[Prevention, Diagnosis, Therapy, and Follow-up of Lung Cancer - Interdisciplinary Guideline of the German Respiratory Society and the German Cancer Society - Abridged Version]. / Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms.

The current S3 Lung Cancer Guidelines are edited with fundamental changes to the previous edition based on the dynamic influx of information to this field:The recommendations include de novo a mandatory case presentation for all patients with lung cancer in a multidisciplinary tumor board before initiation of treatment, furthermore CT-Screening for asymptomatic patients at risk (after federal approval), recommendations for incidental lung nodule management , molecular testing of all NSCLC independent of subtypes, EGFR-mutations in resectable early stage lung cancer in relapsed or recurrent disease, adjuvant TKI-therapy in the presence of common EGFR-mutations, adjuvant consolidation treatment with checkpoint inhibitors in resected lung cancer with PD-L1 ≥ 50%, obligatory evaluation of PD-L1-status, consolidation treatment with checkpoint inhibition after radiochemotherapy in patients with PD-L1-pos. tumor, adjuvant consolidation treatment with checkpoint inhibition in patients withPD-L1 ≥ 50% stage IIIA and treatment options in PD-L1 ≥ 50% tumors independent of PD-L1status and targeted therapy and treatment option immune chemotherapy in first line SCLC patients.Based on the current dynamic status of information in this field and the turnaround time required to implement new options, a transformation to a "living guideline" was proposed.

The Rising Incidence of Early-Onset Colorectal Cancer.

BACKGROUND: The incidence of early-onset (diagnosis before age 50) colorectal cancer (EOCRC) is increasing in some high-income countries. In this study, we examined the trends in EO-CRC incidence in Germany. METHODS: We obtained data on CRC (ICD-10 C18-C20) incidence from the Centre for Cancer Registry Data (excluding cases reported via death certificate only) and on mortality from the official cause of death statistics for 1999-2018 from registries with sufficient incidence coverage. To assess time trends for persons aged 20-49 we calculated the average annual percent changes (AAPC) and corresponding 95% confidence intervals (95% CI). The incidence analyses were stratified by sex, site (proximal colon, distal colon, rectum), age group (20-29, 30-39, and 40-49) and tumor size (T). RESULTS: EO-CRC accounted for 5.1% (9529 cases) of all colorectal cancers in the selected German regions. The EO-CRC incidence rose annually by 1.16% (95% CI: [0.51; 1.81]) in men and 1.32% [0.80; 1.84] in women. The incidence of proximal colon cancer increased in both sexes (men: AAPC = 3.26 [2.00; 4.53]; women: AAPC = 2.99 [2.17; 3.83]), while the incidence of distal colon cancer remained unchanged. CONCLUSION: The incidence of EO-CRC in Germany is rising. The reasons are probably multifactorial, reflecting the changing prevalence of early life exposure to risk and protective factors.

[Seroprevalence of SARS-CoV-2 among children and adolescents in Germany-an overview]. / SARS-CoV-2-Seroprävalenz bei Kindern und Jugendlichen in Deutschland ­ ein Überblick.

BACKGROUND: SARS-CoV­2 serologic studies complement and expand findings from confirmed COVID-19 cases through identification of undetected cases. OBJECTIVES: This article summarizes previous results on SARS-CoV­2 prevalence from seroepidemiological studies in Germany focusing on children and adolescents and complements the already existing overview on seroprevalence in adults from general population samples and especially blood donors in Germany. METHODS: The results are based on an ongoing systematic search in study registries, in literature databases, of preprint publications, and of media reports of seroepidemiological studies in Germany and their results. RESULTS: As of 17 September 2021, we are aware of 16 German seroepidemiological studies focusing on children and adolescents. Results are available for nine of these studies. For almost all settings studied, SARS-CoV­2 seroprevalence was well below 1% for preschool and elementary school children in the first COVID-19 wave and below 2% for adolescents. As the pandemic progressed, higher seroprevalences of up to 8% were found in elementary school children. DISCUSSION: Results of SARS-CoV­2 antibody studies in children and adolescents in Germany are scarce so far and are based on non-representative samples at local or regional level. In future studies, it is necessary on the one hand to estimate which proportion of children and adolescents has already either had an infection or has been vaccinated. On the other hand, it is important to investigate physical and mental health impairments that occur after an infection.

Development of Incidence and Surgical Treatment of Penile Cancer in Germany from 2006 to 2016: Potential Implications for Future Management.

