Prostate Cancer in Men less than 45 Years Old: Influence of Stage, Grade and Therapy

0022-5347/87 /1375-0888$02.00/0 Vol. 137, May

THE JOURNAL OF UROLOGY

Copyright© 1987 by The Williams & Wilkins Co.

Printed in U.S.A.

PROSTATE CANCER IN MEN LESS THAN 45 YEARS OLD: INFLUENCE OF STAGE, GRADE AND THERAPY MITCHELL C. BENSON, STEVEN A. KAPLAN

AND

CARL A. OLSSON

From the Squier Urological Clinic of the Presbyterian Hospital and Department of Urology, College of Physicians and Surgeons of Columbia University, New York, New York

ABSTRACT

We analyzed patients with histologically proved adenocarcinoma of the prostate to determine the natural history of prostatic cancer in men less than 45 years old. The mean age of the patients was 41 years (range 36 to 44 years). At presentation 5 patients were asymptomatic, 5 had voiding symptoms, 3 had bone pain, 3 had hematuria and 1 had testicular pain. Followup in these patients ranged from 19 to 270 months, with a mean of 111 months. Six patients with clinical stage B disease at diagnosis underwent radical retropubic prostatectomy. These patients enjoy projected 10 and 15year survival rates of 100 and 82 per cent, respectively. Four patients with stage C disease died of prostatic cancer, although 1 survived for 204 months. Of 4 patients with stage D disease 3 died within 13 months, while 1 still is alive at 48 months. No patient with a Gleason tumor score of 8 to 10 survived more than 13 months. Patient age at presentation appears to be less important than clinical stage, histological grade or treatment modality in the prediction of the course of prostatic cancer. Young men with localized disease at presentation should be treated aggressively and they should have survival rates comparable to actuarial expectancy. Carcinoma of the prostate generally is regarded as a disease of older men. Men less than 45 years old account for less than 0.6 per cent of all cases of prostatic cancer. 1 Some reports have indicated that survival in younger patients is not as good as in those who present with similar stage disease at an older age. 2• 3 Other reviews have conflicted with this opinion. 4 •5 We examined retrospectively cases of prostatic cancer in men less than 45 years old to determine the natural history of the disease in this young population. MATERIAL AND METHODS

The records of our tumor registry for the last 30 years (1954 to 1984) were examined.for cases of prostatic cancer in men less than 45 years old. The presenting complaints, clinical and pathological stages, and modalities of therapy were noted. All patients underwent prostatic biopsy and the disease was staged according to physical examination, excretory urography, bone scan or skeletal survey, and serum alkaline and acid phosphatasJ:lJeyels. The_Gleason _gLaningJ;ystem was used~to_grnde the tumor pathologically in those cases available for examination.6 Kaplan-Meier survival curves were computed to determine 10 and 15-year survival rates. 7 Actuarial survival was determined for patients in this age category. RESULTS

In 14 patients a diagnosis ofprostatic cancer was established before they were 45 years old (table 1). Age range at diagnosis in these patients was 36 to 44 years, with a mean of 41 years. Five patients were less than 39 years old. The most common clinical presentation was that of an asymptomatic, hard nodule found on routine physical examination, which was noted in 5 patients (36 per cent). Three patients (21 per cent) presented with bone pain and ultimately had metastatic disease. Hematuria was noted in 3 patients (21 per cent), while irritative voiding symptoms prompted 3 patients (21 per cent) to seek medical attention. Two patients (14 per cent) had symptoms of obstruction and 1 (7 per cent) presented with testicular pain. In all 14 patients rectal examination revealed an abnormality of the prostate gland. A firm, solitary nodule was the most common finding and was noted in 7 patients (50 per cent). Accepted for publication December 2, 1986.

