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)     

Five-year trend in new patients with prostatic carcinoma

Seventy-four new cases of prostatic carcinoma treated between 1981 and 1985 were analyzed. The patients were between 40 and 86 years old with a mean age of 72.2 +/- 7.7 years. More than 70% of the patients had clinical stage C and D carcinoma. All cases proved histologically to be adenocarcinoma of the prostate. Eighteen patients had well differentiated, 21 moderately differentiated and 35 poorly differentiated adenocarcinoma. Various hormonal treatments were performed as the initial treatment in 88.9% (64/72) of the cases. Among them, 37 cases were treated by estrogen and 22 cases by luteinizing hormone releasing hormone analogues. Fourteen of 64 patients (21.9%) who received hormonal treatment discontinued the therapy within 10.1 +/- 9.1 months because of relapse of the disease or no therapeutic response. Salvage therapy following hormonal treatment were chemotherapy (9/14) and radiation therapy (4/14). During the 5-year follow up 12.1% (9/74) of the patients died due to prostatic carcinoma.     

A clinical study of prostatic carcinoma

Seventy seven patients with prostatic carcinoma were treated in our clinic between 1977 and 1986. Most of them were treated by a hormonal agent as the first therapy. None of the 9 stage A1 cases showed any reactivation, but 4 of the 5 stage A2 cases relapsed to metastatic disease. The chemotherapy performed in 3 of the 4 reactivated cases had no obvious effect on the disease. Seven of the 8 patients with stage B disease were alive without relapse. Relapse was seen in the other patient who had poorly differentiated carcinoma and chemotherapy in this case resulted in stable disease for the present. Four of the 15 stage C cases including 3 poorly differentiated carcinomas were hormone resistant or reactivated. For these resistant cases radiotherapy and/or the chemotherapy were performed, but a response was seen in only one case. Consequently, the first therapy for stage A2, B and C of poorly differentiated carcinoma must be improved. Of the 40 stage D cases, 4 patients who were treated by an early combination of hormonal therapy and chemotherapy had a better prognosis than the others. These 4 patients had poorly differentiated carcinomas with multiple bone metastases. Two of these 4 patients were alive without relapse for 17 and 72 months, and one of the 2 patients with relapse was also alive for 75 months. We believe that early chemotherapy is the key for better prognosis in stage D cases.     

鸦胆子油乳治疗中、晚期前列腺癌疗效观察(附33例报告)

为探讨治疗中、晚期前列腺癌（PCa）的有效方法，采用中药鸦胆子油乳注射疗法治疗中、晚期PCa33例，其中14例C期PCa采用鸦胆子油乳腺体内注射加卓九切除术（含2例未作睾丸切除术者）治疗，19例D期PCa采用鸦胆子油乳腺体内注射和静脉内滴注加睾丸切除术（含4例未作睾丸切除术者）治疗。结果2年内近期疗效满意，14例C期PCa达到完全缓解，19例D期PCa中有3例达到完全缓解，16例达到部分缓解。3年生存率达78．8％。认为，与既往常用的单纯睾丸切除内分泌治疗和放疗相比，鸦胆子油乳注射治疗中、晚期PCa患者的3年生存率高，且无副作用。     

New approach in the treatment of prostate cancer: complete instead of partial withdrawal of androgens

To completely eliminate androgens of both testicular and adrenal origin, 37 previously untreated patients with advanced (stages C or D) prostatic cancer received the combination therapy using an LHRH agonist (HOE-766) and a pure antiandrogen (RU-23908). The response criteria developed by the National Prostatic Cancer Project were used. A positive response (assessed by bone scan and/or serum prostatic acid phosphatase measured by radioimmunoassay was observed in 29 of the 30 cases who could be evaluated by these objective criteria (97%). The objective response was parallel to a rapid and marked improvement of the clinical signs and symptoms related to prostate cancer (prostatism, bone pain, and general well being). In marked contrast, the same combination therapy applied to patients previously treated with high doses of diethylstilbestrol (13 patients) showed a positive objective response in only 55% of cases. In 23 previously castrated patients showing relapse, an objective response was seen in only 25% of cases after neutralization of adrenal androgens by the antiandrogen. Previous treatment with chlorotrianisene (TACE) had no detectable effect on prostatic cancer and patients having previously received such treatment had a rate of positive response similar to previously untreated patients (five of five). In the previously untreated patients receiving the combination therapy, a 60% fall in serum prostatic acid phosphatase was observed as early as five days after starting treatment, at a time when the serum androgen concentration was 100% to 200% above control. Combined treatment with the pure antiandrogen completely prevents flare-up of the disease, a complication previously found in a significant proportion of patients treated with an LHRH agonist alone. The present data show that complete withdrawal of androgens by combined hormonal therapy with the LHRH agonist (or castration) and a pure antiandrogen leads to a positive objective response in more than 95% of cases as opposed to 60%-70% as reported by many groups using the previous partial hormonal therapy (castration or high doses of estrogens). Adrenal androgens are most likely responsible for this difference. The present study also shows that the proportion of androgen-sensitive cells decreases from more than 95% in untreated patients to 25% to 55% after previous partial hormonal therapy. Such data clearly indicate that the previous partial hormonal therapy exclusively aimed at neutralizing testicular androgens left 25% to 55% of cancer cells having a relatively low sensitivity to androgens in a hormonal milieu compatible with their continuous growth. No clinical or biochemical side effect could be detected except those related to reduced serum androgen levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

