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The natural history of a disease describes its course without treatment. Description may be related to anatomy, pathology, changes on physical examination, symptoms of the disease under discussion, and the changes of all these parameters with time. Most information related to morphology and prostatic size resulted from autopsy series. Histological changes compatible with BPH may be present in the human prostate as early as age 30 years. The normal weight of an adult prostate is in the range of 15-20 g (autopsy specimens). The human prostate undergoes two kinds of growth: the first one is related to puberty, the second one to the development of BPH. The first increase of prostatic weight is clearly related to the endocrine changes occurring with puberty; the reasons for prostatic growth with the development of BPH are unknown as yet but seem to be related to endocrine factors. BPH rarely or never develops in early castrates. The scarce available information also shows that BPH is present at ages 70-80 in 50-75% of males studied. Only a fraction of those males showing benign prostatic enlargement actually become symptomatic. The natural history of the symptoms and their development in time and in relation to prostatic mass or other related factors is largely unknown. The available information on this subject is reviewed. In Europe, the symptomatology of BPH is described commonly in stages I-IV. Death resulting from BPH is usually related to severe infection in combination with obstructive uropathy of the upper urinary tract. Death is rare and is prevented by timely treatment. BPH and prostatic carcinoma frequently occur in the same prostatic specimen. Considering the different location of both entities within the gland, their different incidence, the difference in morphology of their early manifestations within the fine structure of the prostate, and other factors suggest that both disease entities have a different etiology. The incidence of BPH and prostatic carcinoma increases steadily with age. It is likely that age-related endocrine factors contribute to the pathogenesis of this disease.

This report describes the effect of high energy shock waves (HESW) generated by a Siemens Lithostar on four human prostatic carcinoma cell lines in vitro. The effects of temperature, shock wave energy, cell density and the number of HESW were investigated. Pressure measurements were carried out in the focus of the lithotriptor and inside test tubes that were placed in the focus. Direct cell kill was inversely related to temperature, whereas a linear relationship was found with shock wave energy. Cell kill appeared to be independent of cell density. All four cell lines were sensitive to the treatment with HESW, but displayed a different dose-response pattern. In vitro treatment of PC-3 cells retarded their growth upon injection into nude mice. It is concluded that human prostatic tumour cells are killed by HESW. Therefore, HESW could be of potential value in tumour treatment.

The transplantable human prostatic tumor model (PC-82) in nude mice was used to evaluate the indirect and possibly direct effects of estrogens on the growth of prostatic tumor tissue. High (pharmalogical) doses of plasma estradiol (E2) were achieved in tumor-bearing mice by using E2-containing Silastic implants of different lengths. In comparison with the situation in men, in mice much higher concentrations of circulating E2 (exceeding 3 nmol/liter) were necessary to attain (near)-castrate levels of plasma testosterone (T). Treatment of tumor-bearing mice with a high dose of E2 resulted in tumor growth arrest and a subsequent decline of the tumor volume, which equals the effects of castration. No evidence was found that either of the two doses of E2 applied had any additive inhibitory effect on tumor growth when compared to castration alone. It was inferred from these findings that in the PC-82 tumor model, estrogens, rather than having a direct effect on the tumor tissue, mainly act indirectly by their suppressive effect on T secretion in the host animal. A different and unexpected result was obtained in castrated tumor-bearing mice treated with a combination of E2 and T. With both doses of E2 this type of treatment led to a smaller increase of the tumor volume compared with mice receiving T only, the result of the high dose being statistically significant. This antagonistic effect of the two steroids on the PC-82 tissue was paradoxically associated with a sharp increase of nuclear androgen receptor levels and a higher concentration of dihydrotestosterone in the tumor tissue. Plasma and tissue concentrations of T appeared to be unaltered. The present study of the PC-82 prostate tumor shows that only by careful monitoring of plasma steroid levels in tumor-bearing mice can conclusions about the effectiveness of hormonal treatment regimens, such as estrogen therapy, be drawn.

