Clinical study on adenocarcinoma of the prostate

In 92 patients with prostatic carcinoma who were treated at the Takamatsu Red Cross Hospital from January 1976 to December 1985, we analyzed the age, chief complaint, degree of advancement, grade of tumor, way of therapy and prognosis. The age of the patients was between 51 and 87 years (mean: 74.8 years). The most frequent chief complaint was dysuria. In terms of the degree of advancement, 14 cases were assessed as Stage A, 23 cases as Stage B, 16 as Stage C and 39 as Stage D. Analysis of the grade of tumor disclosed that 38 cases (41.3%) had well differentiated adenocarcinoma, 20 cases (21.7%) had moderately differentiated adenocarcinoma and 29 cases (31.5%) poorly differentiated adenocarcinoma. Forty-four of the subjects have already died. The 5-year survival rate was 41.2% when calculated pursuant to life table method. The 5-year survival rate was 85.7% for Stage A, 36.1% for Stage B, 53.4% for Stage C and 24.3% for Stage D. The 5-year survival rate was 54.7% for well differentiated adenocarcinoma, 61.7% for moderately differentiated adenocarcinoma and 12.7% for poorly differentiated adenocarcinoma. Comparison of the 3-year survival rate among the 4 ways of therapy revealed only a small intergroup difference; namely, the rate was 58.5% for hormone therapy, 51.6% for intraarterial neocarzinostatin therapy, 77.1% for total prostatectomy and 57.1% for radiation therapy. These results indicate that our way of chemotherapy, which chiefly employs intraarterial administration of neocarzinostatin as an induction therapy, is at least comparable or superior to hormone therapy in terms of efficacy.     

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).     

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)     

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.     

Clinical study of incidental prostatic carcinoma

At the Center for Adult Diseases, Osaka, between 1961 and 1987, 28 cases (1.8%) of incidental prostatic adenocarcinoma were detected by transurethral or subcapsular prostatectomy for clinically benign prostatic hypertrophy (1388 cases) and cysto-prostatectomy for urinary bladder carcinoma (156). Nine (32%) and 19 (68%) cases were in stages A1 and A2, respectively. Of the 19 A2 cases, 9 were well, 9 were moderately and 1 was poorly differentiated adenocarcinoma. Five of the A2 and 1 of the A1 progressed into clinical carcinoma, but none of these patients died of the cancer. Four of these 5 A2 patients had received no treatment postoperatively and one received castration. The intervals from diagnosis to progression ranged from 11 to 78 months. The survival rates at 5 and 10 years with A1 were 75% and 75%, and those with A2 were 80% and 37%. We conclude that the patients in stage A2 should be treated because stage A2 tumors, especially those with no treatment, progress at a higher frequency than stage A1 tumors.     

Expression of androgen receptor and prostatic specific markers in salivary duct carcinoma: an immunohistochemical analysis of 13 cases and review of the literature

Salivary duct carcinoma (SDC) is an uncommon, pathologically distinct entity characterized by its morphologic resemblance to ductal carcinoma of the breast and highly aggressive behavior. Approximately two thirds of patients die within 4 years of initial diagnosis despite aggressive, combined surgical resection and radiotherapy. Review of the literature indicates that androgen receptor (AR), a marker frequently detected in prostatic carcinoma, is expressed in over 90% of SDCs, whereas two common breast carcinoma markers, estrogen and progesterone receptors (ER and PR), are expressed in only 1.3% and 6% of the tumors, respectively, by immunohistochemistry. This hormonal profile suggests that SDC, in contrast to its histiologic similarity to ductal carcinoma of the breast, is immunophenotypically more related to prostatic carcinoma. To substantiate this hypothesis, we performed immunohistochemical staining of 13 cases of SDC for the presence of AR and two prostatic markers, prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Our results showed multifocal, scattered, moderate immunostaining for PAP and diffuse, moderate immunostaining for PSA in seven (58.3%) and two (16.7%) cases, respectively. These results create a potential diagnostic challenge to surgical pathologists who are dealing with a metastatic adenocarcinoma of AR+/PSA+/-/PAP+/- phenotype, particularly in male patients of unknown primary. Metastatic salivary duct carcinoma should be given serious thought if clinical investigation fails to reveal a prostatic primary. The immunophenotypic homology that exists between SDC and prostatic carcinoma also suggests that antiandrogen therapy as used in the treatment of prostatic carcinoma might be beneficial in patients with metastatic SDC when all other conventional modalities fail.     

