U.H. Stenman

European randomized study of prostate cancer screening: first-year results of the Finnish trial.

SummaryApproximately 20 000 men 55–67 years of age from two areas in Finland were identified from the Population Registry and randomized either to the screening arm (1/3) or the control arm (2/3) of a prostate cancer screening trial. In the first round, the participation rate in the screening arm was 69%. Of the 5053 screened participants, 428 (8.5%) had a serum prostate-specific antigen (PSA) concentration of 4.0 ng/ml or higher, and diagnostic examinations were performed on 399 of them. A total of 106 cancers were detected among them corresponding to a positive predictive value of 27%, which is comparable with mammography screening for breast cancer. The prostate cancer detection rate based on a serum PSA concentration of 4.0 ng ml–1 or higher was 2.1%. Approximately nine out of ten screen-detected prostate cancers were localized (85% clinical stage T1–T2) and well or moderately differentiated (42% World Health Organization (WHO) grade I and 50% grade II), which suggests a higher proportion of curable cancers compared with cases detected by other means.

High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer

Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan–Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR=1.82; 95% CI=1.19–2.79) and disease-free survival (HR=1.56; 95% CI=1.05–2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR=2.85; 95% CI=1.43–5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer.

False-positive screening results in the Finnish prostate cancer screening trial

Background:There is evidence that prostate cancer (PC) screening with prostate-specific antigen (PSA) serum test decreases PC mortality, but screening has adverse effects, such as a high false-positive (FP) rate. We investigated the proportion of FPs in a population-based randomised screening trial in Finland.Methods:Finland is the largest centre in the European Randomized Study of Screening for Prostate Cancer. We have completed three screening rounds with a 4-year screening interval (mean follow-up time 9.2 years) using a PSA cutoff level of 4.0u2009ngu2009ml−1; in addition, men with PSA 3.0–3.9 and a positive auxiliary test were referred. An FP result was defined as a positive screening result without cancer in biopsy within 1 year from the screening test.Results:The proportion of FP screening results varied from 3.3 to 12.1% per round. Of the screened men, 12.5% had at least one FP during three rounds. The risk of next-round PC following an FP result was 12.3–19.7 vs 1.4–3.7% following a screen-negative result (depending on the screening round), risk ratio 3.6–9.9. More than half of the men with one FP result had another one at a subsequent screen. Men with an FP result were 1.5 to 2.0 times more likely to not participate in subsequent rounds compared with men with a normal screening result (21.6–29.6 vs 14.0–16.7%).Conclusion:An FP result is a common adverse effect of PC screening and affects at least every eighth man screened repeatedly, even when using a relatively high cutoff level. False-positive men constitute a special group that receives unnecessary interventions but may harbour missed cancers. New strategies are needed for risk stratification in PC screening to minimise the proportion of FP men.

Prostate cancer incidence among finasteride and alpha-blocker users in the Finnish Prostate Cancer Screening Trial

Background:The Prostate Cancer Prevention Trial has shown a protective effect of finasteride on prostate cancer in low-risk men. It is uncertain whether similar results can be expected when finasteride is used to treat benign prostatic hyperplasia.Methods:We performed an observational cohort study within the Finnish Prostate Cancer Screening Trial. Using a comprehensive prescription database on medication reimbursements during 1995–2004 of men using finasteride or alpha-blockers for benign prostatic hyperplasia, we evaluated prostate cancer incidence among 23u2009320 men screened during 1996–2004.Results:Compared to medication non-users, overall prostate cancer incidence was not significantly affected in finasteride users (hazard ratio 0.87; 95% CI 0.63–1.19). Incidence of Gleason 2–6 tumours, however, was decreased among finasteride users (HR 0.59; 95% CI 0.38–0.91), whereas incidence of Gleason 7–10 tumours was unchanged (HR 1.33; 95% CI 0.77–2.30). The protective effect concerned mainly screen-detected tumours. Overall prostate cancer risk was not significantly reduced among alpha-blocker users relative to non-users, but decreased incidence of high-grade tumours was observed (0.55; 95% CI 0.31–0.96).Conclusions:The detection of low-grade, early-stage tumours is decreased among men who use finasteride for symptomatic BPH. The protective effect of finasteride can also be expected in men with benign prostatic hyperplasia.

