Total Prostatectomy for Clinically Localized Prostatic Cancer: Long-term Results

0022-534 7/89 /1413-0564$2.00 /0 Vol. 141, March Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1989 by The Williams & Wilkins Co.

TOTAL PROSTATECTOMY FOR CLINICALLY LOCALIZED PROSTATIC CANCER: LONG-TERM RESULTS ROBERT P. GIBBONS, ROY J. CORREA, JR., GEORGE E. BRANNEN AND ROBERT M. WEISSMAN From the Section of Urology and Renal Transplantation, The Virginia Mason Clinic, Seattle, Washington

ABSTRACT

The fate of the first 52 patients with clinically localized prostate cancer who underwent total perinea! prostatectomy at our clinic and have been followed for a minimum of 15 years is reviewed to evaluate the long-term impact of this operation on the disease. None of these patients received any adjuvant therapy. Nine patients (17 per cent) had recurrence and 5 (10 per cent) died of disease during this interval. The actual observed over-all survival at 15 years was 64 per cent, the actuarial survival was 67 per cent and the cause-specific survival was 90 per cent. (J. Ural., 141: 564-566, 1989) The goal of those who manage localized prostate cancer should be to provide long-term survival free of disease, with minimal risk or long-term morbidity from the treatment. Patients with clinically localized prostate cancer (stages A and B) comprise approximately 55 per cent of all patients with prostatic adenocarcinoma. 1 To define better and clarify the current role of total prostatectomy in the management of patients with clinically localized prostate cancer, the long-term surgical results from our clinic are reviewed.

regional disease on physical examination, normal acid phosphatase and in recent years normal prostate specific antigen, as well as a normal bone scan if any question of bone disease was present. Radiation or hormonal therapy was given only if recurrent prostate cancer was documented. RESULTS

The results are based on the actual status of the patient at the month he was 15 years postoperative. Of the initial 44 patients 5 (11 per cent) with clinical stage Bl and 6 of 13 (46 per cent) with clinical stage B2 disease had microscopic pathological stage C disease, for an over-all 19 per cent incidence of pathological stage C disease (table 1). The histological grade of disease in the initial 57 patients is shown in table 2. The majority of the patients had intermediate grades (II and IIl). 3 Of the 52 patients 9 (17 per cent) definitively treated by total perineal prostatectomy alone had recurrent disease by the 15year followup interval. The influence of the pathological stage on recurrence is noted in table 3. The recurrence rate was 16 per cent in patients with pathological stage B disease and 22 per cent in those with pathological stage C disease. Recurrence was local in 2 patients, distant in 4, and local and distant in 3. Although the mean interval to recurrence was 8.1 years, 3 patients had recurrences between 12 and 15 years postoperatively. Of the 9 patients with recurrence 5 were followed at intervals of 1 year or less. Two patients had recurrence (postoperative years 6 and 12) after a 2-year period without followup and 2 only returned because of symptoms secondary to metastases (postoperative years 12 and 15). The over-all actual observed survival rates for these 52 patients with clinical stages Bl and B2 disease at risk 15 years was 64 per cent (table 4). During this interval 5 patients (10 per cent) died of recurrent prostate cancer. The mean interval to death was 10.1 years, with a range of 7 to 14 years. The causes of death other than recurrent cancer were cardiovascular in 9 patients, carcinoma of the lung in 3 and other (gastrointestinal bleeding and suicide) in 2. The mean interval to nonprostatic cancer death was 7.3 years, with a range of 1 to 14 years. Over-all survival, survival free of disease and causespecific actuarial survival curves are given in figure 1.

MATERIALS AND METHODS

A total of 57 consecutive patients who underwent total perinea! prostatectomy between 1954 and 1971 and who have been followed for a minimum of 15 years was reviewed to evaluate the long-term impact of this operation on this disease. One patient was lost to followup. Four patients with pathological stage C disease received adjuvant external beam radiation therapy in the immediate postoperative period and 1 of these 4 also received postoperative hormonal therapy. These 4 patients have been excluded, leaving 52 evaluable patients: 43 with clinical stage Bl and 9 with clinical stage B2 disease. Patients were judged to have a stage Bl tumor if it was palpable only in 1 lobe or a stage B2 tumor if it was palpable in both lobes. None of these 52 patients received any form of adjuvant hormonal or radiation therapy, and none underwent pelvic lymphadenectomy. Average patient age was 59 years, with a range of 45 to 73 years. Patient selection. Patients were considered candidates for total (radical) prostatectomy if they had a biopsy proved tumor without palpable evidence of extension beyond the capsule or into the seminal vesicles in the opinion of 2 experienced urologists, normal serum acid phosphatase levels, no evidence of metastatic disease on bone x-rays, or in later years on a bone scan supplemented by radiographs of any abnormal areas, an expected survival of at least 15 years and willingness to undergo an operation. Surgical procedure and follow up. All patients underwent total prostatectomy via the perinea! route described initially by Young." After recovery from the operation, patients were scheduled for followup at 12-month intervals or less to include a history, acid and alkaline phosphatase determinations, and rectal examination. If the history suggested bone involvement or systemic disease repeat bone x-rays or scans were obtained. Evidence of local failure was confirmed by biopsy. Patients were judged to have no evidence of disease if there was no history of failing health, no bone pain, no evidence of local or Accepted for publication August 2, 1988. Supported by The Virginia Mason Research Center.

