survived one year.

In the five cases i n which histopathology was recorded, all were transitional-cell carcinomata.

In three patients, additional radiation in the form of conventional deep X-ray therapy was administered. In two cases it was given merely as palliation following recurrence of the growth after the initial therapy; in the third patient, however, conventional deep X-ray therapy (2,860 r in thirty-two days) was administered, while under the care of another surgeon two years before the open diathermic excision and radon implantation. It is of interest that this patient has produced the best therapeutic result in this group, being alive and free of recurrence on cystoscopy two and a quarter years later.

5 , Open Diathermic Excision plus Radioactive Cobalt.-In one patient with a number of pedunculated transitional-cell carcinomata scattered over the bladder mucosa, a single large papilloma (4 cm. diameter) was given open diathermic excision but the remaining small papillomata (4 cm. diameter) were treated by radioactive isotopic cobalt (Co 60) applied by means of a large intravesical balloon (5,375 r in forty-three hours).

This patient still survives one year later, cystoscopic appearances being normal. 6. Partial Cystectomy plus Radiotherapy.-In four patients a segment of all layers of the

bladder, together with a sufficient margin of normal tissue round the growth, and in all cases including one ureteric orifice, was excised and the ureter reimplanted in the reconstructed bladder. All were instances of transitional-cell carcinomata on the base of the bladder and all reyeived subsequent radiotherapy : two received radon-seed implantation alongside the suture line, and two received conventional deep X-ray therapy.

Of the two patients who received radon-seed implantation at the site of the local segmental excision, both still survive with no cystoscopic evidence of recurrence after periods of one and two years.


Of the two patients who received conventional deep X-ray therapy following the local excision, one survived two years and one continues to survive after one year, but has recurrence of growth.

Cases receiving no Active Therapy.-Of the seventy-one cases of malignant tumours of the bladder, fourteen patients (19.7 per cent.) were assessed as being beyond any constructive therapy except the administration of suitable analgesics. In all cases the local pathological condition rendered the lesion hopelessly inoperable, and the general condition of the patient was inadequate even to allow palliative radiotherapy. With the advent of megavoltage irradiation more patients will probably be admitted to palliative radiotherapy in the future : the considerable diminution in skin reaction and radiation sickness following megavoltage deep X-ray therapy when compared with that following conventional deep X-ray therapy will provide access to treatment of those whose general condition would formerly have excluded any therapy.

In this group of patients the period of time elapsing between the onset of the first symptoms and death finally supervening, varied from three weeks to two years, but averaged ten months ; a more optimistic analysis was recorded by Prout and Marshall (1956), who found in fifty-nine untreated cases that the average duration of survival was sixteen months, and 4 per cent. even survived for five years.

DISCUSSION

It must be generally accepted that the survival rates obtained following the treatment of bladder carcinoma could be appreciably improved by the introduction of treatment at an earlier stage in the disease. It cannot be overstressed that every case of hzmaturia should be urgently investigated, for 60 per cent. of all adult cases are caused by bladder neoplasia (Badenoch, 1956).

In the present series one year elapsed between the onset of the first symptom and adequate investigation being introduced, in no less than 30 per cent. of patients. Similarly Lund and Lundwall (1955) report that only 54 per cent. of their patients reported in the first six months; Reaves (1955) quotes a review of 245 cases of bladder tumours in which the average delay was just over a year in each case; and Millen (1950) reports that in Manchester 25 per cent. of his patients had had symptoms for more than two years.

The statistical analysis of survival rates in relation to the varying forms of therapy available loses in significance in the present series because of the limited number of patients in each group.

Treatment does, however, in contrast to some published series, show a unity of conception and execution, because it has been planned by a single surgeon in collaboration with his radiotherapist colleagues.