The clinical stage at presentation in these 14 patients revealed that 6 (43 per cent) had stage B, 4 (29 per cent) stage C and 4 (29 per cent) stage D disease. Pathological stage was consistent in 5 of 6 patients (83 per cent) with clinical stage B disease. One patient with clinical stage B disease had pathological stage C disease (microscopic extension beyond the prostatic capsule). This patient received postoperative external beam radiotherapy and was free of disease at 19 months (table 1). Patients with stage C disease did not undergo formal pelvic lymph node sampling. Therefore, it is possible that some patients with clinical stage C tumor in this series may have had pathological stage D disease at the initial presentation. Gleason grading of pathological specimens was performed in 11 cases in which slides were available for review. Four patients had a tumor Gleason score of 2 to 4, 4 had a score of 5 to 7 and 3 had a score of 8 to 10. A comparison of tumor stage to Gleason grade is shown in table 2. Initial therapeutic modalities included radical retropubic prostatectomy inthe 6 _patients with stage B disease (43per cent), transurethral resection in 1 (7 per cent), hormonal therapy (orchiectomy and/or diethylstilbestrol) in 6 (43 per cent), and combination radiotherapy and hormonal therapy in 1 (7 per cent). One patient who underwent radical retropubic pr9statectomy and lymph node dissection underwent adjuvant external beam radiotherapy. No patient received initial chemotherapeutic intervention (table 1). Survival. Patients were followed for 19 to 270 months after therapy, with a mean duration of followup of 111 months. The over-all survival of these 14 patients is shown in figure 1. Eight patients (57 per cent) survived longer than 5 years. The 10 and 15-year survival rates were 47 and 42 per cent, respectively. Of the 14 patients 8 (57 per cent) died of prostatic cancer. Although all 6 patients with stage B disease treated by radical retropubic prostatectomy experienced uniform 10 and 15-year survivals of 100 per cent, the Kaplan-Meier curve projects a 15-year survival rate of 82 per cent (fig. 2). Five patients still are free of disease: 3 remain free of disease after 20 years, 1 after 10 years and 1 after 19 months. Of the 6 patients with stage B disease only 1 experienced disease recrudescence (at 13 years) and he subsequently died at 17 years. Of the 4 patients with stage C disease 3 (75 per cent) survived 5 years (fig. 2). The mean survival was 7 years. One patient

888

889

PROSTATE CANCER IN }JiEN LESS THAN 45 YEARS OLD L Patient data

TABLE

Stage

Clinical Symptom

Pt. Age

Gleason Score

Therapy

Pt. Status (mos.)

Radical retropubic prostatectomy Orchiectomy

Alive (130)

44

Asymptomatic

B

4

44

Asymptomatic

C

5

44

Asymptomatic

B

4

44

Asymptomatic

B

4

37

Obstructive voiding, hematuria

C

8

39

Irritative voiding

C

6

36

Obstructive voiding

B

2

Radical retropubic prostatectomy

37

Bone pain

D

9

Diethylstilbestrol

44

Asymptomatic

C

Not applicable

41

Bone pain

D

10

Transurethral prostatic resection Orchiectomy

42

Bone pain, hematuria

D

Not applicable

Orchiectomy

40

Irritative voiding

B

Not applicable

36*

Testicular pain

B

7

44

Irritative voiding, hematuria

D

7

Radical retropubic prostatectomy Radical retropubic prostatectomy, external beam radiotherapy Orchiectomy

Dead of prostatic Ca (204) Alive (258)

Radical retropubic prostatectomy Radical retropubic prostatectomy External beam radiotherapy, orchiectomy Orchiectomy

Alive (243) Dead of pro static Ca (7) Dead of prostatic Ca (87) Dead of pro static Ca(200) Dead of prostatic Ca (13) Dead of prostatic Ca (85) Dead of prostatic Ca (10) Dead of prostatic Ca (7) Alive (270) Alive (19)

Alive (48)

* Patient had pathological stage C disease (microscopic extension beyond the capsule). TABLE 2.

