Clinical study on prostatic cancer patients

Clinical observations on prostatic cancer were studied in 27 patients who had been managed in our department between April, 1980 and December, 1986. The mean age at the time of initial clinical visit was 70.6 years old with a range of 55 to 88 years old. Of all 27 patients, 15 men (55.6%) were senior citizens over 70 years old and indeed 23 men (85.2%) were over 60 years old. According to the general rules for clinical and pathological studies on prostatic cancer, there were 10 patients with stage A, 2 patients with stage B, and 15 patients with stage D disease. However, none of our patients had stage C foci of prostatic cancer. Histopathologically, biopsied or surgically resected specimen all showed adenocarcinoma. More frequently the incidence of poorly differentiated adenocarcinoma was found in the specimen from the patients with advanced clinical disease. Anti-androgen therapy with castration or a combined hormonal manipulation initially was done in 25 patients. Simple hormonal treatment using chlormadinone acetate (CMA) was given in 13 patients. Of 25 patients who received hormone treatment, 22 underwent castration whereas, 12 of 13 having undergone single hormonal therapy were castrated. Combined chemohormonal therapy using UFT and CMA or additionally given estramustine phosphate disodium (Estracyt) was subjected only to stage D disease of prostatic cancer. Of 15 patients surgically treated, 11 received transurethral resection of the prostate on the basis of initial diagnosis of benign prostate hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neoadjuvant therapy before radical prostatectomy for clinical T3/T4 carcinoma of the prostate: 5-year followup,Phase II Southwest Oncology Group Study 9109

PURPOSE: Several investigators have examined the role of hormonal therapy before definitive local therapy for locally advanced prostate cancer to improve outcome. We evaluated the resectability rate and clinical response rate to 16 weeks of total androgen blockage therapy for clinically locally prostate cancer before radical prostatectomy, and progression-free survival in this multi-institutional study. MATERIALS AND METHODS: Southwest Oncology Group 9109 was a phase II feasibility study designed to treat patients with clinical stage C prostate cancer (T3, T4, N0 and M0). Cases were classified by stage T3 versus T4 and bulky (greater than 4 cm.) versus nonbulky (or less 4 cm.) disease. The neoadjuvant agents used were goserelin and flutamide before radical prostatectomy. RESULTS: A total of 62 patients were accrued to the study and 1 patient was ineligible. There were 2 protocol deviations and these patients refused to undergo prostatectomy after hormonal therapy. Four patients went off protocol treatment because they were not considered surgical candidates. The racial distribution was 72% white, 20% black, 7% Hispanic and 2% Asian. Clinical stage at diagnosis was T3 in 97% and T4 in 3% of cases. Of the patients 39% were diagnosed with bulky disease. Of the 61 eligible patients 55 (90%) underwent a prostatectomy. The 5-year progression-free survival estimate was 70% (24 of 61 cases failed) and the 5-year survival estimate was 90% (11 of 61 deaths). Most of the patients in this trial would have been considered inoperable and referred to radiation oncology. CONCLUSIONS: Neoadjuvant hormonal therapy followed by radical prostatectomy is reasonable and appropriate for clinical stage T3 prostate cancer. A progression-free and overall 5-year survival of 70% and 90%, respectively, compares favorably to Radiation Therapy Oncology Group neoadjuvant trial outcomes for this stage of prostate cancer.     

Treatment of an orchiectomized patient with hormone-refractory prostate cancer with LH-RH agonists.

This report confirms experimental data on direct inhibitory effects of LH-RH agonists in growth control of human prostate cancer cells. The patient had hormone-refractory prostatic carcinoma after hormonal therapy, including orchiectomy, and responded successfully to a 6-month treatment with goserelin acetate (3.6 mg depot s.c.). The treatment has led to a reduction of tumor mass and metastases as well as an improvement in the patient's paraclinical indicators and general status. The remission lasted 14 months. The treatment still continues.     