This report analyses the changes in the classification of the genitourinary tumours introduced by the 1987 edition of the TNM system. Criticism and suggestions for improvement are given. These are based on the extensive experience of the EORTC GU Group with clinical trial work particularly the identification of prognostic factors, on their success in reaching international consensus on tumour classification, and on information from the literature. Many of the changes introduced in the 1987 system are not considered to be strictly necessary. These include the introduction of the new additional descriptors, including "C" and "R", the changes in the T classification of prostatic and renal cancer, and the introduction of uniform N categories for all tumours and other features. We regret the omission of minimal requirements, the omission of the V classification for macroscopic or microscopic vascular invasion, the changes in the T categories of carcinoma of the bladder and the introduction of stage groupings for all urological tumours. Some of these changes are considered unacceptable. The attitude of the EORTC GU Group toward the use of the new TNM classification is indicated in detail.

A new method of enabling urodynamic measurements to be made in the conscious dog is reported. A connecting device is located under the skin on the dog's back, and a catheter passes between this device and the bladder. The system described has proved valuable.

At present, outpatient extracorporeal shock wave lithotripsy (ESWL) is practiced in many centers for the treatment of urinary calculi. The safety of outpatient treatment is difficult to assess, no appropriate indications and criteria for patient selection have been established. In a retrospective study 1,203 patients, treated with ESWL using the Dornier HM-3 lithotriptor for the first time over the year 1986, were evaluated to analyze possible risk factors for outpatient ESWL. By multivariate analysis various pretreatment factors were investigated for their relation with complications arising from ESWL therapy. It was shown that stone size and sex of the patient were the strongest determining factors. In the present study a low-risk group (5% complications) could be identified, suitable for outpatient treatment, corresponding to 74% of the patient population. The remaining patients (26%) are at higher risk (18% complications) and should be considered for hospital treatment.

The effects of hormonal manipulation on the growth of a transplantable human prostatic carcinoma line (PC-82) were studied. The histological pattern of the PC-82 tumor, which still closely resembles the original tumor material, and the tumor growth rate did not change during the subsequent mouse passages. Growth of PC-82 tumor tissue on female and castrated male mice did not occur. Castration of tumor-bearing mice resulted in a cessation of tumor growth, after which the tumor volume decreased 50 +/- 27 per cent within 6 weeks after castration. Hormone-independent regrowth of the tumor tissue was not observed after long-term withdrawal of androgens. After a period of 10 weeks following tumor growth arrest, administration of testosterone almost directly resulted in regrowth of the tumor. Hormones, testosterone and estradiol, were administered by silastic implants. Intact male nude mice were shown to have highly fluctuating levels of testosterone. Implantation with testosterone resulted in constant levels of circulating testosterone, which could be maintained for at least 10 weeks, while the mean concentration of plasma testosterone was not different from that in control male mice. The doubling time of tumors grown on testosterone-substituted intact female and intact and castrated male mice was significantly shorter than that of tumors grown on intact male mice. Histologically the tumors grown on androgen-substituted mice were similar to those grown on untreated mice; the mitotic index, however, was much higher in the testosterone treated animals. Implantation of intact male mice with estradiol suppressed plasma testosterone to a mean level of 1 ng. per ml. and prevented the growth of PC-82 tumor tissue almost completely. Treatment of tumor-bearing mice with an estradiol implant following androgen withdrawal did not result in a further decrease of the tumor volume compared to the mice without additional estradiol implantation.

The content of nuclear androgen receptors (ARn) in prostatic carcinoma biopsies is not predictive for the duration of response of the tumor to endocrine therapy. Recently pre-treatment plasma testosterone has been suggested to be predictive in this respect. Therefore, pre-treatment plasma testosterone (T) and sex hormone binding globulin (SHBG) levels were studied in 31 patients aged 72 +/- 10 years (range: 45-87) with stage D2 carcinoma of the prostate treated by orchiectomy. In 26 of these patients, the ARn level of the carcinoma was also known (61 +/- 41 fmol/mg protein; range 0-169). Plasma T levels (mean: 13.7 +/- 6.1 nmol/l) varied widely (range: 2.4-25.4), as did plasma SHBG (32.5 +/- 19.3 nmol/l; range 4.4-78.8), and time to progression (TTP; 14.6 +/- 11.2 months; range 1-48). Plasma T was found to be correlated to age (Rs = 0.537; P less than 0.01) and TTP (Rs = 0.4495; P less than 0.02). Tissue ARn and plasma SHBG did not correlate to any of the parameters studied.

