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Objectives: To assess the value of prostate-specific antigen (PSA) kinetics in predicting survival and relate this to the baseline variables in men with metastatic hormone-refractory prostate cancer (HRPC)., Methods: The data from 417 men with HRPC were included in a logistic regression model that included hemoglobin, PSA, alkaline phosphatase, Soloway score, and performance status pain analgesic score at baseline. The posttreatment variables included the PSA level halving time after the start of treatment, PSA level at nadir, interval to nadir, PSA velocity (PSAV), PSA doubling time after reaching a nadir, patient age, and treatment. These variables were added to the baseline model, forming new logistic regression models that were tested for net reclassification improvement., Results: The area under the receiver operating characteristics curve for the baseline model was 0.67. Of all variables related to PSA kinetics, the PSAV was the best predictor. The addition of PSAV to the baseline model increased the area under the receiver operating characteristics curve to 0.81. Only a moderate increase in the area under the receiver operating characteristics curve (0.83) was achieved by combining the baseline model in a multivariate model with PSAV, PSA doubling time, interval to nadir, and patient age at diagnosis of HRPC., Conclusions: The PSAV alone gave a better prediction of survival value than all other PSA kinetics variables. By combining PSAV with the variables available at baseline, a better ground for treatment decision-making in men with HRPC can be achieved.

Objectives: To compare the effect on overall survival of total androgen ablation (TAA) with that of parenteral estrogen and to pay special attention to cardiovascular mortality. TAA (orchiectomy or a luteinizing hormone-releasing hormone analogue combined with an antiandrogen) has been proposed as superior to other endocrine treatments for patients with prostate carcinoma. Recently, the use of parenteral estrogen has been suggested to reduce or even negate the well-known cardiovascular side effects of oral estrogens., Methods: Nine hundred fifteen patients were randomized to intramuscular injections of 240 mg polyestradiol phosphate (PEP) every second week for the first 8 weeks (5 doses) followed by a maintenance dose of 240 mg every month (n = 458) or to bilateral orchiectomy or triptorelin 3.75 mg every month combined with the antiandrogen flutamide 250 mg three times daily. The choice between orchiectomy and triptorelin was at the discretion of the clinician and patient. Patients were stratified according to performance status, presence of cardiovascular disease, and alkaline phosphatase level. An observer totally unaware of the treatment given classified all deceased patients., Results: At a median follow-up of 18.5 months, no signs of a difference in overall survival were found between TAA and PEP (P <0.001). Of 458 patients, 266 (58.1%) had died in the PEP group compared with 269 (58.9%) of 457 patients in the TAA group. Within the TAA group, no difference in overall survival existed between patients who had undergone orchiectomy or who were given triptorelin. Furthermore, no differences in cardiovascular mortality were found (3.5% in the PEP group and 3.1% in the TAA group)., Conclusions: The current parenteral estrogen regimen seems to be of comparable efficacy and cardiovascular safety as TAA in terms of overall survival. PEP has by far the lowest drug cost and also the lowest cumulative direct costs and thus has the highest cost-effectiveness. We suggest that parenteral estrogen be included as a therapeutic option in the endocrine management of prostate carcinoma.

Objectives: To review the outcome in patients with clinically localized prostate cancer managed conservatively., Methods: A total of 122 patients with palpable, clinically localized, low-grade prostate cancer diagnosed from 1978 to 1982 at the Karolinska Hospital, Stockholm, Sweden, were prospectively followed in a surveillance protocol followed by treatment when the tumor progressed with symptoms., Results: All patients but one had been observed for 10 years or more. No antitumoral therapy had been given to 58 (48%) patients at follow-up or before death. The chance of being untreated 5 and 10 years after diagnosis, if still alive, was 71% and 43%, respectively. The actual disease-specific survival rate at 10 years was 90%. Of the patients with a possible observation period of 15 years or more, 25% died of prostate cancer (ie, an actual disease-specific survival of 75%). Using a survival plot, the projected disease-specific survival rate at 15 years was 62%. The cumulative incidence of death from prostate cancer increased with possible observation time up to 15 years., Conclusions: Our data are mature up to 10 years of observation and, based on these data, deferred treatment is a valid option for patients with clinically localized low-grade prostate cancer with a life expectancy of 10 years or less. The data are not definitive beyond 10 years and firm conclusions will be speculative, but our findings indicate that there probably is room for efficacious local treatment in patients with localized prostate cancer and a life expectancy longer than 10 years.

