Histology-specific standardized incidence ratio improves the estimation of second primary lung cancer risk.

BACKGROUND: Lung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer is unexpectedly low in countries that follow international multiple primary (IARC/IACR MP) rules when compared to the USA, where distinct rules are employed. IARC/IACR rules rely on histology-dependent documentation of SPC with the same location as the first cancer and only classify an SPC when tumors present different histology. Thus, SIR might be underestimated in cancer registries using these rules. This study aims to assess whether using histology-specific reference rates for calculating SIR improves risk estimates for second primary lung cancer (SPLC) in LC survivors. METHODS: We (i) use the distribution of histologic subtypes of LC in population-based cancer registry data of 11 regional cancer registries from Germany to present evidence that the conventional SIR metric underestimates the actual risk for SPLC in LC survivors in registries that use IARC/IACR MP rules, (ii) present updated risk estimates for SPLC in Germany using a novel method to calculate histological subtype-specific SIRs, and (iii) validate this new method using US SEER (Surveillance, Epidemiology, and End Results Program) data, where different MP rules are applied. RESULTS: The adjusted relative risk for lung cancer survivors in Germany to develop an SPLC was 2.98 (95% CI 2.53-3.49) for females and 1.15 (95% CI 1.03-1.27) for males using the novel histology-specific SIR. When using IARC/IACR MP rules, the conventional SIR underestimates the actual risk for SPLC in LC survivors by approximately 30% for both sexes. CONCLUSIONS: Our proposed histology-specific method makes the SIR metric more robust against MP rules and, thus, more suitable for cross-country comparisons.

Longer Survival From Melanoma in Germany.

BACKGROUND: New treatment options for cutaneous melanomas with a poor prognosis have been available since 2011, including immune therapies and targeted drugs. Randomized controlled trials have demonstrated that these treatments improve survival, but no population- level studies have been available to date. METHODS: All patients in the database of the Center for Cancer Registry Data (Zentrum für Krebsregisterdaten) who had a diagnosis of melanoma (ICD10: C43) in the years 2000 to 2019 were included in the study. The relative five-year survival (5YRS) was calculated for four 5-year periods (2000-04, 2005-09, 2010-14, 2015-19). The data were standardized/stratified according to sex, age group, and UICC stage to correct for differences between regions and over time. Regression models were used to detect statistically significant secular trends. RESULTS: 301 486 individuals were included in the study. The overall 5YRS rose from 93% (2000-04) to 95% (2015-19). The 5YRS in 2015-19 was similar to or greater than that in 2000-04 for all subgroups. The largest rises in 5YRS were between 2010-14 and 2015-19, and specifically in advanced stages: for UICC stage IV tumors, the 5YRS rose from 31% to 36%. There was a significant rising trend across the four time periods (p < 0.001). CONCLUSION: The survival of melanoma patients has improved over the past 20 years. From 2010-14 to the most recent period, the largest changes were seen in advanced tumor stages. This favorable development coincided with the introduction of new therapies.

Widening area-based socioeconomic inequalities in cancer mortality in Germany between 2003 and 2019.

Cancer mortality has declined in recent decades, but-due to a lack of national individual-level data-it remains unclear whether this applies equally to all socioeconomic groups in Germany. Using an area-based approach, this study investigated socioeconomic inequalities in cancer mortality and their secular trends on a German nationwide scale for the first time. Official cause-of-death data from 2003 to 2019 were linked to the district-level German Index of Socioeconomic Deprivation. Age-standardised mortality rates for all cancers combined and the most common site-specific cancers were calculated according to the level of regional socioeconomic deprivation. To quantify the extent of area-based socioeconomic inequalities in cancer mortality, absolute (SII) and relative (RII) indices of inequality were estimated using multilevel Poisson models. On average, cancer mortality was 50% (women) and 80% (men) higher in Germany's most deprived than least deprived districts (absolute difference: 84 deaths per 100,000 in women and 185 deaths per 100,000 in men). As declines in cancer mortality were larger in less deprived districts, the socioeconomic gap in cancer mortality widened over time. This trend was observed for various common cancers. Exceptions were cancers of the lung in women and of the pancreas in both sexes, for which mortality rates increased over time, especially in highly deprived districts. Our study provides first evidence on increasing socioeconomic inequalities in cancer mortality on a nationwide scale for Germany. Area-based linkage allows to examine socioeconomic inequalities in cancer mortality across Germany and identify regions with high needs for cancer prevention and control.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

[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.

Population-Based Clinical Cancer Registration in Germany.

