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Objective: To estimate the strength of change in haemoglobin (Hb) concentrations during 1 year of androgen-deprivation therapy (ADT) as a predictor of survival in hormone-naïve patients with bone-metastatic (Stage M1b) prostate cancer., Patients and Methods: The patients included in this study were taken from the randomised trial (number 5) carried out by the Scandinavian Prostate Cancer Group (SPCG), comparing parenteral oestrogen with total androgen blockade (TAB) in hormone-naïve M1b prostate cancer. We identified 597 men where Hb measurements were made at enrolment, as well as at 3, 6 and 12 months of ADT. The time-dependent impact of Hb concentration changes on overall survival (OS) was analysed using multivariate Cox proportional hazards analysis. The 10-year OS according to increase/decrease in Hb concentration for the three treatment periods was demonstrated using Kaplan-Meier curves., Results: Multivariate analysis of changes in Hb concentration between baseline and 3 months showed better survival in patients with a decrease in Hb concentration (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.11-1.80) compared to those with an increase, whilst there was no difference in survival associated with a change in Hb concentration between 3 and 6 months (HR 0.93, 95% CI 0.76-1.12). Contrary to the first 3 months, poorer survival was seen in patients with a decrease in Hb concentration between 6 and 12 months (HR 0.76, 95% CI 0.62-0.92) compared to those with an increase., Conclusions: In a large cohort of Scandinavian men with hormone-naïve M1b prostate cancer, an increase in Hb concentration between baseline and 3 months of ADT was associated with significantly poorer survival, whereas an increase between 6 and 12 months was associated with better survival. These findings provide new information about patterns of change in Hb concentrations during 12 months of ADT for M1b prostate cancer, and survival. Clinicians should be aware of the prognostic value of Hb concentration changes during ADT in M1b prostate cancer., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to investigate the impact of bone metastasis on survival and quality of life (QoL) in men with hormone-naïve prostate cancer., Materials and Methods: The study included 900 patients from a randomized trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Extent of bone metastasis was categorized according to a modified Soloway score: score 1, n = 319; score 2, n = 483; and score 3, n = 98 patients. The primary outcome measurements were mean differences in QoL and overall survival., Results: QoL rating scales showed a decrease with increasing extent of bone metastasis (p < 0.001). The mean global health status decreased from 64.4 to 50.5 for Soloway score 1 and 3, respectively. Following adjustment for performance status, analgesic consumption, grade of malignancy, alkaline phosphatase, prostate-specific antigen, haemoglobin and global health status, Soloway score 2 and 3 had a 47% [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.21-1.80] and 78% (HR 1.78 95%, CI 1.32-2.42) increased mortality, respectively, compared to Soloway score 1. Independent predictive factors of mortality were assessed., Conclusions: Patient grouping based on three categories of extent of bone metastasis related to performance status, haemoglobin and global health status at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.

Objective: To describe characteristics and quality-of-life (QoL), and to define factors associated with long-term survival in a subgroup of patients with prostate cancer with M1b disease., Patients and Methods: The study was based on 915 patients from a prospective randomised multicentre trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Long-term survival was defined as patients having an overall survival of ≥10 years, and logistic regression models were constructed to identity clinical predictors of survival. QoL during follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - C30 version 1 (EORTC-C30) ratings., Results: In all, 40 (4.4%) of the 915 men survived for >10 years. Factors significantly associated with increased likelihood of surviving for >10 years in the univariate analyses were: absence of cancer-related pain; Eastern Cooperative Oncology Group (ECOG) performance status of <2; negligible analgesic consumption; T-category of 1-2; prostate-specific antigen (PSA) level of <231 μg/L; and a Soloway score of 1. In the multivariate analyses, ECOG performance status of <2, PSA level of <231 μg/L, and Soloway score of 1, were all independent predictors of long-term survival. All subscales of the EORTC-C30 were higher in this group than for patients with short survival, but slowly declined over the decade., Conclusion: A subgroup of patients with prostate cancer with M1b disease and certain characteristics showed a positive long-term response to androgen-deprivation therapy with an acceptable QoL over a decade or more. Independent predictors of long-term survival were identified as ECOG performance status of <2, limited extent of bone metastases (Soloway score of 1), and a PSA level of <231 μg/L at the time of enrolment., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Approximately 15% of men with hormone naïve metastatic prostate cancer primarily fail to respond to androgen deprivation treatment (ADT). The reason why the response to ADT differs in this subgroup of men with prostate cancer remains unclear. The aim of this study was to describe the characteristics of these men and to thereby define predictors of early ADT failure in prostate cancer patients with bone metastases. The study was based on 915 men from the prospective randomized multicenter trial (no. 5) conducted by the Scandinavian Prostate Cancer Group comparing parenteral estrogen with total androgen blockade. Early ADT failure was defined as death from metastatic prostate cancer within 12 months after the start of ADT. Multivariate logistic regression models were applied to identify clinical predictors of early ADT failure. Ninety-four (10.3%) men were primarily nonresponders to ADT. Independent predictors of early ADT failure were poor Eastern Cooperative Oncology Group performance status (PS), analgesic consumption, low hemoglobin, and high Soloway score (extent of disease observed on the scan), in where patients with poor PS and/or high analgesic consumption had a threefold risk of early ADT failure. Not significantly factors related to early ADT failure were age, treatment, cardiovascular comorbidity, T category, grade of malignancy, serum estrogen level, and SHBG at enrolment. We analyzed characteristics of a subgroup of patients who primarily failed to respond to ADT. Four independent clinical predictors of early ADT failure could be defined, and men exhibiting these features should be considered for an alternative treatment., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin®) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease., Material and Methods: Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naïve prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin®) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl®) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression., Results: There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p < 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036)., Conclusions: Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e.g. avoidance of osteopenia and hot flushes and the low price, are given priority.

