Knowledge transfer as a tool towards improvement of cancer care in low- and middle-income countries. 6th European Roundtable Meeting (ERTM), June 14th, 2019, Berlin, Germany.

PURPOSE: To identify key factors for the best practice of knowledge transfer from high-income settings to low- and middle-income settings. RESULTS: Interactive sessions led to the identification of European learnings that can and should be shared beyond Europe. Furthermore, methods were characterised which may lead to successful knowledge transfer with subsequent quality improvement. CONCLUSION: To ensure successful implementation of knowledge and new methods, political support is extremely important. A strong focus should be an improvement of collaboration and network development. Rehabilitation, early and late pallative care, cost effectiveness and long-term follow-up are priorities. Limitations are budget constraints which limit the execution of NCCPs.

Age-related incidence of cervical cancer supports two aetiological components: a population-based register study.

OBJECTIVE: To assess whether age-related incidence of cervical cancer supports two aetiological components and to assess trends in these components due to risk factors and to organised screening in Finland. DESIGN: Population-based register study. SETTING: Finnish Cancer Registry. POPULATION: Cervical cancer cases and female population in Finland in 1953-2012. METHODS: Cervical cancer incidence was estimated using Poisson regression where age-specific incidence consists of two (early-age and late-age) normally distributed components. MAIN OUTCOME MEASURES: Accumulated net risks (incidences) and numbers of cancer cases attributed to each age-related component by calendar time. RESULTS: The accumulated cervical cancer incidence in 2008-2012 was only 30% of that in 1953-1962, before the screening started. The fit of the observed age-specific rates and the rates based on the two-component model was good. In 1953-62, the accumulated net risk ratio (RR; early-age versus late-age) was 0.42 (95% CI 0.29-0.61). The early-age component disappeared in 1973-77 (RR 0.00; 95% CI 0.00-0.08). Thereafter, the risk for the early-age component increased, whereas the risk for the late-age component decreased, and in 2008-2012 the RR was 0.55 (95% CI 0.24-0.89). CONCLUSIONS: In Finland, cervical cancer incidence has two age-related components which are likely to indicate differences in risk factors of each component. The trend in risk of both components followed the effects of organised screening. Furthermore, the risk related to the early-age component followed changes in risk factors, such as oncogenic HPV infections and other sexually transmitted diseases and smoking habits. TWEETABLE ABSTRACT: Cervical cancer incidence has two age-related components which are likely to have differencies in their aetiology.

Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland.

BACKGROUND: Screening for colorectal cancer (CRC) with guaiac-based faecal occult-blood test (FOBT) has been reported to reduce CRC mortality in randomised trials in the 1990s, but not in routine screening, so far. In Finland, a large randomised study on biennial FOB screening for CRC was gradually nested as part of the routine health services from 2004. We evaluate the effectiveness of screening as a public health policy in the largest population so far reported. METHODS: We randomly allocated (1:1) men and women aged 60-69 years to those invited for screening and those not invited (controls), between 2004 and 2012. This resulted in 180 210 subjects in the screening arm and 180 282 in the control arm. In 2012, the programme covered 43% of the target age population in Finland. RESULTS: The median follow-up time was 4.5 years (maximum 8.3 years), with a total of 1.6 million person-years. The CRC incidence rate ratio between the screening and control arm was 1.11 (95% CI 1.01 to 1.23). The mortality rate ratio from CRC between the screening and control arm was 1.04 (0.84 to 1.28), respectively. The CRC mortality risk ratio was 0.88 (0.66 to 1.16) and 1.33 (0.94 to 1.87) in males and females, respectively. CONCLUSIONS: We did not find any effect in a randomised health services study of FOBT screening on CRC mortality. The substantial effect difference between males and females is inconsistent with the evidence from randomised clinical trials and with the recommendations of several international organisations. Even if our findings are still inconclusive, they highlight the importance of randomised evaluation when new health policies are implemented. TRIAL REGISTRATION: 002_2010_august.

Outcomes of medical and surgical treatment for lower urinary tract symptoms (benign prostatic obstruction)--a population-based cohort study.