DISCUSSION

The results of treatment for prostate cancer can be judged by its effect on the local control of the primary tumor, recurrence rate (interval free of progression), or over-all survival, survival free of disease or cause-specific (determinate) survival.4· 5 To understand better the influence of treatment for localized disease it is necessary to evaluate the natural history

564

565

.~fOTAL PROS·TATECTO!vx'Y FOR CLINICA,LLY LOC.ALIZED PROS'TATIC CANCER ·TABLE

L Final pathological stage in 57 patients with initial clinical stage B disease treated by total perinea! prostatectomy

1.0

Pathological Stage Clinical Stage

Total No. Pts.

Bl B2 Totals

B No.

C No.(%)

44 13

39 7

57

46

5 (11) 6 (46) 11 (19)

.c

1

94 ±3 %

'

0.8

..a

-.o

OVERALL SURV~VAL

o--<>

Expected survival (age 59)

20

25

77±6% /

~

\

_2 0.6 2 Q.

\

\

'\

~ 04

TABLE

·2:

2. Histological grade in the initial 57 patients according to the

::J (J)

system of Gaeta and associates:i

B

Totals

II

III

IV

5

21 4

19 5

1 2

46 11

5

25

24

3

57

C Totals

0.2

Grade

Pathological Stage

0

5

0

10

15

1.0

Influence of pathological stage B versus stage C disease on recurrence rate, interval free of disease and death rate 15 years after total perinea/ prostatectomy without adjuvant treatment in 52 patients with clinical stage B carcinoma TABLE 3.

B

B

9

(7-14)

No. pts. Alive: Free of disease With disease* Dead: Free of disease With disease Of disease

DISEASE FREE SURVIVAL

o--o

Expected survival (age 59)

..a Ol ..a 0.6

C

2

0..

52

9 (17)

2 (22) 10 (8-12) 1 (11)

13 (8)

Ol .::: 04

9 (17)

8.1 5 (10) 10.1

C:

::J

(J)

0.2

Total No.(%)

43/9

52

26/3 1/3

29 (56) 4 (8)

12/2 0/0 4/1

14 (27) 0 (0) 5 (10)

'' Expected 15-year survival, patient age 59 years = 56 per cent. 11

of untreated localized disease and the clinical course of patients who have recurrence after treatment. Larson and Norlen reported a 77 per cent progression rate in 31 clinical stage B cancer patients who were followed without treatment for a mean of 6.5 years. G Whitmore reported a 54 per cent progression rate (local and distant) in 13 stage Bl cancer patients followed for 5 years with delayed treatment. By 15 years 100 per cent of the patients had progression.' This finding compares to a 17 per cent progression rate in our surgically treated patients during a similar 15-year interval. The importance of disease control is emphasized further when one reviews the fate of patients with newly diagnosed metastatic disease. Kramer and associates showed that 50 per cent of the patients with positive regional lymph nodes were dead at 39.5 months, 8 and Murphy and associates reported that 50 per cent of the patients with newly diagnosed bone metastases were dead at 23 months." When patients have hormone refractory metastatic cancer the average survival time is 10 months. rn The morbidity of hormone refractory metastatic prostate cancer is significant with bone pain and anemia from bone marrow invasion, bladder dysfunction (retention, incontinence and hematuria), urinary tract infection, anorexia and uremia from obstructed ureters being common sequelae in the months before death. In this series total prostatectomy afforded

/

'

0

TABLE 4. Actual observed survival status of 52 patients with clinical stages Bl and B2 disease who underwent total perinea/ prostatectomy without adjuvant treatment at least 15 years ago

Clinical Stages Bl/B2

e---o

.£

Totals 43 (83) 7 (16) 7.6 (3-15) 4 (9)

35

0.8

Pathological Stage

No. pts. (%) No. recurrences(%) Mean yrs. to recurrence (range) No. dead of prostate Ca(%) Mean yrs. to death (range)

30

Follow-up time (years)

0

5

10

15

20

25

14±7%

'O

30

35

Follow-up time (years) 1.0

C

0.8

.£ ..a

Ol .0

0.6

CAUSE SPECIFIC SURVIVAL

2 Q. CTl > 0.4 ·~ CJ (J)

0.2

0

0

5

10

15

20

25

' 30

35

Follow-up time (years) Actuarial survival of 52 patients with clinical stage B prostate cancer treated by total perinea! prostatectomy without adjuvant treatment at risk for minimum of 15 years. A, over-all actuarial survival. B, actuarial (free of progression) survival free of disease. C, cause-specific actuarial (determinate) survival.