Patients selected for treatment by surgical means alone were in a sense ideal subjects, being chosen because in each case the bladder lesion was initially assessed as being capable of complete ablation by the operation decided upon. Yet the survival rates for patients treated by a combination of surgery with radiotherapy (where the lesion was believed to be more advanced in many cases) were at all stages superior to those following surgery only (see Fig. 4). Thus combined therapy demonstrated its superiority over surgery alone, in five-year survivals by 25 per cent. compared to 18 per cent., and in three-year survivals by 54 per cent. compared to 33 per cent.

Simple total cystectomy has proved the least successful of all the basic forms of therapy: of four patients where the growth infiltrated muscle, none has survived five years and only one survived one year. Ferris and Priestley (1 948) found that of I I9 cases treated in this way at the Mayo Clinic only 19 per cent. survived five years, and believed that in 40 per cent. of the cases in which the bladder musculature was deeply infiltrated, metastasis had already taken place. Riches (1956), reporting on sixty-four cases where infiltration of muscle had occurred, found


that total cystectoiny produced only 8 per cent. of five-year survivals, and stresses (Riches, 1957) that when an infiltrating growth involves such an extent of the bladder mucosa as to preclude partial cystectomy, it has almost certainly spread too far beyond the bladder wall to render total cystectomy curative. These considerations have persuaded Whitmore and Marshall ( I 956) to abandon the operation in deeply infiltrating growths in favour of a radical total cystectomy including also the removal of local regional lymph nodes. The mortality of this operation is, however, 17 per cent., and the survival rate (I8 per cent. after four years) inferior to the 25 per cent. of five-year survivals reported, without any therapeutic mortality, by Poole-Wilson ( 1 957), using only conventional deep X-ray therapy in radical dosage : it might therefore appear, as suggested by Riches (1957), that the combination of some form of radiotherapy followed by total cystectomy may yet prove the best treatment for cases too advanced for partial cystectomy.

Partial cystectomy yielded a five-year survival rate of 22 per cent. in this series; other comparable five-year survival rates for infiltrating growths treated in this way are 17 per cent. (Riches, 1957), 24 per cent. (Milner, 1953), and 45 per cent. (Marshall et al., 1956 b), the last representing results obtained in a highly selected series and unapproached by any other surgeons.

I n recent years radon seeds have been implanted along the suture line following partial cystectomy, and into the base of the growth following open diathermic excision of the growth, but sufficient time for adequate follow-up has not yet elapsed to permit of accurate evaluation of the method. Of eight patients so treated, 50 per cent. still survive without obvious recurrence after one to two years, and 37.5 per cent. died after two years. Winsbury-White (1953) also found that 50 per cent. of his patients died in the first year after treatment by radon or radium implantation, but Poole-Wilson ( 1957), using radon implantation following open diathermic excision of localised growths, claims 49 per cent. of five-year survivals at the Christie Hospital and Holt Radium Institute, Manchester.

In this series, radium has proved superior to any other means of irradiation in localised growths. In four patients denied surgery, three survived two years, and in two patients where i t was combined with open diathermic excision it has produced three-year survivors free of cystoscopic recurrence in both instances. Jacobs ( 1949) preferred radium needles to partial cystectomy for growths of the lower half of the bladder, producing 34 per cent. of five-year survivals in a series of 110 patients treated in this way, whereas partial cystectomy yielded only 20 per cent.

Conventional deep X-ray therapy was the mainstay of palliative therapy, where the general condition of the patient allowed, being used in thirteen of twenty-one inoperable cases. Of these, I5 per cent. are still alive after two years, in similar circumstances Poole-Wilson (1957) has found that only 6 per cent. survived five years. Where, however, conventional deep X-ray therapy was combined with surgery (partial cystectomy or open diathermic excision) in six patients of this series, i t has yielded impressive survival rates: 33 per cent. survived five years and 50 per cent. survived three years.

Megavoltage deep X-ray therapy has been used in only five patients, but the palliative use of this apparatus in a more extensive series has been reported by Swinney (1957) ; of eighty-nine patients treated over a period of three years (1954-56) the growth appeared to be destroyed in 36 per cent., unaffected in 42 per cent., and recurred after initial disappearance in 22 per cent. ; 45 per cent. of the patients died.