Comparison of pathological stage and Gleason grade

100

Pathological Stage Gleason Grade

B

~

2-4 5-7

4 1

8-10

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40

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30

60

90

120

30

60

90

120

150

180

210

240

270

PROSTATE CANCER

150

180

210

240

MONTHS FIG. 2. Survival of patients with stage B disease closely approxirnates expected survival for age group. Patient with stage B disease who died at 17 years suffered disease recurrence at 13 years. Patients with stage C cancer exhibited intermediate survival. Mean time to progression in patients with stage C disease was 68 months. Patients with stage D cancer had worst survival rate.

270

MONTHS FIG. 1. Over-all survival of patients less than 45 years old with prostatic cancer. Range of followup was 19 to 270 months. Over-all 10 and 15-year survival rates were 4 7 and 42 per cent, respectively. Ticks on graph represent patients known to be alive while circles represent patient deaths.

survived 17 years before death of disseminated disease, 2 died after 7 years and 1 died after only 7 months. The mean time to progression in this group was 68 months. Among the 4 patients who presented with stage D disease 1 (25 per cent) is alive after 48 months while 3 died within 13 months (fig. 2).

Retrospectively applied, Gleason grading appeared to be a determinant of the ultimate survival in this series. Patients with a Gleason score between 2 and 4 uniformly survived 5 and IO-year intervals. However, 1 patient with a Gleason 2 lesion died of prostatic cancer at 200 months. Patients with tumors of a high Gleason score at initial presentation experienced a poor prognosis (fig. 3). For example, all 3 patients who presented with Gleason scores between 8 and 10 survived less than 13 months. Finally, there appeared to be a correlation between stage of disease and degree of histological differentiation. In general, patients with localized disease had well differentiated tumors.

890

BENSON, KAPLAN AND OLSSON (2-4)

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270

MONTHS Fm. 3. Survival by Gleason grade closely approximates survival by stage. Patients with low grade lesions have survivals that approximate expected survival for age group, while those with high grade lesions uniformly died of disease by 13 months. Lines above curve represent patients with Gleason grades 2 to 4, while lines below curve represent patients with Gleason grades 5 to 7. Conversely, patients who presented with metastatic disease had tumors that were poorly differentiated (table 2). DISCUSSION

Adenocarcinoma of the prostate in men less than 45 years old is rare. Its incidence has been estimated variably to be between 0.5 and 1 per cent of all men with prostatic cancer.1 Thus, accurate predictions regarding survival in this group remain difficult. There are conflicting reports regarding the biological course of carcinoma of the prostate in younger men. Tjaden and associates reviewed 56 cases of prostatic cancer in men less than 50 years old, 12 of whom were less than 45 years old. 2 They observed that prostatic cancer in younger patients is more aggressive and rapidly fatal. This view was supported by Johnson and associates, who suggested in an analysis of 26 patients less than 50 years old that there is a definite relationship between the biological potential of prostatic cancer and the age of the patient.3 In contrast, Byar and Mostofi reported that cancer of the prostate may be less virulent in the younger age group. 4 This premise was based on a review of 51 cases of cancer of the prostate in men less than 50 years old, 21 of whom were less than 45 years old. Their group, as ours, had a high percentage oLpatients w:ith_local disease (38 per cent). Similarly, Silber and McGavran reported equal if not better survival statistics in younger patients.8 However, only 3 of the 65 patients analyzed in that study were less than 45 years old. Most of our patients with localized disease presented with an asymptomatic nodule found on routine rectal examination. Other series report a lower incidence of asymptomatic patients at diagnosis. In fact, neither Silber and McGavran8 nor Harrison5 reported on any patients who initially were asymptomatic. This high percentage of asymptomatic men undoubtedly is responsible for the high ratio of patients with stage B disease. The presence of voiding symptoms in our review was not necessarily correlated with a higher clinical stage or histological grade. More importantly, it was not always associated with a poor prognosis. This observation differs from that of Byar and Mostofi, who found that more advanced tumor grade and poorer survival rates were associated with voiding symptoms. 4 On the other hand, the presence of bone pain at initial presentation was uniformly a negative indicator. The most important predictors of long-term survival in these patients were clinical stage and histological grade. Patients with tumors of Gleason scores 2 to 4 experienced uniform 5 and IO-year survival rates with no evidence of disease. In

