Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study.

BACKGROUND: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. METHODS: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). FINDINGS: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. INTERPRETATION: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. FUNDING: Italian Ministry of Health, European Commission, Estonian Research Council.

Complete cancer prevalence in Europe in 2020 by disease duration and country (EUROCARE-6): a population-based study.

BACKGROUND: Cancer survivors-people living with and beyond cancer-are a growing population with different health needs depending on prognosis and time since diagnosis. Despite being increasingly necessary, complete information on cancer prevalence is not systematically available in all European countries. We aimed to fill this gap by analysing population-based cancer registry data from the EUROCARE-6 study. METHODS: In this population-based study, using incidence and follow-up data up to Jan 1, 2013, from 61 cancer registries, complete and limited-duration prevalence by cancer type, sex, and age were estimated for 29 European countries and the 27 countries in the EU (EU27; represented by 22 member states that contributed registry data) using the completeness index method. We focused on 32 malignant cancers defined according to the third edition of the International Classification of Diseases for Oncology, and only the first primary tumour was considered when estimating the prevalence. Prevalence measures are expressed in terms of absolute number of prevalent cases, crude prevalence proportion (reported as percentage or cases per 100 000 resident people), and age-standardised prevalence proportion based on the European Standard Population 2013. We made projections of cancer prevalence proportions up to Jan 1, 2020, using linear regression. FINDINGS: In 2020, 23 711 thousand (95% CI 23 565-23 857) people (5·0% of the population) were estimated to be alive after a cancer diagnosis in Europe, and 22 347 thousand (95% CI 22 210-22 483) in EU27. Cancer survivors were more frequently female (12 818 thousand [95% CI 12 720-12 917]) than male (10 892 thousand [10 785-11 000]). The five leading tumours in female survivors were breast cancer, colorectal cancer, corpus uterine cancer, skin melanoma, and thyroid cancer (crude prevalence proportion from 2270 [95%CI 2248-2292] per 100 000 to 301 [297-305] per 100 000). Prostate cancer, colorectal cancer, urinary bladder cancer, skin melanoma, and kidney cancer were the most common tumours in male survivors (from 1714 [95% CI 1686-1741] per 100 000 to 255 [249-260] per 100 000). The differences in prevalence between countries were large (from 2 to 10 times depending on cancer type), in line with the demographic structure, incidence, and survival patterns. Between 2010 and 2020, the number of prevalent cases increased by 3·5% per year (41% overall), partly due to an ageing population. In 2020, 14 850 thousand (95% CI 14 681-15 018) people were estimated to be alive more than 5 years after diagnosis and 9099 thousand (8909-9288) people were estimated to be alive more than 10 years after diagnosis, representing an increasing proportion of the cancer survivor population. INTERPRETATION: Our findings are useful at the country level in Europe to support evidence-based policies to improve the quality of life, care, and rehabilitation of patients with cancer throughout the disease pathway. Future work includes estimating time to cure by stage at diagnosis in prevalent cases. FUNDING: European Commission.

Differences in survival and recurrence of colorectal cancer by stage across population-based European registries.

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age-standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5-year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5-year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five-year cumulative rate of recurrence among resected patients with stage I-III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population-based collection of cancer recurrence information is crucial to enhance efforts for evidence-based management of colorectal cancer follow up.

SARS-CoV-2 infection during pregnancy and perinatal outcomes in Estonia in 2020 and 2021: A register-based study.

INTRODUCTION: Data from different countries show partly controversial impact of SARS-CoV-2 infection on pregnancy outcomes. A nationwide register-based study was conducted in Estonia to assess the impact of SARS-CoV-2 infection at any time during pregnancy on stillbirth, perinatal mortality, Apgar score at 5 minutes, cesarean section rates, rates of preterm birth and preeclampsia. MATERIAL AND METHODS: Data on all newborns and their mothers were obtained from the Estonian Medical Birth Registry, and data on SARS-CoV-2 testing dates, test results and vaccination dates against SARS-CoV-2 from the Estonian Health Information System. Altogether, 26 211 births in 2020 and 2021 in Estonia were included. All analyses were performed per newborn. Odds ratios with 95% confidence intervals (CI) were analyzed for all outcomes, adjusted for mother's place of residence, body mass index, age of mother at delivery and hypertension and for all the aforementioned variables together with mother's vaccination status using data from 2021 when vaccinations against SARS-CoV-2 became available. For studying the effect of a positive SARS-CoV-2 test during pregnancy on preeclampsia, hypertension was omitted from the models to avoid overadjustment. RESULTS: SARS-CoV-2 infection during pregnancy was associated with an increased risk of stillbirth (adjusted odds ratio [aOR] 2.81; 95% CI 1.37-5.74) and perinatal mortality (aOR 2.34; 95% CI 1.20-4.56) but not with a lower Apgar score at 5 minutes, higher risk of cesarean section, preeclampsia or preterm birth. Vaccination slightly decreased the impact of SARS-CoV-2 infection during pregnancy on perinatal mortality. CONCLUSIONS: A positive SARS-CoV-2 test during pregnancy was associated with higher rates of stillbirth and perinatal mortality in Estonia but was not associated with change in preeclampsia, cesarean section or preterm birth rates.

