THE TREATMENT OF RECURRENT CARCINOMA OF THE BLADDER BY SUPERVOLTAGE RADIOTHERAPY

By ROBERT MORRISON, M.D., F.R.C.S.E., F.F.R.

and THOMAS J. DEELEY, M.B., F.F.R.

Radiotherapy Department, Hammersmith Hospital, London, W.12

UNTIL fifteen years ago the surgical treatment of carcinoma of the bladder was regarded as the only method likely to bring about either a cure of the disease or a long-term survival. Although localised forms of radiotherapy, using radon or radioactive gold grains, were employed successfully for small and superficial tumours, external radiotherapy was employed mainly as a palliative measure for inoperable tumours and for recurrences which developed after operation.

With the introduction of supervoltage apparatus, such as telecobalt units and linear accelerators, the scope of radiotherapy widened and long-term results have now been published which compare favourably with surgical methods of treatment. For example, in a recent series of cases a five-year survival rate of 22 per cent. was obtained in all cases, with a 37 per cent. survival in the early T1, T2 group (Morrison and Deeley, 1965). Both surgery and radiotherapy, however, have limitations. In surgery the more advanced tumours are technically difficult and often impossible to remove ; in radiotherapy the variation in radiosensitivity and tumour response makes the results unpredictable.

It seems likely that combined methods of treatment by using surgery and radiotherapy may have advantages over either method alone. The possibility of using a combined approach was suggested by Riches (1963) and by Whitmore (1964). Riches reported a 14 per cent. five-year survival rate in sixty-five cases that had supervoltage therapy and surgery. The difficulty of carrying out a radical surgical procedure after a full course of radiotherapy is considerable and the reported results of this combined form of treatment show that it is associated with a high morbidity rate. Because of this, Riches, in a later series of cases, recommends giving half the dose of radiotherapy, i.e., 3,500 rads and then exploring the tumour. Whitmore considers that the cure rate has been improved by pre-operative radiation but advises a lower dose of radiotherapy than that given in radical treatment.

This paper reports on a group of patients who were treated by supervoltage radiation after surgery, where the tumour was known to have recurred, or where the pathological report on the excised tissue suggested that recurrence was inevitable. The reactions following this treatment and the survival rates are given.

Patients Studied.-The group was composed of ninety-seven patients. The operations performed included either a local excision of the tumour or a partial or subtotal cystectomy in ninety cases, and a total cystectomy in seven cases. In the group of ninety patients, forty-seven (52 per cent.) developed a recurrence at the site of operation and in forty-three patients (48 per cent.) the operation was incomplete and there was residual tumour in the pelvis. In the recurrent group the time of recurrence after operation is shown in the histogram. Recurrences developed both at the line of excision and in the extravesical tissues.

Histology.-The histological types of tumour are shown in Table 1. The distribution is

The survival rates have been calculated in those patients with residual tumour and those

The survival rates are similar for both residual and recurrent tumours. The only histological group large enough to analyse further is the group of transitional-cell

similar to that found in a group of untreated cases.

with recurrent tumour. The results are shown in Table 11.

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TABLE I Histological Types of Turnour

Number of

Cases Malignant papilloma . . . . . . 9 Transitional-cell carcinoma . . . . . 55 Undifferentiated carcinoma . . . . . 1 1 Squanious . . . . . . . . 9 Adenocarcinoma . . . . . . . 2 Other . . . . . . . . . 2 Negative, none and N.K. . . . . . 2

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Total . 90 -

T R E A T , M E N T O F R E C U R R E N T C A R C I N O M A O F B L A D D E R 32 1

I n fifty-five of these patients a carcinomata which includes cases of malignant papillomata. radical course of treatment was given and the results at four years are shown in Table l i l .

TABLE I I

Survival in Cases Treated by Local Excision and Partial Cystectom y

One year . . Two years . Three years . Four years . Five years .

I

I Residual Tumour I (43 paticnts)

' Per cent. - - - - - - - - - -

54 42

. , 35

. I 35

. I 28

Recurrent Tunlour , (47 paticnts)

I Per ccnt. I 55

37 33 29 29

- - - - - - - -.