INTRODUCTION: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years later, the current status of the expanded cancer registration is presented, including current figures on cancer in Germany. METHODS: Reporting of cancer is mandatory for physicians, and about 5 to 10 reports from different healthcare providers are expected for each case. A uniform national dataset of about 130 items is used, and reports are usually sent electronically to the registry. We used the most recent data available from cancer registries up to the year of diagnosis in 2019. We calculated incidence rates and 5-year relative survival (5YRS) for common cancers. Data on clinical outcomes and benchmarking based on quality indicators (QIs) from guidelines were provided by the Cancer Registry Schleswig-Holstein (CR SH). RESULTS: All federal state cancer registries met most of the previously defined national eligibility criteria. Approximately 505,000 cancer cases were registered in 2019, with breast, prostate, colorectal and lung cancer being the most common cancers. The age-standardised cancer incidence has slightly decreased during the last decade. and spatial heterogeneity can be observed within Germany. 5YRS for all cancers was 67% and 63% for women and men, respectively. Therapy data for rectal cancer in 2019-2021 from the CR SH are shown as an example: 69% of the registered patients underwent surgery, mostly with curative intent (84%) and tumour-free resection (91%). Radiotherapy was given to 33% of the patients, and chemotherapy was given to 40%. Three selected QIs showed differences between involved healthcare providers. DISCUSSION: The implementation of population-based clinical cancer registration can be considered a success. Comprehensive recording of diagnosis, treatment and disease progression and the use of registry data for quality assurance, benchmarking and feedback have been implemented.

Impact of the COVID-19 pandemic on oncological care in Germany: rapid review.

OBJECTIVES: The COVID-19 pandemic affected medical care for chronic diseases. This study aimed to systematically assess the pandemic impact on oncological care in Germany using a rapid review. METHODS: MEDLINE, Embase, study and preprint registries and study bibliographies were searched for studies published between 2020 and 2 November 2022. Inclusion was based on the PCC framework: population (cancer), concept (oncological care) and context (COVID-19 pandemic in Germany). Studies were selected after title/abstract and full-text screening by two authors. Extracted data were synthesized using descriptive statistics or narratively. Risk of bias was assessed and summarized using descriptive statistics. RESULTS: Overall, 77 records (59 peer-reviewed studies and 18 reports) with administrative, cancer registry and survey data were included. Disruptions in oncological care were reported and varied according to pandemic-related factors (e.g., pandemic stage) and other (non-pandemic) factors (e.g., care details). During higher restriction periods fewer consultations and non-urgent surgeries, and delayed diagnosis and screening were consistently reported. Heterogeneous results were reported for treatment types other than surgery (e.g., psychosocial care) and aftercare, while ongoing care remained mostly unchanged. The risk of bias was on average moderate. CONCLUSIONS: Disruptions in oncological care were reported during the COVID-19 pandemic in Germany. Such disruptions probably depended on factors that were insufficiently controlled for in statistical analyses and evidence quality was on average only moderate. Research focus on patient outcomes (e.g., longer term consequences of disruptions) and pandemic management by healthcare systems is potentially relevant for future pandemics or health emergencies.

[Cancer registries in Germany: what does the future hold for urology?] / Krebsregister in Deutschland: Was bringt die Zukunft für die Urologie?

Cancer registries are defined as systematically collected information in the form of a database on tumour diseases. They can provide information about the quality of oncological care or progress in the treatment of individual cancers over time. Since 1995, all German federal states have been required by law to establish and maintain a cancer registry. The Center for Cancer Registry Data (ZfKD) at Robert Koch Institute has collected this nationwide data since 2009 and compiled it into an annually audited dataset available for research purposes. By virtue of the Cancer Early Detection and Registry Act (KFRG), which was passed in 2013, the cancer registries were given a new perspective. Since then, they have made a central contribution to the quality assurance of oncological care. The cancer registries are mainly financed by the health insurance funds. An upcoming expansion of the dataset including clinical variables and earlier provision by the ZfKD starting next year offers new opportunities for the scientific use of cancer registry data. In particular, the course of the disease will now be mapped in considerable detail. Apart from the cancer registries, there are not many useful supplemental datasets in Germany for the assessment of the nationwide healthcare situation and treatment reality on a national level. The DRG database (case-based hospital statistics) of the Federal Statistics Office records all billing data of all German hospitals with few exceptions. Another interesting supplement to the cancer registry data are the datasets of the structured quality reports, which have been mandatory for hospitals since 2003. In the future, the scientific role of cancer registries is to be further enhanced by the Act on the Pooling of Cancer Registry Data, which was passed in 2021.

Detection of missed deaths in cancer registry data to reduce bias in long-term survival estimation.