Cervical cancer screening history among women diagnosed with cervical cancer in Estonia 2017-18.

BACKGROUND: Despite the national cervical cancer screening programme launched in 2006, Estonia has one of the highest cervical cancer incidence rates in Europe. While the overall coverage of cervical cytology is high, the factors related to cancer screening history prior to cancer diagnosis need to be studied. METHODS: In this study, we aimed to examine the 10-year screening history of women diagnosed with cervical cancer in Estonia in 2017-18, using data collected from laboratory reports from 2007 to 2018. From each report, we extracted information on the date and result of cytology and on the laboratory where the sample was assessed. We analysed these data across cancer histology, the time interval between the last test result and cancer diagnosis and the laboratory type (local or regional). RESULTS: Among 319 women with cervical cancer, 181 (56.7%) did not have any cytology reports available. Among 138 women with at least one cytology, 60% had 1-3, 24% 4-6 and 16% ≥7 tests (mean 3.7) before cancer. In 78% of women, the last test was performed less than 5 years before cancer diagnosis and 62% of these tests did not report any abnormalities. The last cytology results differed significantly between the regional and local laboratories (P = 0.028). CONCLUSION: Women received the cervical cancer diagnosis in Estonia despite having several screening tests 10 years prior to the diagnosis. The proportion of cytology tests without any abnormalities less than 5 years before the diagnosis was worryingly high and needs further investigation together with the difference between laboratory types.

Long-term survival and cure fraction estimates for childhood cancer in Europe (EUROCARE-6): results from a population-based study.

BACKGROUND: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. METHODS: In this population-based study, we analysed 135 847 children (aged 0-14 years) diagnosed during 2000-13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. FINDINGS: 5-year survival for all childhood cancer combined in Europe in 2010-14 was 81% (95% CI 81-82), showing an increase of three percentage points compared with 2004-06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60-79] to 87% [77-93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010-13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73-75) in 1998-2001 to 80% (79-81) in 2010-13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74-100) for retinoblastoma to 60% (58-63) for CNS tumours and reached 90% (95% CI 87-93) for lymphoid leukaemia and 70% (67-73) for acute myeloid leukaemia. INTERPRETATION: Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. FUNDING: European Commission.

Quality Assessment of Cervical Cytology Practices in Estonia From 2007 to 2018.

BACKGROUND: Cervical cancer incidence and mortality in Estonia are among the highest in Europe, although the overall coverage with cervical cytology is high. This indicates potential issues with the quality of collection and/or laboratory evaluation of cervical cytology. OBJECTIVES: The aim of the retrospective observational study was to assess the quality of cervical cytology specimen collection, evaluation, and reporting using laboratory reports in Estonia. METHODS: The study included women with a cervical cancer diagnosis in 2017-2018. Cervical cytology and histology reports for these women in 2007-2018 were obtained from ten laboratories. We described the quality of cytology specimen collection and reporting of cytology results. Multivariate logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) to identify factors associated with NILM as the last cervical cytology result within 5 or 2 years before the cervical cancer diagnosis. Also, we calculated cytology-histology correlation (CHC). RESULTS: We identified 503 cytology and 100 histology reports from 138 women. The laboratories differed greatly regarding human resources, work capacity and volume. Differences between local and regional laboratories were observed in reporting specimen adequacy (P < .001). We found that local laboratories had 3 times higher odds (OR = 2.95, 95% CI: 1.05-8.33) of reporting normal results 2 years before cancer diagnosis than regional laboratories. According to the CHC, 58.9% of pairs were in agreement. CONCLUSIONS: The study showed considerable heterogeneity and suboptimal performance of cervical cytology practices in Estonia, particularly at local laboratories. Efforts to improve laboratory quality assurance are crucial.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

The impact of sociodemographic factors on the utilization of radiation therapy in breast cancer patients in Estonia: a register-based study.

