Risk-adjusted Screening for Prostate Cancer-Defining the Low-risk Group by Data from the PROBASE Trial.

BACKGROUND: Risk-adjusted screening for prostate cancer (PCa) aims to reduce harms by less frequent retesting, especially in men at a low risk of PCa. Definitions of low risk are based mainly on studies in men starting screening at age 55-60 yr. OBJECTIVE: To identify men at age 45 yr with a low risk of PCa. DESIGN, SETTING, AND PARTICIPANTS: A population-based, risk-adjusted PCa screening trial was conducted in Germany using baseline prostate-specific antigen (PSA) starting in young men (PROBASE). INTERVENTION: PSA measurements starting at the age of 45 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The incidence of PCa within 5 yr was assessed in men with screen-negative baseline PSA <1.5 ng/ml compared with those with PSA 1.5-≤3.0 ng/ml. RESULTS AND LIMITATIONS: Of 23301 men who received a first PSA test at age 45 yr, 0.79% had a screen-positive PSA value of ≥3 ng/ml. Among the 89% of men who had a screen-negative baseline PSA value of <1.5 ng/ml, only 0.45% received a positive PSA test ≥3 ng/ml upon retesting after 5 yr. By contrast, for those with a screen-negative baseline PSA value of 1.5-3 ng/ml, 13% surpassed 3 ng/ml upon biennial testing within the next 4 yr. The incidence of PCa in subsequent screening rounds increased with increasing baseline PSA levels, from 0.13 per 1000 person-years for men with initial PSA level of <1.5 ng/ml to 8.0 per 1000 person-years for those with PSA levels of 1.5-3.0 ng/ml. A limitation is a follow-up time of only 5 yr, so far. CONCLUSIONS: Men with baseline PSA <1.5 ng/ml at age 45 yr are at a very low risk of PCa over the next 5 yr. PATIENT SUMMARY: The PROBASE study showed that men with baseline prostate-specific antigen (PSA) <1.5 ng/ml at age 45 yr have a very low prostate cancer detection rate over 5 yr and do not need PSA retesting during this time.

Multiparametric Magnetic Resonance Imaging in Prostate Cancer Screening at the Age of 45 Years: Results from the First Screening Round of the PROBASE Trial.

BACKGROUND: Magnetic resonance imaging (MRI) has been suggested as a tool for guiding biopsy recommendations in prostate cancer (PC) screening. OBJECTIVE: To determine the performance of multiparametric MRI (mpMRI) in young men at age 45 yr who participated in a PC screening trial (PROBASE) on the basis of baseline prostate-specific antigen (PSA). DESIGN, SETTING, AND PARTICIPANTS: Participants with confirmed PSA ≥3 ng/ml were offered mpMRI followed by MRI/transrectal ultrasound fusion biopsy (FBx) with targeted and systematic cores. mpMRI scans from the first screening round for men randomised to an immediate PSA test in PROBASE were evaluated by local readers and then by two reference radiologists (experience >10 000 prostate MRI examinations) blinded to the histopathology. The PROBASE trial is registered as ISRCTN37591328 OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The local and reference Prostate Imaging-Data and Reporting System (PI-RADS) scores were compared, and the sensitivity, negative predictive value (NPV), and accuracy were calculated for both readings for different cutoffs (PI-RADS 3 vs 4). RESULTS AND LIMITATIONS: Of 186 participants, 114 underwent mpMRI and FBx. PC was detected in 47 (41%), of whom 33 (29%) had clinically significant PC (csPC; International Society of Urological Pathology grade group ≥2). Interobserver reliability between local and reference PI-RADS scores was moderate (k = 0.41). At a cutoff of PI-RADS 4, reference reading showed better performance for csPC detection (sensitivity 79%, NPV 91%, accuracy of 85%) than local reading (sensitivity 55%, NPV 80%, accuracy 68%). Reference reading did not miss any PC cases for a cutoff of PI-RADS <3. If PI-RADS ≥4 were to be used as a biopsy cutoff, mpMRI would reduce negative biopsies by 68% and avoid detection of nonsignificant PC in 71% of cases. CONCLUSIONS: Prostate MRI in a young screening population is difficult to read. The MRI accuracy of for csPC detection is highly dependent on reader experience, and double reading might be advisable. More data are needed before MRI is included in PC screening for men at age 45 yr. PATIENT SUMMARY: Measurement of prostate specific antigen (PSA) is an effective screening test for early detection of prostate cancer (PC) and can reduce PC-specific deaths, but it can also lead to unnecessary biopsies and treatment. Magnetic resonance imaging (MRI) after a positive PSA test has been proposed as a way to reduce the number of biopsies, with biopsy only recommended for men with suspicious MRI findings. Our results indicate that MRI accuracy is moderate for men aged 45 years but can be increased by a second reading of the images by expert radiologists. For broad application of MRI in routine screening, double reading may be advisable.