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.

Objective: To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events., Material and Methods: In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg i.m. per month or on an optional basis bilateral orchidectomy., Results: At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001)., Conclusions: PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.

Objectives: Prostate cancer (PC) is a highly lethal neoplastic disease affecting the physical, mental and social well-being of patients, i.e. their quality of life (QOL). Patients suffering from metastatic PC are faced with serious decisions regarding treatment strategies. Therefore, QOL information has become a crucial element of decision making in this group of patients. The first objective of this study was to describe QOL in a group of patients diagnosed with metastatic PC and skeletal metastases. At the time of evaluation the patients had not received any treatment but were evaluated before entering a study of androgen-modulating therapy (the Scandinavian Prostate Cancer Group study 5). The second objective was to identify demographic and disease-related factors affecting QOL., Material and Methods: A total of 917 patients with metastatic PC were evaluated using a well-described and validated questionnaire [European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (EORTC QLQ-C30)]. The characteristics of the PC were noted, and simultaneously patients were evaluated with respect to use of analgesics, pain and performance status using a scoring system. Biochemical tests were performed when patients entered the study. A multivariate regression analysis was performed to analyse the correlations between QOL scores, patient demographics and disease-related data., Results: The patients reported QOL scores significantly lower than those in the background population. Pain and fatigue were pronounced, whereas dyspnoea, insomnia, loss of appetite, constipation and diarrhoea were less prominent. Patients with high tumour grades, high PSPA scores (the sum of the pain score, the performance status and the use of analgesics) and those using analgesics had significantly lower QOL scores than the other patients., Conclusions: Patients with metastatic PC have reduced QOL. Our findings are in line with those of other studies of QOL among patients with this disease as evaluated by means of the EORTC QLQ-C30 questionnaire. Baseline data from studies like this provide important information when treatment modalities for PC are evaluated.

In 1981 the Scandinavian Association of Urology initiated the Scandinavian Prostate Cancer Group (SPCG) as one of eight collaborative groups representing different fields of urology. The task of the SPCG was to promote research, education and information concerning prostate cancer. In particular it became a forum for conducting clinical multicenter studies within the Nordic countries. This paper summarizes some aspects of the history of the SPCG and reviews the clinical trials initiated by the group on the occasion of its 20th anniversary.

Objective: In the mid-1980s, interest in parenteral estrogen therapy for prostate cancer was renewed when it was found that it influenced liver metabolism only marginally and had very few cardiovascular side-effects. In this study high-dose polyestradiol phosphate (PEP; Estradurin) was compared to combined androgen deprivation (CAD) for the treatment of patients with metastatic prostate cancer. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular side-effects., Material and Methods: A total of 917 patients with T0-4, NX, M1, G1-3 prostate cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter once a month or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg per month i.m. or, on an optional basis, bilateral orchidectomy. A total of 556 patients had died at the time of this analysis., Results: There was no difference between the treatment arms in terms of time to biochemical or clinical progression and overall or disease-specific survival. There was no increase in cardiovascular mortality in the PEP arm. The PEP group had a higher prevalence of cardiovascular disease prior to the study and a significantly higher incidence of non-fatal ischemic heart events and heart decompensation during the study., Conclusions: PEP has an equal anticancer efficacy to CAD and does not increase cardiovascular mortality. Final evaluation of cardiovascular morbidity is awaiting further analysis and follow-up. PEP is considerably cheaper than CAD.

