Radiotherapy of Carcinoma of the Prostate: Preliminary Report

Radiotherapy of Carcinoma of the Prostate: Preliminary Report

Vol. 106, December Printed in U.S.A. THE JOURNAL OF UROLOGY Copyright © 1971 by The Williams & Wilkins Co. RADIOTHERAPY OF CARCINOMA OF THE PROSTAT...

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Vol. 106, December Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1971 by The Williams & Wilkins Co.

RADIOTHERAPY OF CARCINOMA OF THE PROSTATE: PRELIMINARY REPORT EDWARDS. LOH,* HAROLD E. BROWN

AND

DAVID D. BEILER

From the Departments of Urology and Radiotherapy, Geisinger Medical Center, Danville, Pennsylvania

The preliminary report by George and associates1 on the use of cobalt 60 as a definitive therapeutic modality led us to use it on a patient with stage B carcinoma. This patient had refused a radical operation since he was afraid he would become incontinent and because he was still sexually active and hoped to remain so after therapy. We were so pleased with the clinical course and post-radiation results in this case that an additional 35 patients have been so treated. An analysis of these patients is presented herein. MATERIAL

Between 1965 and early 1970 we treated 36 patients with prostatic carcinoma to potentially curative doses. The patients were between 49 and 79 years old; the mean age was 65.5. Of 36 patients, 7 had stage B, 28 had stage C and 1 had stage D prostatic cancer. Stage A prostatic cancer is occult or a nodule, stage B prostatic cancer is completely limited to the prostate, stage C prostatic cancer extends through the capsule into the periprostatic tissues and stage D prostatic cancer involves metastases. Seven patients with stage B cancer were treated either because they refused radical operation for fear of impotence and incontinence or for reasons of age or poor general health. One patient with stage D cancer was treated because he had sclerotic changes of uncertain etiology in only 1 lumbar vertebral body and he was only 49 years old. Generalized metastasis has since developed in him. RADIATION TECHNIQUE

There are 2 approaches to radiotherapy of prostatic carcinoma, their differences based on Accepted for publication April 16, 1971. Read ~t annua~ meetin~ of American Urological Assocrat10n, Philadelphia, Pennsylvania May ' 10-14, 1970. * Current address: 2 W. Fern Ave. Redlands ' ' California 92373. 1 George,_F. W., Carlton, C. E., Jr., Dykhuizen, ='1· F. and Dr~l~m, J. R.: Cobalt-60 telecurietherapy m the defimtrve treatment of carcinoma of the prostate: a preliminary report. J. Urol., 93: 102, 1965. 906

the volume of tissue irradiated. One approach is to treat only the prostate and its immediate vicinity. The alternative method is to treat a larger volume of tissue so as to include the possible local extensions of the disease and the most likely lymph node metastases. The small volume method is logically applicable to patients with stage B carcinomas and, generally, we have treated them by 360 degree rotation therapy alone, using 8 by 8, 10 by 8 or 10 by 10 cm. fields. Since the treatment field may come down to the edge of the anus or include the anus, depending upon the tilt of the pelvis in the recumbent patient, we hav.e found it important to give at least half of the rotation therapy with the patient lying prone and with the buttocks pulled apart with tape. This method avoids excessive reactions in the anal area due to electron scatter from the table and from tangential incidence of the radiation on the intergluteal folds. Neglect of these simple precautions will result in unhappy patients. Stage C disease is associated with about a 40 per cent incidence of pelvic node metastases and usually is not well localized centrally. Therefore, we decided to begin treatment of such cases with total pelvic irradiation, narrowing the field to the central area when the limit of tolerance to such large-volume therapy is approached. The dose of the central volume is then carried to the same total dose as in the small-volume technique. The whole pelvic irradiation is given through 4 fields: anterior, posterior (12 by 14 cm.) and both laterals (11 by 9 cm.), which give a rectangular distribution of dosage. Our own early experience and that of others suggest that if the treatment is given at the rate of 1,000R weekly, the total dose to the prostate should be about 7,000R. Higher doses have been given either in the same amount of time or in a longer period. Undoubtedly, higher doses can be tolerated when the treatment volume is kept small. On the other hand, radiation to the whole pelvis with cobalt becomes increasingly hazardous at more than 5,000R in 5 weeks. Therefore, in treating cases of stage C cancer it has been our

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RADIOTHERAPY OF PROSTATIC CARCINOMA

recent practice to stop the whole pelvic irradiation at 5,000R and continue with reduced ports (via rotation) to 7,000R in 7 weeks. RESULTS

