Incidental Carcinoma of the Prostate: a Review of the Literature and Critical Reappraisal of Classification

0022-5347/80/1245-0626$02.00/0

Vol. 124, November

THE JOURNAL OF UROLOGY

Printed in U.S.A.

Copyright© 1980 by The Williams & Wilkins Co.

INCIDENTAL CARCINOMA OF THE PROSTATE: A REVIEW OF THE

LITERATURE AND CRITICAL REAPPRAISAL OF CURTIS A. SHELDON,* RICHARD D. WILLIAMSt

AND

CLASSIFICATION

ELWIN E. FRALEY

From the Department of Urologic Surgery, University of Minnesota Hospitals, Minneapolis, Minnesota

ABSTRACT

The problem in treating incidental carcinoma of the prostate is that of distinguishing between tumors that will have a long, benign natural history and those that will progress rapidly. A review of the English literature concerning incidental prostatic carcinoma reveals that patients with focal low grade tumors have a good prognosis, while patients with high grade lesions often suffer rapid tumor progression. By contrast, the clinical significance of high volume, low grade tumor is unknown. A method has been developed to evaluate the distribution of prostatic cancer using 4-quadrant transurethral prostatic resection. A detailed method for staging these cancers based on a comprehensive, segmental histopathological analysis also is presented. A precise definition of the stages of prostatic cancer should eventually improve our understanding of the natural history of this disease. have a prognosis that actually may be worse than stage B1.1-9 For this reason these lesions have been classified by some as stage B2 disease. 9· 10 Obviously, there is no uniform staging system.

There is confusion regarding the definition, significance and management of incidentally discovered stage A carcinoma of the prostate. Stage A carcinoma of the prostate usually is found after transurethral resection or enucleation of the prostate for clinically benign prostatic hyperplasia. The long natural history of this disease, sometimes 10 to 15 years, often has led to a policy of conservative treatment. However, a significant number of patients suffer rapid progression and eventual death from what begins as incidental prostatic carcinoma. Present understanding of the factors that predispose to a poor prognosis is inadequate and further study in this area is essential.

INCIDENCE

STAGING

Stage A carcinoma of the prostate has been variably referred to as incidental, occult, latent and focal. 1· 2 As indicated by Donohue and associates these tumors clinically are unapparent and unexpected and, therefore, the most appropriate term is incidental. 1An occult tumor is one that manifests itself through either metastatic spread and/ or paraneoplastic syndromes with the actual site of the primary lesion unknown. The term latent is incorrect since it implies lack of biologic potential. Stage A carcinoma of the prostate often is not focal in nature and we use the term focal carcinomas of the prostate to refer to incidental carcinoma that is confined to 1 microscopic segment of the prostate. Since the original appreciation of the heterogeneity of incidental prostatic carcinoma by Jewett in 19753 numerous staging systems have been advanced for incidental cancer of the prostate, most of which divide the lesions into 2 stages, Al and A2 (table 1). Stage Al is defined as a low grade, focal lesion and stage A2 is defined as a high grade or diffuse lesion. The distinction between focal and diffuse varies: 3 studies describe a focal lesion as being ~3 chips,4 ~5 chips5 and <50 per cent gland involvement. 1 A classification system with stages Af (focal), Al (1 lobe only) and A2 (multifocal or diffuse) also has been proposed. 6 Focal disease alternatively has been called stage O and more diffuse disease has been called simply stage A. 7 Diffuse or high grade incidental lesions have been shown to Accepted for publication February 15, 1980. Read at annual meeting of North Central Section, American Urological Association, Phoenix, Arizona, October 13-20, 1979. * Requests for reprints: Department of Urologic Surgery, Box 394 Mayo, University of Minnesota Hospitals, Minneapolis, Minnesota 55455. t Current address: Department of Urology, M553, University of California, San Francisco, California 94903.