中药鸦胆子油乳治疗中、晚期前列腺癌

本文报道33例中、晚期前列腺癌采用中药鸦胆子油乳(以下称鸦油乳)注射疗法,对14例C期用鸦油乳腺体内注射+去势术(含2例未去势术)治疗,对19例D期采用鸦油乳腺体内注射和静肪内滴注+去势术(含4例未去势术)治疗后,近期疗效满意。C期14例达CR,D期3例达CR和16例达PR效果。与既往常用之单纯去势、内分泌治疗和放疗相比3年生存率高且无副作用。     

gamma-Seminoprotein in serum of prostatic cancer

From August, 1981 to May, 1984, we measured gamma-seminoprotein in the serum of 51 untreated patients with prostatic cancer in the Chiba University Hospital. Prostatic acid phosphatase (radioimmunoassay) in serum was also measured in these patients. We also measured gamma-seminoprotein and prostatic acid phosphatase in serum of patients under control by hormonal treatment and of reactivated patients. In untreated stage B and stage C cases, positive rate of gamma-seminoprotein in serum was larger than that of prostatic acid phosphatase. Therefore the measurement of gamma-seminoprotein in serum is considered to be useful in the diagnosis of early prostatic cancer. Four weeks after hormonal treatment, gamma-seminoprotein in the serum of 74% of the patients returned to the normal level. The positive rate of gamma-seminoprotein in the serum of reactivated patients is significantly larger than that of the patients under control by hormonal therapy.     

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).     

Comparison of Hormonal Therapy and Chemohormonal Therapy in Patients with Newly Diagnosed Clinical Stage D Prostatic Cancer

Background: In order to examine the usefulness of chemohormonal therapy, we conducted a multicentered randomized trial comparing hormonal therapy, using a luteinizing hormone-releasing hormone (LH-RH) agonist, with chemohormonal therapy, hormonal therapy plus cyclophosphamide (CPM), in patients with newly diagnosed clinical stage D prostatic cancer.
Methods: Between January 1991 and March 1995, 41 evaluable patients with stage D prostatic cancer were randomized into 2 groups: group A (hormonal therapy alone), goserelin acetate depot 3.6mg subcutaneously every 4 weeks; group B (chemohormonal therapy), goserelin acetate depot 3.6mg subcutaneously and CPM 1000mg/m² intravenously every 4 weeks. The responses to the therapies were evaluated based on the criteria of The Japanese Urological Association.
Results: There were no significant differences between the 2 groups with regard to objective and subjective response rates. No advantage in chemohormonal therapy was observed in the survival rate and progression-free survival rate. However, the survival rate and progression-free survival rate of responders were significantly higher than those of nonresponders in both groups. When the results were categorized by histologic grade patients with poorly-differentiated adenocarcinoma had significantly higher response rates, survival rates, and disease-progression-free survival rates in Group B compared to similar patients in Group A.
Conclusions: We conclude that chemohormonal therapy does not definitely improve the clinical response and prognosis of patients with stage D prostatic cancer; however, for patients with poorly-ditferentiated adenocarcinoma, chemohormonal therapy is a useful treatment.     