83 per cent of the patients a survival free of recurrence, which represents a significantly improved quality of life compared to those who have recurrence. Similar 10 and 15-year control rates free of recurrence have not been recorded with the other currently used treatment modalities for localized stages Bl and B2 prostate cancer. Further evidence that treatment can influence the natural history of the disease can be seen by comparing the survival of treated patients with the life expectancy of the general male population of the same age in the same region during the same interval (part A of figure). 11 The better over-all survival of these

566

GIBBONS AND ASSOCIATES

surgically treated patients with cancer can be explained by effective treatment and selection criteria that exclude poor risk patients with significant cardiovascular, respiratory, metabolic and other diseases. Survival free of disease (free of progression) or cause-specific (determinate) survival addresses better the effectiveness of the treatment alone in preventing recurrence. The survival free of disease in this surgically treated group is comparable to the expected survival rate up to 30 years of observation (part B of figure). A plateau in cause-specific survival was not seen until 17 years had elapsed and stresses the need for long-term observation in evaluating any new form of treatment in patients with clinically localized disease (part C of figure). Forty per cent of the deaths occurred at 10 to 15 years of followup and further emphasizes this point. An additional advantage of total prostatectomy is the benefit of pathological study of the neoplasm. Of the patients 19 per cent had pathological stage C disease. Our prior experience with a larger number of patients followed for a shorter period suggests that in patients whose tumor extends to the surgical margins or who have seminal vesicle invasion adjuvant radiotherapy can decrease the incidence of subsequent local recurrence and its use is considered. 12 In summary, our experience demonstrates that if long-term survival free of disease is most important to the patient with clinically localized carcinoma of the prostate, total perineal prostatectomy remains the proved treatment of choice. Gloria Bailey assisted with data collection and analysis. REFERENCES 1. Murphy, G. P., Natarajan, N., Pontes, J.E., Schmitz, R. L., Smart, C. R., Schmidt, J. D. and Mettlin, C.: The national survey of prostate cancer in the United States by the American College of Surgeons. J. Urol., 127: 928, 1982. 2. Young, H. H.: The early diagnosis and radical cure of carcinoma of the prostate. Being a study of 40 cases and presentation of a radical operation which was carried out in four cases. Johns Hopkins Hosp. Bull., 16: 315, 1905.

3. Gaeta, J. F., Asirwatham, J. E., Miller, G. and Murphy, G. P.: Histologic grading of primary prostatic cancer: a new approach to an old problem. J. Urol., 123: 689, 1980. 4. Gibbons, R. P., Correa, R. J., Jr., Brannen, G. E. and Mason, J. T.: Total prostatectomy for localized prostatic cancer. J. Urol., 131: 73, 1984. 5. Lepor, H., Kimball, A. W. and Walsh, P. C.: Cause-specific actuarial survival analysis: a useful method for reporting survival data in men with clinically localized carcinoma of the prostate. J. Urol., 141: 82, 1989. 6. Larson, A. and Norlen, B. J.: Five year follow-up of patients with localized prostatic carcinoma initially referred for expectant treatment. Scand. J. Urol. Nephrol., suppl. 93, 19: 48, 1985. 7. Whitmore, W. F., Jr.: Panel discussion: management of stages B 1 and B2 disease. In: A Multidisciplinary Analysis of Controversies in the Management of Prostate Cancer. Edited by D. S. Coffey, M. I. Resnick, F. A. Dorr and J.P. Karr. New York: Plenum Press, pp. 143-144, 1988. 8. Kramer, S. A., Cline, W. A., Jr., Farnham, R., Carson, C. C., Cox, E. B., Hinshaw, W. and Paulson, D. F.: Prognosis of patients with stage Dl prostatic adenocarcinoma. J. Urol., 125: 817, 1981. 9. Murphy, G. P., Beckley, S., Brady, M. F., Chu, T. M., deKernion, J. B., Dhabuwala, C., Gaeta, J. F., Gibbons, R. P., Loening, S. A., McKiel, C. F., McLeod, D. G., Pontes, J. E., Prout, G. R., Scardino, P. T., Schlegel, J. U., Schmidt, J. D., Scott, W.W., Slack, N. H. and Soloway, M. S.: Treatment of newly diagnosed metastatic prostate cancer patients with chemotherapy agents in combination with hormones versus hormones alone. Cancer, 51: 1264, 1983. 10. Eisenberger, M. A., Simon, R., O'Dwyer, P. J., Wittes, R. F. and Friedman, M. A.: A reevaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma. J. Clin. Oncol., 3: 827, 1985. 11. Washington State Life Tables for Males. State Life Tables, U. S. Decennial Life Tables for 1969-71. National Center for Health Statistics, Department of Health, Education and Welfare Publication No. HRA 75-1151, 1975. 12. Gibbons, R. P., Cole, B. S., Richardson, R. G., Correa, R. J., Jr., Brannen, G. E., Mason, J. T., Taylor, W. J. and Hafermann, M. D.: Adjuvant radiotherapy following radical prostatectomy: results and complications. J. Urol., 135: 65, 1986.