The over-all incidence of stage A prostatic carcinoma diagnosed by transurethral resection or enucleation is about 10 per cent and varies with age and sectioning technique. Since incidental carcinomas often are confined to the surgical prostatic capsule the autopsy incidence is approximately twice the clinical incidence. Whitmore reviewed the incidence with respect to age and reported values varying from 4 per cent in the third decade to 80 per cent in the ninth decade. 11 His data and those of others are reported in table 2. 11- 11 Bauer and associates reported a series of 847 consecutive suprapubic prostatectomy specimens with a 6.5 per cent incidence of stage A carcinoma.18 Bergman and associates, 19 Smith and Woodruff 20 and V arkarakis and associates21 reported a 3.5, 9.5 and 4.9 per cent incidence, respectively. Lilien and associates showed an incidence of 24 per cent based on simple perinea! prostatectomies. 22 Only about 30 to 50 per cent of stage A carcinoma of the prostate diagnosed with step-sectioning techniques is appreciated on routine sectioning. Denton and associates reviewed 500 specimens from transurethral resection of the prostate for clinically benign disease. 23 Of 100 prostates on which both techniques were done there were 6 incidental carcinomas on routine sectioning and 15 additional carcinomas on step-sectioning, for a total incidence of 21 per cent of which only 28 per cent were diagnosed on routine sectioning. SUBCLASSIFICATION

An appreciable number of incidental carcinomas will be staged as A2 by most staging systems, based on tumor volume and histologic grade. In all autopsy series reported by Butler and associates of 71 patients with stage A carcinoma 56.4 per cent had a single focus, 36.6 per cent were multicentric and 7.0 per cent were diffuse.24 Of the 26 multicentric lesions 4 had >3 foci, 24 were believed to involve > ! lobe and 17 were bilateral. Of 28 stage A lesions in 173 autopsies reported by Edwards and associates 28 per cent were multicentric. 14 Of 103 incidental lesions examined by Barnes and associates 71 per cent were focal (less than a fourth of the gland) and 29 per cent were diffuse (more than a fourth of the gland).8 Seventeen per cent of 47 cases reported by Correa and associates were diffuse. 25 Like the staging system the histologic grading system lacks

626

627

INCIDENTAL CARCINOMA OF PROSTATE TABLE

I. Current staging systems for prostatic carcinoma

Reference Boxer4 Golimbu and associates• Catalona and Scott• Donohue and associates' deVere White and associates7 McCullough 10 Golimbu and Morales•

Stage Al A2 Al A2

Af Al A2 Al A2 0 A A B2 A

B2«

TABLE 2.

Definition Focal, well differentiated, ;a.3 chips More volume or poorly differentiated Anything less than stage A2 >5 chips or poorly differentiated Focal Only l lobe involved Multifocal or diffuse Focal, well differentiated >50% of specimen involved or high grade Focal Diffuse, high grade Well differentiated, ;a.3 microscopic foci More volume or less than well differentiated Focal, well differentiated, ;a.5 chips, ;a.3 separate microscopic foci Incidental, diffuse, multifocal, high grade

Incidence of incidental prostatic carcinoma by age of patient*

Pt. Age

Incidence (%)

Av.(%)

30-39 40-49 50-59 60-69 70-79 80-89 90-99

0.0- 4.0 4.4-17.0 5.3-14.0 17.8-23.0 21.0-36.0 17.6-48.5 40.0-80.0

1.9 6.3 10.4 18.5 28.7 37.1 60.0

* Modified from Whitmore 11 and others. 12- 1'

uniformity. Although encouraging steps have been taken toward establishing a uniform grading system26 it presently is not possible to apply such a system to the majority of reported series. However, one can contrast the well differentiated lesion against the moderately to poorly differentiated lesion. The frequency with which the various histologic grades are reported varies considerably (table 3). 2 ' 5 ' 17' 18' 27- 30 The incidence of well differentiated lesions ranges from 40 to 91. 7 per cent, with an average of 60 per cent. As expected, there is some correlation between tumor volume and histologic grade. Of 39 cases of focal stage A prostatic carcinoma reported by Correa and associates all were believed to be well differentiated, while of 8 diffuse lesions 2 (37.5 per cent) were poorly differentiated. 25 Of23 small (1 section, not >3 low power fields) and 29 large (anything greater than this) incidental lesions reported by Bauer and associates the incidence of moderately to poorly differentiated lesions was 17 and 69 per cent, respectively. 18 There is, then, a tendency toward high grade lesions with large volume disease. UNDERSTAGING

