Discussion:
Prostate cancer is the most common cancer in men [11]. Since the beginning of screening for prostate cancer with serum PSA, we have seen a significant decline in prostate cancer mortality [12].
A systematic analysis suggested that up to 60% of prostate cancers diagnosed in contemporary studies can be safely observed without a need for immediate intervention [13]. However, 20% to 30% of men who are diagnosed with prostate cancer are found to have high-grade disease at presentation [14]. Diagnosis should focus on detection of aggressive tumors, that are more likely to progress to metastatic disease and death, and not the indolent ones.
The 4K ® scores test is a relatively new blood test that identifies the risk of aggressive cancer and has a role as an initial test before performing prostate biopsies in men with an elevated PSA level or an abnormal digital rectal examination result, or after a previous negative prostate biopsy with persistently elevated PSA level. The test result is a personalized positive predictive value of finding Gleason score ≥ 7 cancer on biopsy of the prostate. This provides the patient and physician with quantitative information to aid in clinical decision making regarding performing prostate biopsies.
The COVID-19 era in general had a major effect on health-care related issues such as allocating medical resources to cope with COVID and its implications, delaying or postponing non-emergent diagnostic procedures and even limited availability of primary care providers, not to mention expert consultation
This study is intended to examine the extent of the effect during the first quarantine period of COVID-19 pandemic on performing 4K® blood tests in Israel. We found that the number of tests performed during the study period decreased significantly by about 37% compared to the corresponding period the year before. This fact is consistent with that described in the literature on reduction in malignancy-related tests during the COVID-19 period. One of the subjects being investigated recently is the risk of late diagnosis and mortality from life-threatening diseases in general [15] and cancer in particular [16]. These studies found an increased risk of morbidity and mortality from serious diseases due to neglect and reduction in follow-up and late diagnosis of malignant diseases during this period.
Another component is the psychological consequences of living during a pandemic that causes anxiety and seclusion that have a negative effect on the diagnosis and treatment of patients with serious illnesses [17].
Our study found a significant difference between the study and control groups in the percentage of tests indicating a high-risk (4K® score above 20%) and a very high-risk (4K ® score above 33%) for clinically significant prostate cancer.
A reasonable explanation for these differences would have been an increased PSA levels during screening, which incited both the referring physician and the patient to perform the 4K® test. However, no significant difference in PSA level was found between the study group and the control group. The mean age was not significantly different between the groups but the ratio of patients 65 years or younger out of the total subjects in the study period (211/450=0.47) was higher relative to their ratio in the control group (259/721=0.36). This may be because older patients tended to be more isolated and secluded during the first quarantine period included in the study period.
The patients’ age was found to be an influencing factor on higher 4K ® scores during the study period, even in multivariable analysis. During the study period, more patients aged 65 or younger with high 4K® scores ​​were found compared to the corresponding period the year before. One possible explanation is that 4K ® tests were performed instead of MRI imaging that were canceled or postponed due to the pandemic working schedule [18].
This is the first study to address the implications of this challenging era on the diagnosis of prostate cancer using biological markers.
The strengths of the study are a uniform database with a large number of tests performed in one central laboratory.
The limitations of the study are a relatively short period of time during the pandemic period taken as the study period as well as the lack of the actual biopsy results.
Extensive research with a larger database is required to validate the research findings.