High prostate cancer mortality in Norway: influence of Cancer Registry information?

Norway has among the highest prostate cancer mortality rates in the world. The aim of the present project was to assess whether this can be explained by the unique routine procedure of information transfer from the Cancer Registry of Norway (CR) to the Norwegian Cause of Death Registry (COD Registry). Norwegian prostate cancer patients deceased during 1996 were identified (n=2012). The information basis of the official mortality statistics was reviewed by two physicians, who independently identified the underlying cause of death, primarily prostate cancer or not, supplemented by consensus of two other physicians. The coding was done in two steps; first without, then with CR information. Project physicians identified 1063 deaths from prostate cancer as compared to the official number of 1161, with discrepancy as to prostate cancer death in 126 deceased. Information from the CR increased the project's age-adjusted (world standard population) prostate cancer mortality rate by less than 1% (from 22.7 to 22.9 per 100,000). In conclusion, the high rates of prostate cancer mortality in Norway could not be explained by information transfer from the CR to the COD Registry.

Increased mortality rates in young and middle-aged patients with malignant germ cell tumours.

Cisplatin-based chemotherapy of malignant germ cell tumours (MGCT) has been reported to increase the risk of cardiovascular morbidity. A high incidence of second nongerm cell malignancies is well documented in MGCT survivors. The death risk due to these conditions is, however, more unknown in MGCT patients. Standard mortality rates (SMRs) were established in 3378 Norwegian MGCT patients treated from 1962 to 1997 aged

[Epidemiology of prostatic cancer]. / Prostatakreftens epidemiologi.

Prostate cancer is the most common type of cancer in Norway, with more than 2,400 new cases each year. Hormones, diet, and chemical and genetic factors are implicated in the aetiology. It is not clear whether alcohol and tobacco increase the risk of prostate cancer. Median age at diagnosis is 74-75 years. The incidence has increased steadily with a doubling of the number of cases over 20-25 year periods. Prostate cancer mortality in Norway is the highest among the Nordic countries and among the highest in the world. Five-year relative survival for all cases combined is 60%. Approximately 55-60% of the patients dies from the disease. The incidence is lower in the three northernmost counties. Elsewhere in the country the incidence varies between counties according to variations in diagnostic practice. Serological analysis of Prostate Specific Antigen after 1990 has lead to an increase in the number of new cases, mainly because of earlier diagnosis. Prostate cancer is often a slowly growing tumour which is clinically asymptomatic for many years. Latent carcinoma is found at autopsy in 30-35% of men above 50 years of age. Today, prevention of prostate cancer is not feasible, though specific advice about life style and diet might decrease the risk.

Follow-up of localized prostate cancer, with emphasis on previous undiagnosed incidental cancer.

OBJECTIVE: To determine the natural course of incidental untreated transition zone prostate cancer and thus help to identify criteria to predict the prognosis and to determine treatment for individual patients. MATERIALS AND METHODS: A total of 1135 unselected surgical specimens of the prostate, examined during 1974 and 1975, were reviewed while unaware of case by two experienced pathologists. The patients from which the samples were obtained were followed for up to 20 years or death by The Cancer Registry of Norway and the outcome compared with the histological review. RESULTS: The histology review revealed a total of 311 cancers, of which 73 had not been initially recorded; these patients had received no treatment. The kappa coefficient for interobserver reproducibility was 0.86 for carcinoma. The follow-up showed that patient age was the strongest predictor of survival, followed by histological grade and percentage of tumour involvement. Only two of the 73 patients with untreated transition zone cancer died from prostate cancer during the follow-up, compared with 78 of 144 patients with standard management of transition zone tumours. The 5- and 10-year relative survival rates for the 144 patients with standard management of transitional zone tumours and for the 53 patients with peripheral zone tumours were 56% and 26%, and 45% and 33%, respectively. Metastasis (+ or -) was the only individual prognostic factor in the multivariate analysis. CONCLUSION: This study shows that patients with incidental low-grade tumours have a low probability of dying from prostate cancer and may thus be followed expectantly. The biological distinction between atypical hyperplasia and stage T1a cancer is unclear. The survival of men with prostate cancer is significantly reduced with loss of differentiation and with increasing tumour volvement.