OBJECTIVE: To compare outcome of lower urinary tract symptoms (LUTS) between men with medical and surgical treatment. MATERIALS AND METHODS: A questionnaire was mailed to men aged 55, 65 and 75 years living in Tampere region, Finland in 1999 and the survey was repeated in 2004. LUTS were evaluated using DAN-PSS-1 questionnaire. A total of 1679 men (68% of the eligible) responded to both questionnaires. Of them, 114 men reported LUTS at baseline and medical treatment in the repeat survey and 47 men with LUTS had received surgical treatment. Seventy-two men with prostate cancer were excluded. Men with no medical treatment or surgery for LUTS in either questionnaire were included to no-treatment group. RESULTS: The men after surgical treatment showed a reduction in all LUTS symptom groups. However, among the medically treated and untreated men, all the symptoms worsened during the follow up. The proportion of symptomatic men after surgery was lower than among the medically treated men. In men with medical treatment, the prevalence of all 12 LUTS increased. Dysuria and postmicturition dribble were the only symptoms that had slightly better results in medical than in surgical treatment group. CONCLUSIONS: In this population-based study, operative treatment seemed to relieve LUTS, whereas medical treatment only slowed down their progression. These findings suggest that men with surgical treatment experience a more favourable outcome in LUTS than those receiving medical treatment.

Effects of annual vs triennial mammography interval on breast cancer incidence and mortality in ages 40-49 in Finland.

BACKGROUND: The aim of this study was to evaluate the effects of mammography screening invitation interval on breast cancer mortality in women aged 40-49 years. METHODS: Since 1987 in Turku, Finland, women aged 40-49 years and born in even calendar years were invited for mammography screening annually and those born in odd years triennially. The female cohorts born during 1945-1955 were followed for up to 10 years for incident breast cancers and thereafter for an additional 3 years for mortality. RESULTS: Among 14,765 women free of breast cancer at age 40, there were 207 incident primary invasive breast cancers diagnosed before the age of 50. Of these, 36 women died of breast cancer. The mean follow-up time for cancer incidence was 9.8 years and for mortality 12.8 years. The incidence of breast cancer was similar in the annual and triennial invitation groups (RR: 0.98, 95% confidence interval (CI): 0.75-1.29). Further, there were no significant differences in overall mortality (RR: 1.20, 95% CI: 0.99-1.46) or in incidence-based breast cancer mortality (RR: 1.14, 95% CI: 0.59-1.27) between the annual and triennial invitation groups. CONCLUSIONS: There were no differences in the incidence of breast cancer or incidence-based breast cancer mortality between the women who were invited for screening annually or triennially.

Loss-adjusted hospital and population-based survival of cancer patients.

This chapter presents formulae that methodologically adjust for losses, and gives examples describing magnitude of bias in survival estimates without such adjustment. Loss-adjusted survival is estimated under the assumption that survival of patients Lost to follow-up is the same as that for patients with known follow-up time and similar characteristics of different prognostic factors at first entry. The observed number of Losses to follow-up is then relocated into expected numbers of death and survivors on this basis. Standard methods, such as the actuarial one, are then applied with the sum of observed and expected outcome events. A total of 336 hospital series of treated new breast cancer cases from Mumbai with 24% lost to follow-up revealed a substantial bias of 7 per cent units for 3-year survival estimated with (54%) and without (61%) loss-adjustment. Stepwise adjustment of losses established that increasing the number of prognostic factors explained the bias better. Population-based series comprising 13 371 cases of top ranking cancers from Chennai, with loss to follow-up ranging from 7-24%, revealed negligible bias, ranging from 0-2% in 5-year survival by the loss-adjusted approach for different cancers. Data source seems to affect the need for loss-adjustment, and the loss-adjusted approach is recommended when hospital-based cancer registry data of a low- or medium-resource country are used to evaluate the outcome of cancer patients.

Lifestyle factors and varicose veins: does cross-sectional design result in underestimate of the risk?

OBJECTIVES: To assess whether smoking, alcohol drinking and dietary factors are linked with varicose veins. METHODS: A middle-aged general population of 4903 was studied, and prevalence rates at entry and five-year incidence of varicose veins were assessed. Lifestyle habits were recorded at entry and at the end of the follow-up. RESULTS: New varicose veins were significantly more common in individuals with regular alcohol intake, incidence odds ratio (OR) 1.5 (95% confidence interval [CI]: 1.05-2.3) in a multivariate analysis (of 2202 individuals). The association was particularly strong in women. Smokers had a higher incidence of varicose veins compared with non-smokers, OR 1.3 (95% CI: 0.9-1.8), but without statistical significance. Having daily meals of meat implied less new varicose veins than having 0-2 weekly meals of meat. CONCLUSION: Alcohol was likely to increase the risk of varicose veins in women and smoking in both genders. These findings were seen in the follow-up design, but not when the data of these risk factors were compared with varicose veins prevalent at entry.