Recommended Dose of Flutamide with LH-RH Agonist Therapy in Patients with Advanced Prostate Cancer

Background: In a recent study by the Casodex Combination Study Group, USA, patients in a flutamide (750mg/day) plus LH-RH agonist group showed a high treatment failure rate, mainly due to flutamide-induced diarrhea and hepatotoxicity. Our current study was conducted to determine the optimal dose of flutamide for use in this type of Combination therapy.
Methods: In a randomized, multicenter study, 30 patients (hormone untreated; stage C or D) were divided into 2 groups: flutamide 250mg (125mg × 2; 14 patients) and flutamide 375mg (125mg × 3; 16 patients), and each dose combined with either goserelin acetate (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin and leuprolide were administered to patients in a 1:1 ratio. Flutamide monotherapy at a daily dose of 375 mg was determined to be the optimal dose in Japan in our previous phase II study. The endpoints of this pilot study were the objective response and adverse events during the 12-week treatment.
Results: The objective response rate was 83.3% in the flutamide 250mg group and 85.7% in the flutamide 375 mg group according to the Japanese response criteria for prostate cancer. Elevated PSA levels fell to within the normal range in 83.3% of the patients in the former group and in 93.3% of the patients in the latter group. One patient administered 250 mg of flutamide experienced diarrhea, while the serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide and 4 patients administered 375 mg of flutamide.
Conclusions: Based on the findings of this pilot study of maximal androgen-depletion therapy for advanced prostate cancer, 375mg/day of flutamide is recommended in combination with an LH-RH agonist. Assessment of the effects of our recommended regimen on longer term survival, quality of life and antiandrogen withdrawal syndrome of patients treated requires additional patients and time for foIIow-up.     

Quality of life following endocrine therapy for advanced prostate cancer: a comparative study between LH-RH agonist 1-month depot and 3-month depot

PURPOSE: There were few studies which reported the longitudinal quality of life (QOL) for Japanese men who received endocrine therapy for advanced or metastatic prostate cancer. A pilot randomized trial was conducted to assess QOL and the incidence of hot flash following endocrine therapy using luteinizing hormone-releasing hormone (LH-RH) agonist goserelin acetate 1-month or 3-month depot alone in patients with advanced or metastatic prostate cancer. MATERIAL AND METHODS: A total of 28 patients with advanced or metastatic prostate cancer who received LH-RH analogue goserelin acetate depot alone for 12 months were randomized (1:1) to two different formulations. Fifteen patients received the 1-month depot and thirteen patients received 3-month depot, namely Zoladex 3.6 mg depot and Zoladex LA 10.8 mg depot, respectively. We measured health related QOL using European Organization for Research and Treatment of Cancer (EORTC) and EuroQol (EQ-5D) questionnaire and evaluated the incidence of hot flashes between the two groups for one year after diagnosis. Moreover, we evaluated the incidence of hot flashes between the 1M and 3M depot. A baseline interview was conducted before treatment. Follow-up interviews were conducted in person at scheduled study visits of 3, 6, 9 and 12 months after treatment. RESULTS: Five (18%) patients dropped out of the study. Thus, we analyzed 23 eligible patients (11 in the 1M arms and 12 in the 3M arms). No significant differences between the two treatment arms were detected in categories of age, average pre- PSA values, Gleason scores and clinical T stage. According to EORTC, each treatment group showed similar QOL scores in all domains before and after treatment. With regard to EQ-5D, the 1M-treatnent arm reported better utility scores than 3M treatment arm, which was no significant statistically. The overall incidence of hot flash was 61% (58% in 1M group and 64% in 3M group). CONCLUSION: There were no differences with regard to general and disease specific HRQOL between the both formulations of goserelin acetate. Hot flashes are the major adverse effects of endocrine therapy for Japanese patients with prostate cancer.     

A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. The International Prostate Cancer Study Group.

A prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250 mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6 mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no long-term clinical benefit in patients with advanced prostatic carcinoma compared to goserelin acetate alone.     

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

AIM: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. METHODS: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. RESULTS: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. CONCLUSIONS: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.     

Three-month depot of goserelin acetate: clinical efficacy and endocrine profile

Objectives

To compare the pharmacodynamics and tolerability of the new goserelin acetate 10.8-mg depot with the 3.6-mg depot in patients with advanced prostate cancer during the first 3 months of therapy.

Methods

One hundred sixty patients were randomized in two comparative studies to receive either the 10.8-mg goserelin acetate depot every 12 weeks or the 3.6-mg goserelin acetate depot every 4 weeks for 12 weeks and then the 10.8-mg depot every 12 weeks thereafter. Data for pharmacodynamic assessments were collected prospectively, whereas clinical response data were collected retrospectively.