The 36 patients in this study have been followed from 5 months to 5 years post-treatment. Twenty-five patients received between 7,000 and 7,580R, 10 received from 6,000 to 6,900R and 1 patient received 5,300R. Urinary and rectal symptoms. Reactions in the bladder, urethra and rectum were mild and usually transient. None of the reactions was severe enough to interfere w;th daily life. An analysis of the urinary symptoms prior to, during and after external irradiation is presented in table 1. Urinary frequency and dysuria were the most outstanding complaints during treatment. Thirty-three per cent of the patients experienced nocturia. There was little change in other symptoms except for a 2-fold increase in hesitancy which was mainly due to 8 urethral strictures which developed following external irradiation. During the second or third week of treatment, rectal symptoms developed (table 2). The most common complaint was diarrhea which continued in 9 cases, although mild and intermittent, for several months after treatment. Rectal discomfort described by patients as burning, soreness or pain persisted after treatment in some cases but usually disappeared in about 6 to 9 months. Rectal bleeding, although mild, was noted in 8 patients. Complications. An analysis of complications is given in table 3. There were 10 cases of urethral stricture following treatment. Since 2 strictures had been present before treatment, there were actually 8 new cases. Three strictures occurred among 13 patients who had had transurethral resection of the prostate or open prostatectomy prior to external radiation therapy. However, the remaining 5 were apparently due to radiation alone. Management of post-radiation stricture requires extremely gentle dilatation, which should be only as frequent as needed to control symptoms. Filiforms and followers should be used because of their safety and dilation should never be forced to the maximum but a certain caliber should be reached and maintained. Over-dilatation leads to prolonged tissue reaction and infection with its concurrent distressing symptomatology.

1. Urinary symptoms

TABLE

Pre-Treatment No.(%) Frequency Nocturia

10 9 5 6 1 4

Dysuria Hematuria

Urgency Hesitancy

TABLE

(28) (25) (14) (17) (3) (11)

PostTreatment No.(%)

During Treatment No.(%) 22 12 20 3 3 2

(61) (33) (56) (9) (9) (6)

7 (20) 5 (14)

8 1 1 7

(23) (3) (3) (20)

2. Rectal symptoms During Treatment

Post-Treatment

No.(%)

No.(%)

23 (64) I (3) 7 (20) 3 (9)

9 (25)

Diarrhea Tenesmus Burning

Bleeding

TABLE

2 (6) 5 (14) 5 (14)

3. Complications

Urethral stricture Anal or rectal stenosis Thrombosed hemorrhoids Rectal hleeding Cardiovascular complications: Femoral vein thrombophlebitis, 1 Pulmonary embolism and pelvic vein

thrombosis, 1 Cardiovascular disease and arteriosclerotic vascular disease, 1 Skin reactions (moderate to severe) Epididymo-orchitis Impotence

11

1 16 (84%)

Five patients had mild anal or rectal stenosis. Eight patients had hemorrhoids before treatment. They all underwent considerable discomfort and analgesic suppositories were required. Thrombosed hemorrhoids developed in 5 patients. Two of them were complicated by bleeding during and after treatment. There were 8 cases of rectal bleeding: 3 developed during the treatment and 5 patients continued to notice intermittent spotting for 6 to 16 months after treatment. Seven of these patients underwent barium enema and proctoscopic examinations: 5 were negative except for mild mucosal edema and hyperemia while 2 had thrombosed hemorrhoids. Fifteen patients were on concomitant estrogen therapy. Three of these had cardiovascular complications before treatment which appeared to be aggravated during and after treatment. Skin eruptions were usually mild and limited to epilation, erythema and desquamation. However, in 1 patient the skin reaction was so severe

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LOH, BROWN AND BEILER

TABLE

4. Results of treatment in patients with

stages B and C carcinoma With Cancer

Free of Cancer

No. Pts.

Biopsy

Clinical

--

--

7 28

5 10

Stage B Stage C

Bi- Clinopsy ical

Total

- - - - - ---

2* 6t

7 (100%) 16 (57%)

4t

Total

-- - 8§

12(43%)

* One died of pneumonia.

t One died of natural causes. t One died of metastatic disease.

§ Two have distant metastases.

