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We investigated how histopathological features, such as structural atypism (SAT), nuclear anaplasia (NAN) and Gleason's pattern, influence the prognosis of patients receiving endocrine therapy. Patients with SAT 3 or NAN 3 clearly had a lower survival rate and a shorter survival period than those with other grades of SAT or NAN and this tendency was more prominent in the high stage than low stage. Patients with a higher grade of SAT or NAN had a poorer prognosis as well, when only cancer-related death was considered in the calculation of survival and survival period. The results described above suggest that the grade of SAT and NAN is one of most influential factors for prognosis. In the analysis for the prognosis of patients according to grade of mean value of SAT + NAN, there were differences in prognosis among mean value of SAT + NAN 2-4, 5 and 6. This indicated that the combined grading system would provide more information to the prediction of prognosis. Patients with Gleason's primary (or secondary) pattern 1 and 2, or 3 and 4 had a better survival than those with pattern 5 in the analysis when only cancer-related death was considered. This was coincident with the result that the survival rate for each Gleason's sum 2-3, 4-5, 6, 7-8 and 9-10 was different. Consequently, Gleason's pattern influenced the rate of cancer-related deaths, and this pattern may be another important factor for predicting the prognosis.

The general trend on the treatment for prostatic carcinoma has been changing from endocrine therapy alone to an alternative type according to stage. We evaluated clinically the favorable and unfavorable outcome of endocrine therapy in Japan, so that others will be appropriately evaluated. In a cooperative study made by members of five universities, 572 patients with clinically or histologically reconfirmed prostatic carcinoma were entered in this retrospective study. We studied the true influence of prognostic factors on the prognosis of 497 patients with prostatic carcinoma who had received endocrine therapy, employing multivariate analyses, such as quantification method II, multiple regression analysis and Cox's proportional hazard model. Twelve factors were considered in the study; "age", "stage", "histological findings (structural atypism = SAT, nuclear anaplasia = NAN, Gleason's primary and secondary pattern)", "pretreatment level of total acid (ACP) and of alkaline phosphatase (ALP)", "castration performed or not performed", "doses of estrogen", "type of response of local prostatic tumor and of ACP to endocrine therapy". Analysis of the "importance" of a prognostic factor by a partial correlation determined by quantification method II, revealed "stage" to have the greatest "importance" on prognosis throughout the entire period. "Response of local prostatic tumor", "response of ACP" and "Gleason's primary pattern" tended to be important factors for prognosis, in particular, in the first half period, and "age" and "Gleason's secondary pattern" were important in the latter half. Multiple regression analysis revealed the "stage", once again to be the most influential factor on the prognosis for the entire observation period. Also "response of local prostatic tumor", "SAT" and "Gleason's primary pattern" affected the patients' prognosis in the first half of the observation period. In the latter half, "age" became more of an influential factor than "histological findings". Analysis with Cox's proportional hazard model revealed that "response of ACP", "stage", "age", "Gleason's primary and secondary pattern", and "response of local prostatic tumor" were definitely the more influential prognostic factors, of which chi-square values (or t values) were statistically significant. Comparison of the significant factors in each multivariate analysis revealed that common influential prognostic factors, such as "age", "stage", "histological findings (mainly Gleason's primary and secondary pattern)", "response of local prostatic tumor" and "response of ACP" were coincident to the clinical impression. The clarification of these factors would be clinically beneficial when treating patients with endocrine therapy.

Of 572 patients with prostatic carcinoma, 497 received endocrine therapy as the initial treatment. These patients were surveyed in a cooperative research study by members from five universities. Prognosis, causes of death and side effects of estrogen therapy were studied. The prognosis of patients who had received endocrine therapy became worse, as the stage progressed. The prognosis of those who had received a combination of estrogen therapy with castration tended to be better than that of those who had received estrogen therapy alone. Similarly, the prognosis of those who had received a combination of progesterone therapy with castration tended to be better than that of those who had had progesterone therapy alone. No relationship was found between estrogen doses (low, medium and high) and prognosis, although a precise comparison among the three could not be made because of the smaller number of patents with low doses. A high dose of estrogen may not always be the indication, rather a medium dose such as 300 mg diethylstilbestrol diphosphate may be clinically appropriate. The cause of death could be identified in 303 patients who had received endocrine therapy. Cancer-related death was the most frequent (63.7%), and cardio- or cerebrovascular death accounted for only 14.2% of the cases. When this analysis was confined to the patients who had received estrogen therapy, estrogen administration seemed to be the cause of cardio- or cerebrovascular death of 16.1% of the patients. Daily dosing of estrogen was not definitely related to the incidence, or the interval to cardio- or cerebrovascular death. However, among the patients who had died of cardio- or cerebrovascular disease, 50% of the patients who had received a medium or high dose of estrogen tended to die within two years after treatment, while 50% of those who had received a low dose died within three years.

The incidence of prostatic cancer has been increasing and will probably increase more in Japan in the future, although it may not be probable that the incidence become high as in the western countries. Carcinoma of the prostate gland is one of cancers in which main treatment modality is hormonal manipulation. It is evident through epidemiological study that the development of prostatic cancer is associated with environmental factors such as dietary or sexual life styles which may influence on the hormonal milieu. In animal models aging and androgens are indispensable factors when inducing prostatic cancer. Thus the mechanism of hormone dependency in prostatic cancer should be elucidated to consolidate the basis of its hormonal therapy. It is shown in in vivo or in vitro experiments that the hormonal action is mediated by several growth factors. However, this must be investigated when androgens or growth factors play their roles during the process of carcinogenesis. While the main therapy of prostatic cancer is hormonal it is generally accepted that a radical means to treat prostatic cancer is solely total excision of the prostate gland when cancer is confined to the prostate. Hormone therapy is conservative principally, but is only available means now for treating patients with advanced prostatic cancer. In order to obtain more effective hormonal manipulation, the mechanism of hormone dependency must be understood. We need more effective antiandrogenic agents with lesser adverse effects. The final goal in the treatment of prostatic cancer is in its eradication. Therefore, it is urgently necessary to establish multidisciplinary treatment which includes surgery, hormonal manipulation, chemotherapy, radiation and immunotherapy for the eradication of advanced prostatic cancer.