BACKGROUND: Penile cancer is a rare disease and surgical treatment often entails a significant impact on quality of life. The aim of this study was to analyze trends in surgical treatment patterns in Germany. METHODS: We analyzed data from the nationwide German hospital billing database and the German cancer registry from 2006 to 2016. All penile cancer cases with penile surgery or lymph node dissection (LND) were included. We also analyzed the distribution of cases, extent of surgery, and length of hospital stay, stratified for annual caseload. The geographical distribution of centers for 2016 was presented. RESULTS: During the investigated timespan, tumor incidences increased from 748 to 971 (p = 0.001). We identified 11,353 penile surgery cases, increasing from 886 to 1196 (p < 0.001), and 5173 cases of LND, increasing from 332 to 590 (p < 0.001). Cases of partial amputation increased from 45.8 to 53.8% (p < 0.001), while total amputation remained stable at 11.2%. Caseload in high-volume hospitals increased from 9.0 to 18.8% for penile surgery (p < 0.001) and from 0 to 13.1% for LND (p < 0.001). The increase in LND caseload was caused by an increase in inguinal LND, from 297 to 505 (p < 0.001), with increasing sentinel LND, from 14.2 to 21.9% (p = 0.098). The assessment of geographical distribution of cases in Germany revealed extensive areas without sufficient coverage by experienced centers. CONCLUSIONS: We saw consistent increases in penile surgery and LND, with a growing number of cases in high-volume hospitals, and, accordingly, an increase in tumor incidence. The increasing use of inguinal LND and organ-preserving surgery reflect the adaptation of current guidelines; however, geographical distribution of experienced centers could be improved.

Secondary malignancies in long-term ovarian cancer survivors: results of the 'Carolin meets HANNA' study.

OBJECTIVE: To evaluate the rate of secondary malignancies in long-term survivors with ovarian cancer. METHODS: Long-term survivors with ovarian cancer (survival ≥8 years after initial diagnosis) with multiple malignancies were identified within the Tumorbank Ovarian Cancer and our study 'Carolin meets HANNA - Holistic Analyses of Long-term Survivors with Ovarian Cancer'. RESULTS: Of a total of 225 long-term survivors with ovarian cancer, 36 patients (16%) had at least one more cancer diagnosis before, concomitant with, or after, ovarian cancer. Median age was 52.5 years (range 37-79). A total of 60% were diagnosed with stage III/IV and most tumors were high-grade (88.6%), as well as of serous histology (63.9%). Median overall survival was 10 years (range 8-19). Secondary cancer after ovarian cancer was found in 17 long-term survivors (7.6%). Breast cancer was the most frequent secondary malignancy. Median duration between diagnosis of primary ovarian cancer and secondary cancer diagnosis was 78.5 months (range 12-220). BRCA was tested in 11 patients with seven patients being BRCA1 and one patient BRCA2 positive. Secondary cancers were detected by screening in 35.3% and self-detected in 29.4% of patients (breast self-examination). CONCLUSION: A secondary malignancy was diagnosed in 7.6% of long-term survivors. Routine follow-up and cancer screening should be performed in long-term ovarian cancer survivors.

Seroepidemiological study on the spread of SARS-CoV-2 in Germany: Study protocol of the CORONA-MONITORING bundesweit' study (RKI-SOEP study).

The SARS-CoV-2 coronavirus has spread rapidly across Germany. Infections are likely to be under-recorded in the notification data from local health authorities on laboratory-confirmed cases since SARS-CoV-2 infections can proceed with few symptoms and then often remain undetected. Seroepidemiological studies allow the estimation of the proportion in the population that has been infected with SARS-CoV-2 (seroprevalence) as well as the extent of undetected infections. The 'CORONA-MONITORING bundesweit' study (RKI-SOEP study) collects biospecimens and interview data in a nationwide population sample drawn from the German Socio-Economic Panel (SOEP). Participants are sent materials to self-collect a dry blood sample of capillary blood from their finger and a swab sample from their mouth and nose, as well as a questionnaire. The samples returned are tested for SARS-CoV-2 IgG antibodies and SARS-CoV-2 RNA to identify past or present infections. The methods applied enable the identification of SARS-CoV-2 infections, including those that previously went undetected. In addition, by linking the data collected with available SOEP data, the study has the potential to investigate social and health-related differences in infection status. Thus, the study contributes to an improved understanding of the extent of the epidemic in Germany, as well as identification of target groups for infection protection.

German and international studies on SARS-CoV-2 seroprevalence.