Prostate cancer screening within a prostate specific antigen range of 3 to 3.9 ng./ml.: a comparison of digital rectal examination and free prostate specific antigen as supplemental screening tests.

PURPOSEnPerforming biopsy in all men with a serum prostate specific antigen (PSA) of 3 to 3.9 ng./ml. increases the sensitivity of prostate cancer screening compared with a PSA cutoff of 4 ng./ml. but decreases specificity and may contribute to over diagnosis. Therefore, we evaluated the detection rate and specificity attributable to digital rectal examination and percent free PSA within the PSA range of 3 to 3.9 ng./ml.nnnMATERIALS AND METHODSnSerum PSA was determined in 20,716 participants in the Finnish population based screening trial. Supplementary digital rectal examination was offered to men with a PSA of 3 to 3.9 ng./ml. during 1996 to 1998 (protocol 1). Those with a suspicious digital rectal examination finding were referred for biopsy. The screening algorithm was modified by substituting percent free PSA for digital rectal examination with a cutoff of 16% as a biopsy criterion in 1999 (protocol 2). In addition, biopsies were performed in all men with PSA 4 ng./ml. or greater.nnnRESULTSnA total of 23 cancers (2.9%) were detected by digital rectal examination among 801 men, while percent-free PSA resulted in the diagnosis of 13 cases (4.8%) among 270 men with a PSA of 3 to 3.9 ng./ml. The detection rate of tumors with a Gleason score of 5 or greater increased from 1.6% (13 of 801 cases) to 4.4% (12 of 270) in the modified screening program. The PSA cutoff of 3 ng./ml. alone showed 88.6% and 87.5% specificity in protocols 1 and 2 but specificity increased to 93.3% and 91.7% using digital rectal examination and percent free PSA, respectively.nnnCONCLUSIONSnUsing percent free PSA increased the detection rate of aggressive disease compared with digital rectal examination and provided higher specificity than PSA alone.

Screening for prostate cancer using serum prostate-specific antigen: a randomised, population-based pilot study in Finland

The possibility of screening the general population for prostate cancer using serum prostate-specific antigen (PSA) level (alone or in combination with other tests) as screening test has recently been discussed. A number of studies are on the way, but the published reports have almost exclusively been based on men volunteering for screening. We assessed the feasibility of a screening study based on men identified from a central population registry. A random sample of 600 men in the age groups 55, 60 and 65 years was identified from the Finnish Population Registry as the study population. Half of them were randomised to the intervention group and an invitation to participate was sent to them. The participation rate was 77% (230 out of 300). Twenty-five men had a serum PSA concentration of 4.0 micrograms l-1 or above and were invited for further examination including digital rectal examination, transrectal ultrasound and transrectal Tru-cut biopsies (directed and/or random). Six cases of cancer were detected among the 230 participating men, which corresponds to a detection rate of 2.6% and a positive predictive value of 24%. The number of cases detected is equivalent to the expected number of prostate cancer cases during a 10 year follow-up in this population. The ratio of free to total PSA was also measured and a cut-off level of 0.20 was chosen. Its use as an additional criterion of the screening test would have decreased the prevalence of false-positive screening tests from 8% (19 of 230) to 3% (7 of 230) at a cost of missing one of the six cancers compared with serum total PSA concentration alone. Of the six cancers, five were clinically regarded as localised and locally confined disease was confirmed pathologically in four of them. In conclusion, a population-based study in Finland seems feasible and the properties of the PSA test can be regarded as suitable for a randomised screening study. Thus, all prerequisites for a multicentre study, which is planned, seem to exist.

Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial

Specificity constitutes a component of validity for a screening test. The number of false-positive (FP) results has been regarded as one of major shortcomings in prostate cancer screening. We estimated the specificity of serum prostate-specific antigen (PSA) determination in prostate cancer screening using data from a randomised, controlled screening trial conducted in Finland with 32u2009000 men in the screening arm. We calculated the specificity as the proportion of men with negative findings (screen negatives, SN) relative to those with negative and FP results (SN/(SN+FP)). A SN finding was defined as either PSA⩽4u2009ngu2009ml−1 or PSA 3.0–3.9u2009ngu2009ml−1 combined with a negative ancillary test (digital rectal examination, DRE or free/total, F/T PSA ratio). False positives were those with positive screening test followed by a negative diagnostic examination. Of the 30u2009194 eligible men, 20u2009794 (69%) attended the first screening round and 1968 (9.5%) had a screen-positive finding. A total of 508 prostate cancers were detected at screening (2.4%). Hence, the number of SN findings was 18u2009825 and the number of FP results 1358. Specificity was estimated as 0.933 (18u2009825 out of 20u2009183) with 95% confidence interval (CI) 0.929–0.936. Specificity decreased with age. Digital rectal examination as ancillary examination had similar or higher specificity than F/T PSA. In the second screening round, specificity was slightly lower (0.912, 95% CI 0.908–0.916). The specificity of PSA screening in the Finnish screening trial is acceptable. Further improvement in specificity could, however, improve acceptability of screening and decrease screening costs.

Prostate cancer risk and nonsteroidal antiinflammatory drug use in the Finnish prostate cancer screening trial

Background:The association between nonsteroidal antiinflammatory drugs (NSAIDs) and prostate cancer risk remains controversial. We examined the risk among NSAID users in 78u2009615 men in the Finnish Prostate Cancer Screening Trial.Methods:We obtained information on NSAID prescription usage from Finnish nationwide prescription database and on over-the-counter use by a questionnaire. Prostate cancer cases were identified from the Finnish Cancer Registry.Results:Prostate cancer risk was elevated among current NSAID prescription users irrespective of screening (hazard ratio (HR)=1.45, confidence interval (95% CI)=1.33–1.59 and HR=1.71, 95% CI=1.58–1.86 in the screening and control arm, respectively), but not for previous use of NSAIDs. The risk increase was similar among coxib and acetaminophen current users, and stronger for metastatic prostate cancer (HR=2.41, 95% CI=1.59–3.67 and HR=3.44, 95% CI=2.60–4.55 in the screening and control arm, respectively). Previous use of NSAIDs, aspirin use and over-the-counter NSAID usage were not associated with prostate cancer.Conclusions:Differing association for current and previous use suggests that the risk increase is unlikely to be directly caused by the medication, but may be due to the conditions indicating NSAID prescription usage, such as symptoms of undiagnosed prostate cancer. To reduce inconsistency between the study outcomes, future epidemiological studies on NSAID use and prostate cancer risk should assess the indications for NSAID usage.

13 Polymorphisms in genes of the glucose- and energy-metabolism pathways and prostate cancer: Interplay with metformin

INTRODUCTION AND OBJECTIVES: Emerging data have shown that prostate biopsy infections occur commonly after routine prostate biopsy procedures. Data from a recent Medicare based sample showed hospitalization to occur at a rate of 6.9% (J Urol 186:1830). The primary endpoint of this study was to determine the risk of hospital admission after a prostate biopsy in the Veterans Health Administration (VA) system. Secondary endpoints include determination of risk factors associated with higher risk of hospitalization. METHODS: We performed a data query from the VA Corporate Data Warehouse (CDW) for all prostate biopsies performed in the VA nationally over an 11-year period from 2003 to 2013. Data extracted included age, race, data of procedure, and relevant laboratory data. Information on 30-day rate-of-hospitalization, reason for admission, and other inpatient related data were collected. Multivariable logistic regression was used to examine the risk factors associated with readmission RESULTS: There were 310,334 prostate biopsies performed in the VA between 2003 and 2013. The average number of biopsies per year over this time period was 28,212. The number of biopsies per year remained steady throughout the study period until it decreased in 2012 (26,494) and 2013 (21,388). The mean age was 65.5 yrs., median prostate specific antigen (PSA) was 5.9 ng/ml, mean body mass index was 32.2 kg/m2. The 30-day hospitalization rate after a prostate biopsy was 2.43%. Multivariable logistic regression revealed a significant increased risk of admission following prostate biopsy with increasing age (OR 1.02, 95% CI 1.01-1.02) and African American race (OR 1.20, 95 %CI 1.13-1.28). CONCLUSIONS: The risk of hospitalization within 30 days of prostate biopsy was 2.4%. There was an increased risk of admission following prostate biopsy with increasing age and African American race.