Results

Serum testosterone profiles of the 10.8-mg goserelin acetate depot and the 3.6-mg goserelin acetate depot were similar; testosterone levels in both groups fell below castrate levels by day 21 after administration. Decreases in serum prostate-specific antigen level after 3 months of therapy were also similar in both groups: 94% with the 10.8-mg depot and 92.5% with the 3.6-mg depot. For all patients, the median time to progression was 152.7 weeks and the median time to death was 213.6 weeks. The safety profile of the 10.8-mg goserelin acetate depot was similar to that of the 3.6-mg depot; hot flashes was the most common adverse event. The incidence of injection site reactions was very low (2 [0.3%of 614 administrations).

Conclusions

The new 10.8-mg depot was pharmacodynamically equivalent to the current 3.6-mg depot and was well tolerated, both locally and systemically. The observed times to progression and survival were as expected in this patient population. The 10.8-mg goserelin-acetate depot provided a dosing schedule that was convenient for the patient and the physician, and it has the potential to reduce health care costs while maintaining the quality of life in patients being treated for advanced prostate cancer.     

Effect of tegafur administration combined with hormonal therapy in patients with newly diagnosed stage D prostatic cancer

To study the effect of tegafur administration combined with hormonal therapy on the survival rate of newly diagnosed patients with stage D prostatic cancer, 66 patients, 70.9 years old in mean age, were treated from 1979 to 1986. The cancer was proven by the histological or cytological examination of the specimen which was obtained by the needle biopsy and/or aspiration biopsy of the prostate. The histopathological diagnosis of 59 patients was as follows: well differentiated type of adenocarcinoma was observed in 13 patients, moderately differentiated type in 19 cases, poorly differentiated type in 24 cases and mixed type in 3 cases. Daily 600 mg tegafur was administered orally as long as possible from the beginning of the treatment combined with hormonal therapy. Actual and relative 5 year survival rates calculated with Kaplan-Meier's method were 31.2% and 39.2%, respectively. When deaths other than prostatic cancer death were counted as lost cases, the actual survival rate was 47.5%. The present study also demonstrated that there were some factors affecting the patients' prognosis. They were the age of onset of the disease (patients under 64 years old were worse than those over 65 years old; p less than 0.05), performance status (patients with PS from 0 to 2 at the first admission were better than those with PS 3 to 4; p less than 0.025), differentiation of the tumor (well differentiated type was better than moderately; p less than 0.025 or poorly differentiated type; p less than 0.005).     

A comparison of Zoladex and DES in the treatment of advanced prostate cancer: results of a randomized, multicenter trial.

This open, prospective study was conducted to compare ZOLADEX (goserelin acetate implant) and diethylstilbestrol (DES) in the treatment of stage D2 prostate cancer. Sixty-seven patients were allocated to receive 3.6 mg of ZOLADEX every 28 days by subcutaneous injection (n = 48) or 3 mg of DES daily by oral administration (n = 19). Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dl) within one month of therapy in each group and remained so for up to 120 weeks. According to modified criteria of the National Prostatic Cancer Project, 88% of patients in the ZOLADEX group and 84% in the DES group were objective responders. Time to treatment failure and survival were not significantly different between groups, yet the confidence limits for the hazard ratios were wide. ZOLADEX was better tolerated than DES. We conclude that ZOLADEX is an alternative to DES in patients with stage D2 prostate cancer.     

中晚期前列腺癌临床治疗分析

目的 :探讨放疗、内分泌治疗和联合治疗对前列腺癌的临床疗效及PSA的临床诊断价值。　方法 :回顾总结 1986～ 1997年 5 0例C期以上前列腺癌临床治疗资料 ,比较不同治疗方法的客观生存率及PSA在治疗前后的变化。　结果 :治疗前 93 .7%病人PSA >4μg/L ,内分泌治疗后PSA水平下降 80 %～ 86 % ;80 %肿瘤发展病人PSA升高 1倍以上。手术去势组C期病人 2年和 5年生存率为 10 0 %和 6 6 % ;D期为 82 %和 36 %。放疗组C、D期 2年和 5年生存率分别为 10 0 %、5 0 %和 5 0 %、0。放疗联合去势术治疗C期病人 2年和 5年生存率为 10 0 %和 77%。药物治疗组 2年生存率为 90 %。　结论 :PSA是诊断前列腺癌及评价治疗预后的敏感指标。放疗联合内分泌治疗是C期前列腺癌的有效治疗方法 ,内分泌治疗D期前列腺癌优于放疗     

A New Long Acting Formulation of the Luteinizing Hormone-Releasing Hormone Analogue, Goserelin: Results of Studies in Prostate Cancer

Purpose

To assess the pharmacodynamic equivalence of the new 10.8 mg. goserelin depot with the current 3.6 mg. depot 3 studies were performed in patients with advanced prostate cancer.

