A metric for comparison and visualization of age disparities in cancer survival.

AIMS: Diagnostic age is an important determinant of cancer survival but the methods generally used to analyze age-group-specific survival are not developed for ready visualization of survival differences. We aim at developing a novel metric for comparing and visualizing age-group-specific survival data over different cancers, sexes, periods and countries. METHODS: The metric describes the mean absolute deviation between age-groups. The metric can be used in two variations, one showing the mean variation and its 95% confidence intervals and the other highlighting individually each age-groups distinguishing positive or negative deviations. We demonstrate the applications with age-group- specific 5-year relative survival data from the NORDCAN database RESULTS: The mean absolute deviation between age-groups for Swedish colon cancer survival declined from about 5% in 1972-1981-1% in 1992-2001 and to 1.3% in 2012-2021. Patients diagnosed before age 50 years accounted for the largest positive deviation. For acute myeloid leukemia (AML) the mean deviation increased from 4% (female) to 17% and 23%. Patients diagnosed at age below 50 years showed the largest deviations. Comparing colon cancer mean deviations between the Nordic countries, a time-related decline was observed for all, those in Sweden ending at the lowest and in Finland the highest level. CONCLUSIONS: We demonstrated the usefulness of the devised metric for summarizing age-specific survival data between cancers, sexes, periods and countries. The two variations of the metric allow a simple visual presentation of the survival experience as to deviation of the survival data, its 95%CIs and its highlighted individual age-group components.

Critical survival periods in prostate cancer in Sweden explored by conditional survival analysis.

BACKROUND: We wanted to characterize conditional survival in prostate cancer (PC) in Sweden around and after 2005 when the vast increase in incidence due to the opportunistic testing for prostate specific antigen (PSA) culminated. We hypothesize that analyzing survival data during that time period may help interpret survival trends. We focus on stage-specific analysis using conditional survival in order to define the periods when deaths most commonly occurred. METHODS: Data on PC patients were obtained from the Swedish cancer registry for analysis of 1-, 2.5- and 5-year relative survival and conditional relative survival between years 2004 and 2018. Tumor-node-metastatic stage classification at diagnosis was used to specify survival. RESULTS: Small improvements were observed in stage- and age-related relative survival duriring the study period. Applying conditional relative survival showed that survival in stage T3 up to 2.5 years was better than survival between years 2.5 and 5. Survival in stage T4 was approximately equal in the first and the subsequent 2.5-year period. For M1, the first 2.5 year survival period was worse than the subsequent one. The proportion of high risk and M1 disease in old patients (80+ years) remained very high and their survival improved only modestly. CONCLUSIONS: The data indicate that M1 metastases kill more patients in the first 2.5 years than between years 2.5 and 5 after diagnosis; T4 deaths are equal in the two periods, and in T3 mortality in the first 2.5-year period is lower than between years 2.5 and 5 after diagnosis. Conditional survival could be applied to explore critical survival periods even past 5 years after diagnoses and to monitor success in novel diagnostic and treatment practices. Improvement of survival in elderly patients may require clinical input.

Major improvement in thyroid cancer survival of elderly patients in the Nordic countries.

OBJECTIVES: We describe age-specific survival in thyroid cancer (TC) from Denmark, Finland, Norway, and Sweden over a 50-year period. DESIGN: Population-based survival study. METHODS: Relative 5-year survival data were obtained from the NORDCAN database for the years 1972-2021. RESULTS: In the first period 1972-1976, 5-year survival in TC in Finland, Norway, and Sweden was 90% or higher, but a strong negative step-wise age gradient was observed, which was worse for men than women. Over time, survival increased, and in the final period, 2017-2021, survival for all women and Danish men up to age 69 years was about 90% or higher and, for men from the other countries, only marginally lower. Even for older women survival reached 80%, for older men somewhat less. CONCLUSIONS: Age disadvantage in TC survival was for the most part corrected over the 50-year period, and the remaining task is to boost survival for the oldest patients.

Survival in oral and pharyngeal cancers is catching up with laryngeal cancer in the NORDIC countries through a half century.

BACKGROUND: Cancers of the head and neck (HN) are heterogeneous tumors with incidence rates varying globally. In Northern Europe oral and oropharyngeal cancers are the most common individual types. Survival for HN varies by individual tumor type but for most of them survival trends are not well known over extended periods of time. METHODS: Data for a retrospective survival study were obtained for Danish, Finnish, Norwegian, and Swedish patients from the NORDCAN database from 1971 to 2020. Relative 1- and 5-year survival rates and 5/1-year conditional survival for years 2-5 were calculated. RESULTS: Both 1- and 5-year survival improved for all HN cancers but only marginally for laryngeal cancer. For the other cancers a 50-year increase in 5-year survival was about 30% units for nasopharyngeal and oropharyngeal cancers, 20% units for oral cancer and somewhat less for hypopharyngeal cancer. CONCLUSIONS: 5-year survival reached about 65% for all HN cancers, except for hypopharyngeal cancer (30%). Human papilloma virus infection is becoming a dominant risk factor for the rapidly increasing oropharyngeal cancer, the prevention of which needs to emphasize oral sex as a route of infection.