The risk of congestive heart failure is increased in persons with varicose veins.

AIM: Varicose veins are a common condition but their etiology and relationship with other cardiovascular diseases are not well established. The aim of the study was to find out if persons with varicose veins have a higher risk of congestive heart failure (CHF) than persons without varicose veins. METHODS: The prevalence of CHF at entry and the incidence of CHF during a five-year follow-up period were studied in persons with and without varicose veins. A study was conducted with a questionnaire in a population of 4903 middle-aged residents in Tampere, Finland. RESULTS: Marginally higher prevalence of CHF was found in persons with varicose veins than in those without (2.9% vs. 1.9%) with OR 1.6 (1.0-2.3) and sex and age adjusted OR 1.2 (0.8-1.9). The incidence of CHF was higher in subjects with varicose veins than in others (4.9 vs. 2.6 per 1000 person-years) with IDR 1.9 (1.1-2.9) and sex and age adjusted IOR 2.5 (1.4-4.6). The result was further adjusted for body mass index, arterial disease and hypertension; multi-adjusted IOR for the incidence of CHF by varicose veins was 2.1 (1.1-4.0). CONCLUSIONS: Our longitudinal observation is consistent with the hypothesis that persons with varicose veins have a higher risk of CHF which is not mediated through sex, age, overweight, arterial disease or hypertension.

Implementation of colorectal cancer screening in Finland: experiences from the first three years of a public health programme.

BACKGROUND AND STUDY AIMS: Colorectal cancer mortality can be reduced by repeated screening, using faecal occult blood testing. This report describes the implementation of service screening in Finland and performance indicators from the first three years. METHODS: The programme is based on gradual expansion over six years of implementation. It involves individual-level randomisation into screening or control arms among a target population of men and women aged 60-69 years. The effects will be evaluated comparing incidence of and mortality from colorectal cancer in the invited arm with the controls. The screening test is a biannual guaiac-based faecal occult blood test with three test cards for consecutive samples and colonoscopies offered to those with any blood observed. RESULTS: Between September 2004 and December 2006, 52,994 test kits (to 26,247 men and 26,747 women) were sent out in 160 municipalities out of 444. Attendance to screening was 71% overall, 63% in men and 78% in women. People from the youngest age-group (born in 1946) were less compliant than those from the oldest one (born in 1940). Among the screened, 2.1% were found with blood in the stools, 3% of men and 1.5% of women. Cancers and adenomas were detected according to expectations, in 8.6 and 43.2%, respectively, among those who underwent colonoscopy. CONCLUSIONS: The implementation measured with attendance and performance of the test of colorectal cancer screening in Finland has been successful. The programme meets the criteria both for a randomised trial and for a public health programme allowing unbiased data to be collected during the implementation period.

Arterial disease but not hypertension predisposes to varicose veins.

OBJECTIVES: The aim of the study was to find out if persons with cardiovascular diseases (CVD) (arterial disease or hypertension) have additional risk of varicose veins (VV) compared with those without arterial disease (AD) or hypertension. METHODS: We studied, using a validated questionnaire, the prevalence and incidence of VVs in those with and without CVD in a population of 4903 including 40-, 50- and 60-year-old men and women in Tampere, Finland. During the five years of follow-up, we had a special interest on the appearance of new VVs in those without VVs at entry (n = 3065). RESULTS: We found a higher prevalence of VVs in persons with CVD than in those without CVD (with sex and age adjusted odds ratio [OR] 1.3 [95% confidence interval, CI 1.1-1.5]). The prevalence of VVs was higher in persons with AD (OR 1.7 [CI 1.4-2.2]), but not in persons with hypertension (OR 1.1 [CI 0.9-1.2]) than in those who were free of AD or hypertension, respectively. Subjects with AD had higher incidence of VVs (incidence odds ratio, IOR 1.4 [CI 0.8-2.7]) than subjects without AD and the effect was statistically significant in women (IOR 2.2 [CI 1.1-4.5]). Also the incidence of VVs was more affected by AD than by hypertension (IOR 1.1 [CI 0.7-1.8]). CONCLUSION: There seems to exist a relatively strong additional risk of VVs in persons with AD and practically none in those with hypertension compared to those without.

