Prostate cancer case study

One of the main goals of cancer screening is to detect localized tumors early and reduce cancer mortality. The belief or prediction that early detection reduces the likelihood of advanced-stage cancer is called a “stage shift.” Unfortunately, stage shift does not consider progressive cases after diagnosis. In addition, screening for advanced cancer diagnosis does not always reduce disease-specific mortality. The decrease in advanced cases at the time of diagnosis is limited to organs, and the number of cases subject to metastasis increases. Progressive cases can also reduce the incidence of metastatic disease at diagnosis, resulting in the same number of metastatic cases in the screened and unscreened groups.

To date, most population-based screening trials have not analyzed the overall risk of metastases in screening and controls at diagnosis, not during follow-up. Determining the effectiveness of screening for metastases can be difficult and time consuming. Follow-up of localized cases in both study groups is required. Predicting staging changes and case differences observed in advanced-stage disease helps to develop practical and realistic predictions and the effects of long-term screening.The· Ezioni Group (Fred Hutchin, Department of Public Health Sciences) has developed a modeling framework to predict the reduction of metastases at diagnosis to the overall reduction of metastases during screening. This framework contained important data and assumptions to realistically predict the long-term effects of screening.Published in the study Medical Screening JournalResearchers have used the framework to predict how low incidence of metastasis diagnosis translates into overall metastasis incidence, which is reflected in the overall metastasis pattern observed from the study. Compared with.

The modeling framework includes three main components: stage-specific disease incidence at diagnosis with and without screening, overdiagnosis and non-overdiagnosis of cases with overdiagnosis of the screening arm. Non-overdiagnosed, local cases from division, diagnosis. European Randomized Screening (ERSPC) data for prostate cancer were used for stage shifts, and data from the Scandanavia Prostate Cancer Group 4 study were used for the risk of metastatic progression. The ERSPC Randomized Controlled Screening Trial was started in 1993 and compared prostate-specific antigen (PSA) screening every 2-4 years in adult males aged 55-69 years. This analysis used a total of 76,813 men from four centers in the ERSPC study (N = 36,270 screening; N = 40,543 controls). An SPCG-4 randomized controlled trial, started in 1989, observed the progression of prostate cancer cases. A total of 695 men (N = 347 interventions; N = 348 controls) were used in the study.

A micro-simulation model of Fred Hatchin’s natural history of prostate cancer was used to predict the incidence of de novo metastatic cancer. This model correlates PSA proliferation in individuals with the onset and progression of preclinical prostate tumors. For example, men with a fast PSA growth rate may have a shorter time to clinical diagnosis and are more likely to have a metastatic stage at the time of diagnosis. Progression of metastasis was predicted at the time of clinical diagnosis (screen arm). Hazard ratio (time to metastasis), relative risk (metastasis rate ratio measured at 12 years), and absolute risk (difference at 12 years) are used to analyze metastasis at diagnosis and overall metastasis. It was.

Simulations showed that there were fewer cases of de novo metastases at diagnosis than in the control group. In the 12-year mock study screening and control groups, the relative risk was 0.57, the hazard ratio was 0.60, and the absolute risk reduction was 39.6 / 10,000. The modeled effect of screening on progressive metastases in the screening and control groups showed a reduction in absolute and relative benefits for overall metastatic disease. Compared to each other, the simulated trial and ERSPC metastases (at diagnosis and overall) were in agreement.

In conclusion, the Etzioni group has created a new modeling framework to investigate the long-term effects of cancer screening on the incidence of metastases. This model is more accurate than other predictions that use only stage shifts at diagnosis because researchers have measured new and progressive cases. Screening has been shown to reduce the number of advanced cases at diagnosis, but it also increases the number of undiagnosed localized cases and is eligible for progression. Therefore, when assessing disease mortality, expectations for the benefits of stage-shift-based screening need to be reduced.

This study was supported by the National Cancer Institute, Cancer Intervention and Surveillance Modeling Network.

Ruth Etzioni, a member of the Fred Hutchin / UW Cancer Consortium, contributed to this work.

Lange J, Remmers S, Gulati R, Bill-Axelson A, Johannsson JE, Kwiatkowski M, Auvinen A, Hugosson J, Hu JC, Roobol MJ, Carlsson SV, Etzioni, R. Survey. Medical screening journal. February 9, 2021.. https://doi.org/10.1177/0969141321989738