Correlation between histological grading and the prognosis of prostatic carcinoma--a comparative study of the Japanese General Rules of Prostatic Cancer (JGRPC) and Gleason's classification

One hundred and sixty-seven patients with newly diagnosed, previously untreated prostatic adenocarcinoma, during the period between July, 1971 and March, 1934, were studied. The histopathologic specimens of the prostate were classified by the Japanese General Rules of Prostatic Cancer (JGRPC) and by Gleason's classification. The number of patients with well, moderately and poorly differentiated prostatic carcinomas according to the JGRPC classification was 42, 74 and 51 respectively, and the number of the patients with Gleason's pattern 1, 2, 3, 4, and 5 was 24, 20, 32, 43 and 48, respectively. The number of patients with Gleason's score (primary plus secondary pattern) 2 to 4, 5 to 7 and 8 to 10 groups was 40, 76 and 51 respectively. There was no significant difference in survival rate between well and moderately differentiated groups, but the survival rate of the group with poorly differentiated tumor was significantly lower than that of the moderately differentiated (p less than 0.01) and well differentiated (p less than 0.001) groups. There was no significant difference in 10-year survival rate between the score 2-4 and score 5-8 groups, but the score 9-10 group had a significantly lower survival rate than the score 5-8 group (p less than 0.01) and score 2-4 (p less than 0.005) group. JGRPC and Gleason's classification are thought to be equally useful in estimating prognosis of prostatic cancer, but the former is more concise and easily applicable than the latter.     

M1 prostate cancer with a serum level of prostate-specific antigen less than 10 ng/mL

BACKGROUND: M1 prostate cancer, which is invasive, is usually associated with a serum level of prostate-specific antigen (PSA) greater than 10 ng/mL, but cases are occurring where the serum PSA level is less than this. The present study investigated the clinical and pathologic characteristics of these cases of M1 prostate cancer. METHODS: Between April 1989 and March 1998, 167 cases of M1 prostate cancer were diagnosed by transrectal needle biopsy and eight of these with a serum PSA level less than 10 ng/mL were investigated. The patients' ages ranged from 57 to 79 years (median, 73) and the serum PSA levels ranged from less than 4.0 to 9.8 ng/mL. In all cases except one, the distal metastasis was to bones only. All cases had received hormonal therapy as the initial therapy. Immunostaining of PSA, chromogranin A, neuron-specific enolase, carcinoembryonic antigen and vimentin were performed in five of the eight cases. RESULTS: Four cases were poorly differentiated, two were undifferentiated, one was a mixture of poorly differentiated and undifferentiated and one case was moderately differentiated. Of the five cases in the immunohistochemical study, three cases with an undifferentiated carcinoma component showed negative staining reactions for PSA and all cases were positive for carcinoembryonic antigen. Four of the patients died of prostate cancer. In two of these four cases, hormonal therapy was ineffective, but systemic chemotherapy and irradiation therapy had been moderately effective. The overall 3-year survival rate was 33.3%. CONCLUSIONS: The cases of M1 prostate cancer with a serum PSA less than 10 ng/mL are almost always poorly differentiated or undifferentiated and have a poor prognosis compared with the usual M1 prostate cancer. Because hormonal therapy is ineffective in these cases, systemic chemotherapy and irradiation therapy should be chosen as the initial therapy.     

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.     

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.     

Transrectal fine-needle aspiration biopsy for cytologic diagnosis and grading of prostatic carcinoma

In this article, the Karolinska experience of transrectal fine-needle aspiration biopsy of prostatic carcinoma, which now extends over more than twenty years, is evaluated. The cytologic criteria for diagnosing prostatic carcinoma in aspirates are well defined. While accuracy for cytodiagnosis is similar to that of histopathologic diagnosis, fine-needle aspiration is a less traumatic, cheaper procedure compared with histologic biopsy methods. Accuracy depends very much upon the skill of the examiner taking the cell samples and on the alertness of the cytopathologist for possible diagnostic pitfalls. Cytologic grading of prostatic carcinoma into well, moderately, and poorly differentiated types has been shown to be correlated significantly not only to histopathologic grading, but also to clinical stage, response to hormonal therapy and survival. The degree of tumor differentiation is well reproduced by independent observers. Cytochemical parameters, such as DNA measurement, constitute a potential refinement of cytologic grading, especially in moderately differentiated carcinomas. In medical centers with long experience of fine-needle aspiration biopsy, the method has a central role in diagnosis and management of prostatic carcinoma, including posttherapy follow-up.     

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.     