Since the beginning of the year 2020, the SARS-CoV-2 coronavirus has spread globally at a tremendous pace. Studies on the prevalence of SARS-CoV-2 antibodies in the population help estimate the number of people that have already been infected. They also allow an estimate of the number of undetected infections i.e. infections that do not appear in data on officially reported cases. The interpretation of study results needs to consider bias from selective sampling and the diagnostic test properties. To promote networking and co-operation between scientists, the Robert Koch Institute has compiled an overview of the seroepidemiological studies conducted in Germany on its website, which is regularly updated. The RKI conducts searches, for example of press releases, study registry entries or preprint server publications, and contacts the lead investigators of these studies. Of the 40 studies contacted so far, 24 have already provided information (as of 25.06.2020). We can differentiate between studies of the general population, of selected population groups such as healthcare workers, or of ongoing cohorts. This article provides an overview of such studies from Germany, but also of selected international studies. A special focus is set on studies of children and adolescents, which are now of particular interest due to the planned reopening of childcare facilities and schools.

Guidelines and recommendations for ensuring Good Epidemiological Practice (GEP): a guideline developed by the German Society for Epidemiology.

OBJECTIVE: To revise the German guidelines and recommendations for ensuring Good Epidemiological Practice (GEP) that were developed in 1999 by the German Society for Epidemiology (DGEpi), evaluated and revised in 2004, supplemented in 2008, and updated in 2014. METHODS: The executive board of the DGEpi tasked the third revision of the GEP. The revision was arrived as a result of a consensus-building process by a working group of the DGEpi in collaboration with other working groups of the DGEpi and with the German Association for Medical Informatics, Biometry and Epidemiology, the German Society of Social Medicine and Prevention (DGSMP), the German Region of the International Biometric Society (IBS-DR), the German Technology, Methods and Infrastructure for Networked Medical Research (TMF), and the German Network for Health Services Research (DNVF). The GEP also refers to related German Good Practice documents (e.g. Health Reporting, Cartographical Practice in the Healthcare System, Secondary Data Analysis). RESULTS: The working group modified the 11 guidelines (after revision: 1 ethics, 2 research question, 3 study protocol and manual of operations, 4 data protection, 5 sample banks, 6 quality assurance, 7 data storage and documentation, 8 analysis of epidemiological data, 9 contractual framework, 10 interpretation and scientific publication, 11 communication and public health) and modified and supplemented the related recommendations. All participating scientific professional associations adopted the revised GEP. CONCLUSIONS: The revised GEP are addressed to everyone involved in the planning, preparation, execution, analysis, and evaluation of epidemiological research, as well as research institutes and funding bodies.

[Cancer screening in Germany: availability and participation]. / Krebsfrüherkennungsuntersuchungen in Deutschland: Angebot und Inanspruchnahme.

In Germany, approximately 227,000 women and 249,000 men developed cancer in 2014, and nearly 223,000 patients died from the disease that year. Many cancers are curable or have a very good prognosis when they are diagnosed at an early stage. This is where the concept of early detection examinations comes into play.This article describes the current conditions of and participation in examinations for the early detection of cervical, breast, skin, prostate, and colon cancer as provided by Germany's statutory health services. Participation was derived from claims data from the statutory health insurance system as well as from Germany's mammography screening program (MSP). The survey "German Health Update" (GEDA 2014/2015-EHIS) served as an additional data source. According to the claims data and considering the intended intervals, participation quotas among insured persons who are entitled to participate lie between 16% (colonoscopy) and 48% (Pap test). In 2015, 51.5% of invited women participated in the MSP. The results according to self-reports of the GEDA survey lie in part substantially higher. The results according to the claims data, the MSP, as well as the self-reports suggest that a large part of the population utilizes the examinations. Colon and cervical cancer examinations will be expanded as organized and quality-assured early detection programs with regular invitations and information on benefits and risks. These efforts should contribute to reaching eligible people who have thus far not participated.

Corrigendum: Human papillomavirus (HPV) vaccination of girls in Germany. Results of the cross-sectional KiGGS Wave 2 study and trends.

[This corrects the article DOI: 10.17886/RKI-GBE-2018-102.2.].

Human papillomavirus (HPV) vaccination of girls in Germany. Results of the cross-sectional KiGGS Wave 2 study and trends.