A procedure for the estimation of nuclear androgen receptors in benign prostatic hyperplastic tissue is described, which employs extraction of receptors from nuclei with buffers containing heparin. Extraction of a nuclear pellet with a heparin-containing (1 g/l) buffer appeared to have definite advantages over 0.4 mol/l KCl extraction. Heparin appeared to be twice as efficient in extracting androgen receptors. In addition aggregated receptor proteins, formed after storage at -80 degrees C, were partly deaggregated by heparin. Specific isolation of the androgen receptor was performed using either agar gel electrophoresis, protamine sulphate precipitation or LH-20 gel filtration. A comparison was made between the amounts of estimated receptors with these different techniques. Protamine sulphate precipitation resulted in the highest estimates of receptor-bound 5 alpha-[3H]dihydrotestosterone (3H-DHT). Treatment of the labelled nuclear extracts with a charcoal suspension prior to the receptor assay resulted in lower amounts of estimated androgen receptors. A method for routine evaluation of nuclear androgen receptors in prostatic tissue has been evaluated, which involves extraction of nuclear pellets with a heparin-containing (1 g/l) buffer, exchange labelling of the nuclear extracts for 20 h at 10 degrees C and quantification of the receptors with protamine sulphate precipitation.

The effects of administration of a luteinizing hormone-releasing hormone (LHRH) analogue (ICI-118,630) on plasma concentrations of hormones and weights of reproductive organs were studied in male mice. A single injection of the analogue (54 micrograms/kg body weight) caused a transient elevation of the concentration of LH in the plasma, up to 7 times the level in control mice. Daily administration of the analogue for a period of 3 weeks caused a small but significant decrease of the weight of the ventral prostate. The weight of the seminal vesicles in mice treated with the analogue, however, did not differ from that in control animals. The concentration of testosterone and LH in the plasma of these mice was not significantly different from those in control mice. It is demonstrated that the LHRH-analogue has no "castration-like" effect on the accessory sex organs of the male mouse, which is therefore not a suitable model in the study of these compounds.

The cytogenetic evolution of the prostatic adenocarcinoma cell line LNCaP was investigated during long term in vitro culture. Study of five different sublines demonstrated that the original karyotype was well preserved in all sublines, with respect to the chromosome number as well as to the primary markers. All sublines showed additional, subline specific secondary marker chromosomes. Comparison of these markers in androgen responsive and nonresponsive sublines showed rearrangement of the short arm of chromosome 8 in both unresponsive sublines. The breakpoints were in 8p21 and 8p23, respectively, resulting in deletion of the 8p23----pter region in both sublines. In contrast, the hormone responsive sublines did not show any aberrations in chromosome 8. Review of published karyotypes of patients and cell lines seems to support our finding of partial deletion of 8p in androgen unresponsive prostate tumor cells.

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

The diagnostic pitfalls of multilocular renal cystic disease are illustrated by the medical histories of 4 patients. Although ultrasonography and CAT scans are considered reliable diagnostic methods in cystic renal disease, in the 4 cases reported these methods could not give the correct diagnosis. In multilocular cystic disease, segmental excision is the preferred treatment, if frozen section does not show malignancy. However, frozen section done intraoperatively can give misleading results, as illustrated in these cases.

The metabolism of [1,2,6,7-3H]testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC.

