Eberhard Varenhorst

Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005

Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer

Randomised prostate cancer screening trial: 20 year follow-up

Objective To assess whether screening for prostate cancer reduces prostate cancer specific mortality. Design Population based randomised controlled trial. Setting Department of Urology, Norrköping, and the South-East Region Prostate Cancer Register. Participants All men aged 50-69 in the city of Norrköping, Sweden, identified in 1987 in the National Population Register (n=9026). Intervention From the study population, 1494 men were randomly allocated to be screened by including every sixth man from a list of dates of birth. These men were invited to be screened every third year from 1987 to 1996. On the first two occasions screening was done by digital rectal examination only. From 1993, this was combined with prostate specific antigen testing, with 4 µg/L as cut off. On the fourth occasion (1996), only men aged 69 or under at the time of the investigation were invited. Main outcome measures Data on tumour stage, grade, and treatment from the South East Region Prostate Cancer Register. Prostate cancer specific mortality up to 31 December 2008. Results In the four screenings from 1987 to 1996 attendance was 1161/1492 (78%), 957/1363 (70%), 895/1210 (74%), and 446/606 (74%), respectively. There were 85 cases (5.7%) of prostate cancer diagnosed in the screened group and 292 (3.9%) in the control group. The risk ratio for death from prostate cancer in the screening group was 1.16 (95% confidence interval 0.78 to 1.73). In a Cox proportional hazard analysis comparing prostate cancer specific survival in the control group with that in the screened group, the hazard ratio for death from prostate cancer was 1.23 (0.94 to 1.62; P=0.13). After adjustment for age at start of the study, the hazard ratio was 1.58 (1.06 to 2.36; P=0.024). Conclusions After 20 years of follow-up the rate of death from prostate cancer did not differ significantly between men in the screening group and those in the control group. Trial registration Current Controlled Trials, ISRCTN06342431.

Cohort Profile: The National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

The role of arterial embolization in renal cell carcinoma.

Twenty-five years ago arterial embolization was introduced to facilitate the surgical excision of the carcinomatous kidney or to palliate symptoms, such as haemorrhage from non-resectable tumours. The role of this technique in the therapeutic armamentarium has been a source of debate in the literature. We reviewed all the available literature. A total of 389 papers were evaluated. Fifty-one publications and 3225 case histories met explicit entry criteria for inclusion. Until now no prospective randomized study of this approach to the management of renal carcinoma has been published. In the majority of studies the patients are grouped together irrespective of indication, i.e. pre-operative or palliative. Few articles are prospective or contain clear information regarding tumour stage, indication and adequate follow-up. Although we are not able to distinguish with certainty the effect of embolization on the course of the disease, it seems that complete pre-operative renal artery embolization facilitates the excision of large vein-invading tumours. The optimal delay between embolization and operation is probably one day. The embolization material of choice is ethanol. Palliative embolization in non-operable tumours with serious haemorrhage seems to have been successful in most cases. The scientific basis for the implementation of renal artery embolization in renal cell carcinoma is weak. We believe that either controlled trials or parallel prospective cohort studies should be undertaken to compare treatment of selected locally advanced renal carcinomas with and without embolization.

A Multicenter Randomized Trial Comparing the Luteinizing Hormone-Releasing Hormone Analogue Goserelin Acetate Alone and with Flutamide in the Treatment of Advanced Prostate Cancer

AbstractA prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no ...

Parenteral Estrogen versus Combined Androgen Deprivation in the Treatment of Metastatic Prostatic Cancer - Scandinavian Prostatic Cancer Group (SPCG) Study No. 5

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.

Quality of life after radical retropubic prostatectomy for carcinoma of the prostate

131 patients treated by radical prostatectomy for localized prostatic cancer were studied with regard to quality of life. The patients perception of his state of health before operation and 3, 6, 12 and 18 months later was assessed by questionnaires on 272 occasions. In the short term the patients complained of anxiety, voiding disorders, and loss of potency. In the long term only distress due to lack of erection persisted, but the overall well-being after 18 months was nevertheless better than before treatment.