[Undiagnosed microinvasive carcinomas of the prostate]. / Ikke-diagnostiserte mikroinvasive karsinomer i prostata.

Quality assurance is becoming increasingly important in all aspects of health care, but a growing workload in recent years may delay the introduction of new quality assurance procedures. In 1994-95, in order to evaluate the standard of quality in executing routine histopathological procedures, a total of 1,135 prostatic specimens representing all surgical material taken from the prostate during 1974-75 were reviewed. The patients were followed up for to 20 years by comparing with the files of The Norwegian Cancer Registry. Only a few registration errors were found. Microscopic examination in 1994-95 revealed 311 carcinomas, 83 of which were not recorded in 1974-75. 73 of the patients had not received treatment. The histology reports revealed suspected malignancy, with irregular or atypical epithelium, or both, in 42% of the 83 carcinomas not reported in 1994-95, whereas for 45 carcinomas the histology reports did not describe changes suggestive of malignancy. Only 3% of the patients not treated died of prostate cancer during the follow-up time, compared with 78 (54%) cancer deaths in the group that had received treatment. Most undiagnosed cancers were well differentiated and in the pT1a category. It is important that the clinician is aware of the fairly benign outcome of these borderline tumors in order to avoid overtreatment.

Is prostatic intraepithelial neoplasia in the transition/central zone a true precursor of cancer? A long-term retrospective study in Norway.

Prostatic intraepithelial neoplasia (PIN) has been considered as a precursor of prostatic cancer. Few reports have dealt with the long-term follow-up of PIN lesions, and there is still a lack of proof that PIN is a true premalignant lesion. The objective of this study was to evaluate PIN in the transition/central zone as a marker for subsequent development of prostatic cancer. The PIN status of tissue specimens from 789 men without prostate cancer was determined in 508 transurethral resections and 281 transvesical prostatic enucleations. All slides were reviewed blind and independently by two pathologists. The patients were followed for an average of 11 years, and the incidence of subsequent cancer and cause-specific survival were analysed. Thirty-six cases of clinical prostatic cancer occurred among the cohort of 789 men through follow-up. No association between the presence of PIN in the transition/central zone and subsequent cancer development was found. There was also no difference in survival related to PIN status among the subsequent cancer patients.

The importance of marital and socioeconomic status in incidence and survival of prostate cancer. An analysis of complete Norwegian birth cohorts.

BACKGROUND: Previous studies of the association between social and family status and prostate cancer (PCa) have given somewhat divergent results. Little attention has been paid to the possible importance of these factors for survival. METHODS: In this study, hazard regression models for PCa incidence and mortality were estimated on the basis of register- and census-based histories for complete Norwegian birth cohorts, giving a follow-up time of 16 million person years and 30,000 cases of PCa. RESULTS: A significant excess incidence of about 20% was found for ever-married men and for those with higher education. Marriage and socioeconomic resources appeared, however, to have a favorable effect on survival. Five-year relative survival from metastasized cancer among men with a high educational level was found to be 15 percentage points higher than among men with lower education. CONCLUSIONS: The observed differences in incidence are not easily explained. They apparently run counter to the hypothesis that multiple partners give a higher PCa risk, but may be consistent with the view that fat and meat consumption is risky. Better survival from PCa in higher socioeconomic groups and among married men may reflect differences in the search for, access to, or quality of treatment or a better constitution to fight the disease.

Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway.