Parenchymal brain metastases from adenocarcinoma of prostate

Two patients with parenchymal brain metastases from adenocarcinoma of the prostate (CaP) are presented. Both patients had the diagnosis made antemortem by biopsy, and tumor immunoreactivity for prostatic phosphatase and prostate specific antigen confirmed prostatic origin. Brain metastases from prostatic adenocarcinoma are unusual, occurring in only 0.2 per cent of all patients with CaP. Patients present with symptoms of motor dysfunction, headache, and seizures. The mean age at presentation of brain metastases from CaP is fifty-nine years old, which is younger than most patients with CaP. The majority of patients die within weeks after diagnosis. Craniotomy with tumor debulking, radiation therapy, and androgen deprivation may be useful in prolonging survival. All reported cases of CaP metastatic to brain have been histologically moderately differentiated or poorly differentiated. The periprostatic venous plexus is considered the most likely route of tumor spread to the brain.     

Influence of tumour differentiation on survival after resection for rectal cancer in a series of 1296 patients

The influence of differentiation grade on tumour staging, local recurrence and long term survival prospects has been evaluated in a series of patients managed by resection for rectal cancer. Differentiation was known in 1095 of 1296 patients. Well-differentiated tumours were over-represented among Dukes' stage A cases and poorly differentiated among those with disseminated disease (P less than 0.001). Local recurrence was twice as common (31%) after curative resection of poorly differentiated tumours than of well (14%) or moderately (17%) differentiated. Five year cancer specific survival rates after resection (curative and palliative combined) of tumours of good, average or poor differentiation were 68%, 59% and 33%, respectively. After potentially curative resection, survival was also significantly worse in patients with poorly differentiated tumours (P less than 0.001); 5 year survival rates of patients with tumours of good, average or poor differentiation were 75%, 71% and 51%, respectively. Survival prospects beyond 5 years in patients with Dukes' stage A tumours were significantly reduced when the tumour was poorly differentiated; 5 and 10 year survival rates were 76% and 40%, respectively. However, patients with Dukes' stage C tumours of poor differentiation had an identical 5 and 10 year cancer specific survival, 26%. Patients with mucoid type tumours had worse survival prospects than those with non-mucoid type (P less than 0.02).     

Effect of local tumor control on distant metastasis and survival in prostatic adenocarcinoma

Of 495 patients definitively irradiated for prostatic carcinoma, 286 with a minimum follow-up of thirty-six months were studied. While tumor histology appeared to predict prognosis, the poorly differentiated tumors showing the highest incidence of distant metastasis and the lowest survival, local tumor control was an important factor within the poorly differentiated group. Of those with local recurrence, distant metastases developed in 68 per cent compared with 37 per cent of those with no local disease (p = 0.025). Survival was similarly affected with 86 per cent of those with locally controlled tumor who were alive at five years (not significantly different from the more well-differentiated tumors) versus a 56 per cent actuarial survival in those with locally recurrent disease (p less than 0.05).     

Biopsy after external beam radiation therapy for adenocarcinoma of the prostate: correlation with original histological grade and current prostate specific antigen levels.

We obtained post-irradiation biopsies in 37 men with initially stage T3 prostatic adenocarcinoma treated by external beam radiotherapy. Eligibility for post-irradiation biopsy included no clinical local failure, interval since treatment of 24 months or more and no endocrine therapy. Of the 37 patients 23 (62%) had negative biopsies while 14 (38%) had positive biopsies. Of 23 patients whose original cancer was well or moderately differentiated 18 (78%) had negative biopsies, compared to only 5 of 14 (36%) of those with poorly differentiated cancer (p less than 0.03). Among 19 patients whose current serum prostate specific antigen (PSA) value is less than 2.5 ng./ml. 15 (79%) had negative biopsies, compared to only 4 of 14 (29%) with a PSA level of greater than 2.5 ng./ml. (p less than 0.02). These results strongly suggest that there is a low probability of positive post-irradiation biopsy regardless of its significance in men with a normal prostate by palpation and a normal serum PSA value. However, short followup since biopsy precludes analysis of the predictive value of post-irradiation biopsy on long-term local and distant disease status.     

