Prognostic factor analysis from EORTC trials in advanced prostatic cancer. EORTC-GU Group.
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Biomedical subjects
Publications and source records attributed to M Pavone-Macaluso.
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To distinguish prostatic dysplasia (or adenosis) from well differentiated adenocarcinoma on transrectal needle biopsy, a morphometric study was conducted on 20 cases of adenosis and 20 cases of well differentiated adenocarcinoma of the prostate. About 100 cells for each patient were analyzed by means of a computerized image analyzer, and mean nuclear diameter, mean nuclear area, mean form factor and number of cells in eight classes of nuclear diameter were studied. The best predictors of malignancy (evaluated by means of Receiver Operating Characteristics curves) were mean nuclear area greater than 28 mu2, presence of more than 5% of cells with nuclear diameter greater than 6.15 mu, and mean nuclear diameter greater than 5 mu. Using these diagnostic criteria the probability of malignancy for a positive specimen rises from 14% (pre-test) to 75% (post-test).
The effect of purified human fibroblast beta-interferon (B-IFN) and recombinant alpha-2b-interferon (A-IFN) on cell proliferation was investigated in two human prostate carcinoma cell lines, named PC-3 and DU-145. Both cell lines respond to the antiproliferative action of interferon, B-IFN being more effective than A-IFN. PC-3 is more sensitive than DU-145 cell line, showing 95% inhibition of cell proliferation at the highest concentration of B-IFN. As interferons, besides reducing cell growth, are able to modify steroid receptor content in different hormone-sensitive human tumours, our results may be of some relevance as these drugs might be used to regulate both cell proliferation and hormone-sensitivity in prostate cancer.
In Europe, antiandrogens have been used for many years to treat prostate cancer, either as monotherapy or as part of a "combination therapy" with either surgical or chemical castration. However, considerable debate still exists regarding the relative benefits of combination therapy versus antiandrogen monotherapy or castration alone. This article reviews the European experience with antiandrogen therapy, including the personal experiences of the authors.
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The European Organization for Research on Treatment of Cancer Genitourinary Group performed a multivariate statistical analysis of prognostic factors based on 436 patients entered between 1976 and 1981 in 2 randomized prospective trials that compared 4 different hormonal treatment regimens. Only previously untreated patients with advanced (stage T3/T4/M0 or M1) prostatic cancer were eligible. After identification of prognostic factors by means of univariate analyses a multivariate analysis using Cox's proportional hazards regression model was done. This test identified performance status (according to the Eastern Cooperative Oncology Group scale) as the most important factor, followed by acid phosphatase (more than 2 times normal) for stage M0 cancer patients, and alkaline phosphatase, T category and the presence or absence of associated chronic disease for stage M1 cancer patients. Based on these 4 variables nonbedridden patients with metastatic disease can be divided into 2 groups: poor and good risk patients, with median survivals of 1 and 3 years, respectively. This study shows that routine clinical and laboratory data already provide an excellent indication as to the prognosis.
Morphometric analysis on two human prostate cancer cell lines (PC3 and DU-145) was carried out to better characterize these cells and to approach some problems concerning their polymorphism. In our hands, these cells appear to differ either in their ability to oxidize testosterone or in their androgen receptor content. Morphometric evaluation was performed by means of an Interactive Image Analysis System (IBAS 1), which computes several parameters related to the whole cell and to the nucleus. Our results clearly indicate that nuclear parameters alone may discriminate PC3 from DU-145 cells. Particularly, the Nuclear Roundness Factor appeared important, since it quantifies changes in nuclear shape. Nevertheless, the value of this parameter for "in vitro" morphometry may be overshadowed by the polymorphism common to the cultured cells. However, morphometric evaluation of PC3 and DU-145 cells is relevant to a better understanding and definition of the biologic nature of these cells, even if polymorphism, heterogeneity and genetic instability, specially of PC3, require further investigations.
A case of vaginal metastasis from a renal cell carcinoma is reported. This rare localization is often the first clue leading to the diagnosis of an occult renal adenocarcinoma. The role of electron microscopy is emphasized, since the histologic aspect of the lesion is similar to that of a primary vaginal mesonephric adenocarcinoma.
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This study undertaken on antiandrogens alone or in combination for treatment of prostate cancer shows the efficacy of flutamide in advanced prostate cancer. At 6 and 12 months after beginning treatment, 37% of the patients showed an objective response. Patient follow up at 2 and 3 years revealed a partial response in 33% and 19%, respectively. In one patient with stage C carcinoma, a long-lasting complete response was achieved, with a duration of approximately 3 years. A marked palliative effect was observed. Transrectal ultrasound revealed prostate volume had decreased in 73% of the patients and 86% showed functional improvement. Sexual function was not substantially altered during treatment. Similarly, there was no dramatic increase in serum testosterone. The foregoing findings demonstrate that flutamide monotherapy is an effective treatment for prostatic cancer and can be chosen for younger patients who wish to conserve their sexual potency.
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This report analyses the changes in the classification of the genitourinary tumours introduced by the 1987 edition of the TNM system. Criticism and suggestions for improvement are given. These are based on the extensive experience of the EORTC GU Group with clinical trial work particularly the identification of prognostic factors, on their success in reaching international consensus on tumour classification, and on information from the literature. Many of the changes introduced in the 1987 system are not considered to be strictly necessary. These include the introduction of the new additional descriptors, including "C" and "R", the changes in the T classification of prostatic and renal cancer, and the introduction of uniform N categories for all tumours and other features. We regret the omission of minimal requirements, the omission of the V classification for macroscopic or microscopic vascular invasion, the changes in the T categories of carcinoma of the bladder and the introduction of stage groupings for all urological tumours. Some of these changes are considered unacceptable. The attitude of the EORTC GU Group toward the use of the new TNM classification is indicated in detail.
Transrectal ultrasonography was performed in 121 patients with the chronic prostatitis syndrome (CPS), and in 20 patients with urological pathology not involving the prostate gland. The ultrasonographic aspects of the seminal vesicles (SV) in normal subjects and in patients with the CPS are described. In the latter group, characteristic ultrasonographic patterns can often be obtained, even in patients affected by prostatodynia, in whom all the other clinical and laboratory findings were absent. They consisted of: (a) dyshomogeneous echo-structure of the prostate; (b) constant dilatation of the periprostatic venous plexus, greater than 150 mm2; (c) dilated, elongated SV, with thickening of their inner septa (they are sometimes asymmetrical), and (d) bladder neck hypertrophy.
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Diagnostic accuracy in clinical staging of bladder cancer, using traditional methods, is still imperfect. Clinical and pathological staging do not always correlate. The accuracy of the new imaging techniques in the staging and in the follow-up of this kind of neoplasia, has yet to be assessed. Our study involved 7 patients with invasive bladder cancer who had undergone transurethral ultrasonography, CT scan, NMR and transurethral resection of the tumour. We have compared the clinical staging accuracy of the three imaging methods with the pathological reports. We conclude that transurethral ultrasonography is superior to the other methods, as far as local staging is concerned. In regional staging, NMR has shown very promising results and, in our preliminary opinion, may be more accurate than CT scan.