We tested the hypothesis that serum levels of testosterone (T), dihydrotestosterone (DHT), and the DHT metabolite 3 alpha,17 beta-androstanediol glucuronide are positively associated with the risk of prostate cancer. This nested case-control study was based on the cohort of men who donated blood to the Janus serum bank at Oslo University Hospital (Oslo, Norway) between 1973 and 1994. Cancer incidence was ascertained through linkage with the Norwegian Cancer Registry. The study included sera from 59 men who developed prostate cancer (cases) subsequent to blood donation and 180 men who were free of any diagnosed cancer (controls) in 1994 and were of similar age (+/- 1 year) and had similar blood storage time (+/- 6 months) to the cases. Neither T, DHT, nor the ratio T:DHT was associated with risk of developing prostate cancer. Compared to the bottom quartile, the odds ratio (OR) associated with the top quartile of T was 0.83 [95% confidence interval (CI), 0.36-1.93]; the OR for the top (compared to the bottom) quartile of DHT was 0.83 (95% CI, 0.36-1.94), and the equivalent OR for T:DHT was 1.31 (95% CI, 0.58-2.97). Similarly, 3 alpha,17 beta-androstanediol glucuronide showed no association with prostate cancer risk; the OR for the top (compared to the bottom) quartile was 1.10 (95% CI, 0.41-2.90). These results showed no association, positive or negative, between androgens measured in serum and the subsequent risk of developing prostate cancer.

Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer.

Ecological and case-control studies have demonstrated a positive correlation between consumption of fat and the risk of prostate cancer. Two recent human studies have focused on alpha-linolenic acid as a risk factor for prostate cancer. Animal experiments have shown that dietary omega-6 polyunsaturated fatty acids have generally stimulated tumour development, whereas omega-3 polyunsaturated fatty acids have diminished it. The aim of our study was to investigate the association between these fatty acids and the subsequent risk of prostate cancer. Blood donors to the Janus serum data bank in Norway, who later developed prostate cancer, were matched to blood donors without prostate cancer (141 matched sets); the proportional level of fatty acids measured before diagnosis in the donors' serum was examined. The risk of later prostate cancer was analysed by conditional logistic regression. Increasing risk for prostate cancer was found with increasing quartiles of palmitoleic, palmitic and alpha-linolenic acid. An inverse risk association was found with increasing levels of tetracosanoic acid, for the ratios of linoleic to alpha-linolenic acid and arachidonic to eicosapentaenoic acid. There was no clear association between the risk effect of total omega-3 and total omega-6 fatty acids. There were no indications of a relationship between fatty acids and more aggressive cancers. Our results verify recent findings of a positive association between alpha-linolenic acid and a negative association between the ratio of linoleic to alpha-linolenic acid and the risk of prostate cancer.

Prostatic intraepithelial neoplasia in surgical resections: relationship to coexistent adenocarcinoma and atypical adenomatous hyperplasia of the prostate.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is associated with coincident prostate carcinoma, and has been considered to be a precursor of prostate carcinoma. Most studies on PIN have been performed on total prostatectomy or core needle biopsy specimens. Few reports deal with the occurrence of PIN in consecutive surgical resections, which is the objective of the current study. METHODS: A total of 1135 nonselected surgical specimens from the prostate, examined during 1974 and 1975, underwent blind review by 2 experienced pathologists. There were 79 core needle biopsies, 731 transurethral resections of the prostate and 325 transvesical prostatic enucleations. The kappa coefficient for interobserver reproducibility was 0.66 for PIN and 0.86 for carcinoma. RESULTS: Grade 1 PIN was found in 9%, Grade 2 PIN in 32%, and Grade 3 PIN in 20% of the total cases. Atypical adenomatous hyperplasia (AAH) was found in 11% and adenocarcinoma in 27% of the cases. Grade 3 PIN was associated with coincident adenocarcinoma in 39% of the cases. The prevalence of carcinoma for cases with Grade 1 and 2 PIN did not exceed that of those with Grade 0 PIN. PIN was most commonly found in association with small carcinomas. The mean age of the entire group of patients was 70.0 years, and was 69.4 years for patients with PIN without coincident carcinoma. Patients with PIN and coincident carcinoma had a mean age of 71.7 years, similar to all PIN grades, but patients with carcinoma without PIN had the highest mean age, 73.3 years. CONCLUSIONS: PIN is a common histologic finding in tissues from prostatic resections. In this study, Grade 3 PIN was strongly associated with coincident carcinoma, but lower grade PIN was not. There was no association between PIN and AAH. Patients with PIN did not appear to have a higher mean age than corresponding patients without PIN.