A multimodal treatment of prostatic carcinoma and the 5-year survival rate

One hundred and twenty-nine patients with prostatic carcinoma were treated in our hospital. They were between 49 and 88 (average, 70.3) years old and histological diagnosis was adenocarcinoma in all 129 patients; 42 had well differentiated, 55 moderately differentiated, 31 had poorly differentiated carcinomas, and one undeterminated type. Twenty two patients had stage A carcinoma, 18 stage B, 14 stage C and 75 stage D. As the therapeutic principle no castration was done, radiation therapy was delivered to cases with carcinoma more advanced than stage B in combination with estrogen or alone, and antimetabolites were given to some patients. Cryosurgical procedure to prostate was adjunctively used in patients with dysuria. Since 1986, total prostatectomy was carried out in patients with stage B disease and younger than 60 years old, and total combined resection of the urinary bladder and prostate was performed in patients with more advanced than stage C disease. Etoposide was given to patients with recurrent or metastatic lesions. Twenty-two of the 124 patients who did not receive castration surgery were categorized in stage A, 17 in stage B, 14 in stage C, and 71 in stage D. The 5-year survival rate in each stage group was 100%. 56.2%, 70.0%, and 28.8%, respectively, and the statistical difference between stage A and B, and between stage C and D was respectively significant. The relative 5-year survival rate among the total patient group, 71 patients in stage D, 40 patients in stage D treated with hormone therapy, and 15 patients in stage D treated with radiation therapy was 44.5, 28.7, 18.4 and 36.1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical characteristics of prostatic adenocarcinoma with ductal features]

PURPOSE: To determine the incidence and prognosis of prostatic ductal adenocarcinoma. MATERIALS AND METHODS: From November 2002 to December 2005, we performed 122 radical prostatectomies and pelvic lymph node dissections. We further analyzed 64 cases after excluding 56 cases that had received neoadjuvant hormone therapy and two cases for which we were only able to perform limited follow-up examinations. We reviewed all of the surgical specimens and reclassified them according to the 2004 WHO classification system. We differentiated prostatic cases of ductal adenocarcinoma that were larger than 5 mm in diameter from cases of acinar adenocarcinomas. We then examined these two groups for the pathological stages of the neoplasms and the incidence of postoperative prostate-specific antigen (PSA) failure. Postoperative PSA failure was defined as a PSA value more than 0.2 ng/ml. RESULTS: We found eight cases (12%) of prostatic ductal adenocarcinoma among the 64 cases treated with radical prostatectomies. The mean age (+/- SD) of these patients was 65.3 (+/- 4.3) years old, and the mean PSA level (+/- SD) was 12.4 (+/- 5.4) ng/ml. Seven of the cases (11%) were mixed-type ductal adenocarcinomas, which contained acinar and ductal components. In addition, one case was identified as pure ductal adenocarcinoma. Seminal vesicle invasion was detected in four cases and lymph nodes metastases were identified in one case. During the follow-up period, four of the eight cases of ductal adenocarcinoma (50%) and twelve of the 56 cases of acinar adenocarcinoma (21%) showed postoperative PSA failure. The median follow-up period was 24 months (range: 12 to 48 months). CONCLUSIONS: We identified eight cases of ducal adenocarcinoma (12% of the examined cases), which suggests this disease is not as rare as previously reported. Compared to the cases of acinar adenocarcinoma, the cases of ductal adenocarcinoma were at a more advanced pathological stage and resulted in a higher rate of postoperative PSA failure. Therefore, we believe that patients that show even a limited degree of ductal adenocarcinoma should receive aggressive therapy.     

Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.     