BACKGROUND: Radiation therapy is an important part of multimodal breast cancer treatment. The aim was to examine the impact of sociodemographic factors on radiation therapy use in breast cancer (BC) patients in Estonia, linking cancer registry data to administrative databases. METHODS: Estonian Cancer Registry provided data on women diagnosed with BC in Estonia in 2007-2018, including TNM stage at diagnosis. Use of radiation therapy within 12 months of diagnosis was determined from Estonian Health Insurance Funds claims, and sociodemographic characteristics from population registry. Receipt of radiation therapy was evaluated over time and by clinical and sociodemographic factors. Poisson regression with robust variance was used to calculate univariate and multivariate prevalence rate ratios (PRR) with 95 % confidence intervals (CI) for receipt of radiation therapy among stage I-III BC patients age < 70 years who underwent primary surgery. RESULTS: Overall, of 8637 women included in the study, 4310 (50 %) received radiation therapy within 12 months of diagnosis. This proportion increased from 39 to 58 % from 2007 to 2009 to 2016-2018 (p < 0.001). Multivariate regression analysis showed that compared to women with stage I BC, those with more advanced stage were less likely to receive radiation therapy. Receipt of radiation therapy increased significantly over time and was nearly 40 % higher in 2016-2018 than in 2007-2009. Use of radiation therapy was significantly lower for women with the lowest level of education compared to those with a university degree (PRR 0.88, 95 % CI 0.80-0.97), and for divorced/widowed women (PRR 0.95, 95 % CI 0.91-0.99) and single women (PRR 0.92, 95 % CI 0.86-0.99), compared to married women. Age at diagnosis, nationality and place of residence were not associated with receipt of radiation therapy. CONCLUSIONS: The study showed considerable increase in the use of radiation therapy in Estonia over the study period, which is in line with increases in available equipment. The lack of geographic variations suggests equal access to therapy for patients living in remote regions. However, educational level and marital status were significantly associated with receipt of radiation therapy, highlighting the importance of psychosocial support in ensuring equal access to care.

Endocrine treatment and incidence of relapse in women with oestrogen receptor-positive breast cancer in Europe: a population-based study.

PURPOSE: Endocrine therapy (ET) is the mainstream adjuvant treatment for ER-positive breast cancer (BC). We analysed 9293 ER-positive BC patients diagnosed in nine European countries in 2009-2013 to investigate how comorbidities at diagnosis, age, stage and subtype affected ET use over time, and relapse. METHODS: Adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) of receiving ET were estimated according to Charlson comorbidity, age, stage and subtype using logistic regression. The 2-year cumulative incidence and adjusted sub-hazard ratios (SHRs) of relapse were estimated using competing risk analysis, with all-cause death as the competing event. The z-test was used to assess differences in the proportion of patients receiving ET in 1996-1998 and 2009-2013. RESULTS: Ninety percent of the patients started adjuvant ET, range 96% (Belgium, Estonia, Slovenia, Spain)-75% (Switzerland). ORs of starting ET were lower for women aged > 75 years, with severe comorbidities, or luminal B HER2-positive cancer. The factors independently increasing the risk of relapse were: not receiving ET (SHR 2.26, 95%CI 1.02-5.03); severe comorbidity (SHR 1.94, 95%CI 1.06-3.55); luminal B, either HER2 negative (SHR 3.06, 95%CI 1.61-5.79) or positive (SHR 3.10, 95%CI 1.36-7.07); stage II (SHR 3.20, 95%CI 1.56-6.57) or stage III (SHR 7.41, 95%CI 3.48-15.73). ET use increased significantly but differently across countries from 51-85% in 1996-1998 to 86-96% in 2009-2013. CONCLUSIONS: ER-positive BC patients in Europe are increasingly prescribed ET but between-country disparities persist. Older women and women with severe comorbidity less frequently receive ET. ET omission and severe comorbidity independently predict early disease relapse.

Changes in therapy and survival of metastatic renal cell carcinoma in Estonia.