In advanced prostate cancer when the tumor has metastasized, endocrine therapy is the primary treatment alternative. Endocrine therapy was introduced 60 years ago by Huggins and Hodges in the form of castration or estrogen treatment. Unfortunately we must now concede that no decisive breakthrough in the pharmacological treatment of prostate cancer has occurred since that time. We do have several different endocrine treatment alternatives at our disposal today--all with varying advantages and drawbacks. We do, however, eagerly await new therapeutic options for the pharmacological eradication of prostatic adenocarcinoma. Today our interest is focused on methods of tailoring endocrine therapy in ways that offer the individual patient an optimal combination of quality of life and anticancer efficacy. The various opinions and research results which inform current strategies of endocrine therapy are described briefly.

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.

Endocrine treatment of prostate cancer can be performed under several different regimes. They all have side effects which in different ways influence quality of life and the patient's general health. This paper is a survey of the most important early side effects of the different modes of endocrine treatment, their etiology, and possible ways to avoid or treat them., (Copyright 2000 Wiley-Liss, Inc.)

Purpose: We prospectively investigated long-term survival in select men with locally advanced, nonmetastatic prostate cancer managed with deferred treatment., Materials and Methods: A total of 50 patients with prostate cancer clinically outside the prostatic capsule and without distant metastases were included in a surveillance protocol. The men were treated if and when symptoms occurred or upon request. The series was followed until December 1994. No patient was lost to followup., Results: Median patient age at diagnosis was 71 years. All patients were followed more than 144 months or died before then. Actual (cumulative incidence) overall and disease specific survival rates at 5, 10 and 12 years were 68 and 90, 34 and 74, and 26 and 70%, respectively. A third of the patients had not received antitumor treatment at followup or before death., Conclusions: When managed with deferred treatment nonpoorly differentiated, locally advanced nonmetastatic prostate cancer seems to have a poorer survival outcome than similarly managed clinically localized prostate cancer. However, compared with other treatments and in terms of survival deferred treatment may be an option for select patients with such tumors and a life expectancy of 10 years or less.

The Scandinavian Prostatic Cancer Group (SPCG) was founded in 1981 as one of eight collaborative groups instituted by the Scandinavian Association of Urology within different fields of urology. The purpose of these groups was to promote research, education and information provision within their different fields and to stimulate collaboration between the Nordic countries. The main purpose of the SPCG gradually evolved into conducting clinical trials. This paper presents a summary of the different clinical trials carried out by the group and reviews some of its history and other activities.

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.

Between 1984 and 1989, 197 patients with T1-4, NX, M1, G2-3 or G3 prostate cancer were randomized to treatment with 560 mg estramustine phosphate (EMP, Estracyt, Emcyt) or 3 mg diethylstilbestrol (DES) per day in a double blind study with stratification on presence or absence of cancer pain at start. A total of 194 patients were evaluated for efficacy of therapy. Time to progression (p = 0.054), to treatment failure (p = 0.036), cancer-specific survival (p = 0.068) as well as overall survival (p = 0.021) were longer in the DES group. There were more patients with prognostic parameters indicating bad prognosis in the EMP group. This trial was designed to study whether EMP had better effect than DES as the primary treatment of high-grade, disseminated prostate cancer. The results did not confirm this hypothesis. On the contrary, treatment with DES had relatively good effect on this very aggressive form of prostate cancer.

More than 50 years ago, orally given estrogen was already used in the treatment of prostate cancer. Due to cardiovascular side-effects with a high morbidity of 25%, this treatment has not become standard. Recent investigations show that parenteral application reduces the risk of cardiovascular side-effects, because it avoids the first passage through the liver with high concentrations of estrogen which normally occur after oral application. Therefore, an increased synthesis of so-called "steroid-sensitive" liver proteins, such as coagulation factors (especially factor VII) can be avoided. This newer parenteral estrogen application shows encouraging results of a cheap and effective hormonal therapy with a low rate of side-effects in patients with prostate cancer.

From 1978 to 1982, 172 patients with stages T1 to 3NxM0 prostate cancer were included in a surveillance protocol with deferred treatment on symptomatic progression. Median patient age at diagnosis was 68 years (range 38 to 89 years). Mean followup was 80 +/- 32 months. Of the patients 58% had local and 19% had distant progression, and 52% had received treatment at followup. Disease specific survival rate at 10 years was 80% for the total series, 84% for the subgroup with stage T1 or T2 tumor and 92% for those with stage T1 or T2 tumor who were less than 70 years old at diagnosis. For the subgroup with stage T3 tumor the disease specific survival rate at 9 years was 70%. In all subgroups the competing mortality rate was higher than the prostate cancer mortality rate. Deferred treatment appears to be an acceptable option for patients with tumor clinically confined to the prostate and a life expectancy of 10 years or less.