Radiotherapy of prostatic carcinoma]

Forty-one patients with adenocarcinoma of the prostate localized in the pelvis (stage A2, NX; 3, A2, pN0; 5, B, NX; 5, B, pN0; 1, C, NX; 13, C, pN0; 7, C, pN1; 7) underwent curative external radiotherapy. Thirty-two cases were treated by fast neutron combined with or without Liniac X-ray and 9 cases were treated by Liniac X-ray. Twenty-six cases were well controlled by radiotherapy, but 15 cases recurred and were followed by endocrine therapy. The types of recurrence were local growth in 3, distant metastases in 11, and both in 1. These recurrences occurred in the cases of large prostatic carcinoma, small radiation field in NX cases or low radiation dose. The five-year disease-free survival rates of stage A2, B, C were 86, 66, and 47%, respectively and the five-year overall survival rates were 100, 100, and 53%, respectively. The cases with well differentiated carcinoma had better prognosis than those with poorly differentiated carcinoma (p less than 0.05). As 58% of the cases which were given concomitant endocrine therapy were controlled for over 2 years, endocrine therapy seems to be effective in the cases of failure after radiotherapy. Most of the complications were slight and only one case with complication of sacral decubitus needed surgical treatment. It was concluded that external radiotherapy was a good modality for prostatic carcinoma localized in the pelvis.     

Prostatic carcinoma presenting as neck lymph node metastases: report of two cases]

We report two cases of prostatic carcinoma presenting as neck lymph node metastases. Case 1: A 56-year-old man was admitted to our hospital with the chief complaint of left lower abdominal pain. A lymph node was palpable on the left side of the neck swollen. Rectal examinations revealed prostatic stony-hard mass. Computed tomography showed a swollen neck and paraaortic lymph nodes on the left side. PSA level was 380 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma, and neck lymph node biopsy also revealed metastatic adenocarcinoma. We diagnosed him with prostatic carcinoma stage D2 (LYM). He underwent hormonal therapy (TAB) but died 13 months later. Case 2: A 66-year-old man was admitted to our hospital with the chief complaint of a large palpable mass on the left side of the neck. Resection of this mass revealed metastatic adenocarcinoma. Rectal examination revealed no malignant lesions, but the PSA level was high, 1,700 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma. Computed tomography revealed paraaortic and pelvic lymph node metastases and bone scintigram revealed abnormal uptake, bone metastases. We diagnosed him with prostatic carcinoma stage D2 (LYM OSS). We performed bilateral testectomy followed by hormonal therapy (TAB). The lymph node metastases disappeared after 4 months of therapy.     

Hormonal treatment of carcinoma of the prostate]

Efficacy of orchiectomy and intravenous administration of diethylstilbestrol diphosphate (DESP) for the treatment of prostatic carcinoma was evaluated on 184 patients treated between 1975 to 1989. The patients were between 49 to 88 years old with a mean age of 73.4 +/- 8.3 years. Clinical stage was A in 9.8%, B in 12%, C in 26.6% and D in 51.6%. The histologically well, moderately and poorly differentiated adenocarcinoma were observed in 20.9, 29.4 and 49.7%, respectively. The 5-year survival rate of stage A, B, C and D calculated with the Kaplan-Meier method were 90, 49, 60 and 34%, respectively. The 5- and 10-year survival rate of the patients who had received orchiectomy was 53 and 24%, respectively, while that of the patients without orchiectomy was 38 and 14%, respectively. The 5 and 7-year survival rate of the patients treated with intravenous administration of DESP was 54 and 34%, respectively while that of the patients without DESP was 46 and 31%, respectively. These findings suggest that orchiectomy and intravenous administration of DESP in any form prolonged patient survival compared with only oral administration of estrogens or antiandrogens. Reactivation was seen in 24 (40%) of the 60 patients under sufficient observation. Clinical relapse occurred within an average of 32.3 +/- 26.4 months after primary hormonal manipulation. The average time to relapse in stage D was shorter than that in stage B and C. Reactivation was observed in the patients on interrupted treatment earlier than in the patients on continuous administration of drugs. Cardiovascular death followed by endocrine therapy was 7.4% in this study.     