Since 2007, the Standing Committee on Vaccination (STIKO) has recommended that all girls receive vaccinations against the human papillomavirus (HPV) in order to reduce the disease burden of cervical cancer. Persistent infections with high-risk HPV subtypes increase a woman's risk of developing cancer. In the second wave of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014-2017), 42% of 2,958 11- to 17-year-old girls reported that they had received at least one HPV vaccination, and 31.4% reported a full HPV vaccination. 45.3% of 14- to 17-year-old girls reported a complete series of HPV vaccinations. Compared to the figures reported in KiGGS Wave 1 five years ago, HPV vaccination coverage has therefore remained stable. A vaccination coverage below 50% in girls is too low to exploit the potential of HPV vaccination to reduce cervical cancer rates in Germany.

Incidence Patterns and Survival of Gynecological Sarcoma in Germany: Analysis of Population-Based Cancer Registry Data on 1066 Women.

OBJECTIVE: Sarcomas of the female genital tract are rare tumors. They are described to be associated with a poor prognosis when compared with gynecogical carcinoma. The aim of this study was to report incidence patterns and survival rates for gynecological sarcoma (GS) in Germany. METHODS/MATERIALS: Clinical data and survival rates for patients with GS diagnosed in Germany between 2009 and 2013 were extracted from the German national center for population-based cancer registry data. Incidence patterns and 5-year relative survival rates were calculated. RESULTS: A total of 1066 GSs were included in our analysis during a 5-year time span. The uterus was the most common site, with 87.9% of all cases. The annual age-standardized incidence rate (old European standard) was 8.7 per 1 million women for all GSs. The median age at diagnosis was 59 years. The prognosis ranged according to site, stage, and subtype, for example, from a 5-year relative survival of 53.0% (uterine leiomyosarcoma) if confined to the pelvis, to a very good 5-year relative survival of 97.2% (endometrial stromal sarcoma). CONCLUSIONS: Despite the rareness of GS, the size of the data set allows for a differentiation of subtypes according to morphology and site of origin. Clinically relevant differences in incidence and prognosis between subgroups were observed.

Cancer incidence in Germany attributable to human papillomavirus in 2013.

BACKGROUND: It is estimated that a total of 120,000 new cancer cases in men and in women in more developed countries could be avoided if exposure to HPV was prevented. We used the nationwide pool of German population-based cancer registry data to estimate the burden of HPV-attributable cancer in this population for the year 2013. METHODS: Incident cases of cervical cancer, squamous cell carcinoma of the anus, oropharynx (OP), as well as of the vulva, vagina and penis were classified as potentially HPV-associated and identified from the nationwide cancer registry data-pool. We calculated the incidence and proportions of cancer with potentially HPV-associated morphologies. Estimation of the HPV-attributable incidence was based on prevalence-estimates of viral DNA in tumor cells in the respective sites, as provided from the international literature. RESULTS: From the overall 15,936 incident cases of anogenital and OP cancers in 2013, 6239 female and 1358 male cancer cases were estimated to be attributable to HPV. The majority of HPV-attributable cases were contributed by cervical cancer (70.9% of female cancers) and oropharyngeal cancer (46.9% of male cancers). CONCLUSIONS: Even if most HPV-attributable cases were contributed by cervical cancer, anogenital cancer at sites other than the cervix, and oropharyngeal cancer substantially contribute to the burden of HPV-associated cancer. Our nationwide cancer registry data-analyses provide the baseline for long-term population-based monitoring of vaccination-effects on cancer incidence in Germany.

The utilization of colonoscopy in Germany.

Colorectal cancer is one of the three most common cancers in German adults. There are several legally based examinations for the early detection of colorectal cancer. People aged 50 to 54 years can have a faecal blood test annually. From the age of 55, this test is offered every two years as part of cancer screening, or alternatively a preventive colonoscopy, which can be repeated after ten years if the findings are inconspicuous. However, colonoscopies are also carried out to clarify complaints or other diseases (curative colonoscopy). In the GEDA 2014/2015-EHIS study, the respondents provided the date of their last colonoscopy. No data was collected on the reason why this colonoscopy was performed. 57% of women and 61% of men aged 55 years or older reported that they had a colonoscopy within the last 10 years. New legal regulations envisage the expansion of colorectal cancer screening and its development into an organised, quality-assured early detection programme.

Incidence patterns and temporal trends of invasive nonmelanotic vulvar tumors in Germany 1999-2011. A population-based cancer registry analysis.