Digital Rectal Examination Is Not a Useful Screening Test for Prostate Cancer.

BACKGROUND: Annual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial. OBJECTIVE: To determine DRE diagnostic performance in a screening trial. DESIGN, SETTING, AND PARTICIPANTS: This analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa. INTERVENTION: (1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen-driven biopsies (N = 578). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: (1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome at the time of a prostate biopsy were evaluated. RESULTS AND LIMITATIONS: (1) A prospective analysis of 57 men with suspicious DRE at age 45 revealed three PCa. Detection rate by DRE was 0.05% (three of 6537) as compared with a four-fold higher rate by PSA screening (48 of 23 301, 0.21%). The true-positive detection rate by DRE relative to screening by PSA was 0.22 (95% confidence interval [CI] = [0.07-0.72]) and the false-positive detection rate by DRE was 2.2 (95% CI = [1.50-3.17]). (2) Among PSA-screen-detected PCa cases, 86% had unsuspicious DRE (sensitivity relative to PSA was 14%), with the majority of these tumors (86%) located in the potentially accessible zones of the prostate as seen by magnetic resonance imaging. CONCLUSIONS: The performance of stand-alone DRE to screen for PCa is poor. DRE should not be recommended as a PCa screening test in young men. Furthermore, DRE does not improve the detection of PSA-screen-detected PCa. PATIENT SUMMARY: Our report demonstrated the poor diagnostic performance of digital rectal examination in the screening for prostate cancer in young men.

Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial.

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high risk (>3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening.

Low positive predictive value of computed tomography screening for lung cancer irrespective of commonly employed definitions of target population.

Screening for lung cancer (LC) by low-dose computed tomography (LDCT) has been demonstrated to reduce LC mortality in randomized clinical trials (RCTs), and its implementation is in preparation in many countries. However, definition of the target population, which was based on various combinations of age ranges and definitions of heavy smoking in the RCTs, is subject to ongoing debate. Using epidemiological data from Germany, we aimed to estimate prevalence of preclinical LC and positive predictive value (PPV) of LDCT in potential target populations defined by age and smoking history. Populations aged 50 to 69, 55 to 69, 50 to 74 and 55 to 79 years were considered in this analysis. Sex-specific prevalence of preclinical LC was estimated using LC incidence data within those age ranges and annual transition rates from preclinical to clinical LC obtained by meta-analysis. Prevalence of preclinical LC among heavy smokers (defined by various pack-year thresholds) within those age ranges was estimated by combining LC prevalence in the general population with proportions of heavy smokers and relative risks for LC among them derived from epidemiological studies. PPVs were calculated by combining these prevalences with sensitivity and specificity estimates of LDCT. Estimated prevalence of LC was 0.3% to 0.5% (men) and 0.2% to 0.3% (women) in the general population and 0.8% to 1.7% in target populations of heavy smokers. Estimates of PPV of LDCT were <20% for all definitions of target populations of heavy smokers. Refined preselection of target populations would be highly desirable to increase PPV and efficiency of LDCT screening and to reduce numbers of false-positive LDCT findings.

Prostate Cancer Screening with PSA: Ten Years' Experience of Population Based Early Prostate Cancer Detection Programme in Lithuania.