Objectives: The aim of this discussion is to review the design and conduct of phase III trials in metastatic prostate cancer, to seek ways of improving their study design, accuracy, relevance to clinical practice, acceptability to patients, and ease of participation by clinicians. We also aim to try to set uniform definitions for the evaluation of the different endpoints used in clinical trials on metastasized prostate cancer., Methods: The work was started by correspondence between the participants in the group for the year before the consensus meeting. Two comprehensive questionnaires were circulated and the answers were distributed to all the members of the group. The statements were finalized during the consensus meeting., Results: There were some differing opinions concerning the methods of evaluation of endpoints for follow-up, such as time to tumor progression and time to treatment failure. After the consensus conference, there were no major disagreements within the group., Conclusions: The aim of phase III trials is to influence clinical management. To obtain a credible result they require a sound statistical basis with appropriate power and encompassing patients from small urologic practices as well as large or academic institutions. However, deviation from routine practice may affect the accrual rate, and the trial procedure should therefore be as similar as possible to routine management. Trials inevitably involve extra work and cost. Both should be kept to a minimum to encourage participation and hasten a timely conclusion. It is mandatory to create uniform ways of designing and evaluating clinical trials in prostate cancer.

A prospective study of 59 hormonally treated prostatic cancer cases was undertaken during follow-up with sequential transrectal palpation and fine-needle aspiration. At initiation of therapy patients' ages ranged from forty-eight to eighty-two years (median, 68 years). The usual follow-up interval was 6 +/- 3 months, and follow-up periods ranged from six months to one hundred twenty months (median 48 months). The cytologic findings were categorized under four cytologic response types and palpation findings under five response grades. Four different degrees of squamous metaplasia (1+, 2+, 3+, 4+) were observed in smears, depending on semiquantitative determination of squamous metaplastic cells in relation to the total amount of benign and malignant epithelial cells in the smear. There were 341 follow-up observations in which both transrectal fine-needle aspiration cytology and palpation were done. In 306 of these, cytologic findings were found to be adequate. Comparison of squamous metaplasia with cytologic response types revealed a highly significant difference between the benign state and recurrence/frank malignancy. This was also true when frequency of squamous metaplasia was compared with palpatory response grades. It was found that squamous metaplasia can be a valuable adjunct to other cytomorphologic changes such as shrinkage of tumor cell size and decrease in size of nucleoli or its disappearance, in determining response to hormonal therapy.

Fifty-nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal examination and fine needle aspiration cytology at six-month intervals for periods ranging from six to one hundred twenty months (median follow-up 48 mos). The cytologic findings and clinical impressions were divided into four or five categories, respectively, ranging from benign to clearly malignant. Cytologic material and clinical descriptions suitable for evaluation were available for 306 follow-up examinations. Of these, 209 were cytologically benign (including 191 without and 18 with clinical evidence of malignancy). The remaining 97 examinations showed cytologic evidence of malignancy of which 50 were clinically apparent (51.5%). While the correlation of clinical and cytologic findings was good (91.4%) in cases with no evidence of disease activity, our findings indicate that many recurrences which are occult to clinical examination may be detected by cytologic examination.

Despite several studies comparing the diagnostic accuracy of core needle biopsy and fine-needle aspiration (FNA) in the diagnosis of prostatic adenocarcinoma, no clear picture of the false negative rate for FNA is available. We studied 101 follow-up FNA evaluations in 30 patients with untreated well-differentiated carcinoma. The patients were followed for a median of two years and seven months and had from two to seven FNA follow-up evaluations (median = 2.5 evaluations per patient). If three inadequate evaluations are omitted, the combined rate of positive plus suspicious FNA biopsies was 92.9 percent (88.8% plus 4.1%, respectively). The residual false negative rate was 7.1 percent. The clinical features and follow-up data are described. A semiquantitative definition of "suspicious for malignancy" is suggested. We conclude that in experienced hands. FNA is a highly efficacious method for the diagnosis of prostatic adenocarcinoma.