Blood hormone levels related to stages and grades of prostatic cancer

Human follicle stimulating hormone (FSH), human luteinizing hormone (LH), human prolactin, testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured in the blood of 100 consecutive new patients with prostatic carcinoma. According to the VACURG classification, 14% of the patients were in Stage 1,25% in Stage 11, 25% in Stage III, and 36% in Stage IV. Within each stage the tumors were further subdivided into either highly, moderately, or poorly differentiated carcinomas. Thus the whole group consisted of 12 categories (stages and grades) of prostatic carcinoma. No specific hormonal pattern emerged which could distinguish any particular category or group of categories. We, therefore, conclude that single hormone measurements are of no practical value for diagnostic purposes related to staging and grading of prostatic carcinoma.     

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.     

Antiandrogens in the treatment of prostatic cancer.

Since prostatic carcionma is hormone dependent, treatment of this tumor has been carried out in this department over the last 10 years employing antiandrogens, particularly cyproterone acetate (CPA), associated in some cases with orchiectomy. Of 500 patients thus treated, the author reports on 236 patients with a 5-year follow-up and 184 with a 7-year follow-up. Of these, 126 (53.4%) had not received hormone treatment whereas 110 (46.6%) had been treated with estrogens. The mean survival rate was 64.4% at 5 years and 56.3% at 7 years in these patients and 51 and 43%, respectively, in the estrogen-treated patients. The author emphasizes that not only is CPA of great value in the treatment of prostatic carcinoma, but it is also useful in determining the hormone dependency of the tumor which is indispensable before proceeding with hormone therapy.     

Megestrol acetate in relapsed carcinoma of prostate

A series of 22 patients with advanced carcinoma of the prostate who had failed first-line hormonal therapy (orchiectomy, stilboestrol, luteinising hormone-releasing hormone agonist) were treated with 160 mg megestrol acetate daily. Treatment was well tolerated, side effects were minimal and 21 patients were evaluable. There were no complete or partial responses, although 8 patients had a good subjective response. In 6 patients the disease was stabilised for 6 to 12 months and there was a 40 to 50% reduction in their prostatic acid phosphatase (PAP) levels. It was concluded that megestrol acetate has a role as second-line hormonal therapy in the management of prostatic carcinoma.     

Prostate cancer: retrospective study of long-term follow-up cases. Is it possible to discontinue hormonal medications?

We reviewed retrospectively the medical records of 70 patients treated for prostate cancer who were followed for more than 10 years or until they died. All patients were treated by hormonal therapy and 54 of 70 patients (77 per cent) were combined with castration. Of 70 patients 10 (14.3 per cent) are alive now with an average follow up for 180.5 months. Of 60 patients with stage A and B only 3 died of the tumor. Of 56 patients with stage C and D, 10 and 18 patients died of the tumor, respectively. From the point of pathology, none of the patients with well differentiated adenocarcinoma died of the tumor. And in patients with stage A and B, pathologically well and moderately differentiated adenocarcinoma, there were no cancer death. On the other hand, a group of patients of poorly differentiated adenocarcinoma had a poor prognosis. In cases with well differentiated adenocarcinoma who discontinued hormonal medication (diethylstilbestrol diphosphate) no patients died of the tumor. From these observations we consider that, after long term hormonal medication, we can stop the hormonal medication for patients who have no positive prostate biopsy results for 4 years with well differentiated adenocarcinoma of stage A and B.     

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.     

Gestagens in the management of prostatic carcinoma

Two different hormonal gestagens, cyproterone acetate and norethisterone, were studied in prostatic carcinoma, for the greatest part in advanced cases. Cyproterone acetate was administered to 80, norethisterone to 38 unselected patients. The period of study extended over 2 years or more. The mechanism of action of gestagens and the role of the hormone receptors are discussed. The significance of serial measurements of plasma testosterone by providing a monitor of hormonal therapy is emphasized. The relevant literature is reviewed. The value of gestagens as an alternative to the traditional hormone therapy of prostatic carcinoma is pointed out.