The potential for rapid progression of carcinoma among the substages can be estimated by the incidence of clinical understaging and survival data. Boxer and associates reported 369 radical prostatectomies, 35 of which were for clinically stage A disease. 31 The operative stages were described as A (31 per cent), B (46 per cent) and C (23 per cent). Of the 24 patients in whom the disease was understaged 75 per cent had moderately to poorly differentiated lesions. Donohue and associates reported 23 patients with stage A disease (5 with stage Al and 18 with stage A2 cancer) who had pelvic lymphadenectomies. 1 None of the patients with stage Al disease had positive nodes, while 4 (22 per cent) of the patients with stage A2 cancer had positive nodes. All 4 of these patients had high grade primary tumors compared to 50 per cent in the remaining stage A2 lesions. Golimbu and associates reported 53 patients with stages A and B disease who underwent pelvic lymphadenectomies, 36 of whom had radical prostatectomies. 5 Of 4 patients with stage Al lesions none had positive nodes, while of 16 patients with stage A2 lesions 37.5 per cent had lymph node involvement. This figure falls between those for lymph node involvement in patients with stages Bl and B2 lesions (17.6 and 62.5 per cent,

respectively). There was a similar incidence of moderately to poorly differentiated lesions in the A2, Bl and B2 groups. Positive nodes were found in 3 of the 4 patients with poorly differentiated stage A2 lesions. Of those who underwent radical prostatectomy the incidence of extension through the capsule for patients with clinical stages A2, Bl and B2 disease was 6.25, 29 and 25 per cent, respectively. These data were updated 9 at which time 8 of 24 (33 per cent) patients with stage A2 lesions were found to have positive nodes (table 4). 1• 5• 9• 31 - 33 Of interest is the finding that only 1 of 15 patients with well differentiated stage A2 lesions had lymph node involvement, in contrast to 22 of 27 with moderately to poorly differentiated stage A2 lesions. PROGNOSIS

Survival rates differ among studies, probably because of the variance in definition of stage A2 lesions and the inadequate length of followup of many patients. The over-all survival rate of patients with stage A disease at 5, 10 and 15 years has been reported to be 54 to 82, 35.4 to 56.3 and 27 to 30 per cent, respectively. 2' 8 ' 18' 31 ' 34' 35 In some series patients with stage A lesions, especially stage A2, had survival rates that are comparable to or less than those with stage Bl disease. 7• 8 • 26 • 35 Not only are there histologic data to support the concept that larger tumor volume and higher histologic grade are associated with greater tumor aggressiveness but there are survival data to support this fact as well (tables 5 and 6). Barnes and associates reported a considerable difference in 10 and 15-year survival rates between focal and diffuse lesions. 8 Khalifa and Jarman reported a sizable difference in survival at 10 years in patients with >3 foci of tumor as opposed to less tumor volume. 2 The difference in survival was by a factor of approximately 2 in both series. When survival rates of patients are compared by histologic grade a significant difference is observable as early as 5 years.2- 30• 36 Unfortunately, insufficient data are available to correct these survival statistics for age and general medical condition. Nonetheless, the data suggest that large tumor volume and high histologic grade are associated with diminished survival. TABLE 3.

Histologic grade of incidental carcinoma Histologic Grade (%) Total No. Well DifPts. ferentiated

Reference

Golimbu and associates' Blackard and associates" Bauer and associates 18 Scott and associates" Lehman and associates28 Munsie and Foster29 Khalifa and Jarman2 Heaney and associates30 Present study

TABLE 4.

20 91 52 62 25 20 48 100 30

Moderately Differentiated

45 40 54 79 76 60 91.7 50 77

Moderately to Poorly Differentiated

Poorly Differentiated

35 54

20 6 46 21 24 40 8.3 10

40 23

Surgical stage of incidental carcinoma

Reference

Stage

No. Pts.