The aim of this study is to report key performance estimates from the ten years of a population-based prostate cancer screening programme in Lithuania. Retrospective analysis of screening activities recorded in 2006-2015 among men aged 50-74 years was performed. We estimated screening coverage, cancer detection rate, compliance to biopsy, and positive predictive values in each screening round inside and outside the target population. In the first 10 years of screening, 16,061 prostate cancer cases were registered within the screening programme, 10,202 were observed among screened men but reported outside the screening programme, and 1455 prostate cancers were observed in a screening-naïve population. Screening cover reached up to 45.5% of the target population in the recent rounds. The proportion of prostate specific antigen (PSA) test-positive men decreased from 16.9% in 2006 to 10.7% in 2014-2015. Up to 40.0% of PSA test-positive men received a biopsy, of whom 42.0% were positive for prostate cancer. The cancer detection rate was 10.4-15.0% among PSA test-positives and 1.4-1.9% among screened individuals. Screening participants were more likely to be diagnosed with organ-confined disease as compared to non-participants. Despite the unorganized screening practices being employed and low coverage per screening round, 70% of the target population were screened at least once in the first 10 years of screening.

Commonly Applied Selection Criteria for Lung Cancer Screening May Have Strongly Varying Diagnostic Performance in Different Countries.

Lung cancer (LC) screening often focuses heavy smokers as a target for screening group. Heavy smoking can thus be regarded as an LC pre-screening test with sensitivities and specificities being different in various populations due to the differences in smoking histories. We derive here expected sensitivities and specificities of various criteria to preselect individuals for LC screening in 27 European countries with diverse smoking prevalences. Sensitivities of various heavy-smoking-based pre-screening criteria were estimated by combining sex-specific proportions of people meeting these criteria in the target population for screening with associations of heavy smoking with LC risk. Expected specificities were approximated by the proportion of individuals not meeting the heavy smoking definition. Estimated sensitivities and specificities varied widely across countries, with sensitivities being generally higher among men (range: 33-80%) than among women (range: 9-79%), and specificities being generally lower among men (range: 48-90%) than among women (range: 70-99%). Major variation in sensitivities and specificities was also seen across different pre-selection criteria for LC screening within individual countries. Our results may inform the design of LC screening programs in European countries and serve as benchmarks for novel alternative or complementary tests for selecting people at high risk for CT-based LC screening.

Associations of diet and lifestyle factors with common volatile organic compounds in exhaled breath of average-risk individuals.

BACKGROUND: Detection of diseases via exhaled breath remains an attractive idea despite persisting gaps in understanding the origin of volatile organic compounds (VOCs) and their relationship with the disease of interest. Data on factors potentially influencing the results of breath analysis remain rather sparse and often controversial. In this study, we aimed to investigate the associations of common VOCs in exhaled breath of average-risk individuals with socio-demographic and lifestyle factors, medical conditions as well as diet. METHODS: Alveolar breath samples of 1447 men and women were collected in the morning after fasting and were analyzed using gas-chromatography linked with mass-spectrometry. Study participants were 40-64 years old, cancer-free, with overall good health status. The associations between selected VOCs and various factors determined from the questionnaire data were assessed using two-part-Wilcoxon test and Jonckheere-Terpstra trend test. RESULTS: Fifteen VOCs where each of them was detected in at least 80% of the study population were included in this analysis. Statistically significant associations with various VOCs were demonstrated for gender and consumption of certain foods, such as coffee, leeks and garlic, while smoking was not associated with any of the analyzed compounds. CONCLUSION: Factors potentially modifying the composition of exhaled breath, such as dietary factors, deserve careful attention in the design and analysis of studies accessing the use of VOCs as diagnostic markers.

Systematic review: Gut microbiota in fecal samples and detection of colorectal neoplasms.