In this series the operative mortality for the thirty-five patients receiving surgery (with or without radiotherapy) was 8.6 per cent. ; for open diathermic excision it was 6.7 per cent., for partial cystectomy it was nil, and for total cystectomy 50 per cent. Comparable statistics from published series are: for partial cystectomy 18 per cent. (Jewett, 1952 b), 8.5 per cent. (Masina, 1954), and 6.5 per cent. (Marshall et al., 1956 b) ; for total cystectomy 20 per cent. (Kerr and Colby, 1951), 15 per cent. (Jewett, 1952 b), 12 per cent. (Riches, 1956), and 1 1 per cent. (Marshall ef a/., 1956 a).


SUMMARY

An analysis is given of seventy-one cases of infiltrating growths of the bladder, treated by

The relevance of growth-site, sex and age incidence, symptomatology, and pathology is

Treatment by surgery, radiotherapy, or a combination of both is compared, to the advantage

a general surgeon having a special interest in genito-urinary surgery.

discussed in the context of survival rates.

of the latter.

My grateful thanks are offered to Mr John Brumwell in whose wards in the Royal Victoria Infirmary, Newcastle upon Tyne, all the patients here considered were treated, and by whom all treatment was planned and most of the major surgery executed ; to Mr C. J. L. Thurgar, Director of the Department of Radiotherapy, who with his staff was responsible for all radiotherapy used ; and to Mr P. J. van Miert who dispensed all radiotherapy in the later years of the series, and contributed much to the analysis.

REFERENCES

BADENOCH, A. W. (1956). Practitioner, 177, 267. BAND, D. (1950). Brit. J. Urol., 22, 381. CASE, R. A. M. (1953). Brit. J.prev. soc. Med., 7, 14. FERRIS, D. O., and PRIESTLEY, J. T. (1948). J. Urol., 60, 98. JACOBS, A. (1949). Brit. J. Radio!., 22, 393. JEWETT, H. J. (1952 a). J. Amer. rned. Ass., 148, 187. __ (1952 b). J. Urol., 67, 672. I_ (1956). KERR, W. S., and COLBY, F. H. (1951). J . Urol., 65, 841. LUND, F., and LUNDWALL, F. (1955). Acta. path. microbiol. scand. Suppl., 105, 118. MARSHALL, V. F., BRICE, M., GREEN, J. L., and WHITMORE, W. F. (1956~) . Cancer, 9, 576. MARSHALL, V. F., HOLDEN, J., and MA, K. T. (I956 b). Cancer, 9, 568. MASINA, F. (1954). Brit. J. Surg., 41, 494. MILLEN, J. L. E. (1950). Brit. J. Urol., 22, 430. MILNER, W. A. (1953). J. Urol., 69, 657. ORR, L. M. (1951). Amer. Surg., 17, 1. POOLE-WILSON, D. S. (1957). Brit. J . Urol., 29, 244. PROUT, G. R., and MARSHALL, V. F. (1956). Cancer, 9, 551. RAMEY, P. W., ASHBURN, L. L., GRABSTALD, H., and HAINES, J. S. (1953). J. Urol., 70, 906. REAVES, J . U. (1955). J . rned. Ass. Ala., 24, 161. RICHES, E. W. (1952). Proc. R . Soc. Med., 45, 191. __ (1956). Ann. R. Coil. Surg. Engl., 18, 178. __ (1957). Brit. J. Urol., 29, 232. SWINNEY, J. (1957). Brit. J. Urol., 29, 241. WHITMORE, W. F., and MARSHALL, V. F. (1956). WINSBURY-WH~TE, H. P. (1953). Luncet, 1, 757.

Maryland St. med. J . , 5 , 79.

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CARCINOMA OF THE BLADDER