Materials and Methods

In 2 comparative studies 160 patients were randomized for dosing every 12 weeks using the 10.8 mg. depot or every 4 weeks using the 3.6 mg. depot. In the noncomparative study 35 patients received the 10.8 mg. depot. Blood sampling for serum testosterone and evaluation of toxicity was done during the 48-week study period.

Results

Serum testosterone profiles of the 10.8 and 3.6 mg. goserelin depots were similar with testosterone levels decreasing into the castrate range by day 21 after depot administration. The safety profile of 10.8 mg. goserelin is comparable to that of the current monthly depot with the main side effects related to androgen deprivation.

Conclusions

The new long acting depot was pharmacologically equivalent, and well tolerated locally and systemically, and will offer added convenience to patients and health care personnel.     

Evaluating the use of early hormonal therapy in patients with localised or locally advanced prostate cancer

This article evaluates the use of early hormonal therapy in patients with localised or locally advanced prostate cancer. In patients receiving radiotherapy, an overall survival benefit is proven for adjuvant goserelin ('Zoladex') in locally advanced disease. Adjuvant to radical prostatectomy, castration (goserelin or orchiectomy) has demonstrated an overall survival benefit in patients with lymph node metastases. Survival advantages have not yet been proven with nonsteroidal antiandrogens, but immediate or adjuvant bicalutamide ('Casodex') improves objective progression-free survival in patients with locally advanced disease, with certain quality-of-life advantages over castration.     

Chemohormonal therapy as primary treatment for metastatic prostate cancer: A randomized study of estramustine phosphate plus luteinizing hormone-releasing hormone agonist versus flutamide plus luteinizing hormone-releasing hormone agonist

BACKGROUND: The present study was undertaken mainly to investigate whether chemohormonal therapy with estramustine phosphate plus luteinizing hormone-releasing hormone (LHRH) agonist has a more beneficial effect than the hormonal therapy with flutamide plus LHRH agonist for newly diagnosed patients with metastatic prostate cancer. METHODS: A total of 57 patients with metastatic prostate cancer aged 59-80 years (median 74 years) were entered in the study and were randomized to the treatment of estramustine phosphate (560 mg/day) plus LHRH agonist (estramustine group) or flutamide (375 mg/day) plus LHRH agonist (flutamide group) with stratification for the degree of performance status, histological differentiation and bone metastasis. RESULTS: Both of the treatment regimens were well tolerated with similar incidences of adverse drug reactions. The overall response rates (complete response plus partial response) at 12 weeks after treatment in the estramustine and flutamide groups were 76 and 55%, respectively. The median time to objective progression for the estramustine group (25.4 months) was longer than that of the flutamide group (14.6 months). The serum levels of follicle stimulating hormone and testosterone were significantly lower in the estramustine group. CONCLUSIONS: Chemohormonal therapy with estramustine phosphate plus LHRH agonist showed longer clinical progression-free survival than the hormonal therapy with flutamide plus LHRH agonist (P = 0.03), although there was no significant difference in the overall survival. A larger-scaled trial with more statistical power is required to clarify that the former regimen is more beneficial than the latter for newly diagnosed patients with advanced prostate cancer.     

Guideline of surgical treatment of prostatic adenocarcinoma

Based on study of 274 cases of prostate cancer treated in our clinic, selection of patient for radical surgical treatment and choice of procedures were discussed. The radical surgical procedures experienced in our clinic were classified as 31 cases of radical prostatectomy, 4 cases of radical cystoprostatectomy and 7 cases of pelvic exenteration. The endocrine therapy was added to non curative cases postoperatively. In the radical prostatectomy group, the 5-year survival rate of patients with stage A and stage B prostatic adenocarcinoma were 100 and 93 per cent, respectively, and 5-year survival rate of patients who had stage C prostatic adenocarcinoma was 75 per cent. The 5-year survival rates of patients with stage C prostatic adenocarcinoma treated by radical cystoprostatectomy and pelvic exenteration were 50 per cent and 66 per cent, respectively. Cancer recurrence has not seen in the bladder in the patients with stage C prostatic adenocarcinoma treated by radical prostatectomy. Operation of urinary diversion had improved the quality of life. From this data, radical prostatectomy would be indicated for the treatment of patients with stage A, stage B and stage C prostatic adenocarcinoma.     

