Short summary

This project aims to investigate whether it is possible to use ultrasound as a screening tool for kidney cancer in high-risk populations. As part of the study, 200 patients who have been treated for high blood pressure for the past five years will undergo screening. The objective is to determine how many patients need to be examined in order to detect a kidney tumor, which could inform decisions about the potential need for a national screening program.

Rationale

Kidney cancer (KC) accounts for 2-3% of all cancer cases, age standardized incidence for men in Denmark was 10.7 in 1961 and 18 in 2016. The most prominent KC is renal cell cancer (RCC). Men are affected twice as often as women and the incidence increases with age. Most are diagnosed between the ages of 55-75. The mortality of RCC in Denmark in 2016 was 6.1 per 100,000 for men and 3.9 for women. Survival is increasing in Denmark from a five-year survival rate of 21% (1967-1971) to 67% (2014-2018). Part of the explanation for this improvement is due to stage migration, with almost half of cases diagnosed incidentally. The etiology of RCC is not clear, but predisposing factors are tobacco smoking, adiposity and hypertension. Most cases of RCC occur sporadically, while only 3% appear with a genetic predisposition. An individual with a first degree relative who has or have had RCC increases risk of developing RCC by 2-3 times. Referral for genetic testing should be considered in bilateral or multifocal RCC, early onset < 45 years and two or more relatives with RCC. The most frequent histological type is clear cell RCC. In recent years, more SRMs have been diagnosed, partly due to an increase in the prevalence of risk factors, partly because more patients are examined due to stomach symptoms. However, the majority of RCC deaths are still associated with late diagnosis, which is often associated with a more aggessive phenotype and higher risk of metastastic disease. 80% of Small Renal Masses (SRM), which are renal tumors below 4 cm in size, have been shown to be malign. To improve patients' chances of survival and quality of life after treatment, we need more knowledge to improve diagnosis and treatment. This should include an investigation of a screening program targeting patients with the most important RCC risk factors. The development of SRMs is not only strongly associated with hypertension (HT), but also smoking and obesity. A screening program that targets HT patients could potentially detect SRMs before they develop, which has been poorly investigated. Screening for RCC has repeatedly been identified as a research priority. Ultrasound has been proposed as a screening tool, as it is well tolerated, inexpensive, and widely available. National abdominal aortic aneurysm (AAA) screening programmes for 65-yr-old men are established in the UK and Sweden, and have demonstrated that an ultrasound-based screening programme can be delivered in the community by trained technicians and the studies showed later that lives were saved. Non randomised observational studies evaluating screening for RCC using ultrasound have been conducted for more than a decade but not in patients "in potential risk". In order to provide high quality data for a cost-benefit analysis of a RCC and SRM ultrasound screening program with clinical and social-economic outcome we will perform a pilot study which later should be caried out as a national screening programme in order to investigate whether the screening will benefit the patient and prove cost effective for society. The aim of the DARECA 1 trial will be to investigate if targeted ultrasound screening of hypertensive patients for renal masses in a community setting will increase the detection of early stage tumors and if this can improve survival in a cost-effective manner. In a study of 21 Von-Hippel-Lindau (vHL) patients with 205 renal masses removed (92% were <3 cm), detection rates and accuracy of CT and ultrasound scans in the characterization of renal morphology were correlated with lesion size before surgery. They found that CT and ultrasound scan detection rates for lesions of 0-5 mm were 47% and 0%, respectively; 5-10 mm, 60% and 21%; 10-15 mm, 75% and 28%; 15-20 mm, 100% and 58%; 20-25 mm, 100% and 79%; and 25-30 mm, 100% and 100% (17). Normally further diagnostic work-up is offered to patients with a tumor size over 2 cm so the study showed that ultrasound scan can detect the tumors that need to be investigated further. The aim of this pilot study is to quantify the number of small renal masses that will be detected when using ultrasound scan to screen patients with hypertension thereby estimating the number needed to screen to detect one early stage tumor.

Description of the cohort

We will collaborate with general practitioners to recruit patients. Our study will include 200 participants over the age of 55 who have received treatment for hypertension for a minimum of five years. Patients will be excluded from the project if they are not able to speak Danish, have a psychiatric disorder, or have a known medical cause for hypertension, such as adrenal disease.

Data and biological material

The data consists of information collected from ultrasound screenings of the kidneys, including details such as kidney size, and potential cysts and tumors. Additionally, demographic data will be collected, which may include date of birth, sex, weight, height, as well as current or previous medications and medical history. During participation in the trial, we will request access to patient records related to high blood pressure and the medications the patient is receiving for it. We will review the medical records to identify any other possible causes of high blood pressure, such as adrenal gland disease. We will also document if the patient has other conditions, such as diabetes or metabolic disorders. Furthermore, the patient's height and weight will be noted. The purpose of collecting this data is to gain a comprehensive understanding of each patient's medical history and how high blood pressure might affect kidney function. Relevant demographic information, medical history, and clinical parameters will be gathered from the group. Additionally, specific ultrasound measurements or findings, such as the presence of structural renal abnormalities or other pertinent markers, will be recorded for further analysis.

Collaborating researchers and departments

Department of Radiology, Odense University Hospital

• Nicolaj Lyhne Christensen

Research Unit of General Practice, University of Southern Denmark

• Jens Søndergaard