Recent data show that carcinoma of the prostate is not radioresistant. But not all prostatic cancers are radiosensitive. All information available in the literature on histologically proven local destruction of prostatic cancer tissue, all survival data and reported complications after radiation treatment are reviewed and discussed. The results of radical surgical treatment from various authors but mainly from the series of Belt and Schröder are used for comparison. From these data it is evident that total prostatectomy of stage B and C tumors is superior to radiation therapy as far as local eradication of tumor goes. Five- and ten-year actuarial survival rates are about identical for stage B disease but favor total prostatectomy in stage C patients. Sexual impotence, the most important lasting complication of total prostatectomy, is present in 23-47% of patients after radiotherapy. Urinary incontinence is not known after irradiation but reported after surgery. Long term damage of the lower urinary tract, the gastrointestinal system, or the lymphatics was reported in 2-24% of patients after radiotherapy. The indication for radiation treatment in stage D patients is very questionable. Exact surgical staging by iliac and obturator lymphadenectomy is desirable to rule out stage D disease in locally confined tumors. Radiation treatment is indicated in patients who are not willing to undergo surgery, who are unwilling to accept sexual impotence, or who are poor candidates for surgery from other reasons.

Recently extracorporeal shockwave lithotripsy (ESWL) has been introduced as a nonoperative treatment for gallstone disease. Except for lung damage, no significant adverse effects of ESWL of gallbladder stones have been observed in animals. In clinical use ESWL of gallbladder stones is now confined to 15% to 30% of symptomatic patients. To achieve complete stone clearance, ESWL of gallbladder stones must be supplemented by an adjuvant therapy. ESWL of bile duct stones is highly effective and can be considered in patients in whom primary endoscopic or surgical stone removal fails. Second generation lithotriptors allow anesthesia-free (outpatient) treatments, but the clinical experience with most of these ESWL devices is still limited. The likelihood of gallbladder stone recurrence is a major disadvantage of ESWL treatment, which raises the issue of cost-effectiveness. ESWL for cholelithiasis is a promising treatment modality with good short-term and unknown long-term results.

Chromosomal studies were performed on primary cultures from human prostatic adenomas and carcinomas. All cells from both tumor types showed diploid chromosomal counts with a normal human karyotype. Chromosomal analysis was also performed on cells of the permanent epithelial line EB 33 derived from a human prostatic carcinoma in this laboratory. In contrast to the primary cultures, hypotriploid chromosome numbers were found during continuous culture for more than 1 year. The range of chromosome numbers increased with time in culture and was reduced to the original model number of 64 by only one animal passage ("nude" mice). Feulgen fluorometry on different passages of the permanent cell line EB 33 showed tetraploidy. This discrepancy to the hypotriploid chromosome number can be explained by different Feulgen hydrolytic properties of the different cell types.

The nuclear androgen receptor (ARn) content of cancerous prostatic tissue has been investigated as a prognosticator for time to progression under endocrine therapy. In 1981 a prospective study was started to investigate whether the ARn content in biopsy specimens of patients with prostatic carcinoma predicts the duration of response following hormonal treatment. ARn was estimated by a microassay which involves extraction of nuclear pellets with a heparin-containing buffer, exchange labeling of the nuclear extract with 3H-R1881, and quantitation of the receptor with protamine sulphate precipitation. One hundred and fifteen patients with prostatic cancer entered this study; 47 patients had evidence of metastatic disease as proven by bone scan. Forty-two patients were treated by orchiectomy; 37 of these patients are evaluable with a minimal follow-up of 30 months. A relationship between the nuclear androgen receptor content and the time to progression following orchiectomy in these patients with metastatic disease of the prostate was not found. This could possibly be attributed to the heterogeneous nature of the prostatic tumor tissue with respect to the distribution of the ARn. We conclude that androgen receptor assay in needle biopsies, at least in this study, had no value for the prediction of the time to progression after orchiectomy.

Staging lymphadenectomy revealed stage D1 disease in 30 of 94 patients with clinically localized prostatic carcinoma. Early orchiectomy resulted in a 46 per cent treatment failure rate after 45 months and established local disease control in almost all patients. The interval to treatment failure in this group compares favorably to the progression rate in patients treated with other modalities.