contrast, all patients with tumors of Gleason scores 8 to 10 died within 13 months. However, a low Gleason score does not ensure survival, as noted by patient 7 who had a stage B, Gleason score 2 lesion, and who suffered progression at 13 years and died 4 years later. Patients with stage B disease at initial presentation who were treated by radical retropubic prostatectomy had a projected survival rate of 82 per cent at 15 years, while those with stage C disease had intermediate survivals and those with stage D disease did poorly. This finding is in agreement with other reports in which patients with advanced stage, high grade tumors had a poor survival. The 82 per cent 15-year projected survival rate in the 6 patients who underwent radical reti'opubic prostatectomy is significantly higher than reported survival rates in older patients undergoing radical prostatectomy. The 15-year survival rate in patients who underwent radical prostatectomy reported on by Hodges and associates was 30.8 per cent. 9 Walsh and Jewett reported a 15-year survival rate of 51 per cent in patients undergoing radical prostatectomy. 10 This survival rate was equal to the actuarial rate for men in the age group reported. The 82 per cent 15-year survival rate in our series also equals the predicted actuarial survival for this given age group. The excellent long-term survival of patients undergoing radical prostatectomy for stage B cancer of the prostate reinforces the concept that radical therapy in these patients appears to be superior to other treatment modalities at 15 years. 11 Our review does not support the premise that younger men with prostatic cancer have a worse prognosis than older men with the same stage and grade of the disease. In most major series addressing survival of patients with stage B disease the survival rates equal actuarial expectations and this also is the case in our study. Since in our experience the majority of patients were asymptomatic at presentation, it is incumbent upon all physicians to perform routine digital examinations of the prostate on men more than 35 years old. The presence of symptoms does not necessarily preclude long-term survival. The association of localized disease and low histological grade appears to be a more important predictor of ultimate survival than age alone. Young individuals, like their older counterparts, with disease localized to the prostate should be treated aggressively by radical prostatectomy. REFERENCES

1. Chisholm, G. D.: Prostate. In: Tutorials in Postgraduate Medicine, Urology. London: Heinemann, chapt. 15, p. 223, 1980. 2. Tjaden, H. B., Culp, D. A. and Flocks, R. H.: Clinical adenocarci··· iioina of tlie prostate in patients under 51l years ofage~ J. Urol., 93: 618, 1965. 3. Johnson, D. E., Lanieri, J. P., Jr. and Ayala, A. G.: Prostatic adenocarcinoma occurring in men under 50 years of age. J. Surg. Oncol., 4: 207, 1972. 4. Byar, D. P. and Mostofi, F. K.: Cancer of the prostate in men less than 50 years of age: an analysis of 51 cases. J. Urol., 102: 726, 1969. 5. Harrison, G. S. M.: The prognosis ofprostatic cancer in the younger man. Brit. J. Urol., 55: 315, 1983. 6. Gleason, D. F.: Histologic grading and clinical staging of prostatic carcinoma. In: Urologic Pathology: The Prostate. Edited by M. Tannenbaum. Philadelphia: Lea & Febiger, part II, chapt. 9, p. 171, 1977. 7. Kaplan, E. L. and Meier, P.: Nonparametric estimation from incomplete observations. J. Amer. Stat. Ass., 53: 457, 1958. 8. Silber, I. and McGavran, M. M.: Adenocarcinoma of the prostate in patients less than 56 years old: a study of 65 cases. J. Urol., 105: 283, 1971. 9. Hodges, C. V., Pearse, H. D. and Stille, L.: Radical prostatectomy for carcinoma: 30-year experience and 15-year survivals. J. Urol., 122: 180, 1979. 10. Walsh, P. C. and Jewett, H.J.: Radical surgery for prostatic cancer. Cancer, 45: 1906, 1980. 11. Paulson, D. F.: Carcinoma of the prostate: the therapeutic dilemma. Ann. Rev. Med., 35: 341, 1984.