Conditional Survival in Prostate Cancer in the Nordic Countries Elucidates the Timing of Improvements.

BACKGROUND: The incidence of prostate cancer (PC) increased vastly as a result of prostate-specific antigen (PSA) testing. Survival in PC improved in the PSA-testing era, but changes in clinical presentation have hampered the interpretation of the underlying causes. DESIGN: We analyzed survival trends in PC using data from the NORDCAN database for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) by analyzing 1-, 5- and 10-year relative survival and conditional relative survival over the course of 50 years (1971-2020). RESULTS: In the pre-PSA era, survival improved in FI and SE and improved marginally in NO but not in DK. PSA testing began toward the end of the 1980s; 5-year survival increased by approximately 30%, and 10-year survival improved even more. Conditional survival from years 6 to 10 (5 years) was better than conditional survival from years 2 to 5 (4 years), but by 2010, this difference disappeared in countries other than DK. Survival in the first year after diagnosis approached 100%; by year 5, it was 95%; and by year 10, it was 90% in the best countries, NO and SE. CONCLUSIONS: In spite of advances in diagnostics and treatment, further attention is required to improve PC survival.

Conditional survival in breast cancer up to 10 years in the Nordic countries.

BACKGROUND: Survival in breast cancer (BC) has developed favorably but late recurrences are still a problem. METHODS: We model survival data from the NORDCAN database and analyze 1-, 5-, and 10-year relative survival and 5/1- and 10/5-year conditional survival in BC from Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) between 1971 and 2020. Conditional survival measures survival in those who had survived year 1 to reach year 5 (5/1), or in those who had survived year 5 to reach year 10 (10/5). RESULTS: Almost all survival metrics were best for SE but survival in all countries improved in the course of time approaching the SE levels which were 98.3% for 1-year, 92.3% for 5-year, and 87.8% for 10-year survival. Conditional 10/5-year survival, covering 5 years, was better than 5/1-year survival, covering 4 years. A contributing factor is most likely the high rate of recurrence in period 2-5 years. The difference was observed for all countries but for DK 10/5-year survival approached 1-year survival and for NO and SE 10/5-year survival was only barely better than 5/1-year survival. The explanation to this was the excellent 10/5-year survival in DK compared to SE and particularly to NO. Literature search suggested that the reason for the relatively low 10/5-year survival in NO might be stagnant survival development in old patients. CONCLUSIONS: We assume that late mortality is critically limiting survival in BC and either interference with the late metastatic process or effective treatment will be key to future improvements in BC survival.

Altered Expression of MBNL Family of Alternative Splicing Factors in Colorectal Cancer.

BACKGROUND/AIM: Colorectal cancer is currently the third leading cause of cancer-related deaths and recently, alternative splicing has risen as its important regulator and potential treatment target. In the present study, we analyzed gene expression of the MBNL family of regulators of alternative splicing in various stages of colorectal cancer development, together with the MBNL-target splicing events in FOXP1 and EPB41L3 genes and tumor-related CD44 variants. MATERIALS AND METHODS: Samples of tumor tissue and non-malignant mucosa from 108 patients were collected. After RNA isolation and reverse transcription, the relative gene expression of a selected gene panel was tested by quantitative real-time PCR, followed by statistical analysis. RESULTS: MBNL expression was decreased in tumor tissue compared to non-tumor mucosa. In addition, lower expression was observed for the variants of FOXP1 and EPB41L3, while higher expression in tumor tissue was detected both for total CD44 and its cancer-related variants 3 and 6. Transcript levels of the MBNL genes were not found to be related to any of the studied clinicopathological characteristics. Multiple significant associations were identified in the target gene panel, including higher transcript levels of FOXP1 and CD44v3 in patients with distant metastases and connections between recurrence-free survival and altered levels of FOXP1 and CD44v3. CONCLUSION: Our results identified for the first-time deregulation of MBNL genes in colorectal cancer. Down-regulation of their transcripts in tumor tissue compared to matched non-tumor mucosa can lead to transition of alternative splicing patterns towards a less differentiated phenotype, which highlights the importance of alternative splicing regulation for tumor growth and propagation.