The pharmacokinetics and endocrine effects of the LHRH analogue buserelin [D-Ser(TBU)6-LHRH], released from biodegradable implants, were studied in 14 patients with stage C and D prostate cancer. Six patients received a subcutaneous implant of 3.3 mg buserelin monthly, and 8 patients received a subcutaneous implant of 6.6 mg buserelin every two months. Serum levels of buserelin decreased rapidly immediately after implantation. After 1-2 weeks a more gradual decline occurred, while in the two-monthly treated group a third phase of the elimination curve started after 5 weeks. Mean serum buserelin levels just before the next implantation in the two groups were not different. Urinary excretion of buserelin followed the same pattern. Serum LH levels in both groups became non-detectable 2 weeks after the first implant. This decrease of LH levels was accompanied by a suppression of serum testosterone to concentrations below 1 nmol/l (castration level). Side effects were not different from those observed with the intranasal application of buserelin. It is concluded that the subcutaneous application of buserelin is an easily administered form of treatment which has more profound and more reliable endocrine effects when compared with the intranasal administration of the drug. The greatest advantage of the new preparation is that the intervals between applications may be prolonged to at least 2 months.

Extracorporeal shock wave lithotripsy was performed for treatment of calculi of the upper urinary tract in 73 children. All patients were treated with the standard HM3 Dornier lithotriptor. A total of 138 calculi in 86 renal units was treated, requiring 111 extracorporeal shock wave lithotripsy sessions. After therapy no serious complications were encountered. Six months after treatment 79 per cent of the patients were free of stones and 17 per cent had small residual fragments (less than 3 mm.), while extracorporeal shock wave lithotripsy was considered to be unsuccessful in 3 children, although disintegration could be obtained in all patients. During a median followup of 24 months (range 13 to 40 months) growth of residual fragments was noted in 33 per cent of the patients and the recurrence rate was 10 per cent.

Permanent transplantable human tumors in nude mice offer the possibility of studying the impact of different (endocrine) treatment regimens on human cancer tissue. Among the limited number of human tumor models in athymic nude mice developed so far, the PC-82 tumor (which was established in our institution) mimics many of the important properties of clinical prostate cancer. The absence of PC-82 tumor growth in intact female and in castrated male mice indicates the absolute requirement of androgen for the growth of this tumor. Delayed testosterone (T) substitution (up to 70 days after tumor grafting) in PC-82 transplanted female mice resulted in tumor growth. This indicated that after androgen withdrawal at least part of the cells do not die and keep the capability to respond to androgens. Androgen withdrawal from T-implanted tumor-bearing female mice caused a rapid reduction (90% within 1 day) of the tissue T and a slower decline (up to 90% within 7-10 days) of tissue DHT concentrations. By the use of Silastic implants, containing different proportions of T mixed with cholesterol, circulating T levels of 0.2-20 nmol/L were obtained. It was observed that a constant plasma T level between 1 and 2 nmol/L (achieved with 10% T implants) is the threshold below which growth of the PC-82 tumor tissue is no longer stimulated.

Epithelial cells were isolated from human prostatic hyperplasia (BPH) after mechanical disruption of the tissue. The tissue was cut into small pieces, then mechanical pressure was applied. Stroma and epithelium were separated by a sequence of sedimentation steps. The recovery rate of epithelial cells was around 20 million cells per gram of tissue and more than 95% of the cells did exclude trypan blue. Epithelial cells can be identified by phase contrast microscopy and by the acid phosphatase content of the cells. In more than 95% of the cells the presence of acid phosphatase could be shown cytochemically with phosphorylcholine as a substrate. This finding indicates that the contamination with other cell types is very small. Histological study of the remaining stroma indicates that most of the epithelial cells are removed. Also, the acid phosphatase content of this fraction was found to be very low. The problem of obtaining large quantities of stromal cells in suspension has not yet been resolved. However, the technique described may be more suitable than others for the separate study of stroma and epithelium from BPH.