No. With Capsular Invasion (%)

Donohue and associates' Golimbu and associates' Boxer and associates31 Wilson and associates32 Bruce and associates" Golimbu and Morales• Av.

Al A2 Al A2

A Al A2 A A2 Al A2

No. With Lymph Node Involvement (%)

0

5

18

4 (22.0)

4

0 6 (37.5)

16 35 4 8 3

24 13 50

1 (6.25) 8 (23.00) 0 0

0 0 0

8 (33.0) 0 (0.0) 12 (24.0)

628

SHELDON, WILLIAMS AND FRALEY

A potentially more meaningful statistic than survival alone is the number of patients who actually die of carcinoma of the prostate (table 7). Khalifa and Jarman report that up to 22.7 per cent of patients with stage A prostatic cancer will die of cancer by 10 years after diagnosis and 27 per cent of patients followed >10 years will die of cancer.2 Correa and associates reported a 25 per cent rate of death from cancer in patients with diffuse lesions25 and Bauer and associates reported a 50 per cent incidence of death from cancer in patients with high histologic grade lesions. 18 The rate of cancer deaths is much less for well differentiated and small volume lesions. It is more difficult to ascertain the number of patients who suffer progression of this disease that is not reflected in mortality statistics. In the series of Correa and associates, of 39 patients with focal and well differentiated lesions only 3 patients (7.7 per cent) had disease progression and none died of cancer. 25 Of 8 patients with diffuse lesions 5 (63 per cent) had progression of the disease and 2 died of cancer. Bauer and associates reported that the percentage of favorable outcomes for patients with well differentiated as contrasted to moderately to poorly differentiated lesions was 71.5 and 12.5 per cent, respectively. 18 Similarly, favorable outcomes for patients with small compared to large lesions were 60.9 and 31.0 per cent, respectively. One must keep in mind that it presently is impossible to dissociate the effect of volume from histologic grade on the course of the disease. TABLE

5. Survival rates by tumor volume Tumor Volume

Reference Khalifa and Jarman'

5 Yrs.

10 Yrs.

15 Yrs.

75.8 73.6 58 58 63

44.8 21 56 26 50 28

35 14 35 14

1-3 foci >3 foci Focal Diffuse Focal Diffuse

Barnes and associates8 Av.

TABLE

Over-All Survival(%)

66

6. Survival rates by histologic grade Over-All Survival(%)

Reference

Histologic Grade

Khalifa and Jarman' Barnes and associates• Hanash and associates36

Well differentiated Poorly differentiated 1-11 III-IV I

II Heaney and associates30 Av.

TABLE

10 Yrs.

77 50 61 60 100 89 55

38.5 25 44 44

75 59

71

39 36 25 25 48 31

15 Yrs.

32 25 29 28 0

30 15

7. Patient deaths from prostatic carcinoma

Reference Bauer and associates 18 Varkarakis and associates21 Correa and associates25 Heaney and associates30 Av.

III-IV Well differentiated Moderately to poorly differentiated Well differentiated Moderately to poorly differentiated

5 Yrs.

Tumor Description

No. Deaths/ No. Pts. (%)

Well differentiated Moderately to poorly differentiated Volume <12 per cent Volume a:;40 per cent Focal Diffuse Well differentiated Moderately to poorly differentiated Well differentiated Moderately to poorly differentiated Focal Diffuse

4/28 (14.0) 12/24 (50.0) 0/11 2/20 (10.0) 0/39 2/8 (25.0) 1/50 (2.0) 7/50 (14.0) 5/78 (6.4) 19/74 (25.7) 2/104 (1.9) 10/82 (12.2)

