Grading Of Prostatic Carcinoma Research Articles

Prediction of Radionuclide Bone Imaging Findings by Gleason Histologic Grading of Prostate Carcinoma

To evaluate a relationship between Gleason scores and Tc-99m HMDP bone imaging findings, data from 48 men (aged 45 to 77; mean, 67) with prostate carcinoma who had a bone imaging study at the time of presentation were reviewed. Cumulative Gleason scores were divided into two groups: high scores (6-10), 32 men; low scores (2-5), 16 men. Of the 32 men with high Gleason scores, 15 tested positive for multiple metastases and 17 tested negative. Tumors of the 16 men with low Gleason scores were negative for metastasis. A chi-square association between Gleason scores and the presence of metastases, either of a superscan pattern or multiple metastases, was 10.9 (1 df, P less than 0.001). The results indicate that a superscan pattern or multiple metastases were found exclusively in the bone images of patients with high histologic grades; bone images negative for metastases were associated with low-grade tumors. We conclude that positive bone imaging for metastases at the initial scan occurs only in patients who have high Gleason scores, that patients with high Gleason scores might or might not have skeletal metastasis, and that skeletal metastasis is not predictable in patients with low Gleason scores.

Histological Grading of Prostatic Carcinoma in Prostatectomy Specimens: Comparison of Prognostic Accuracy of Five Grading Systems

The prognostic accuracy of 5 histological grading systems (Broders, Anderson, Mostofi, Gleason and Mostofi-Schroeder) was compared. Grading was performed on 50 prostatectomy specimens by 5 pathologists. The results were averaged so as to reduce the impact of inter-observer variation. The Cox proportional hazards model was used to estimate the relationship between average grading scores and both time-to-recurrence and time-to-death by prostatic carcinoma. Age at surgery was considered to be a possible confounding factor and adjusted accordingly. The prognostic impact of the 5 grading systems (related to both recurrence and death caused by prostatic carcinoma) was judged by the likelihood ratio (LR) test score (chi 2 distributed with 1 df); for time-to-recurrence for the Mostofi-Schroeder score the LR was 6.54 and for the Gleason system it was 1.79. A stepwise procedure demonstrated that the best prognostic performance was reached with the Mostofi-Schroeder and Broders systems used together (with Mostofi-Schroeder weighted 1.5 times larger than Broders). For time-to-recurrence the median grading result was also used, giving results similar to the mean grading result. For time-to-death from prostatic carcinoma the LR test scores for all grading systems were relatively low. In this analysis the outcome of the Gleason system showed a minimum of prognostic ability, whereas the Broders and Mostofi-Schroeder systems had a reasonable predictive ability. Since the inter-observer variation of the Mostofi-Schroeder system was large, the Broders system is preferable. The restrictions and implications of this study are discussed and a brief review of the prognostic importance of grading of prostatic carcinoma is presented.

Problems in grading of prostatic carcinoma: interobserver reproducibility of five different grading systems

In order to investigate the reproducibility of grading systems for prostatic carcinoma currently in use, a comparative histological grading study was done. These studies were carried out on tissue sections from radical prostatectomy specimens (N=50) stained with hematoxylin and eosin. Five pathologists with varying professional experience participated in the study, using five different grading systems: those of Broders, Brawn, Gleason (for statistical compilation the modified version), Mostofi, and a modified Mostofi grading method recently described by Schroeder and Mostofi. Weighted kappa coefficients ranged from 0.21 to 0.52. None of the systems investigated demonstrated a high degree of reproducibility (k>0.70). Reproducibility of the systems described by Broders and Brawn was reasonably good (k=0.52 and 0.41, respectively). With the modified Gleason method (rearrangement of Gleason scores into 3 grades), a considerable difference was noted between the numerical agreement score (among at least 3 observers) and the measured kappa value (100% and 0.30, respectively). The methods described by Mostofi and Schroeder-Mostofi revealed only limited reproducibility (k=0.21 and 0.34, respectively).