The sense of coherence and risk of injuries: role of alcohol consumption and occupation.

STUDY OBJECTIVE: To test the hypothesis that individuals with a strong sense of coherence (SOC) have a decreased incidence of external cause injuries and to study the role of alcohol consumption and occupational category in that association. DESIGN: Participants of the Helsinki Heart Study were followed up for injuries for eight years through the national hospital discharge register and cause of death statistics. Cox proportional hazards models were used to calculate the relative risks. SETTING: The Helsinki Heart Study, a clinical trial to prevent coronary heart disease. PARTICIPANTS: 4405 Finnish middle-aged employed men. MAIN RESULTS: The SOC was inversely associated with the risk of injuries, with a significant 25% lower incidence in the highest tertile of SOC (7.6 per 1000 person-years) compared with the lowest (10.2 per 1000 person-years). The association remained significant if adjusted for age, but not if adjusted additionally for alcohol consumption or occupation. When considered jointly with occupational category, the injury risk showed a decreasing trend (p = 0.02) with increasing SOC among blue collar but not among white collar workers. The use of alcohol had a great impact on injury risk among those with weak SOC, with incidences of 7.7, 10.2, and 14.9 per 1000 person-years in the non/light, medium, and heavy categories of consumption (p for trend 0.01). No such trend was seen in other SOC tertiles. CONCLUSIONS: There was an effect of SOC on the incidence of injury especially among blue collar workers. A substantial part of the effect was mediated by alcohol consumption.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

The 15-Country Collaborative Study of Cancer Risk Among Radiation Workers in the Nuclear Industry: design, epidemiological methods and descriptive results.

Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.

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 32 000 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

Erectile dysfunction influences the subsequent incidence of lower urinary tract symptoms and bother.

It is unclear whether lower urinary tract symptoms (LUTS) cause erectile dysfunction (ED) independently or through common underlying pathophysiology and shared risk factors. The aim of this study was to investigate the effect of ED on the incidence of frequency and bother of LUTS. Target population consisted of men aged 50, 60 or 70 years residing in the study area in Finland in 1994. Questionnaires were mailed to 3143 men in 1994 and to 2837 of them 5 years later. The follow-up sample comprised 1683 men who responded to both baseline and follow-up surveys. ED was assessed by two questions on subject's ability to achieve or maintain an erection sufficient for intercourse and LUTS by the Danish Prostatic Symptom Score questionnaire. A dose-response relation was found between the severity of ED at baseline and the incidence of LUTS or bother during follow-up. After adjustment for the confounders, the incidence rate ratio (RR) of LUTS was higher in men with moderate (RR 1.5, 95% confidence interval (CI) 1.0-2.3) or severe ED (RR 2.3, 95% CI 1.4-3.8) than in those free of ED at entry. Compared with men free of ED at baseline, the RRs of urinary bother were 1.6 (95% CI 1.1-2.4), 1.9 (95% CI 1.1-3.2) and 2.2 (95% CI 1.1-4.3) for minimal, moderate or severe ED, respectively. In summary, ED is associated with an increased incidence of LUTS and bother. ED and LUTS may have a common underlying pathophysiology or shared risk factors.

Cardiovascular drug use and the incidence of erectile dysfunction.

It is unclear whether high blood pressure per se or antihypertensive drug use causes erectile dysfunction (ED). The aim of this study was to investigate the effect of cardiovascular diseases and their concomitant medications use on the incidence of ED. The target population consisted of men aged 55, 65 or 75 years old residing in the study area in Finland in 1999. Questionnaires were mailed to 2837 men in 1999 and to 2510 of them 5 years later. The follow-up sample consisted of 1665 men (66% of those eligible) who responded to both baseline and follow-up questionnaires. Men free of moderate or severe ED at baseline (N=1000) were included in the study. ED was assessed by two questions on subject ability to achieve or maintain an erection sufficient for intercourse. Poisson regression model was used in the multivariable analyses. The risk of ED was higher in men suffering from treated hypertension or heart disease than in those with the untreated condition. The risk of ED was higher in men using calcium channel inhibitor (adjusted relative risk (RR)=1.6, 95% confidence interval (CI) 1.0-2.4), angiotensin II antagonist (RR=2.2, 95% CI 1.0-4.7), non-selective beta-blocker (RR=1.7, 95% CI 0.9-3.2) or diuretic (RR=1.3, CI 0.7-2.4) compared with non-users. ED was not associated with using organic nitrates, angiotensin-converting enzyme inhibitors, selective beta-blockers and serum lipid-lowering agents. In summary, calcium channel inhibitors, angiotensin II antagonists, non-selective beta-blockers and diuretics may increase the risk of ED.