COMMENT

Conservative management of stage A carcinoma of the prostate has long been advocated. Since there is little evidence that hormonal therapy alters the course of stage A disease the decision to follow conservative management must presume either a slowly progressive natural history or irradication of stage A carcinoma by transurethral resection or enucleation of the prostate. However, all available evidence suggests that for a considerable number of patients with incidental carcinoma of the prostate the disease will not have a benign natural history. There also is ample evidence that transurethral resection or enucleation alone is not effective in eliminating all incidental carcinomas of the prostate. Blackard and associates reported a series of 91 patients with stage A disease. 27 Of 24 who underwent radical prostatectomy 87.5 per cent had residual tumor in the surgical specimen. In a series by Lehman and associates 25 patients with stage A disease underwent radical prostatectomy and 60 per cent had residual tumor. 28 Heaney and associates found residual tumor in 50 per cent of 8 specimens. 30 Obviously, these were all selected series. McMillen and Wettlaufer performed second, staging transurethral resections on 27 of 61 patients with stage A disease who had focal disease on initial pathologic specimens. 37 An average of 4 gm. of tissue was resected. Sixty-three per cent had no residual cancer and 11 per cent had a single remaining focus resected. However, 26 per cent had a significant amount of tumor resected, reclassifying them as having stage A2 disease. Approximately a third of localized prostatic carcinoma is restricted to the surgical capsule and a third involves the surgical capsule. 22 Certainly, we would agree with other investigators that high grade, large volume incidental carcinoma of the prostate merits aggressive therapy in most cases. If a patient has focal disease and is young and in good health we would consider a second staging transurethral resection with definitive therapy predicated on the estimated stage at that point. Otherwise, we continue to follow patients with stage A disease expectantly. .The results of management will likely become more interpretable as more detailed staging systems become available. The distinction between focal and diffuse lesions presently is imprecise. The difficulty in determining the significance of tumor volume is compounded by the fact that multifocal and diffuse disease tends to be more poorly differentiated than focal disease. Golimbu and Morales found that only 33 per cent of 24 lesions classified as stage A2 were well differentiated, while 67 per cent were moderately to poorly differentiated. 9 In reviewing the literature, they found that 78 per cent of stage A2 lesions were moderately to poorly differentiated. Heaney and associates reported on 100 patients who had had stage A disease and found that 92 per cent of well differentiated tumors were small and focal, while 80 per cent of moderately or poorly differentiated tumors were large and diffuse. 30 The survival rate of patients with stage A2 prostatic carcinoma appears to be equal to or lower than the rate for those with Bl disease. This fact correlates with the observation that 86 per cent of stage Bl lesions are well differentiated in contrast to only 22 per cent of stage A2 lesions. 9 In addition, as noted by Golimbu and Morales, 9 the incidence of lymph node involvement is higher for patients with clinical stage A2 lesions than for those with stage Bl lesions (24 and 14 per cent, respectively). These data suggest that the major indicator of prognosis is the histologic grade and, therefore, a staging or scoring system considering this factor such as that presented by Gleason and associates26 would appear most appropriate. However, there are few data available to direct the therapeutic approach to the patient with well differentiated, incidental carcinoma with non-focal disease. PROPOSED STAGING SYSTEM

We currently are pursuing a study designed to isolate the variables of histologic grade and tumor volume, with consider-

629

INCIDENTAL CARCINOMA OF PROSTATE

ation being given to the following facts: 1) incidental prostatic carcinoma currently is diagnosed primarily by transurethral resection, 2) there has been no systematic approach to analysis of incidental carcinoma, making it impossible to compare the results of various therapeutic modalities in different series, and 3) the relative contribution of tumor volume and histologic grade to patient death is unknown, making therapeutic intervention imprecise in many instances. For the last 21 months we have collected data on tumor distribution within the resected prostate gland, with specific analysis of the importance of tumor volume presently unknown. The following protocol is used for transurethral resection: all patients undergoing transurethral resection of the prostate are resected in 4 quadrants (fig. 1) and each quadrant is sent separately for pathologic examination, the surgical specimen is analyzed by routine sectioning techniques and the histologic grade is estimated according to the system described by Gleason and associates. 26 Between June 1, 1978 and April 30, 1980, 404 transurethral resections of the prostate for clinically benign disease were done at our hospitals and the Minneapolis Veterans Administration Medical Center. Fifty-six cases of incidental carcinomas were found, for an incidence of 14 per cent. Of these 56 cases 43 (77 per cent) were well differentiated (Gleason stages I and II),