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. Dysbiosis in the gut microbiota may be associated with CRC. This systematic review focuses on differences in gut microbial community between people diagnosed with CRC or adenoma and healthy individuals using fecal samples, emphasizing non-invasive fecal microbiome models for CRC early diagnosis. Nineteen studies were identified in a systematic literature search of Pubmed, Web of Science and ScienceDirect. Several bacteria were reported to differ in abundance between CRC and adenoma cases and healthy controls, with Fusobacterium the most common. Fecal multi-bacterial predictive models used to distinguish CRC patients from healthy controls had reported areas under the receiver operating curve (AUCs) in external validation populations of 0.68-0.77. Though advanced sequencing techniques could in the future complement current non-invasive methods for CRC early detection, more studies with high statistical power, comparable and reproducible methods and external validation of predictive models are needed.

Potential of non-invasive breath tests for preselecting individuals for invasive gastric cancer screening endoscopy.

BACKGROUND: Regular screening for gastric cancer (GC) is based on invasive upper gastrointestinal endoscopy and is limited to few high-incidence countries. As GC is a major cause of cancer death worldwide, a non-invasive, simple screening test is of value. We assessed the prevalence of preclinical GC and the corresponding numbers needed to screen (NNS) to detect GC cases both without and with preselection using breath tests from the literature in various populations. METHODS: Using age- and sex-specific GC incidence data and rates of transition from preclinical to clinical GC, we estimated the prevalences of preclinical GC worldwide in populations aged 50-74 years, and we evaluated the accuracy of breath testing for GC detection based on published studies. We then derived the expected positive predictive values for breath testing in populations with different preclinical GC prevalences. RESULTS: Four studies reporting the sensitivity and specificity of breath tests were identified, and summary estimates of 83% sensitivity and 91% specificity were derived by meta-analysis. The estimates of the overall prevalence of preclinical GC were <0.5% in men and <0.2% in women aged 50-74 years across different regions of the world. The positive predictive values, the prevalence among breath test positive people, were approximately nine-fold higher in all populations, resulting in an approximately nine-fold lower NNS to detect one GC case when breath tests were used for preselection for screening. CONCLUSION: Given the low prevalence of preclinical GC, non-invasive breath tests show promise for making screening more efficient. Further validation of breath tests and evidence on the rates of transition from preclinical to clinical GC are needed to validate the breath test approach.

Increasing suicide risk among cancer patients in Lithuania from 1993 to 2012: a cancer registry-based study.

Certain groups of individuals seem to have an increased risk of committing suicide, and a number of studies have reported an increased risk of suicide among cancer patients. In this study, we aim to estimate the risk of suicide among cancer patients in Lithuania over the period 1993-2012. The records of patients diagnosed with primary cancer were extracted from the population-based Lithuanian Cancer Registry and 273 511 cases of first cancer were included in the analysis. Sex, age and calendar period-standardized mortality ratios (SMRs) were calculated by dividing the observed numbers of suicides among cancer patients by the expected number using national rates. An increased suicide risk was found for both sexes combined [SMR=1.31, 95% confidence interval (CI): 1.21-1.41] compared with the general population. For all cancer sites except melanoma and skin, and breast and thyroid cancers, the relative suicide risk was elevated. The suicide risk was almost three-fold higher for advanced-stage patients compared with the general population (SMR=2.89, 95% CI: 2.24-3.73). The highest suicide risk observed in our study was during the first 3 months following cancer diagnosis (SMR=2.43, 95% CI: 1.96-3.01), indicating a critical period shortly after diagnosis. Despite ongoing increases in survival among cancer patients and decreases in suicide mortality in the general Lithuanian population during our study period, the increasing risk for suicide indicates that cancer patients' clinical and psychosocial needs remain unsatisfied. The major clinical implication of these data suggests the importance of multidisciplinary preventive interventions.

International variation in the prevalence of preclinical colorectal cancer: Implications for predictive values of noninvasive screening tests and potential target populations for screening.