Gleason histologic grading of prostatic carcinoma. Correlations between biopsy and prostatectomy specimens

The Gleason histologic score of prostatic adenocarcinoma in biopsy specimens (needle cores or transurethral chips) was compared with the Gleason score of corresponding radical prostatectomy specimens from 53 patients with localized prostatic carcinoma. The Gleason score assigned to the biopsy specimen was identical to that of the prostatectomy specimen in 51% of cases, was greater than that of the prostatectomy specimen in 4%, and was less than that of the prostatectomy specimen in 45%. The magnitude of discrepancy between the scores of the biopsy specimen and the prostatectomy specimen was directly related to the quantity of neoplastic tissue in the biopsy specimen. Discrepancies between the Gleason score of biopsy material and prostatectomy specimens were greater among biopsy specimens with low Gleason scores as compared with biopsy specimens with high Gleason scores. Given the small number of cases, these differences were not statistically significant. Clinical understaging of the primary tumor did not correlate with histologic undergrading of the prostatectomy specimen. It was concluded that prostatic biopsy should be repeated when the initial diagnosis of adenocarcinoma is based on only limited quantities of neoplastic tissue with a low Gleason score and management decisions may be influenced by the true Gleason score of the tumor.

Grading of Prostatic Cancer: III. Multivariate Analysis of Prognostic Parameters

This work is based on the two previous publications which are concerned with grading prostatic carcinoma. In the present communication the technique of multivariate analysis is applied to quantify the prognostic importance of parameters which were earlier identified as contributing in a significant manner to grading. The results of this analysis are used to construct a scoring system which differentiates five significantly different prognostic groups. When compared to the results of grading, the new system is shown to be superior. The large group of 228 patients with G2 tumors can be split into three groups, each with a significantly different prognosis. The correlation of the scoring system to local tumor extension (pT category) is described. Recommendations for grading of prostatic carcinoma resulting from this work are the following: Only three independent parameters are of significance for grading prostatic cancer: tumor architecture, nuclear anaplasia, and the presence or absence of mitoses. The combination of these parameters in a scoring system identifies five separate prognostically different groups. The separation achieved by this new system is superior to conventional grading and is suggested for grading prostatic cancer.

Grading of prostatic cancer: III. Multivariate analysis of prognostic parameters.

This work is based on the two previous publications which are concerned with grading prostatic carcinoma. In the present communication the technique of multivariate analysis is applied to quantify the prognostic importance of parameters which were earlier identified as contributing in a significant manner to grading. The results of this analysis are used to construct a scoring system which differentiates five significantly different prognostic groups. When compared to the results of grading, the new system is shown to be superior. The large group of 228 patients with G2 tumors can be split into three groups, each with a significantly different prognosis. The correlation of the scoring system to local tumor extension (pT category) is described. Recommendations for grading of prostatic carcinoma resulting from this work are the following: Only three independent parameters are of significance for grading prostatic cancer: tumor architecture, nuclear anaplasia, and the presence or absence of mitoses. The combination of these parameters in a scoring system identifies five separate prognostically different groups. The separation achieved by this new system is superior to conventional grading and is suggested for grading prostatic cancer.

Reliability of Cytological Grading of Prostatic Carcinoma Compared with Histological Grading

Thirty prostatic carcinomas diagnosed simultaneously by fine needle aspiration cytology and punch biopsy were graded into three groups according to their cytological and histological appearances. Among them 23 carcinomas were graded equally by both methods. Cytological examination appears to be suitable for grading prostatic carcinoma, thus being a possible indicator of the patient's prognosis and response to hormonal therapy. In addition to the results obtained here, fine needle aspiration cytology has many advantages such as simplicity, quickness and safety. With increase of attention of urologists and pathologists to fine needle aspiration cytology, this evaluation will become comparable to the histological examination not only as a routine diagnostic tool.

Transrectal thin-needle aspiration biopsy of prostate: Four years' experience

Fine-needle aspiration biopsy of the prostate is of great advantage in the diagnosis of prostatic disease. The procedure is quick, safe, and reliable. Several aspirations can be done even in outpatients with minimum trauma. Complications are rare. In this study cytologic diagnosis was obtained in 511 consecutive patients. To evaluate the cytologic accuracy, 195 cytologic diagnoses were compared with histologic findings obtained from transperineal biopsy on the same patients. Correlation was achieved in 96.42 per cent of these cases. The findings in 127 histologically graded prostatic cancers were compared with the cytologic differentiation observed in aspiration smears of the same patients. Cytologic grading of prostatic carcinoma corresponded to the histologic grading in 85.8 per cent of the cases.

Combined histologic grading of prostatic carcinoma.