INCIDENTAL PROSTATIC CARCINOMA STAGING TECHNIQUE

which is comparable to the available literature as outlined previously. These patients are being followed closely for evidence of progression of the disease. Based upon the current literature and the expected outcome of our study we propose a preliminary classification as follows (fig. 2): stage Af-;;a3 chips of carcinoma, stage Al->3 chips of carcinoma, restricted to 1 quadrant or 2 contiguous quadrants and stage A2-carcinoma in 2 non-contiguous quadrants, or greater tumor volume. Each of these stages is then subdivided according to histologic grade (table 8). The distribution of these lesions is shown in figure 3. Thirty patients (54 per cent) have low grade focal lesions, 13 (23 per TABLE

8. Incidental prostatic carcinoma grading system

Grade Class

Gleason Grade

Low High

~3*

Histologic Score ;;a5

,a;4

se;6

* Grade 3 only included if it is the minor pattern.

RESULTS 32

54%

INCIDENCE 56/404 (14%)

28

(/)

C:

24

Q)

:;::: ell

c.. 20

-... 0

Q)

16

.0

E ::,

LATERAL

LATERAL

z

[23%]

12

%1

[

14%

8

23

13%1

9% 4

,,,, ,,,' POSTERIOR

5%

IAf

A1

A2 I IA,

~LOW_]

FIG. 1. Protocol for transurethral resection and staging of incidental carcinoma.

A1

GRADE

GRADE

FIG. 3. Distribution of incidental prostatic carcinoma lesions

INCIDENT AL PROST ATIC CARCINOMA ST AGING SYSTEM

FOCAL

A2J

~HIGH

LOCALIZED

DIFFUSE

FIG. 2. Staging system for incidental carcinoma of prostate

630

SHELDON, WILLIAMS AND FRALEY Incidence ( overall -10 ¾)

~ 0

., u .,

Well Differentiated 40 - 92% Avg. 60%

40 Focal

C

:2 u

-'=

Mod. to Poorly Differentiated

8- 60% Avg. 40%

Average Reported Survival(%)

56 - 83% Avg. 70%

20 0

3 4

~

5 6 7 8 9 Decade

I

Multifocal or Diffuse 17- 44% Avg. 30%

5 yr.

IOyr. 15yr.

75

48

30

Mod. to 59 Poorly Diff.

31

15

Well Diff.

Expected* 81

60

39

Mod. to 26 Poorly Diff.

Focal

50

35

Focal

14

Diffuse

Well Diff.

Diffuse

63 66

28

Average Reported Death Rate from CAP(%)

Reported Lymph Node Involvement (Avg.) Stage

Involvement

Focal and Well Diff.

0

Diffuse or Mod. to Poorly Diff.

6

2

12

24%

Frc. 4. Summary of major features of incidental carcinoma reported in literature. Asterisk denotes expected survival rates extrapolated from United States survival analysis tables of 1965 for 65-year-old man. 38

cent) have high grade lesions and 13 (23 per cent) have low grade high volume disease. Of the non-focal (stages Al and A2) lesions 50 per cent were high grade, while of the truly diffuse (stage A2) lesions 58 per cent were of high histologic grade. This fact may account for the aggressive nature of large volume tumors reported in the literature. This simple staging system will be tested in a prospective manner during the next several years. Obviously, it will be some time before the results of such a study reach statistical significance. Because of the potential significance of such information we hope to encourage similar studies in other institutions. Patients currently are divided into non-homogeneous subgroups, and therapy based on these divisions is not always justified. Only more precise subclassification can resolve this issue.

several large series should promote understanding of the natural history of this disease, and would make reports of therapeutic trials interpretable. REFERENCES 1. Donohue, R. E., Pfister, R.R., Weigel, J. W. and Stonington, 0. G.:

2. 3. 4. 5.