Screening for colorectal cancer (CRC) is implemented in an increasing number of countries. We aimed to assess international variation in the prevalence of preclinical CRC and the resulting variation in positive and negative predictive values (PPVs, NPVs) of existing and potential CRC screening tests in various countries. Using age- and sex-specific CRC incidence data and transition rates from preclinical to clinical CRC we estimated overall and age- and sex-specific prevalence of preclinical CRC in the target population aged 50-74 years in different parts of the world. These prevalence estimates were used to derive PPVs and NPVs for existing and potential noninvasive screening tests with varying levels of sensitivity and specificity. Within all regions and countries, prevalence strongly increases with age and is higher in men than in women. In addition, major variation was seen between regions and countries, with overall prevalence varying between 1 and 0.1%. As a result, PPVs are expected to strongly vary between ∼10% for men in high incidence countries, such as Australia and Germany, and 1% for women in low incidence countries, whereas NPVs are expected to be consistently well above 99%. Variation in CRC prevalence profoundly affects expected PPVs of screening tests, and PPVs should be carefully considered when decisions on screening tests and strategies are made for specific populations and health care systems. Here, we provide estimates of preclinical CRC and expected PPVs and NPVs of noninvasive screening tests, which may enhance the empirical basis for planning of population-based CRC screening strategies.

Comparison of prostate cancer survival in Germany and the USA: can differences be attributed to differences in stage distributions?

OBJECTIVES: To better understand the influence of prostate-specific antigen (PSA) screening and other health system determinants on prognosis of prostate cancer, up-to-date relative survival (RS), stage distributions, and trends in survival and incidence in Germany were evaluated and compared with the United States of America (USA). PATIENTS AND METHODS: Incidence and mortality rates for Germany and the USA for the period 1999-2010 were obtained from the Centre for Cancer Registry Data at the Robert Koch Institute and the USA Surveillance Epidemiology and End Results (SEER) database. For analyses on stage and survival, data from 12 population-based cancer registries in Germany and from the SEER-13 database were analysed. Patients (aged ≥ 15 years) diagnosed with prostate cancer (1997-2010) and mortality follow-up to December 2010 were included. The 5- and 10-year RS and survival trends (2002-2010) were calculated using standard and model-based period analysis. RESULTS: Between 1999 and 2010, prostate cancer incidence decreased in the USA but increased in Germany. Nevertheless, incidence remained higher in the USA throughout the study period (99.8 vs 76.0 per 100,000 in 2010). The proportion of localised disease significantly increased from 51.9% (1998-2000) to 69.6% (2007-2010) in Germany and from 80.5% (1998-2000) to 82.6% (2007-2010) in the USA. Mortality slightly decreased in both countries (1999-2010). Overall, 5- and 10-year RS was lower in Germany (93.3%; 90.7%) than in the USA (99.4%; 99.6%) but comparable after adjustment for stage. The same patterns were seen in age-specific analyses. Improvements seen in prostate cancer survival between 2002-2004 and 2008-2010 (5-year RS: 87.4% and 91.2%; +3.8% units) in Germany disappeared after adjustment for stage (P = 0.8). CONCLUSION: The survival increase in Germany and the survival advantage in the USA might be explained by differences in incidence and stage distributions over time and across countries. Effects of early detection or a lead-time bias due to the more widespread utilisation and earlier introduction of PSA testing in the USA are likely to explain the observed patterns.

Basal cell skin cancer and the risk of second primary cancers: a cancer registry-based study in Lithuania.

PURPOSE: The aim of this population-based cohort study was to determine the risk of second primary cancer in basal cell carcinoma (BCC) patients in Lithuania. METHODS: This analysis was based on patients diagnosed with BCC in Lithuania between 1998 and 2007 and followed until 2011. Standardized incidence ratios for subsequent cancers as a ratio of observed number of cancer cases in people with previous BCC diagnosis to the expected number of cancer cases in the underlying general population were calculated. RESULTS: After diagnosis of BCC, 1442 new cases of selected cancers were diagnosed. Compared with the general population, the incidence of all new primaries combined after BCC was very close to expected. Statistically meaningful increase in developing subsequent cancer was obtained for Hodgkin's lymphoma, prostate cancer, and leukemia in men, and for cancers of the lip, lung, and breast in women. Risk of melanoma and thyroid cancer was significantly elevated in both sexes. Relative risk of cancer of the eye was increased although not significant. CONCLUSIONS: In our study, we found increased cancer risk for cancers related to sun exposure. In addition, increased risks were identified for Hodgkin's lymphoma, thyroid cancer, leukemia, prostate, and breast cancer in BCC patients.