The TNM working group acknowledges the multinational agreement reached in the 1992 TNM classification, but nevertheless gives some suggestions for modifications. The main interest of the group has been to evaluate parameters suitable for further ramification of the system. The group found that parameters such as DNA ploidy, PSA, nuclear roundness factor, are not yet ready for this purpose. Grade is an established parameter and should be incorporated into the TNM-categories of localized disease. In metastatic disease a number of parameters are available to subdivide this category according to prognosis, and these will be more uniformly and extensively studied in the several large trials that are now in progress.

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.

This is a presentation of some preliminary data from SPCG-I, a multicenter study started in 1984 by the Scandinavian Prostatic Cancer Group. It is a randomized double-blind study comparing estramustine phosphate and diethylstilbestrol in the primary treatment of 195 patients with T1-4, NX, M1, G2-3 prostatic cancer. The code is not yet broken. This presentation describes the impact of the pretreatment parameters performance status, pain, tumor burden, grade and DNA-ploidy of the prostate tumor, on time to progression and overall survival. DNA studies have so far only been completed in 66 of the 195 patients. For the whole group of 195 patients, pain (p less than 0.004) and tumor grade (p less than 0.02) had the most significant impact on time to progression, and performance status (p less than 0.01) and grade (p less than 0.03) on overall survival. In the small group of 66 patients where the DNA pattern of the primary tumor was evaluated, no parameter had any significant correlation to time to progression and overall survival. This study is still continuing.

We selected for a prospective surveillance study 167 patients with untreated grades 1 and 2 prostate cancer. The tumors were classified regarding modal deoxyribonucleic acid value (ploidy) by flow cytometry, cytological grade by transrectal fine needle aspiration biopsy and local tumor stage. Of the patients 146 could be evaluated. Mean followup was 50 months. The initial ploidy was statistically correlated to cytological grade but not to initial local tumor stage, prostatic acid phosphatase activity or patient age. Initial ploidy and cytological grade had a prognostic value regarding local tumor progression when considered as single predictors and in combination. Two patients with diploid and 8 with nondiploid tumors initially had metastases during the surveillance. Five patients (1 with diploid and 4 with nondiploid disease) died of prostatic cancer. Modal deoxyribonucleic acid value and cytological grade were of prognostic value in untreated prostate cancer.

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.

A surveillance study was carried out on 167 patients with low grade, low stage prostatic carcinoma without known metastases; of these, 146 were evaluated, the mean follow-up time being 50 months. Local tumour progression occurred in 77 patients (53%), corresponding to a 5-year cumulative probability of progression of 67%. Ten patients developed metastases, 5 died of prostatic carcinoma and 24 died of other causes. Cox's regression analysis showed that the initial cytological grade of the tumour was of prognostic importance, but initial local tumour stage, prostatic acid phosphatase activity and age had no statistically significant prognostic value. Although the number of patients developing metastases and dying of prostatic carcinoma was low, most tumours seemed to progress locally.

Serum lipoprotein concentrations were related to hemostatic parameters in a group of 31 men before and during three different hormone treatment regimens for prostate cancer in an attempt to analyse to what extent the changes in these two systems correlate. In a correlation matrix the number of significant relationships at the 5% and 1% level corresponded to what could be expected by chance. The study thus failed to demonstrate any consistent relationship between any lipoprotein lipid concentration and the hemostatic parameters in men treated for prostate cancer. Most significant relationships were found for HDL-TG versus plasminogen, but the clinical significance of this observation is not clear.

Fifty-nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal palpation and fine needle aspiration cytology (FNAC) at 6 month intervals for periods ranging from 6 to 120 months (median follow-up, 48 months). The cytologic impressions and palpatory findings were divided into four categories, respectively, ranging from benign to clearly malignant. Cytologic material and palpatory descriptions suitable for evaluation were available for 306 follow-up examinations, with a mean number of follow-up examinations per patient of five (range, 1-13). Tumor relapse was noted in 26 patients and was diagnosed at the same time by FNAC and palpation in six patients. In 16 of the patients tumor progression was first noted by cytology, and in four patients relapse was first detected by rectal palpation. Different patterns of cytologic and palpatory findings during the development of remission and progression of the tumors and drawbacks of the methods are discussed.