CONCLUSION

Incidental prostatic carcinoma is a common but poorly understood tumor. Much has been written on the subject and many critical features can be extrapolated from these data (fig. 4). 38 There would appear to be sufficient data to merit aggressive therapy in most cases of high grade lesions. However, the significance of tumor volume is unknown. Specifically, patients with stage A2 disease classified by current criteria, for which aggressive therapy is advocated by many, represent a nonhomogeneous population. The natural history and, therefore, the appropriate management of large volume, well differentiated lesions are unknown. They account for about 23 per cent of stage A lesions and 50 per cent of stage A2 lesions classified by current criteria. In other words, half of the patients for which aggressive management currently is advocated have an entirely unknown natural history. More refined descriptive techniques for incidental prostatic cancer based upon 4-quadrant analysis of the resected specimen should produce a more precise staging system. Such a system used prospectively in

6. 7. 8. 9. 10.

11. 12. 13. 14.

Pelvic lymphadenectomy in stage A prostatic cancer. Urology, 9: 273, 1977. Khalifa, N. M. and Jarman, W. B.: A study of 48 cases of incidental carcinoma of the prostate followed 10 years or longer. J. Urol., 116: 329, 1976. Jewett, H.J.: The present status ofradical prostatectomy for stages A and B prostatic cancer. Urol. Clin. N. Amer., 2: 105, 1975. Boxer, R. J.: Adenocarcinoma of the prostate gland. Urol. Survey, 27: 75, 1977. Golimbu, M., Schinella, R., Morales, P. and Kurusu, S.: Differences in pathological characteristics and prognosis of clinical A2 prostatic cancer from Al and B disease. J. Urol., 119: 618, 1978. Catalona, W. J. and Scott, W. W.: Carcinoma of the prostate.: a review. J. Urol., 119: 1, 1978. deVere White, R., Paulson, D. F. and Glenn, J. F.: The clinical spectrum of prostate cancer. J. Urol., 117: 323, 1977. Barnes, R., Hirst, A. and Rosenquist, R.: Early carcinoma of the prostate: comparison of stages A and B. J. Urol., 115: 404, 1976. Golimbu, M. and Morales, P.: Stage A2 prostatic carcinoma. Should staging system be reclassified? Urology, 13: 592, 1979. McCullough, D. L.: Diagnosis and staging of prostatic cancer. In: Genitourinary Cancer. Edited by D. G. Skinner and J. B. deKernion. Philadelphia: W. B. Saunders Co., chapt. 16, p. 295, 1978. Whitmore, W. F., Jr.: Symposium on hormones and cancer therapy; hormone therapy in prostatic cancer. Amer. J. Med., 21: 697, 1956. Hirst, A. E., Jr. and Bergman, R. T.: Carcinoma of the prostate in men 80 or more years old. Cancer, 7: 136, 1954. Andrews, G. S.: Latent carcinoma of the prostate. J. Clin. Path., 2: 197, 1949. Edwards, C. N., Steinthorsson, E. and Nicholson, D.: An autopsy