Survival in patients with acute myeloblastic leukemia in Germany and the United States: Major differences in survival in young adults.

Previous epidemiologic studies on AML have been limited by the rarity of the disease. Here, we present population level data on survival of patients with AML in Germany and the United States (US). Data were extracted from 11 population-based cancer registries in Germany and the Surveillance, Epidemiology, and End Results (SEER13) database in the US. Patients diagnosed with AML in 1997-2011 were included. Period analysis was used to estimate 5-year relative survival (RS) and trends in survival in the early 21st century. Overall 5-year age-adjusted RS for patients with AML in 2007-2011 was greater in Germany than in the US at 22.8% and 18.8%, respectively. Five-year RS was higher in Germany than in the US at all ages, with particularly large differences at ages 15-24 for whom 5-year RS was 64.3% in Germany and 55.0% in the US and 35-44, with 5-year RS estimates of 61.8% in Germany and 46.6% in the US. Most of the difference in 5-year RS was due to higher 1-year RS, with overall 1-year RS estimates of 47.0% in Germany and 38.5% in the US. A small increase in RS was observed between 2003-2005 and 2009-2011 in both countries, but no increase in survival was observed in either country for ages 75+. To our knowledge, this is the first detailed description of AML survival in Germany. Comparison to the US suggests that further analysis into risk factors for poor outcomes in AML in the US may be useful in improving survival.

Lung cancer survival in Germany: A population-based analysis of 132,612 lung cancer patients.

OBJECTIVES: Lung cancer is the most common cancer-related death worldwide. In Germany it accounts for 25% of cancer deaths in men, and 14% in women. The aim of this study is to provide an overview of 5-year relative survival by sex, age, histology, and tumour stage in Germany representing a population of 26.7 million people. MATERIALS AND METHODS: The study is based on a pooled German dataset including data from 12 population-based cancer registries covering around one third of the German population. A total of 132,612 patients diagnosed with lung cancer from 2002 to 2010 were included in the analysis. Survival estimates for the time period 2007-2010 were calculated using period analysis. Differences in survival between sexes were tested for statistical significance by model-based period analysis (poisson regression model). The relative excess risk (RER) of death (women vs. men) was extracted from the model with the p value for the difference in RER. RESULTS: The overall age adjusted 5-year relative survival was 15.5% (standard error (SE) 0.2) for men and 20.3% (SE 0.3) in women. Survival differed markedly according to age (men: <60 years 18.5% vs. 80+ years 8.4% and women 23.7% vs. 10.6%, respectively), histology (largest difference between histological groups: men 25.7 and women 44.4% points) and stage (men: UICC Ia 62.9%, vs. UICC IV 4.6% and women 75.2% vs. 7.0%, respectively). Our study showed survival advantages for women compared to men, most notably in younger aged patients (RER 0.83, p<0.0001), patients with adenocarcinoma (RER 0.80, p<0.0001), and patients with lower stage cancer (RER 0.62, p<0.0001). CONCLUSIONS: This study presents up-to-date survival estimates for lung cancer in Germany. Compared to other European countries survival was relatively high. Women showed higher survival than men independent of age, histology and stage. The reasons for the survival differences require further clarification.

Detection of cancer through exhaled breath: a systematic review.