BACKGROUND: Before the era of targeted therapies, cytokines were the main therapy for metastatic renal cell carcinoma (mRCC). Our aim was to analyze the changes in treatments and overall survival (OS) of all mRCC patients in Estonia in relation to the introduction of new medications. METHODS: All patients with mRCC who started medical therapy in Estonia during the years 2004-2012 were identified using the database of the Estonian Health Insurance Fund. Tumor and treatment data were gathered from medical records. Vital status data were obtained from the Estonian Population Registry. The only available therapy before 2008 was interferon alpha-2A (INFa2A), targeted agents added from 2008. For survival analysis, patients were divided into 2 groups: INFa therapy only (group 1) and INFa followed by targeted agents or targeted agents therapy only (group 2). RESULTS: Out of 416 identified patients, 380 were eligible for analysis. The most common 1st-line treatments were INFa (55%), sunitinib (32%) and INFa+bevacizumab (13%). 28% of patients received 2nd-line therapies and 15% 3rd-line treatments. Median survival of all patients was 13.7 months [95% confidence interval (CI) 11.3-16.2]; 7.6 months (CI 6.4-8.6) for group 1 and 19.8 months (CI 15.6-22.9) for group 2. In multivariate analysis, group 1 had nearly four times higher risk of dying than group 2 [hazard ration (HR) 3.88, 95% CI 2.64-5.72]. CONCLUSIONS: The implementation of targeted therapies significantly changed the outcomes of mRCC in Estonia: it prolonged median survival, reduced the risk of death and also enlarged the proportion of patients who received medical therapy.

Childhood cancer incidence and survival trends in Estonia (1970-2016): a nationwide population-based study.

BACKGROUND: Childhood cancers represent a small proportion of all cancers but are still a major public health problem. The study analysed long-term trends in childhood cancer incidence and survival in Estonia in relation to societal and health care transition. METHODS: Data on all malignant tumours, diagnosed in children aged 0-14 during 1970-2016, were derived from the Estonian Cancer Registry. Age-standardised (World standard) incidence rates were calculated by ICCC-3 site groups and joinpoint regression was used to estimate annual percentage change (APC) for incidence trends. Cohort and period approach were used to estimate 5-year survival. Internal age standardisation was applied. RESULTS: A total of 1628 incident cancer cases were diagnosed during the study period and overall incidence increased significantly at a rate of 0.5% per year. Significant increases were seen for neuroblastoma and germ cell tumours, for lymphoid leukemias and some CNS sub-sites. At the same time, decline in incidence was seen in almost all subgroups of unspecified neoplasms. The overall 5-year survival improved from 24% in 1970-1979 to 73% in 2010-2016, with the largest changes occurring in the 1990s and 2000s. For many sites, survival increase thereafter has been marginal. CONCLUSION: In this first comprehensive population-based study of childhood cancer incidence and survival in Estonia, long-term trends are shown in the context of societal and health care changes. Even though the increasing incidence of some sites may, at least partially, be explained by improved diagnostics reflected in the decreased incidence of unspecified neoplasms, the overall cancer incidence in children seems to be rising. Rapid progress in diagnosis and care have improved childhood cancer survival immensely, but deficit in Estonia persists compared to other European countries. Results of the study accentuate the need for a more in-depth analysis of clinical data, but also for the prioritization of childhood cancer in Estonia, to ensure access to standard care and innovative treatments.

Comorbidities, age and period of diagnosis influence treatment and outcomes in early breast cancer.

Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 stage I/IIA cases diagnosed in 9 European countries in 2009-2013, and 4 STs: surgery; breast-conserving surgery plus radiotherapy (BCS + RT); reconstruction after mastectomy; and prompt treatment (≤6 weeks after diagnosis). Covariate-adjusted models estimated odds of receiving STs and risks of death/relapse, according to comorbidities. Pearson's R assessed correlations between odds and risks. The z-test assessed the significance of time-trends. Most women received surgery: 72% BCS; 24% mastectomy. Mastectomied patients were older with more comorbidities than BCS patients (p < 0.001). Women given breast reconstruction (25% of mastectomies) were younger with fewer comorbidities than those without reconstruction (p < 0.001). Women treated promptly (45%) were younger than those treated later (p = 0.001), and more often without comorbidities (p < 0.001). Receiving surgery/BCS + RT correlated strongly (R = -0.9), but prompt treatment weakly (R = -0.01/-0.02), with reduced death/relapse risks. The proportion receiving BCS + RT increased significantly (p < 0.001) with time in most countries. This appears to be the first analysis of the influence of comorbidities on receiving STs, and of consequences for outcomes. Increase in BCS + RT with time is encouraging. Although women without comorbidities usually received STs, elderly patients often received non-standard less prompt treatments, irrespective of comorbidities, with increased risk of mortality/relapse. All women, particularly the elderly, should receive ST wherever possible to maximise the benefits of modern evidence-based treatments.