[Increased incidence of prostatic cancer. The significance of prostate-specific antigen]. / Okt påvisning av prostatakreft. Betydningen av prostataspesifikt antigen.

Patients with newly diagnosed prostate cancer who were registered in one hospital during two recent one-year periods were studied with regard to causes and consequences of the diagnosis. 65 new cases were registered in 1991 and 102 in 1994. These constitute about 90% of all new cases in the area served by the hospital, and are representative of the population to this extent. In only one of the 16 patients treated with curative intent was the diagnosis made as a consequence of routine determination of prostate specific antigen (PSA) when he was asymptomatic. On the other hand, PSA-assay in asymptomatic men led to an increasing number of patients being made aware of a disease for which no treatment was recommended. This was partly because most of the patients diagnosed in this manner were elderly (mean age 72). A plea is made to restrict this practice to younger men.

[Prostatic cancer in Oslo--a real decline?]. / Prostatakreft i Oslo--reell nedgang?

Incidence of prostate cancer has increased steadily in Norway since the cancer registration started in the 1950s. In Oslo, however, the figures show decreasing incidence since the 1970s, a trend not observed in any other region. These changes have occurred in the groups older than 70 years of age. The most important change is a marked decrease in the number of cases first diagnosed at autopsy, from 12.7% in 1957-61 to 3.8% in 1987-91. However, even after these cases are excluded, a slight downward trend in incidence still exists. The same tendencies are not observed for other forms of cancer. It seems as if the diagnostic intensity has become lower in Oslo than in the rest of the country. This pattern may be explained by a change of priority in diagnostics, owing to scarce resources, but other reasons, such as stabilization of the incidence of prostatic cancer, are also possible.

Quality of prostate cancer data in the cancer registry of Norway.

Completeness of reporting and internal validity of the coding of prostate cancer in the Cancer Registry (CR) in Norway were examined. Data were matched and evaluated against diagnostic indices at eight selected hospitals in the country and against death certificates from Statistics Norway. Validity control was based on detailed re-analysis of an approximately 1% sample of the registered data during the period 1957-1986. The deficiency in reporting of prostate cancer was less than 1%. The grave deficiencies in hospital patient registers were considered to be of non-systematic nature and should, therefore, not impair the reliability of our investigation of incompleteness. The validity control revealed errors in 0.5% of the data elements, or, illustrated differently, 6% of the patient files had an error, of importance or not, in one of the data elements. One false positive registration was found among 298 controlled patient files (0.3%).

Cancer of the prostate in Norway 1957-1991--a descriptive study.

The incidence and mortality of prostate cancer from 1957 to 1991 were studied in the Cancer Registry of Norway. The age-adjusted incidence rate increased from 26.3 to 46.6 per 100,000 person-years during the period, and more than 2000 cases are now registered yearly. The increase tends to be higher in the younger age groups, 50-59 years, and among the oldest, 90+ years. An increase was also found in cause-specific mortality, signifying a real increase in incidence over time. There is a slight urban dominance in incidence of prostate cancer. Autopsy findings account for less than 1.7% of the total. The histo- and cytological verification rate reached 94% in 1987-1991 and the percentage of localised cases was 68.4%. The median age at diagnosis in 1987-1991 was 75.1 years. Data on stage at time of diagnosis, histological differentiation and survival, reflect a small influence of earlier diagnosis. Model analysis revealed no particular birth cohort effect, either on incidence or on mortality.

The burden of prostate cancer from diagnosis until death.