BACKGROUND: Timely diagnosis of cancer represents a challenging task; in particular, there is a need for reliable non-invasive screening tools that could achieve high levels of adherence at virtually no risk in population-based screening. In this review, we summarize the current evidence of exhaled breath analysis for cancer detection using standard analysis techniques and electronic nose. METHODS: Relevant studies were identified searching Pubmed and Web of Science databases until April 30, 2015. Information on breath test performance, such as sensitivity and specificity, was extracted together with volatile compounds that were used to discriminate cancer patients from controls. Performance of different breath analysis techniques is provided for various cancers together with information on methodological issues, such as breath sampling protocol and validation of the results. RESULTS: Overall, 73 studies were included, where two-thirds of the studies were conducted on lung cancer. Good discrimination usually required a combination of multiple biomarkers, and area under the receiver operating characteristic curve or accuracy reached levels of 0.9 or higher in multiple studies. In 25% of the reported studies, classification models were built and validated on the same datasets. Huge variability was seen in different aspects among the studies. CONCLUSIONS: Analyses of exhaled breath yielded promising results, although standardization of breath collection, sample storage and data handling remain critical issues. In order to foster breath analysis implementation into practice, larger studies should be implemented in true screening settings, paying particular attention to standardization in breath collection, consideration of covariates, and validation in independent population samples.

Cancer surveillance using registry data: Results and recommendations for the Lithuanian national prostate cancer early detection programme.

INTRODUCTION: We describe long term trends in prostate cancer epidemiology in Lithuania, where a national prostate specific antigen (PSA) test based early detection programme has been running since 2006. METHODS: We used population-based cancer registry data, supplemented by information on PSA testing, life expectancy and mortality from Lithuania to examine age-specific prostate cancer incidence, mortality and survival trends among men aged 40+ between 1978 and 2009, as well as life expectancy of screening-eligible men, and the proportion of men with a first PSA test per year since the programme started. RESULTS: The number of prostate cancer patients rose from 2.237 in 1990-1994 to 15.294 in 2005-2009. By 2010, around 70% of the eligible population was tested, on average around two times. The early detection programme brought about the highest prostate cancer incidence peaks ever seen in a country to date. Recent incidence and survival rises in the age groups 75-84 suggest PSA testing in the elderly non-eligible population. Life expectancy of men aged 70-74 indicates that less than 30% of patients will live for 15 years and may have a chance to benefit from early detection. CONCLUSIONS: Early detection among men aged 70-74, and particularly among the elderly (75+) may have to be reconsidered. Life expectancy assessment before testing, avoiding a second test among men with low PSA values and increasing the threshold for further evaluation and the screening interval may help reducing harm. Publishing information on treatment modalities, side-effects and patient reported quality of life is recommended.

Survival of patients with gastric lymphoma in Germany and in the United States.

BACKGROUND AND AIM: This study aims to examine survival for gastric lymphomas and its main subtypes, mucosa-associated lymphoid tissue lymphoma (MALT), and diffuse large B-cell lymphoma (DLBCL), in Germany and in the United States. METHODS: Data for patients diagnosed in 1997-2010 were used from 10 population-based German cancer registries and compared to the data from the US Surveillance, Epidemiology and End Results (SEER) 13 registries database. Patients age 15-74 diagnosed with gastric lymphomas were included in the analysis. Period analysis and modeled period analysis were used to estimate 5-year and 10-year relative survival (RS) in 2002-2010 and survival trends from 2002-2004 to 2008-2010. RESULTS: Overall, the database included 1534 and 2688 patients diagnosed with gastric lymphoma in 1997-2010 in Germany and in the United States, respectively. Survival was substantially higher for MALT (5-year and 10-year RS: 89.0% and 80.9% in Germany, 93.8% and 86.8% in the United States) than for DLBCL (67.5% and 59.2% in Germany, and 65.3% and 54.7% in the United States) in 2002-2010. Survival was slightly higher among female patients and decreased by age for gastric lymphomas combined and its main subtypes. A slight, nonsignificant, increase in the 5-year RS for gastric lymphomas combined was observed in Germany and the United States, with increases in 5-year RS between 2002-2004 and 2008-2010 from 77.1% to 81.0% and from 77.3% to 82.0%, respectively. Five-year RS of MALT exceeded 90% in 2008-2010 in both countries. CONCLUSIONS: Five-year RS of MALT meanwhile exceeds 90% in both Germany and the United States, but DLBCL has remained below 70% in both countries.