Tranexamic acid is a potent antifibrinolytic drug frequently used in the treatment of haematuria and a number of other haemorrhagic conditions. Since it is eliminated mainly in the urine, the drug accumulates in patients with uraemia. The excretion of tranexamic acid in patients with renal failure has been investigated and dosage recommendations are given for tranexamic acid therapy in cases of renal failure.

In a prospective randomized multicenter trial patients with highly or moderately differentiated prostatic carcinoma, previously untreated, were allotted either to oral Estramustine phosphate or to intramuscular polyestradiol phosphate plus oral ethinyl estradiol. As regards frequency and duration of tumour remission there was no statistical difference between the two groups. Nor did they differ significantly with respect to adverse reactions. This is an interim report and will be followed later on by a final evaluation.

Two hundred and twelve patients treated for prostatic cancer grade I or II were investigated for cardiovascular complications. The patients were part of a multicentre study in the Stockholm area and had been randomized to treatment with either estramustine phosphate (Estracyt) or polyestradiol phosphate and ethinyl estradiol. Cardiovascular complications categorized as impaired arterial circulation including ischemic heart disease, venous thromboembolism, cardiac incompensation and cerebral depression were found to be equally frequent following the two different forms of treatment. Among the patients getting cardiovascular complications, these occurred within two months after the start of treatment in 50% and within one year in 85% of them. There was a statistically significant correlation between the incidence of cardiovascular complications and a history of previous cardiovascular disease. This criterion was however in retrospect found to predict cardiovascular complications in only 67 of the 126 patients getting one or several of these complications.

Post-operative venous thrombosis, blood loss and pre- and post-operative plasma heparin concentrations were studied in a prospective double blind trial with low-dose heparin therapy in 59 patients undergoing transvesical prostatectomy. Thrombosis rate, diagnosed with the 125I-fibrinogen method, was significantly reduced in the first 5 post-operative days, i.e. during but not after the period of heparin therapy. One patient who developed major thrombosis in spite of heparin prophylaxis is presented. Heparin therapy did not increase average blood loss, but was suspected to be the cause of severe bleeding in 1 patient, who may have had a latent hemorrhagic diathesis. Plasma heparin levels were significantly raised during heparin therapy, and were significantly lower in both heparin and placebo treated patients on days when thromboses started.

We studied 32 patients with prostatic cancer before, and after 1 and 6 months of treatment with orchiectomy, estramustine phosphate or conventional estrogens (polyestradiol phosphate plus ethinyl estradiol). Lipid metabolism was evaluated by lipoprotein analysis and the intravenous fat tolerance test. Effects on the cardiovascular system were studied by exercise electrocardiography, blood volume estimation and thoracic electrical impedance measurement, a sensitive method to detect early signs of fluid retention. Present treatment programs for prostatic cancer seem to result in effects on lipoprotein metabolism that probably are of minor importance for the development of atherosclerotic manifestations. Measurement of thoracic impedance may be of value to detect fluid retention in individual patients.

Heparin was administered subcutaneously 5.000 IU twice daily using a double blind method to ten of twenty-one patients undergoing transvesical prostatectomy. Platelet count, APTT, throbin time, Reptilase time, Normotest, fibrinogen, Factor-VIII, ethanol gelation test, antithrombin III, fibrinolytic degradation products, alpha1-antitrypsin and alpha2-macroglobulin were studied pre- and postoperatively up to the 10th postoperative day. Statistical analysis of parameters of blood coagulation and fibrinolysis showed no significant difference between the two groups. The mechanism by which low dose heparin exerts its thromboprophylactic effect could not be elucidated from the study of the investigated parameters. The laboratory data gave no indication to a possible increased risk of postoperative hemorrhage.

It is a common belief that the female urethral syndrome is an infectious disease, caused by ascending vestibular microorganisms or bacteria harboured in the paraurethral glands. To study the flora of different parts of the urethra in patients with urgency, cultures were obtained in 36 cases from the proximal urethra, the external urethral opening, the distal urethra after paraurethral massage and from the upper vagina for comparison. All locations were dominated by lactobacillae. Enterobacteria and anaerobic bacteria occurred in approximately one third of the cases at all sites, although only in small amounts in the urethra, especially in the proximal part. The urethral and the vaginal flora resembled each other very closely. Only in a few cases did a possible pathogen reside solely in the urethra, i.e. it could not be found in the vagina or in the vestibular flora. On the whole, no appreciable amount of any microorganism was present in the urethra or in secretion from the paraurethral glands. The clinical significance which a very small amount of enterobacteria or anaerobes may have in these locations remains to be established.