OBJECTIVE: To quantify the need for treatment and care in patients with conservatively treated prostate cancer. PATIENTS AND METHODS: All men who had been diagnosed with prostate cancer in a defined geographical area and who died within the period 1987-91 were identified. Patients treated with curative intent were excluded. Medical records from hospitals, nursing homes and community nurses for the period from diagnosis until death were scrutinized for the remaining 174 patients. RESULTS: Of the 174 patients, 95% were symptomatic at diagnosis and 62% died from prostate cancer. All but two patients were hospitalized for prostate cancer, for a mean of 1 month. Thirty-six per cent needed regular nursing in nursing homes or by community nurses at home. Complications requiring hospitalization or long-term catheterization occurred in 49%. Prostatic surgery was performed in 66% and androgen ablation in 76% of the patients; palliative irradiation was given to 16% and 50% received analgesics regularly, including opiates or equivalents in 37%. Prednisone was given to 29%, after the failure of androgen ablation. CONCLUSION: Our findings demonstrate the considerable burden imposed both on patients and health-care resources by symptomatic prostate cancer, conservatively treated. There are few data available for comparison.

Prostatic carcinoma: a multivariate analysis of prognostic factors.

Tissue specimens from 150 patients with localised prostatic carcinomas and 116 patients with prostatic carcinomas with distant metastases were analysed for histological grade (WHO and Gleason) and immunoreactivity for prostate acid phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After stratification for the presence or absence of distant metastases, multivariate regression analysis revealed that WHO grading was the most powerful independent prognosticator, followed by age and prostate acid phosphatase expression. There was a trend towards reduced survival with decreasing prostate-specific antigen reactivity. The Gleason system showed poor prognostic ability. The analysis predicted reduced survival in the presence of extensive neurone-specific enolase reactivity, mostly because of one case of small-cell carcinoma.

Survival after transurethral and transvesical surgery in localized cancer of the prostate, Norway 1957-1981.

BACKGROUND: During the period 1957-1981, there has been a gradual change in the choice of surgical methods for patients with prostate cancer in Norway, from transvesical surgery to transurethral resections (TUR-P). Radical prostatectomy was practically nonexistent in the early years of this time period. Sixty-five percent (17,696 patients) of all patients with prostate cancer reported to the Cancer Registry had no metastases at the time of diagnosis. Of these, 5414 patients underwent TUR-P, whereas 6160 patients underwent transvesical operations as primary surgery. Interest was raised in analyzing survival after primary surgery. METHODS AND RESULTS: Five-year relative survival rates were calculated for the groups of patients undergoing each type of surgery; the rates increased steadily for both groups during the later years of the 1957-1981 period. However, survival consistently was better for patients who had transvesical surgery. The difference in 5-year relative survival rates was 10-15%. The same pattern was seen long-term survival (more than 10 years). In addition, survival rates for patients with similar grade of tumor differentiation were better for patients undergoing transvesical surgery. A multivariate analysis of survival that related age, surgical methods, grades of tumor differentiation, and diagnostic periods showed that survival was influenced most by differentiation, followed by surgery. Age was not an important factor in this analysis. CONCLUSION: The results underline the importance of additional research regarding the precise classification of prostatic cancer at the time of diagnosis so that clinicians can better choose the proper method of surgery.

[Data respect--data discipline--data understanding]. / Datarespekt--datadisiplin--dataforståelse.

All hospitals are obliged to have an index of diagnoses made in the hospital. This file should be the basis for evaluation, planning and research. Our view is that such files are today incomplete and not very fit for above-mentioned purposes. The introduction of EDP in hospitals does not seem to have improved the situation very much. Therefore the hospitals should improve the professional responsibility for these files, in order to obtain complete and correct registration. Administrators and physicians in administrative positions must feel responsible for feed-back of patient data to the different departments for analysis, discussion and evaluation. This will hopefully increase the interest for data and registration, and supply a better medical basis for planning hospital activities.