Population based study of hormonal therapy and survival in men with metastatic prostate cancer

PURPOSE: Although the palliative benefits of hormonal therapy for metastatic prostate cancer are widely recognized, little information is available regarding the effect of hormonal therapy on cancer specific and overall survival, and the types of patients who might benefit the most or least from hormonal therapy. MATERIALS AND METHODS: Prostate cancer specific and overall survival according to hormonal therapy use was determined by the Kaplan-Meier method in 6,098 men 65 years or older diagnosed with metastatic prostate cancer in 1991 to 1999 who were identified through the population based Surveillance, Epidemiology, and End Results, and Medicare linked database. Cox proportional hazards and propensity score methods were used to adjust for potential confounders, such as disease status and patient comorbidity. RESULTS: Propensity score adjusted median overall survival was 26 months in men who received hormonal therapy compared with 13 months in those who did not (HR 0.66, 95% CI 0.17-0.70, p <0.0001). The benefit of hormonal therapy was observed across all comorbidity strata and races. Effects were most evident in patients with poorly differentiated cancer (cancer specific mortality in favor of treatment HR 0.60, 95% CI 0.53-0.69, p <0.001). Benefit was not found in patients with well differentiated cancer (cancer specific mortality in favor of no treatment HR 1.92, 95% CI 0.90-4.10, p = 0.09). CONCLUSIONS: Hormonal therapy is associated with improved prostate cancer specific and overall survival in men with poorly differentiated cancer. Improved survival does not appear evident in men with well differentiated disease.     

A case of advanced prostatic cancer in a 44-year-old treated effectively with combination chemo-endocrine therapy]

In a 44-year-old man with persistent back-pain for 3 months duration, radiological and echological investigations revealed prostatic mass lesion with multiple osteoblastic involvements. Transrectal biopsy to the prostate demonstrated pathohistologically poorly differentiated adenocarcinoma (Gleason's score 4-4:8). Serum ACP, ALP and IAP were elevated at the initial diagnosis pathologically. The clinical and pathological stage was D2, without metastasis to lung and liver. Combination chemo-endocrine therapy (methotrexate, adriamycin, pepleomycin, Estracyt and tegafur) with bilateral orchiectomies was performed exclusively as initial treatment. These consecutive treatments brought remarkable reduction of the prostatic mass lesion, decrease of tumor markers to normal range, rapid improvement of subjective symptoms and distinct decrease of abnormal activity in bone scintigram. More than 3 years survival was obtained, and normal performance-status was kept. Prostatic cancer in middle-aged adults is reviewed and discussed.     

A pathological study of incidental carcinoma of the prostate. Pathological study of age-groups]

We reviewed 66 patients with stage A adenocarcinoma of the prostate who were treated at our 7 affiliated hospitals in Yokohama between 1984 and 1988. Of 1377 patients who underwent subcapsular prostatectomy (SCP) or transurethral resection of the prostate (TUR-P) for benign prostatic hyperplasia, 66 patients (4.8%) were diagnosed as an incidental carcinoma of the prostate. Of these patients, 36 and 30 were in stage A1 and A2, respectively. In the 66 patients, 59 (4.5%) were detected in 1315 TUR-P and 7 (11.3%) in 62 SCP. Elderly patients over 80 years of age had a higher risk of stage A2 disease. In histological grade, well, moderately and poorly differentiated adenocarcinoma were found in 48 patients (72.7%), 13 (19.7%) and 5 (7.6%), respectively. Among the patients with stage A prostate carcinoma the majority of the age-group less than 79 years old had well differentiated adenocarcinoma. In the age-group more than 80 years old, there were 6 (37.5%) moderately and 2 (12.5%) poorly differentiated tumors. In other words, the age-group more than 80 years old tended to have the moderately or poorly differentiated adenocarcinoma more frequently than those other decades. We expect an increase in the number of patients with stage A2 disease in the future with the expansion of the operative indication, especially in elderly patients.     

Prostatic neuroendocrine carcinoma with priapism : a case report

An 84-year-old man presented with priapism in May, 2009. At 79 years old, he was diagnosed with stage C prostate cancer and then, was treated with hormonal therapy. The serum level of prostate-specific antigen (PSA) was within the normal range (0.02 ng/ml). Penile caverno-dorsal vein shunt (Barry shunt) and caverno-spongiosum shunt (Quackels shunt) were performed for the purpose of managing local symptoms. Following operation, the penile pain was mitigated. Postoperative computed tomography (CT) revealed the enlarged prostate and multiple metastases to lungs and multiple bone metastases. Histological examination of the prostatic needle biopsy revealed poorly differentiated neuroendocrine carcinoma of the prostate.     

Prostatic cancer in Aust-Agder County, Norway. Age, stage, grade and mode of presentation

Two hundred and five patients (89 per 100,000 men) with newly diagnosed prostatic cancer comprises all cases in the Aust-Agder County in Norway over a 5-year period. There were 36% stage T0 M0, 19% T1-2 M0, 16% T3-4 M0 and 29% T0-4 M1. In patients with well differentiated disease (G1), 8% had distant metastases on presentation, whereas in the moderately differentiated tumors (G2) and the poorly differentiated tumors (G3) distant metastases occurred in 30% and 62%, respectively. A statistically significantly higher proportion of well differentiated (G1) tumors were observed in the younger age groups (less than 70 years). On presentation diagnosis was suspected on routine digital rectal examination in 9% of the patients, while 12% had symptoms on disseminated disease as mode of presentation. Of patients operated upon for apparently benign hyperplasia 13% had prostatic cancer.     