Prostatic acid phosphatase measured by immunoenzyme assay

Prostatic acid phosphatase was determined with Merck-Kanto's test kit on the cases of prostatic cancer experienced at our University Hospital from August in 1983 to February in 1985. Untreated cases were 4 stage A cases, 1 stage B case, 3 stage C cases, 3 stage D1 cases and 12 stage D2 cases. Nine cases were determined before and after hormonal treatment. From 67 controlled cases and 19 recurrent cases, 144 and 56 samples were selected, respectively. This method showed good reproducibility and even the serum stored at -80 degrees C after separation could be used for determination by addition of tartrate just before the measurement. The occurrence of abnormal values in untreated prostatic cancer cases, was 0% for stage A, 1 case for stage B, 33% for stage C and D1 and 75% for stage D2. Hormonal treatment decreased the high values of 5 cases and 1 case returned to normal. Compared to the recurrent cases, controlled cases showed a significantly larger ratio of negative, and it suggests that the test is useful for follow-up. Prostatic hypertrophy showed the increase of the value in 6% of the cases. Both prostatitis and urinary tract stone cases remained in the normal range.     

Histological effects of hormono-chemotherapy on prostatic cancer]

Using new criteria for histological effects of anti-cancer treatment, the effects of hormono-chemotherapy on 10 patients with prostatic cancer not previously treated were compared with those on 10 patients who received conventional hormone therapy. Marked effects were observed in 4 (40%) patients received hormono-chemotherapy but not observed in patients who received conventional hormone therapy (chi 2 test, p less than 0.05). All four cases who showed marked effects were in stage B at the beginning of treatment. Hormonal effects were more obvious in well differentiated cancer, and the effects of chemotherapy were observed in some cases with moderately and poorly differentiated cancer. Therefore, the addition of chemotherapy is recommended as the initial therapy on prostatic cancer to reduce the relapsing rate, especially for patients with poorly and moderately differentiated cancer.     

Comparison of procarbazine, imidazole-carboxamide and cyclophosphamide in relapsing patients with advanced carcinoma of the prostate.

In this third cooperative chemotherapy trial of the National Prostatic Cancer Project 165 patients with histologically confirmed, relapsing clinical stage D prostatic cancer were randomized to receive either imidazole-carboxamide, procarbazine or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on initial therapy were crossed over or randomized to receive an alternate drug. There were 129 patients available for comparison of treatments. The objective response rates (partial regression plus stable disease) were 26% for cyclophosphamide, 27% for imidazole-carboxamide and 14% for procarbazine. Subjective responses were noted in pain relief, improvement in performance status and weight gain. Procarbazine was associated with excessive toxicity, resulting in many patients (28%) discontinuing therapy within the first 3 weeks and closure of this particular arm of the study. The regimen of initial imidazole-carboxamide therapy with a later cross-over to cyclophosphamide when the disease continues to progress is associated with the longest increase in survival. Imidazole-carboxamide and cyclophosphamide appear to be active agents in advanced prostatic cancer and are worthy of continued use in this disease.     

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.     

Evaluation of a monoclonal antibody-based enzyme immunoassay (IQ(Bio) PAP-AELIA kit) for prostatic acid phosphatase

The clinical application of enzyme immunoassay (EIA) for prostatic acid phosphatase (PAP) is reported. PAP concentration was measured by an IQ(Bio)PAP-AELIA kit. Serum samples were collected from 20 healthy individuals, 31 patients with benign prostatic hypertrophy, 14 patients with prostatis, 23 patients (47 samples) with prostatic cancer and 29 patients with various other malignancies. The coefficients of variation (%CV) in intraassay and interassay ranged from 2.3 to 4.4%, and from 3.0 to 3.6%, respectively. The recovery rate in the dilution test and recovery test were 106.2 +/- 8.9% and 101.3 +/- 6.9% respectively. A significant correlation (r = 0.994, p less than 0.01) was observed between EIA and RIA methods in the prostatic cancer patients. PAP concentration was elevated above 2.0 ng/ml in 0/2 (0%) of the treated patients with stage B prostatic cancer, 1/5 (20%) of those with stage C, 6/16 (38%) of those with stage D, and in 4/5 (80%) of the untreated patients with stage D prostatic cancer. False positive results were seen in 2/31 (6%) of the patients with benign prostatic hypertrophy, 3/14 (21%) with prostatis and 3/29 (10%) of the patients with various other malignancies. In the majority of the false positive cases, elevated levels were only just above the normal value. In conclusion, the PAP level measured by this EIA kit was correlated with the clinical response to hormone therapy for prostatic cancer.     

Ketoconazole therapy for hormonally refractive metastatic prostate cancer

Twenty-two patients who had progressive metastatic prostatic carcinoma (Stage D2) despite androgen-deprivation therapy (bilateral orchiectomy, 10 cases; bilateral orchiectomy followed by diethylstilbestrol, 7 cases; diethylstilbestrol, 3 cases; combined megestrol acetate and low-dose estrogen, 2 cases) were treated with ketoconazole. Of 19 evaluable patients, 2 (11%) achieved a partial response (for 6 and 8 months) and 7 others (37%) achieved stabilization of disease (for periods of 3-8 months). Of 16 patients in whom pain was a prominent clinical feature, 13 (81%) noted improvement in pain for periods of one to eight months (median 3 months). We conclude that ketoconazole is a useful addition to our current armory for management of patients with metastatic prostatic cancer resistant to prior hormonal therapy.     