Background: Population-based cancer survival estimates can provide insight into the real-world impacts of healthcare interventions and preventive services. However, estimation of survival rates obtained from population-based cancer registries can be biased due to missed incidence or incomplete vital status data. Long-term survival estimates in particular are prone to overestimation, since the proportion of deaths that are missed, for example through unregistered emigration, increases with follow-up time. This also applies to registry-based long-term prevalence estimates. The aim of this report is to introduce a method to detect missed deaths within cancer registry data such that long-term survival of cancer patients does not exceed survival in the general population. Methods: We analyzed data from 15 German epidemiologic cancer registries covering the years 1970-2016 and from Surveillance, Epidemiology, and End Results (SEER)-18 registries covering 1975-2015. The method is based on comparing survival times until exit (death or follow-up end) and ages at exit between deceased patients and surviving patients, stratified by diagnosis group, sex, age group and stage. Deceased patients with both follow-up time and age at exit in the highest percentile were regarded as outliers and used to fit a logistic regression. The regression was then used to classify each surviving patient as a survivor or a missed death. The procedure was repeated for lower percentile thresholds regarding deceased persons until long-term survival rates no longer exceeded the survival rates in the general population. Results: For the German cancer registry data, 0.9% of total deaths were classified as having been missed. Excluding these missed deaths reduced 20-year relative survival estimates for all cancers combined from 140% to 51%. For the whites in SEER data, classified missed deaths amounted to 0.02% of total deaths, resulting in 0.4 percent points lower 20-year relative survival rate for all cancers combined. Conclusion: The method described here classified a relatively small proportion of missed deaths yet reduced long-term survival estimates to more plausible levels. The effects of missed deaths should be considered when calculating long-term survival or prevalence estimates.

Upper tract urothelial carcinoma in Germany: epidemiological data and surgical treatment trends in a total population analysis from 2006 to 2019.

PURPOSE: To report contemporary epidemiological data and treatment trends for upper tract urothelial carcinoma (UTUC) in Germany over a 14-year period. METHODS: We analyzed data from the nationwide German hospital billing database and the German cancer registry from 2006 to 2018/2019. The significance of changes over time was evaluated via regression analysis. Survival outcomes were calculated using the Kaplan-Meier method. RESULTS: There was a non-significant increase in the age-standardized incidence rate from 2.5/100,000 in 2006 to 2.9/100.000 in 2018. 13% of patients presented with lymph node metastasis and 7.6% of patients presented with distant metastasis at primary diagnosis. The 5-year overall survival was estimated at 45% and the 10-year overall survival at 32%. Endoscopic biopsies of the renal pelvis and ureter as well as ureteroscopies with excision/destruction of UTUC all increased significantly over the study period. The number of radical nephroureterectomies (RNU) for UTUC steadily increased from 1643 cases in 2006 to 2238 cases in 2019 (p < 0.005) with a shift from open surgery towards minimally invasive surgery. Complex reconstructive procedures like ileal ureter replacement or autotransplantation are rarely performed for urothelial carcinoma of the ureter. CONCLUSION: Diagnostic and therapeutic procedures for UTUC have increased and minimally invasive nephroureterectomy is the predominant approach concerning radical surgery in 2019.

Analyses of Basal and Squamous Cell Carcinoma Reported as an Adverse Drug Reaction and Comparison with Cases from the Cancer Registry from Germany.

INTRODUCTION: In Germany, incidence rates of basal cell (BCC) and squamous cell carcinoma (SCC) rose significantly from 1998 to 2010. Ultraviolet (UV) light exposure, immunosuppressants and drugs with photosensitising potential are known to increase the risk to develop BCC and SCC. The aim of our study was to analyse the adverse drug reaction (ADR) reports from Germany referring to BCC and SCC and to compare them to BCC and SCC occurring in the general population. METHODS: We analysed all validated spontaneous ADR reports referring to BCC (n = 191) and SCC (n = 75) from Germany contained in the European ADR database EudraVigilance prior to 6 March 2019. These reports were compared to 1,267,210 BCC and 476,903 SCC cases from the German Centre for Cancer Registry Data recorded from 2006 to 2018. RESULTS: The number of BCC and SCC reports as well as the BCC and SCC incidences in the registry increased in the analysed time period. Patients with drug-associated BCC (60 years) and SCC (64 years) were younger than patients with BCC (72 years) and SCC (76 years) in the registry. In 57.1 and 60.0% of BCC and SCC reports immunosuppressants were reported as suspected. The reported suspected drug was assumed to possess a photosensitising potential in 41.9 and 44.0% of BCC and SCC reports. CONCLUSIONS: In Germany, drug-associated BCC and SCC occurred at a younger age than in the general population. The results underline the necessity for skin cancer screening of patients treated with immunosuppressants or with drugs with photosensitising potential.

Descriptive analysis of 179 German reports of melanoma reported to an adverse drug reaction database as a drug-related adverse effect, and comparison with melanoma cases contained in German cancer registries.