Combined endocrine effects of LHRH agonist (Zoladex) and tamoxifen (Nolvadex) therapy in premenopausal women with breast cancer

In premenopausal women with breast cancer, the use of the luteinizing hormone releasing hormone agonist, goserelin, results in the production of serum levels of oestradiol equivalent to those after surgical o?phorectomy or in postmenopausal women. The standard first line hormonal treatment for systemic breast cancer in postmenopausal women is tamoxifen. The combination of goserelin and tamoxifen in premenopausal women has been proposed. We have treated 34 premenopausal breast cancer patients with goserelin (3.6 mg) monthly and tamoxifen (20 mg) twice daily: endocrine data are available on all 34 patients. As with goserelin alone, patients on goserelin and tamoxifen showed transient stimulation of serum follicle stimulating hormone over the first 7-10 days with subsequent low gonadotrophin levels. Serum oestradiol and progesterone levels were reduced to castrate levels in all patients studied; no peaks of serum oestradiol were detected. There is no endocrinological contraindication to the use of goserelin and tamoxifen together in premenopausal women with breast cancer either as adjuvant therapy or in treating advanced disease.     

Clinical effects of a 3-month formulation LH-RH agonist (Zoladex LA 10.8 mg depot) in patients with prostate cancer]

Pharmacodynamics (PD), anti-tumor effects, safety and pharmacokinetics of a 3-month formulation of goserelin (Zoladex LA 10.8 mg depot: "10.8 mg depot") were investigated in a collaborative multicenter study. Study participants were 40 Japanese patients with prostate cancer comprising 20 untreated patients and 20 switch patients who had been receiving Zoladex 3.6 mg depot for 3 months or longer. Serum testosterone levels, serum LH levels, prostate-specific antigen (PSA) levels and drug concentrations were measured until 12 weeks after a single subcutaneous dose of 10.8 mg depot. Anti-tumor effects were evaluated by means of changes in the tumor lesions and the PSA levels at 12 weeks. After administration to the untreated patients, 10.8 mg depot reduced serum testosterone to the castrate range within 4 weeks and the reduction was maintained for up to 12 weeks. In the switch patients, serum testosterone suppression that had been produced by previous treatment with Zoladex 3.6 mg depot was maintained for up to 12 weeks following 10.8 mg depot administration. The anti-tumor effect at 12 weeks was 90.0% including partial response cases. The ratio of PSA normalization at 12 weeks was 75.0%. Fifty-seven adverse reactions were observed in 27 of the 40 patients (67.5%), but none were clinically significant. Although a disease flare presented as urinary retention in 1 of the untreated patients, all patients completed the study. Serum goserelin was detected up to 12 weeks after the administration of 10.8 mg depot. In conclusion a single dose of 10.8 mg depot showed a satisfactory PD-effect and brought about clinical efficacy persisting for at least 12 weeks and was well tolerated in patients with prostate cancer.     

Serum concentrations of flutamide and goserelin in a prostate cancer patient with obstructive nephropathy: a case report]

A 72-year-old man presented with pollakiuria and dysuria. His prostate was the size of an apple and hard on digital rectal examination and the serum prostate specific antigen (PSA) level was 73 ng/ml (RIA). Ultrasonography revealed bilateral hydronephrosis and the serum creatinine level was 13.2 mg/dl. CT scanning of the abdomen demonstrated swelling of paraaortic lymph nodes. Transrectal needle biopsy of the prostate gave a diagnosis of moderately differentiated adenocarcinoma. Accordingly, the final diagnosis was prostate cancer (cT3N4M1, stage D2). Immediately after bilateral percutaneous nephrostomy, treatment with an LH-RH agonist (goserelin) and flutamide was commenced. Serum creatinine was 6.6 mg/dl at the start of antiandrogen therapy and decreased to 1.8 mg/dl after 27 days. A 125 mg flutamide capsule was administered at 7 a.m., and blood samples were collected 4 hours later on days 1, 2, 3, 5, 6, 8, 12, 14, 17, 18 and 27. The OH-flutamide concentration was measured. There was no significant correlation between serum creatinine and the OH-flutamide concentration. After implantation of goserelin (3.6 mg depot), blood samples were obtained at 11 a.m. on days 8, 12, 14, 15 and 25. The serum goserelin level was measured. The serum goserelin level increased to a peak on day 14, as described previously, but the peak value of 9.63 ng/ml was higher than that reported before (mean +/- SD 2.848 +/- 0.199).     