Androgen receptors (ARn) were assayed in nuclear extracts of prostatic biopsies from 60 patients with benign prostatic hyperplasia (BPH) and 82 patients with prostatic cancer (PC), with an exchange assay using heparin extraction, labelling with 3H-R1881, and protamine sulphate precipitation. The content of ARn of BPH biopsies (38 +/- 34 fmol/mg protein [mean +/- SD]; n = 70) was not different from that of PC biopsies (39 +/- 32 fmol/mg protein; n = 115). Biopsies showing essentially normal prostatic tissue had a lower ARn content (12 +/- 13 fmol/mg protein; n = 6). The content of ARn was independent of the age of the patient and of the histological grade of the carcinomas. A considerable variation in ARn content within tumors of individual patients was found, indicating that ARn are not uniformly distributed over prostatic tissue; ie, cells with high and low receptor content may coexist in different proportions in different regions of the prostate. Therefore, assays on multiple biopsies may be required for a proper estimation of the mean receptor content. The question remains, however, whether the behavior of the tumor is adequately predicted by the mean receptor level or, for instance, by the region with the lowest receptor content.

The rat ventral prostate contains prolactin receptors, and during sexual maturation prolactin stimulates the growth of this gland. The aim of the present investigation was to evaluate whether prolactin is involved in the regulation of the number of its own receptor sites in the rat ventral prostate. To this end, the content of prolactin receptors was estimated in prostate membranes of control and chronically hyperprolactinemic rats both before and after in vitro desaturation with 4 M MgCl2. Hyperprolactinemia resulted in a 40% increase in the number of available prolactin receptors (P less than 0.05). In vitro desaturation of receptors resulted in loss of 84% of protein and 36 +/- 6% and 52 +/- 6% of prolactin receptors from ventral prostate membranes of control and hyperprolactinemic rats respectively (P less than 0.05). We have concluded that the rat ventral prostate membranes are not suited to in vitro desaturation of prolactin receptors with MgCl2. From the increase in the number of available prolactin receptors after hyperprolactinemia we have concluded that prolactin is involved in the regulation of the number of its own receptors in the rat ventral prostate.

In most western countries, carcinoma of the prostate is the second most frequent cause of cancer death following carcinoma of the lung. In the pathogenesis of clinical carcinoma of the prostate, several mutational steps can be distinguished which correlate with subclinical and clinical situations. Focal carcinoma is identified in autopsy series at least 500-1,000 times more than is appreciated on clinical grounds alone. Still, focal carcinoma must be considered the precursor of all clinical disease. At least three mutational steps must be involved in the pathogenesis: the development of focal carcinoma from normal cells, the progression to hormone-dependent clinical carcinoma, and the progression to hormone-independent carcinoma. The geographic variation of these events suggests that exogenous factors play an important role in the pathogenesis of prostatic cancer. Focal, noninvasive carcinoma is found in the clinical situation incidentally upon treatment of obstruction in 8-12% of cases with benign prostatic hyperplasia. This lesion is usually not treated aggressively. The incidence of clinical prostatic carcinoma is strictly age-related. Because the tumor largely occurs after age 50, and competing causes of death play an important role, only about 50% of all patients with clinical prostatic carcinoma are likely to die of this disease. Prostatic carcinoma is most frequently diagnosed in the metastatic state (40-50%). The remainder are locally confined with an incidence of lymph node metastases of roughly 35%. Tumors diagnosed in the metastatic state have a distinctly poorer prognosis than tumors diagnosed as potentially curable lesions. Metastatic prostatic carcinoma is usually managed by means of androgen suppression. Hormone-dependent human tumor lines in nude mice suggest that endocrine-dependent cells are not killed by androgen withdrawal, but remain dormant and can be restimulated to grow. In the same sense, management of prostatic carcinoma appears to be palliative. Patients die of prostatic carcinoma because hormone-independent cell populations develop and cannot be influenced by hormonal management. Still-open questions concerning endocrine management are the timing of androgen withdrawal (early versus delayed) and the degree of androgen withdrawal (total versus subtotal). Luteinizing hormone-releasing hormone (LHRH) agonists and antiandrogens allow endocrine management with minimal side effects. Prolongation of life and cure can only be expected from simultaneous effective treatment of hormone-independent tumor cell populations.