Patterns of survival and surgical treatment in lung cancer patients in Estonia by histologic type and stage, 1996-2016.

Background: Lung cancer (LC) remains the most frequent cause of cancer death worldwide. We aimed to examine long-term trends in LC survival in Estonia by age, gender, histologic type and stage, with specific focus on surgical treatment.Material and methods: Data on all incident cases of LC diagnosed from 1996 to 2016 were obtained from the Estonian Cancer Registry. Logistic regression was used to examine receipt of surgical treatment in localized LC. Relative survival ratios (RSR) were calculated, and excess hazard ratios (EHR) of death were estimated by stage with gender, age, histology and period of diagnosis as independent variables.Results: Among the total of 16,423 cases, squamous cell carcinoma remained the most common histologic type. The odds of receiving surgical treatment in localized LC increased significantly over time and were associated with age, gender and histologic type. Overall, the age-standardized 5-year RSR improved significantly from 10% in 1996-2002 to 16% in 2010-2016 (from 8% to 15% in men and from 15% to 20% in women). Larger survival gain was seen in younger patients, for non-small cell LC subtypes, and for surgically treated patients. For localized disease, the 5-year RSR increased by more than 20 percentage units, reaching 50% in men and 69% in women. For all stages, the adjusted EHR of death was significantly associated with age, histologic type and period of diagnosis.Conclusions: We observed a substantial improvement of relative survival, with considerable variations across patient groups. After adjustment for age, gender and histology, a significant survival increase over time was seen for all stages. The considerable survival gain observed for localized LC can largely be attributed to rapidly growing proportion of surgically treated patients. Further investigation of LC management practices, particularly the use of non-surgical treatment options is warranted.

Increasing kidney cancer incidence and survival in Estonia: role of age and stage.

BACKGROUND: Kidney cancer rates in Estonia are high. The study aimed to examine long-term trends in kidney cancer incidence, mortality and survival in Estonia, with special focus on age, birth cohorts, morphology and TNM stage. MATERIAL AND METHODS: Estonian Cancer Registry provided data on all incident cases of kidney cancer (ICD-10 C64), diagnosed in adults (age ≥15 years) in Estonia during 1995 - 2014. Relative survival ratios (RSR) were calculated and excess hazard ratios of dying were estimated with gender, age, period of diagnosis and TNM stage as independent variables. Joinpoint regression modeling was used to calculate estimated annual percentage change for incidence (1970-2014) and mortality (1995-2016) trends. Age-specific incidence rates were presented by birth cohort and period of diagnosis. RESULTS: Incidence increased significantly in both sexes, with the steepest rise seen for localized cancer. Cohort effects were pronounced particularly in men, while period effects were seen from the mid-1980s to mid-1990s in both sexes. Age-standardized five-year RSR for total kidney cancer increased by 13 percentage units (from 53% to 65%) over the study period; the increase was larger for renal cell carcinoma (from 63% to 78%). Survival increases of about five percentage units were seen for stages I/II and III. Age and gender were not associated with excess risk of dying from renal cell carcinoma after adjusting for stage. CONCLUSION: Estonia is currently among countries with the highest incidence of kidney cancer. The results suggest a combined effect of changing risk profiles in successive birth cohorts and increasing diagnostic activity around 1990. Large survival increase can mostly be attributed to earlier detection, but improved diagnosis and treatment have probably influenced stage-specific survival. High proportion of tumors with unspecified morphology and those with unknown stage among the elderly warrants further investigation of diagnostic and treatment practices.

Gastric cancer trends in Estonia 1995-2014 by age, subsite, morphology and stage.