The effects of parity, oral contraceptive use and hormone replacement therapy on the incidence of varicose veins.

Three population-based age cohorts (40-, 50- and 60-years old) of women (n = 3,590) were followed up to find out if pregnancies, use of oral contraceptives (OCs) or hormone replacement therapy (HRT) affect the appearance of varicose veins. Results were presented as odds ratios (OR) of prevalences at entry (POR) and as incidence odds ratios (IOR) during the 5-year follow-up. Parity with three or more births was an independent risk factor for varicose veins IOR 2.0 (95% confidence interval (CI), 1.0 - 3.9). OC use showed a small and not significant protective effect for varicose veins, both POR and IOR equal to 0.9. HRT use indicated an increased risk of varicose veins, with POR 1.3 (1.0 - 1.7), but in the follow-up, the effect disappeared, IOR 1.0 (0.5 - 1.9). As a conclusion, higher age and high parity are characteristic for varicose veins. The use of HRT or OCs do not increase the risk.

Effect of nonsteroidal anti-inflammatory drug use on the incidence of erectile dysfunction.

PURPOSE: We estimated the effect of nonsteroidal anti-inflammatory drug use on the incidence of erectile dysfunction. MATERIALS AND METHODS: The target population consisted of men 50, 60 or 70 years old residing in the study area in Finland in 1994. Questionnaires were mailed to 3,143 men in 1994 and to 2,864 men 5 years later. The followup sample consisted of 1,683 men who responded to baseline and followup questionnaires. We estimated the effect of NSAIDs on the incidence of ED in men free from moderate or complete ED at baseline (in 1,126). ED was assessed by 2 questions on subject ability to achieve or maintain an erection sufficient for intercourse. Confounding was assessed by stratification and by adjustment in multivariate Poisson regression model. RESULTS: The incidence of ED was 93 cases per 1,000 person-years in men who used and 35 in those who did not use NSAIDs. Among men with arthritis, the most common indication for NSAID use, ED incidence was 97 cases per 1,000 in those using and 52 in men who did not use NSAIDs. Compared with men who did not use NSAIDs and were free from arthritis, the relative risk of ED after controlling for the effects of age, smoking, and other medical conditions and medications was higher in men who used NSAIDs but were free of arthritis (IDR 2.0, 95% CI 1.2-3.5) and in those who used NSAIDs and had arthritis (IDR 1.9, 95% CI 1.2-3.1). The relative risk was only somewhat higher in men who had arthritis but did not use NSAIDs (IDR 1.3, 95% CI 0.9-1.8). CONCLUSIONS: The use of nonsteroidal anti-inflammatory drugs increases the risk of ED and the effect is independent of indication.

Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting.

The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present report on first-year results was to assess the cross-sectional relative validity parameters for routine hrHPV screening, in comparison with conventional screening. An equal number of women invited to routine screening was randomly allocated to primary hrHPV screening (n=7060) and to cytological screening (n=7089). In the hrHPV screening arm, after a single positive hrHPV test result, the need of colposcopy referral was determined by a cytological triage test. Compared with the conventional arm, more colposcopy referrals were made in the hrHPV screening arm (relative risk 1.51, confidence interval 95% 1.03-2.22). Specificity of the primary screening with sole hrHPV test (91.5-92.1%) was much lower than that with the cytology triage (98.7-99.3%), which was not quite as specific as screening with conventional cytology (99.2-99.6%). Compared with conventional cytology, primary screening with hrHPV test results in increased cross-sectional relative sensitivity at the level of all positive lesions at the cost of substantial loss in specificity. With cytology triage, the specificity improves to the level of conventional cytology.