A new histologic grading system for prostatic adenocarcinomas is presented, and its clinical significance tested. Histologic growth patterns and nuclear anaplasia found therein are evaluated independently of each other. The diagnostic categories are in accordance with the histologic classification recently published by the WHO. The tumor is denominated according to the least differentiated fraction. Three grades of malignancy, which correspond to significantly different survival probabilities, are distinguished. The prognosis of grade I patients is not reduced in comparison to that of healthy males of the same age. Grade I patients did not reveal metastases. The rate of tumor-specific deaths increases with the malignancy grade of the tumor. Interobserver reproducibility of this grading is found to be 91%. With 5% undergradings, the representativity is found to be satisfactory. Prostatic carcinomas tend to change their malignancy grades in time. The question of whether grade I prostatic carcinoma patients with early clinical stages benefit from therapy is discussed.

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 I, 25% in Stage II, 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.

Cell kinetic and cytological grading of prostatic carcinoma.

In 69 cases of prostatic carcinomas The 3H-thymidine labelling index was studied, and a cytological analysis was performed in addition to the histological classification. The following cytological variables were measured: nuclear size and shape, nuclear-cytoplasmic-ratio, nuclear chromasia, size and form of nucleoli. Only prostatic carcinomas with a labelling index of less than 0.4% showed mild nuclear anaplasia. These carcinomas were histologically classified as well differentiated adenocarcinomas. Prostatic carcinomas with a labelling index from 0.4% to 1.0% showed moderate nuclear anaplasia. These carcinomas were poorly differentiated adenocarcinomas. Carcinomas with labeling indices between 1.4 and 2.3% had moderate - marked nuclear anaplasia and exhibited a transition to undifferentiated carcinomas. Carcinomas with a labelling index higher than 2.3% were cribriform and undifferentiated carcinomas with marked nuclear anaplasia. The present studies have shown a correlation between both histological classification and cytological appearances with indicators of cell kinetics.U

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.

Histological Grading of Prostatic Carcinoma and Its Clinical Evaluation

The clinical control of patients with T1--T3, N0--M0 prostatic carcinomas allows us to draw the following conclusions regarding the grading. (1) The grading of the primary tumor is of great help in establishing the prognosis. (2) The results of the various applied treatments, like radical prostatectomy, radiation, and heterosexual hormone therapy, depend on the primary grade. The use of cytostatics in badly or undifferentiated prostatic carcinomas deserves on the contrary, better attention. (3) The changing of the grading at the various check-ups is of great therapeutical significance.

Classification and grading of prostatic carcinoma.

There exists general agreement that the therapy and prognosis of prostatic cancer depend on the quantitative spread of the tumor within the organ and beyond. The clinical staging A-D or I–IV, as first proposed by WHITMORE (23), meets in the same way the demands which we may claim from such a classification as the TNM classification. In recent years German urologists have classified tumors according to the A-D stagings as presented by FLOCKS (1971) at the 1969 Berlin Symposium (Fig. 1). Deviating from the prior American classification (24) here stage A is a clinically palpable nodule in an otherwise well-demarcated gland, stage B is a tumor occupying a whole lobe, but still restricted to the organ, while in stage C the tumor extends beyong the organ capsule. In stage D there exist distant metastases, particularly within the skeleton, independent of the size of the primary tumor.

Cytologic malignancy grading of prostatic carcinoma by transrectal aspiration biopsy. A five-year follow-up study of 469 hormone-treated patients.

In 469 patients with prostatic carcinoma diagnosed by transrectal aspiration biopsy, the tumours were cytologically graded according to cell differentiation. The classification was grade I (highly differentiated) in 131 patients, grade II (moderately differentiated) in 265 and grade III (poorly differentiated) in 73 patients.Five-year follow-up was possible in all 469 patients. All received hormonal therapy (oestrogens and/or bilateral orchiectomy). Most of the highly differentiated carcinomas responded well to treatment, but most of the poorly differentiated tumours did not respond.Comparisons between differentiation grades and crude survival rates showed that 73% of the patients with highly differentiated tumours, 61% of those with moderately differentiated tumours and 29% with poorly differentiated tumours were still alive after 3 years. The corresponding percentages after 5 years were 68, 55 and 11.The importance of malignancy grading of prostatic carcinoma prior to commencing treatment is emphasized.