OBJECTIVES: Time trends on the incidence and characteristics of invasive vulvar cancer in Germany have so far been studied in few local population- and hospital based tumor registries. We aimed to provide an overview on recent developments of vulvar cancer in Germany, using population-based cancer registry data. METHODS: We analyzed the data on vulvar cancer of eight population-based German cancer registries for the period 1999-2011. ICD-10 codes and ICD-O-3 morphology codes were used to select site and histologic types. The annual percentage change was calculated on age-adjusted incidence rates with a joinpoint regression model. RESULTS: A total of 12,711 registered cases of invasive carcinoma of the vulva were included in the analyses, hereof were 12,205 of squamous cell origin. Age-standardized incidence rates of vulvar cancer annually increased by 6.7% (95% confidence limits: 5.6-7.9) from 1.7 per 100,000 women in 1999 to 3.6 per 100,000 women in 2011. An increase was observed among women of all ages, and especially between 30 and 69 years of age. CONCLUSION: The annual incidence of invasive carcinoma of the vulva nearly doubled in the past decade in Germany, considerably exceeding the rates observed in other Western European countries. A combination of changes in risk factors, and documentation practice might have contributed to the observed substantial increase in vulvar cancer incidence.

Utility and Reproducibility of the International Federation for Cervical Pathology and Colposcopy Classification of Transformation Zones in Daily Practice: A Multicenter Study of the German Colposcopy Network.

OBJECTIVE: To compare the distribution of International Federation for Cervical Pathology and Colposcopy (IFCPC) transformation zone (TZ) types among women in different age groups referred to 8 colposcopy clinics. MATERIALS AND METHODS: Between February 2012 and February 2013, we prospectively collected individual patient data from 8 clinics within the German Colposcopy Network (G-CONE). Data were analyzed using ODSdysplasie, software designed to allow continuous quality assessment in colposcopy clinics. The distribution of IFCPC-classified TZ was compared between different centers for the following age groups: younger than 30 years, between 30 and 50 years, and older than 50 years. RESULTS: Of 3,761 patients included in the analysis, 2,153 (57%) were classified as having type 2 TZ, 906 (24%) as type 1 TZ, and 702 (19%) as type 3 TZ. Type 3 TZ was the most commonly reported type in women older than 50 years (70%). We found that the relative distribution of type 3 TZ between age groups was similar in the participating colposcopy clinics. However, there was evidence of heterogeneous distribution of types 1 and 2 TZ between age groups in different clinics, ranging from 7.8% to 66.4% for type 1 TZ in women younger than 30 years and 28.9% to 78.1% for type 2 TZ in women 30 to 50 years old. CONCLUSIONS: Although IFCPC type 3 TZ seems to be a reproducible finding, the distribution of types 1 and 2 TZ showed significant heterogeneity. A more precise anatomic distinction between types 1 and 2 TZ in the IFCPC terminology could improve reporting of colposcopy findings.

Early detection of CIN3 and cervical cancer during long-term follow-up using HPV/Pap smear co-testing and risk-adapted follow-up in a locally organised screening programme.

We evaluated compliance with human papillomavirus (HPV) testing and risk-adapted patient pathways and monitored changes in high-grade cervical disease during long-term follow-up. Women aged >30 years attending routine screening for cervical cancer were managed according to results from first-round screening tests (cytology and high-risk HPV; Hybrid Capture 2). Between February 2006 and January 2011, 19,795 of 19,947 women agreed to participate, of whom 4,067 proceeded to a second screening round 5 years after recruitment. Predefined endpoints were compliance, grade 3 cervical intraepithelial neoplasia or cancer (CIN3+), new HPV infection, HPV persistence and abnormal smears in round 2. A total of 765 of 19,795 women (3.9%) in round 1 and 41 of 4,067 (1.0%) in round 2 were referred for colposcopy. Compliance rates with colposcopy were 93.1 and 92.7%, respectively, while histological assessment was performed in 680 of 712 (95.5%) and 36 of 38 (94.7%), respectively. CIN3+ rates were 172 of 19,795 (0.87%; 95% confidence intervals: 0.7-1.0) in round 1 and 2 of 4,064 (0.05%; 95% confidence intervals: 0.006-0.2) in round 2; the difference was statistically significant (Fisher's exact test, p<0.001). After 5 years, the incidence of new HPV infection was 124 of 3,906 (3.2%) and HPV persistence was observed in 22 of 161 (13.7%). Locally organised HPV/cytology co-testing is feasible and acceptable to women. Risk-adapted management rapidly detected a high rate of prevalent CIN3+, while the subsequent long-term risk of new high-grade cervical disease was surprisingly low. It remains unclear if this phenomenon is explained by CIN3 mostly occurring early in life or by modifying the natural course of HPV infection with colposcopy and histological assessment.