Statistical analysis of the prostatic cancer patients detected from 1985 to 1989 in and around Gunma prefecture]

Prostatic cancer is one of the most common malignant tumors in the field of urology. The number of patients is increasing rapidly and its importance as a mortal disease is gathering attention. In 1985, we organized a registration system for prostatic cancer patients found in and around Gunma prefecture. In this study, we analyzed the clinical characteristics of the 730 patients registered from 1985 to 1989. The results were as follows. Mean age was 74.0 years old and the number of the patients was the greatest in the eighth decade. Voiding disturbance was the most common chief complaint, followed by pollakisuria, gross hematuria and miction pain. Stage and grade distribution were as follows. Stage A 16.2%, B 21.1%, C 17.0%, D 45.7%, well differentiated 27.4%, moderately differentiated 48.2% and poorly differentiated 24.5%, respectively. A statistically significant relationship between stage and grade was observed. Bone was the most common metastatic site. The highest incidence of bone metastasis was in lumbar vertebra, followed by ribs, ilium, thoracic vertebra and ischium. The value of PAP, ALP and ESR tended to be higher in high stage patients, and that of Hb was lower. Fifty two patients were detected by mass screening. Most of these patients were in an early stage. Most of the patients were treated by hormonal therapy. LH-RH agonists constituted 39.2% of the cases given hormonal therapy.     

Definitive radiation therapy for prostatic carcinoma: Mayo clinic experience

Primary radiation therapy for clinically localized prostatic cancer is effective and safe. Of our 147 patients treated between 1964 and 1973, 144 were evaluated 5 years after the initial date of radiation therapy. At 5 years the over-all survival rate was 80 per cent and the rate of survival free of disease was 63 per cent. More than 70 per cent of the patients were free of progression 5 years after the date of the first radiation treatment. Analysis revealed a highly significant association between tumor grade and patient survival (p less than 0.001), and between tumor grade and the interval free of disease (p less than 0.002). The relationship between tumor stage and time to progression of disease also was significant (p approximately equal to 0.01) but there was no relationship between lower stage and longer survival. Of the 142 patients who completed treatment only 20 (14 per cent) had local recurrence of the prostatic cancer after radiation therapy, representing a local control rate of 86 per cent 5 years after treatment. A few of the patients underwent post-treatment prostatic biopsy after radiation therapy. If a biopsy is done for increased prostatic induration and the results are positive adjuvant treatment is recommended. In the absence of urologic symptoms of progressive induration of the prostate gland biopsy is not instrumental in predicting the course of the cancer.     

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.     

Mass screening of prostate cancer in a Chinese population：the relationship between pathological features of prostate cancer and serum prostate specific antigen

Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). Methods: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.     

Buserelin treatment of advanced prostatic carcinoma: prognostic factor analysis.

From August 1986 to August 1990, 116 patients with prostatic carcinoma, advanced disease (stage C-D1 only in patients older than 75 years, or D2) were treated with Buserelin (0.5 mg 3 times/day subcutaneously for 7 days, followed by 0.4 mg 3 times/day intranasally) until progression. No concomitant antiandrogens were administered. Of the 108 evaluable patients, 10 had complete remission (CR), 49 partial remission (PR), 46 remained stable while 3 progressed (response rate = 54.6%). Median duration of response was 31 months, median survival was 34 months. The toxicity of treatment was mild and mainly related to the hormonal effect of the drug. Castrate testosterone levels were obtained in all patients except 7. Slight, transient pain increase was noted at day 8 in 12 patients. Absence of symptoms at the start of treatment, well- or moderately differentiated tumor and serum testosterone negativization following Buserelin were associated with a significantly higher response rate as compared to presence of symptoms, poorly differentiated tumor and failure to obtain castrate testosterone levels, respectively. The following prognostic factors were found, at univariate analysis, to be associated with a prolonged survival: stage (C-D1 versus D2), PS (greater than 80 versus equal or less than 80), symptoms (absent versus present) and histological grade (G1 + G2 versus G3). Age and basal T levels did not influence survival. Those patients who obtained a CR or PR survived significantly longer than those with stable disease or progression.(ABSTRACT TRUNCATED AT 250 WORDS)