BACKGROUND: Gastric cancer (GC) is among the most common cancers and one of the leading causes of cancer deaths globally. In general, the incidence of GC has declined and survival improved in Europe. Nevertheless, previous analysis has shown that survival of GC patients in Estonia is still significantly lower compared to some European countries. Therefore, to improve patient outcomes, better overview of GC epidemiology is needed. The aim of this study was to describe the incidence and survival of GC in Estonia 1995-2014 in relation to age, subsite, morphology, and the extent of disease. MATERIAL AND METHODS: We used data from the population-based Estonian Cancer Registry on all incident cases of GC diagnosed in 1995-2014. Incidence rates and relative survival were calculated. Joinpoint regression modeling was used to estimate annual percentage change for incidence trends. Data were analyzed by age, sex, subsite, morphology, and the extent of disease. Changes between 1995-1999 and 2010-2014 were assessed. RESULTS: The overall incidence of GC in Estonia decreased in 1995-2014. The age-standardized (world) incidence declined significantly for both sexes, for patients below 70 years of age, adenocarcinomas, NOS and other morphologies, non-cardia and unspecified cases, and for all known stages. Approximately 40% of GC cases were diagnosed with distant metastasis. Overall age-standardized 5-year relative survival of GC patients increased from 20% to 28%. Survival improved the most in age group 50-69 years. A large survival gain was also seen for localized (from 55% to 70%) and locally/regionally spread disease (from 23% to 37%). CONCLUSIONS: In Estonia, the incidence of GC has declined and relative survival increased. However, special emphasis needs to be put on improving survival among men, elderly and in patients with metastatic disease.

Trends in cervical cancer incidence and survival in Estonia from 1995 to 2014.

BACKGROUND: Cervical cancer (CC) incidence in Estonia is the third highest in Europe, even though an organised nation-wide screening program has been in place since 2006. The aim of the study was to analyse the incidence and survival of CC in Estonia, focusing on age, morphology and stage at diagnosis. METHODS: Data from Estonian Cancer Registry were used to analyse age-standardized (world) and age-specific incidence for 1968-2014 rates. Joinpoint regression was used to estimate the annual percentage change (APC) for incidence trends. Age-period-cohort model was used to summarise time trends in terms of cohort and period effects. Relative survival ratios (RSR) were calculated for cases diagnosed in 1995-2014. Union for International Cancer Control version 7 of the TNM classification for malignant tumours was used to categorise stage. RESULTS: The age-standardized incidence of CC increased since 1980s at a rate of 0.8% per year. A significant increase was seen for all age groups except for 70+. The incidence of squamous cell carcinoma mimicked the overall trend, while adenocarcinoma showed increase since mid-1990s (APC 6.7). Age-period-cohort modelling showed strong cohort effects with the lowest risk for birth-cohorts born around 1940 and significantly increasing risks for successive cohorts born thereafter. No period effects were seen. The proportion of stage IV cases increased from 13% in 2005-2009 to 18% in 2010-2014. A significant increase was seen in the overall 5-year RSR from 1995 to 1999 to 2010-2014 (58% vs 66%). In 2010-2014, the 5-year RSRs ranged from 89% in women aged 15-39 to 41% in age group 70+. For stages I to IV, the respective RSRs were 98, 74, 57 and 22%. CONCLUSIONS: The inadequate uptake and insufficient quality of the Pap-smear based screening program has not brought along a decline in the incidence of CC in Estonia. Stage distribution has shifted towards later stages. New approaches are needed to prevent CC in Estonia.

Divergent trends in lung cancer incidence by gender, age and histological type in Estonia: a nationwide population-based study.