5. Result of patients with intermediate arid high grade carcinoma after cobalt 60 treatment

TABLE

Free of Cancer

With Cancer

No. Bi- Clinopsy ical ntermediate grade High grade

TABLE

Total

Bi- Clinopsy ical

Total

-- -- -- - - -- -- - 21 19 12 7 2 2 14

3

1

(90%) 4 (29%)

4

(10%) 10 (71%)

6

6. Results of cobalt treatment correlated with stage and grade of carcinoma

Stage

Stage B, 7

Grade

Intermediate

No. Results

69

6

Stage C, 28

High

Intermediate

High

1 19

15 13 (87%) 2 EB

13 38 (23%) 10 EB

e

that treatment had to be discontinued at a tumor dose of 5,300R. Of 3 patients who had urinary retention and were on indwelling Foley catheters throughout the treatment, 2 tolerated the treatment well but had epididymo-orchitis. Data on sexual activity were obtained from 21 patients who had never been on any estrogen therapy or orchiectomized. Two patients were impotent before treatment and remained so. However, of 19 patients who claimed to have been potent before treatment, 16 claimed to have become impotent following treatment whereas 3 claimed to have had no change in potency. Results of treatment. The 35 patients in this study with stages B and C cancer have been followed from 5 months to 5 years post-treatment. Twenty-one have no clinical evidence of persistent disease. Two have died but showed

no evidence of disease. Eleven are living with carcinoma and one died of metastatic disease. Therefore, 23 patients (66 per cent) have obtained apparent local control of the carcinoma. Table 4 presents the results of treatment in patients with stages B and C tumors. Followup biopsy is done at least 1 year after treatment is completed because there is progressive decrease in size over at least that period. Biopsy was often difficult because the prostate was difficult to palpate after treatment. In the 7 patients with stage B tumors, post-radiation needle biopsy revealed no residual tumor or rectal examination disclosed normal palpable prostatic tissue. One patient died of pneumonia 4 months after treatment-post-treatment rectal examination had revealed no residual tumor. Sixteen patients with stage C cancer obtained apparent local control. Of 12 patients with persistent carcinoma, 2 now have metastatic tumor and 1 died of widespread metastatic disease 4H years post-treatment. At this hospital prostatic carcinoma is graded as low, intermediate or high in increasing order of malignancy. The distribution according to grade and results following radiotherapy is shown in table 5. Nineteen of 21 intermediate grade carcinomas responded favorably to treatment while only 4 of the 14 high grade carcinomas responded. Table 6 shows results of treatment correlated with stage and grade of the tumor. All intermediate and high grade tumors in stage B responded favorably. With stage C tumors, 13 of 15 intermediate grade tumors responded but only 3 of 13 high grade tumors responded. DISCUSSION

Tumors in stages A and B generally lend themselves well to radical prostatectomy by either the perinea! or retropubic approach. 2 • 3 Flocks' extensive experience revealed that less than 5 per cent of all patients were candidates for radical prostatectomy when first seen. 4 There are occasions when radical prostatectomy is not indicated because of age, poor general health or fear of impotence or incontinence. Fifty per cent of patients have definite metas2 Jewett, H.J.: Radical perinea! prostatectomy for carcinoma. An analysis of cases at John Hopkins Hospital, 1904-1954. J.A.M.A., 166: 1039, 1954. 3 Jewett, H.J.: The results of radical perineal prostatectomy. J.A.M.A., 210: 324, 1969. 4 Flocks, R. H.: Present status of interstitial irradiation in managing prostatic cancer. J.A.M.A., 210: 328, 1969.

RADIOTHERAPY OF PROSTATIC CARCINOMA

tases, and castration, estrogenic hormones or local external radiation should play the major therapeutic role in such cases. The remaining 45 per cent, that is those patients with local invasion, may be candidates for an attempt at local control of the disease by radiation therapy since radical prostatectomy is not successful in these patients. Such patients represent a high percentage in most series. We believe that these patients now may have a chance for cure if they do not have disseminated disease. It is noteworthy that in our ser:es only 29 per cent of high grade tumors responded while 90 per cent of the intermediate grade tumors responded favorably with no demonstrable residual

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tumor. The question of the maintenance of sexual potency is often of considerable interest to the patient. A substantial reduction or loss of potency following radiotherapy seems to have occurred more often in our series than would have been expected from other series. SUMMARY

During the past 5 years 36 patients with prostatic carcinoma were treated with cobalt irradi9,tion therapy. Most patients tolerated therapy well on an outpatient basis. While intermediate grade tumors responded well, high grade tumors did rather poorly. There was significant change in potency following radiation therapy.