Trends in patterns of care for prostatic cancer in Japan: statistics of 9 institutions for 5 years

Five hundred and sixty-five patients with prostatic cancer, who first visited 9 institutions in Japan between 1981 and 1985, were analyzed. The peak of age distribution was in the seventies. As clinical symptoms, disturbance on micturition was the most frequent and pain caused by metastasis was a complaint in approximately one tenth of the cases. Alkaline phosphatase measurement, prostatic biopsy, intravenous pyelography, bone scintigraphy, cystourethrography, and measurements of serum prostatic acid phosphatase and serum acid phosphatase were performed on more than 80% of the patients. The clinical stage was stage A1 in 6.2%, A2 in 3.7%, B in 14.9%, C in 20.7%, D1 in 7.4%, and D2 in 43.7%. According to the histological grade, well, moderately and poorly differentiated adenocarcinoma were observed in 20.4, 33.3 and 32.7%, respectively. Increased ratio of high grade to low grade was noticed in the lower age group as well as in the advanced stage. In this series, endocrine therapy was still accepted in most of the patients. Almost all were treated with hormonal medication and half of them had undergone bilateral orchiectomy. Surgery, radiation, chemotherapy or multidisciplinary therapy were attempted judging from the clinical stage and histological grade. However, old age restricted the therapeutic modality. Actuarial survival rate at 5 years for stage A1, A2, B, C, D1 and D2 was 89.2, 66.1, 72.7, 51.0, 47.5 and 28.0%, respectively. In the patients with stage D2, the 5-year actuarial rate of poorly differentiated adenocarcinoma was lower than that of well or moderately differentiated adenocarcinoma, even though more intensive therapy was given to the former.     

ROLE OF EARLY ADJUVANT HORMONAL THERAPY AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER

PURPOSE: Recent prospective randomized studies have shown that adjuvant hormonal therapy combined with local treatment can significantly improve overall survival in patients with locally advanced disease. This finding challenges the previous belief that adjuvant hormonal therapy may not be beneficial for minimal stages TxN + M0 or less prostate cancer, particularly when combined with local treatment. We reviewed the benefits of adjuvant hormonal therapy in patients at risk for disease progression, especially when administered after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the current literature and evaluated clinical information on stage pT3b cancer from a large single institution prostate cancer database to determine the current role of adjuvant hormonal therapy after radical prostatectomy for prostate cancer. RESULTS: Retrospective experimental and clinical studies have proved the impact of adjuvant hormonal therapy for decreasing prostate specific antigen (PSA) and clinical disease progression in patients with regionally limited prostatic cancer. This finding applies to stage pT3b as well as to lymph node positive cancer. Our literature review and current data from the Mayo Clinic database show that adjuvant hormonal therapy after prostatectomy has a significant impact on prostate specific antigen (PSA) progression but it also decreases systemic progression and cause specific death in patients with stage pT3b and lymph node positive disease. After adjusting for preoperative PSA, margins, grade, ploidy and patient age the risk ratio for stage pT3b disease in 707 cases was 0.3 (95% confidence interval 0.2 to 0.7). A recent prospective randomized trial showed a significant decrease in cancer death in N+ cases when adjuvant hormonal therapy was administered after radical prostatectomy, supporting previous Mayo Clinic data on N+ disease that favors combination therapy. In the PSA era, that is 1987 and after, our database data on stage pTxN+ cancer indicates that radical prostatectomy and hormonal therapy for single node positive disease resulted in 94% 10-year cause specific survival, which was not significantly different from the rate in patients with N0 disease after adjusting for local stage, Gleason grade, margins, ploidy, PSA and adjuvant hormonal therapy. CONCLUSIONS: Our literature review, including prospective randomized studies, and more recent results in the PSA era from our database indicate that early adjuvant hormonal therapy has a significant impact on time to progression and cause specific survival in patients with seminal vesicle invasion and limited lymph node disease who undergo radical prostatectomy, although in a retrospective nonrandomized study. Future prospective studies with longer followup are needed to evaluate the potential benefit of adjuvant treatment in regard to survival for stages pT2 and pT3a disease with unfavorable pathological variables.