Reliability of death certificates in prostate cancer patients

Objective. To evaluate the reliability of cause-of-death diagnoses among prostate cancer patients. Material and methods. Information from death certificates obtained from the Swedish Death Register was compared with systematically reviewed medical records from the population-based Swedish Regional Prostate Cancer Register, South-East Region. In total, 5675 patients were included who had been diagnosed with prostate cancer between 1987 and 1999 and who had died before 1 January 2003. Results. The proportion of prostate cancer cases classified as having died from prostate cancer was 3% higher in the official death certificates than in the reviewed records [0.03, 95% confidence interval (CI) 0.02 to 0.04]. Overall agreement between the official cause of death and the reviewed data was 86% (95% CI 85 to 87%). A higher accuracy was observed among men with localized disease (88%, 95% CI 87 to 89%), aged 60 years or younger at death (96%, 95% CI 93 to 100%), or who had undergone curative treatment (91%, 95% CI 88 to 95%). This study indicates a relatively high reliability of official cause-of-death statistics of prostate cancer patients in Sweden. Conclusion. Mortality data obtained from death certificates may be useful in the evaluation of large-scale prostate cancer intervention programmes, especially among younger patients with localized disease.

Screening for carcinoma of the prostate by digital rectal examination in a randomly selected population.

OBJECTIVE--To study the acceptability, costs, psychosocial consequences, and organisation of screening for carcinoma of the prostate. DESIGN--A randomly selected population was personally invited for digital rectal examination by a urologist and a general practitioner. Further examinations were performed if induration was felt. Each man completed a questionnaire on his response to the examination. SETTING--General practices in the area of Norrköping. PATIENTS--1494 Men aged 50-69 randomly selected from a population of 9026. MAIN OUTCOME MEASURE--Prostates having a firm nodular consistency. RESULTS--Carcinoma of the prostate was suspected in 45 of 1163 patients examined; in 10 by the general practitioners, in 10 by the urologists, and in 25 by both. Forty four men had a fine needle aspiration biopsy, and carcinomas were found in 13 cases. Of these, one had been suspected by the general practitioner, four by urologists, and eight by both. The cost for each man was 11.60 pounds, and the cost for each case of carcinoma detected and treated by potentially curative methods was 2477 pounds. Of the 13 men with carcinoma, 10 underwent radical prostatectomy and one radiotherapy. One man had advanced disease and was given endocrine treatment, another was not treated. Only 193 men felt distress during the initial examination. Of the 44 men who had an aspiration biopsy, 25 experienced anxiety. CONCLUSIONS--Screening for carcinoma of the prostate by a urologist or a general practitioner using digital rectal examination is a cost effective method of early diagnosis. Whether such screening leads to prolonged survival, however, remains doubtful.

Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate.

PURPOSE We evaluated the incidence and frequency of, and distress due to hot flashes after castration therapy with polyestradiol phosphate and complete androgen ablation. MATERIALS AND METHODS A total of 915 men with metastatic prostate carcinoma enrolled in the Scandinavian Prostatic Cancer Group-5 trial study were randomized to intramuscular injections of 240 mg. Polyestradiol phosphate every 2 weeks for 8 weeks followed by monthly subcutaneous injections or complete androgen ablation, that is bilateral orchiectomy or 3.75 mg. of the gonadotropin-releasing hormone analog triptorelin monthly combined with 250 mg. of the antiandrogen flutamide 3 times daily. The incidence and frequency of, and distress due to hot flashes were recorded at regular intervals using a questionnaire. RESULTS Of the 915 men 901 were evaluated at a median followup of 18.5 months. The incidence of hot flashes was 30.1% and 74.3% in the polyestradiol phosphate and complete androgen ablation groups, respectively (p <0.001). In the polyestradiol phosphate group the frequency of and distress due to hot flashes were significantly lower than in the androgen ablation group. There was complete relief from hot flashes in 50% of the men on polyestradiol phosphate during followup compared with none on androgen ablation. The incidence of hot flashes did not differ in men with and without tumor progression. CONCLUSIONS Endocrine treatment with polyestradiol phosphate induced fewer and less distressing hot flashes than complete androgen ablation. Flashes also disappeared to a greater extent during polyestradiol phosphate than during androgen ablation. The data in this study enable us to provide thorough individual information to patients on the risk and grade of expected distress and duration of hot flashes during polyestradiol phosphate or complete androgen ablation treatment.