BACKGROUND: Malignant melanoma (MM) is one of the most aggressive forms of skin cancer. The occurrence of MM associated with drug therapy has been described in the literature. However, there is no analysis of a substantial number of validated reports of drug-associated MM. AIM: To analyse a substantial number of validated spontaneous reports of drug-associated MM with regard to the suspected drug and the reported characteristics, and to compare these analyses with those of MM cases occurring in the general population in Germany. METHODS: Spontaneous reports of MM associated with drug therapy in Germany were identified in a large adverse drug reaction database (EudraVigilance). These results were then compared with analyses of MMs in the pooled data from a population-based German cancer registry. RESULTS: The 10 most frequently suspected drugs in the MM reports all target the immune system, with 7 of these being immunosuppressants. The median time to onset to MM diagnosis was 2.0 years. Patients with drug-associated MM were 11 years (median) younger than patients with MM in the cancer registry, and this age difference was greater for female than for male patients. CONCLUSIONS: Our results emphasize the importance of regular dermatological examinations of patients being treated with immunosuppressants. Physicians should be aware that in these patients, MM might be detected at younger ages and even within 2 years after initiating therapy.

Prevalence of mental disorders in patients with cancer compared to matched controls - secondary analysis of two nationally representative surveys.

AIM: To compare prevalence rates of mental disorders in patients with cancer and general population controls. METHOD: In two stratified nationally representative surveys, the 12-month prevalence of mental disorders was assessed in 2141 patients with cancer and 4883 general population controls by the standardized Composite International Diagnostic Interview (CIDI). We determined odds ratios (ORs) to compare the odds for mental disorders (combined and subtypes) in cancer patients with age- and gender-matched controls. RESULTS: The 12-month prevalences rate for any mental disorder was significantly higher in patients with cancer compared to controls (OR 1.28, 95% CI 1.14-1.45). Prevalence rates were at least two times higher for unipolar mood disorders (major depression: OR 2.07, 95% CI 1.71-2.51; dysthymia: OR 2.93, 95% CI 2.13-4.02) and mental disorders due to a general medical condition (OR 3.31, 95% CI 2.32-4.71). There was no significant elevation for anxiety disorders overall (OR 0.95, 95% CI 0.81-1.11). Mildly elevated prevalence rates emerged for post-traumatic stress disorder (OR 1.57, 95% CI 1.11-2.23) and social phobia (OR 1.57, 95% CI 1.07-2.31), while specific phobia (OR 0.82, 95% CI 0.67-1.00) and agoraphobia (OR 0.49, 95% CI 0.33-0.73) were significantly less frequent in cancer. CONCLUSIONS: While elevated depression rates reinforce the need for its systematic diagnosis and treatment, lower prevalences were unexpected given previous evidence. Whether realistic illness-related fears and worries contribute to lower occurrence of anxiety disorders with excessive fears in cancer may be of interest to future research.

Incidence of Smoking-Related Second Primary Cancers After Lung Cancer in Germany: An Analysis of Nationwide Cancer Registry Data.

INTRODUCTION: Approximately 80% of lung cancer cases in Germany are attributable to smoking. Patients with a lung cancer diagnosis may remain at increased risk of developing smoking-related second primary cancers (SPCs). METHODS: Anonymous data from 11 population-based cancer registries covering approximately 50% of the German population were pooled for the analysis. Included patients were diagnosed with having an index lung cancer between 2002 and 2013, aged 30 to 99 years old at diagnosis, and survived for at least 6 months. We calculated standardized incidence ratios (SIRs)-stratified by age, sex, region, and period-comparing the incidence of smoking-related and other SPCs to the general population. RESULTS: Of the 135,589 lung cancer survivors (68.2% male; mean follow-up 30.8 mo) analyzed, 5298 developed an SPC. In males, the risk was particularly high for SPCs of the larynx (SIR = 3.70, 95% confidence interval [CI]: 3.14-4.34), pharynx (3.17, 2.61-3.81), and oral cavity (2.86, 2.38-3.41). For females, SIRs were notably elevated for the esophagus (4.66, 3.15-6.66), oral cavity (3.14, 2.03-4.63), and urinary tract (2.68, 2.04-3.45). When combining all smoking-related cancer sites, SIR was 1.41 in males (95% CI: 1.36-1.47) and 1.81 in females (95% CI: 1.68-1.94). We observed that males had a 1.46-fold (95% CI: 1.37-1.56) and females a 1.33-fold (95% CI: 1.20-1.47) increased risk for smoking-related compared with other cancers. CONCLUSIONS: Patients with primary lung cancer were at increased risk for developing a smoking-related SPC. Therefore, the advantages of increased patient surveillance and the benefits of smoking cessation strategies should be considered.