Induction therapy with CDDP and ADM for stage D prostatic cancer and its clinical response

From September 1983 to September 1989, 20 patients with newly diagnosed stage D prostatic cancer were treated with cis-platinum (CDDP) and adriamycin (ADM) as the induction therapy. Analysis of histological and clinical effects on the induction therapy revealed partial response (PR) in 13 cases and no change (NC) in 7 cases according to Shimazaki's response criteria, and PR in 4 cases, NC in 15 cases and progression (PD) in 1 case according to NPCP criteria. Histological Ef 0-b effect was found in 2 cases, Ef 1 in 7 cases, Ef 2 in 3 cases, Ef 3 in 2 cases and Ef 4 in 2 cases. Analysis of long-term results revealed relapse in 9 cases and cancer death in 6 cases. The 1-year, 3-year and 5-year continued response rates for all cases were 85.7, 40.2 and 32.1%, respectively. The 1-year, 3-year and 5-year survival rates were 100, 64.3 and 53.6% respectively. Histologically, low responsive cases showed a tendency of relapse and cancer death more frequently than high responsive cases. These results suggest that CDDP and ADM therapy is more effective than hormone therapy in newly diagnosed stage D prostatic cancer as an induction therapy.     

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     

Chemo-endocrine therapy for newly diagnosed stage D2 prostate cancer

We evaluated 175 patients with newly diagnosed stage D2 prostate cancer who had been treated in our hospital between 1992 and 2003 to compare chemo-endocrine therapy with endocrine therapy alone. One hundred and thirty seven patients were treated with endocrine therapy alone. The other 38 patients received chemo-endocrine therapy, which included medical or surgical castration with/without antiandrogen plus VIP (Vincristine, Ifosfamide, Peplomycin) regimen or other cytotoxic agents. The patients treated with chemo-endocrine therapy had a significantly better prognosis than the patients treated with endocrine therapy alone (p<0.05), although treatment was not randomized. The cause-specific survival rates at 5 years for the chemo-endocrine therapy group and the endocrine therapy group were 61.6% and 34.8%, respectively. These data suggest that chemo-endocrine therapy is a potentially effective treatment for newly diagnosed stage D2 prostate cancer.     

Clinical and pathological study of 152 cases of prostatic cancer]

A total of 152 prostatic cancer patients who underwent mainly hormone therapy was conducted. Our histological grading system combined with structure atypsim--SAT and nuclear anaplasia--NAN allowed for more accurate prognosis of prostatic cancer patients. The prognosis of G3 patients was obviously poor. The over-all 5-year survival rate for prostatic cancer patients with G1, G2 and G3 was 80%, 57% and 17%, respectively. The 5-year reactivation rate for patients with G1, G2 and G3 was 14%, 32% and 87%, respectively. The period for reactivation after initial hormone therapy for prostatic cancer patients with G1, G2 and G3 was 11.4, 10.0 and 3.2 years, respectively. Further improvements in survival for the patients with G3 prostatic cancer will require the development of effective systemic chemotherapy and the re-consideration of appropriate use of hormone therapy.     

Long-term survival of stage D2 prostatic carcinoma patient treated with total cysto-prostatectomy: a case report

A 52-year-old male was admitted to this hospital as stage D2 prostatic carcinoma. He had been previously treated with transurethral resection of prostate and hormonal therapy. Rectal examination revealed the prostate bigger than a hen-egg with stony-hard nodules. Both whole body bone X-ray and bone scintigram showed multiple bone metastasis. Total cysto-prostatectomy and pelvic lymph node dissection were performed because the patient was relatively young, was in good general status and the tumor was not sensitive to hormonal therapy. In addition, he was expected to have obstructive uropathy soon and the reported results of radiotherapy for local control of advanced prostate cancer were unsatisfactory. He was followed by bone X-ray and bone scintigram every six months. Osteoplastic area diminished in size and hot lesions in bone scintigram disappeared gradually. The patient is very active in his daily life without evidence of local recurrence or new metastasis more than seven years after operation. The validity of mass reduction surgery for hormone-resistant stage D2 prostatic carcinoma is discussed.