INCIDENTAL CARCINOMA OF PROSTATE

study of latent prostatic cancer. Cancer, 6: 531, 1953. 15. Moore, R. A.: The morphology of small prostatic carcinoma. J. Urol., 33: 224, 1935. 16. Gaynor, E. P.: Zur Frage des Prostatakrebses. Virchows Arch. f. Path. Anat., 301: 602, 1938. 17. Scott, R., Jr., Mutchnik, D. L., Laskowski, T. Z. and Schmalhorst, W. R.: Carcinoma of the prostate in elderly men: incidence, growth characteristics and clinical significance. J. Urol., 101: 602, 1969. 18. Bauer, W. C., McGavran, M. H. and Carlin, M. R.: Unsuspected carcinoma of the prostate in suprapubic prostatectomy specimens. Cancer, 13: 370, 1960. 19. Bergman, R. T., Turner, R., Barnes, R. W. and Hadley, H. L.: Comparative analysis of one thousand consecutive cases of transurethral prostatic resection. J. Urol., 74: 533, 1955. 20. Smith, G. G. and Woodruff, L. M.: The development of cancer of the prostate after subtotal prostatectomy. J. Urol., 63: 1077, 1950. 21. Varkarakis, M., Castro, J. E. and Azzopardi, J. G.: Prognosis of stage 1 carcinoma of the prostate. Proc. Roy. Soc. Med., 63: 91, 1970. 22. Lilien, 0. M., Schaefer, J. A., Kilejian, V. and Andaloro, V.: The case for perinea! prostatectomy. J. Urol., 99: 79, 1968. 23. Denton, S. E., Choy, S. H. and Valk, W. L.: Occult prostatic carcinoma diagnosed by the step-section technique of the surgical specimen. J. Urol., 93: 296, 1965. 24. Butler, J., Braunstein, H., Freiman, D. G. and Gall, E. A.: Incidence, distribution, and enzymatic activity of carcinoma of the prostate gland. Arch. Path., 68: 243, 1959. 25. Correa, R. J., Jr., Anderson, R. G., Gibbons, R. P. and Mason, J. T.: Latent carcinoma of the prostate-why the controversy? J. U rol., 111: 644, 1974. 26. Gleason, D. F., Mellinger, G. T. and The Veterans Administration Cooperative Urological Research Group: Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Urol., 111: 58, 1974. 27. Blackard, C. E., Mellinger, G. T. and Gleason, D. F.: Treatment of stage 1 carcinoma of the prostate: a preliminary report. J. Urol., 106: 729, 1971. 28. Lehman, T. H., Kirchheim, D., Braun, E. and Moore, R.: An evaluation of radical prostatectomy for incidentally diagnosed carcinoma of the prostate. J. Urol., 99: 646, 1968. 29. Munsie, W. J. and Foster, E. A.: Unsuspected very small foci of carcinoma of the prostate in transurethral resection specimens. Cancer, 21: 692, 1968. 30. Heaney, J. A., Chang, H. C., Daly, J. J. and Prout, G. R., Jr.:

31. 32. 33. 34. 35. 36. 37. 38.

631

Prognosis of clinically undiagnosed prostatic carcinoma and the influence of endocrine therapy. J. Urol., 118: 283, 1977. Boxer, R. J., Kaufman, J. J. and Goodwin, W. E.: Radical prostatectomy for carcinoma of the prostate: 1951-1976. A review of 329 patients. J. Urol., 117: 208, 1977. Wilson, C. S., Dahl, D. S. and Middleton, R. G.: Pelvic lymphadenectomy for the staging of apparently localized prostatic cancer. J. Urol., 117: 197, 1977. Bruce, A. W., O'Cleireachain, F., Morales, A. and Awad, S. A.: Carcinoma of the prostate: a critical look at staging. J. U rol., 117: 319, 1977. Greene, L. F. and Simon, H. B.: Occult carcinoma of the prostate. Clinical and therapeutic study of eighty-three cases. J.A.M.A., 158: 1494, 1955. Barnes, R. W. and Ninan, C. A.: Carcinoma of the prostate: biopsy and conservative therapy. J. Urol., 108: 897, 1972. Hanash, K. A., Utz, D. C., Cook, E. N., Taylor W. F. and Titus, J. L.: Cancer of the prostate: a 15-year followup. J. Urol., 107: 450, 1972. McMillen, S. M. and Wettlaufer, J. N.: The role of repeat transurethral biopsy in stage A carcinoma of the prostate. J. Urol., 116: 759, 1976. Vital Statistics of the United States: 1965, Vol. II: Mortality. Hyattsville, Maryland: Department of Health, Education and Welfare: Public Health Service, National Center for Health Statistics, pp. 5-9, 1965.

EDITORIAL COMMENT The authors provide an exhaustive review of incidental carcinoma of the prostate and propose a prospective study of this disease. In our retrospective review of 326 patients with stage A carcinoma we observed that the majority of incidental cancers were focal, well differentiated, of low biologic potential and did not affect survival. In addition, the majority of multifocal or diffuse tumors also were well differentiated and did not affect survival but they appeared to be more aggressive, as demonstrated by increased incidence of progression of disease. Finally, the decisive factor associated with progression of the disease and decreased survival was the degree of differentiation of the neoplasm. Thus, poorly differentiated neoplasms, even if focal, behaved aggressively. Laurence F. Greene Division of Surgery/Urology University of California San Diego, California