I

TABLE I l l

Four-year Survival Rate for Recurrent Transitional-cell Tumours having Radical Radiotherapy after Surgery

Number of patients . . 55 Four-year survival . . 36 per cent.

For comparison the results obtained at four years in a series of Stages 1 and 2 transitional-cell carcinomata, where the initial treatment was radiotherapy only, are given in Table IV. I t will be seen that the results are similar (Morrison and Deeley, 1965).

TABLE IV

Four-year Survival Rate for TI and T2 Transitional-cell Tumours having Radical Radiotherapy only

Number of patients . Four-year survival .

82 39 per cent.

Techniques of Treatment Employed.-The radiation techniques employed have been similar to those used for cases treated without previous operation ; the whole pelvis has been irradiated and the fields have been extended to include any area where recurrence was likely to develop. For example, the operation scar and the adjacent tissues of the anterior abdominal wall have been included in all cases because of the likelihood of recurrence after operation in this area. N o attempt has been made to localise the fields of radiation to the tumour only. A tumour dose of 4.500 rads was planned to be given in one month. Because of the previous surgery the tolerance of normal tissues is probably reduced and the tumour dose is limited to 4,500 rads. The dose has been well tolerated and it has not been necessary to curtail the treatment course in any of the patients because of systemic upset and severe local reactions.

Complications and Late Radiation Effects.-In seventy-eight patients who had a tumour dose of over 4,000 rads and who survived for four months the immediate reactions are shown in Table V.

In a series of patients having radical radiotherapy as the only method of treatment we reported an incidence of intestinal diarrhea in nine out of 315 patients (2.9 per cent.) In this

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group of patients having local excision or partial cystectomy five out of seventy-eight (6.4 per cent.) developed intestinal diarrhoea, but these differences are not significant. There is also

TABLE V Immediate Complications

Number of cases None . . Rectal diarrhea Intestinal diarrhoea Dysuria . Frequency . Cystitis . Leucopsenia . Renal pain .

. 78

. 44 (58 per cent.)

. 20 (26 per cent.)

. 5 (6 per cent.)

. 3 (4 per cent.)

. 4 (5 per cent.)

. 1 (1 per cent.)

. 1 (1 per cent.) . . . 1 (1 per cent.)

no significant difference in the incidence of the other immediate effects of radiation when compared with the patients having no previous radical surgery.

Late complications occurred in four patients ; two had telangiectasia of the bladder, one had a contracted bladder and a further patient had a breakdown of the suprapubic wound and perforated diverticulitis. There is nothing to suggest that the incidence or the nature of late complications is worse after previous radical surgery at the dose levels given.

Total Cystectomy.-Total cystectomy had been performed in seven patients and there was tumour present at the time that each patient was referred for radiotherapy. Six of these patients died at 22, 17, 10, 5, 3 and 3 months and one patient with an anaplastic squamous lesion is still alive at 79 months with no evidence of disease.

DISCUSSION

The result in a group of ninety cases reviewed shows that there is no significant difference in the survival rate in patients having a residual or a recurrent tumour after radical surgery. The survival rate is similar to the results reported for early cases treated by supervoltage therapy alone.

The results show that if recurrence occurs after radical surgery or if it is impossible to remove the lesion completely, the patient should be given radiotherapy to a radical tumour dose.

The reactions are only slightly greater than in patients treated by radiotherapy alone. There is also no significant increase in the incidence of late complications. The anastomosis between the ureter and the colon is normally outside the field of irradiation and no difficulty has been encountered from radiation effects.

SUMMARY

An analysis of ninety-seven patients with residual or recurrent lesions of the bladder after surgical removal and treated by supervoltage radiotherapy showed that the survival rates were similar to those obtained by radiotherapy alone. Reactions and complications were only slightly increased.

We would like to thank the surgeons who have referred their cases to us for treatment.

REFERENCES MORRISON, R., and DEELEY, T. J. (1965). Brit. J. Radio]., 38, 449. RICHES, E. (1963). WHITMORE, W. F. (1964). Brit. med. J., 2, 750.

J. urol., 90, 339.