BACKGROUND: Lung cancer (LC) is the leading cause of cancer deaths in men and the second most frequent cause of cancer deaths in women in Estonia. The study aimed to analyze time trends in LC incidence and mortality in Estonia over the 30-year period, which included major social, economic and health care transition. The results are discussed in the context of changes in tobacco control and smoking prevalence. Long-term predictions of incidence and mortality are provided. METHODS: Data for calculating the incidence and mortality rates in 1985-2014 were obtained from the nationwide population-based Estonian Cancer Registry and the Causes of Death Registry. Joinpoint regression was used to analyze trends and estimate annual percentage change (APC) with 95% confidence interval (CI). Nordpred model was used to project future incidence and mortality trends for 2015-2034. RESULTS: Incidence peaked among men in 1991 and decreased thereafter (APC: -1.5, 95% CI: -1.8; -1.3). A decline was seen for all age groups, except age ≥ 75 years, and for all histological types, except adenocarcinoma and large cell carcinoma. Incidence among women increased overall (APC: 1.6, 95% CI: 1.1; 2.0) and in all age groups and histological types, except small cell carcinoma. Age-standardized incidence rate (world) per 100,000 was 54.2 in men and 12.9 in women in 2014. Changes in mortality closely followed those in incidence. According to our predictions, the age-standardized incidence and mortality rates will continue to decrease in men and reach a plateau in women. CONCLUSIONS: The study revealed divergent LC trends by gender, age and histological type, which were generally consistent with main international findings. Growing public awareness and stricter tobacco control have stimulated overall favorable changes in men, but not yet in women. Large increase in incidence was observed for adenocarcinoma, which in men showed a trend opposite to the overall decline. LC will remain a serious public health issue in Estonia due to a high number of cases during the next decades, related to aging population, and previous and current smoking patterns. National tobacco control policy in Estonia should prioritize preventing smoking initiation and promoting smoking cessation, particularly among women.

Trends in incidence and survival of cutaneous malignant melanoma in Estonia: a population-based study.

BACKGROUND: Previous studies have shown an increase in the incidence of cutaneous melanoma (CM) in Estonia, but also poor survival in international comparisons, with a significant survival gap between the sexes. The aim of this study was to analyze the time trends in CM incidence and relative survival by age, TNM stage and anatomical subsite among men and women in Estonia. MATERIALS AND METHODS: Data from the Estonian Cancer Registry were used to calculate age-standardized (World) and age-specific incidence of CM in 1995-2013, and five-year relative survival ratios (RSR) for cases diagnosed in 1995-2012 and followed through in 2014. Period hybrid analysis was used to calculate the most recent survival estimates for 2010-2014. RESULTS: Between 1995 and 2013, the age-standardized incidence of CM increased significantly in Estonia among both sexes, at a rate of around 4% per year. Among women, the proportion of trunk melanomas increased from 26% in 1995-1999 to 39% in 2010-2012 and became the most common site. The proportion of stage I cases and T1 tumors increased considerably. Women had more favorable stage distribution and thinner tumors than men. The age-adjusted five-year RSR increased significantly, from 64% in 1995-1999 to 81% in 2010-2014. The latest age-adjusted RSRs were 76% among men and 84% among women. Survival gains were the largest in patients below 50 years, those with head and neck or trunk melanomas, and stage III cancer. CONCLUSIONS: The proportion of stage I and T1 cases is lower in Estonia compared with the Scandinavian data and is likely a major contributor to the persisting overall survival deficit in Estonia. The apparent deficit in stage II survival also warrants further investigation. A public health program is necessary in Estonia to raise awareness of CM and to significantly increase early stage diagnosis.

Time Trends in Ovarian Cancer Survival in Estonia by Age and Stage.

OBJECTIVE: The objective of the study was to examine temporal trends in ovarian cancer (OC) survival in Estonia during 1995 to 2009 in relation to age and stage. MATERIALS AND METHODS: Estonian Cancer Registry data on all adult cases of primary OC diagnosed during 1995 to 2009 and followed up for vital status until 2014 were used to estimate relative survival ratios (RSRs). Cohort analysis was used to estimate 1-, 2-, and 5-year RSRs for patients diagnosed in 1995 to 1999, 2000 to 2004, and 2005 to 2009. Analysis was performed by age at diagnosis (<50; 50-59; 60-69; 70+ years) and stage (International Federation of Gynecology and Obstetrics 1988). RESULTS: Among 2296 women included in the study, the age-adjusted 5-year RSR improved from 27% in 1995 to 1999 to 38% in 2005 to 2009. Survival increase of 10% units from 1995 to 1999 to 2005 to 2009 was seen for women aged 50 to 59 and 60 to 69 years. Among younger and older women, the respective changes were smaller. In 1995 to 1999, the difference in survival between the youngest and oldest age groups was 41% units. This decreased over the study period to 37% units. From 1995 to 1999 to 2005 to 2009, the 5-year RSR increased from 82% to 91% for stage I patients; from 48% to 67% for stage II patients; from 25% to 35% for stage III patients; and from 11% to 16% for stage IV patients. CONCLUSIONS: The study showed an improvement of OC survival in Estonia in all age and stage groups, but particularly among younger women and those with early stage disease. Slower progress among older women is of great concern.