To the best of our knowledge, this study is the first to compare the incidence and mortality of ccRCC at different stages within two year-circles of diagnosis (first and second decades) to provide a comprehensive understanding of the epidemiology of ccRCC. Our study also aimed to examine the increasing trend of cancer incidence, and to analyze it together with the trend of cancer mortality and different stages and grades.
According to population-based research, there were 3.59 incidences of ccRCC per 100,000 individuals between 1973 and 2014 (6). A similar trend of increasing annual incidence of ccRCC was observed in our study, which rose from 2.63 to 8.79 per 100,000 from 2000–2017. This rise in the incidence of ccRCC is mainly due to the increased rate of early localized disease detection in recent years. Epidemiological studies on ccRCC are of great significance to better understanding the disease, improving medical practices, and reducing the burden on society.
Our study found an increased incidence of ccRCC over time, which is consistent with the overall trend in cancer incidence. Studies have reported that the incidence of ccRCC began to increase in the mid-1990s (6) and we found that the incidence increased at a relatively steady rate between 2000 and 2017. We explored and considered some possible mechanisms. First, with the improvement in social progress and living standards, people's health awareness and opportunities for physical examination have increased, and some medical examination methods, such as computed tomography and magnetic resonance imaging, are widely used (7–12). This is one of the reasons why, over time, we have observed an increasing number of patients in the early stages of disease at diagnosis. Second, some risk factors for ccRCC such as smoking, alcohol consumption, and obesity play a significant role (13, 14).
In addition, our study found that, although the incidence of ccRCC has increased, the mortality rate decreased. We attribute this to advances in medical technology and implementation of preventive strategies to allow for early detection and treatment. However, this disease should not be underestimated. Although surgery has prolonged the survival of ccRCC patients, studies have found that 30–40% of postsurgical patients still develop metastatic recurrence (15). This is similar to the patients in our study, in which most patients underwent surgery; however, a proportion of patients still developed metastases. Currently, immune-targeted therapy is an indispensable component of metastatic ccRCC treatment. It mainly includes inhibitors of mammalian targets of rapamycin (mTOR) and vascular endothelial growth factor receptors (VEGFR), such as sunitinib, tivozinib, and temsirolimus (16). Nivolumab plus ipilimumab is approved for the treatment of low- to moderate-risk ccRCC (17). Combination regimens of pembrolizumab plus axitinib (18), avelumab plus axitinib (19, 20) and atezolizumab plus bevacizumab (21) in have been used in various clinical studies.
Many studies have confirmed that tumor stage is an important prognostic factor for ccRCC (22, 23). Neuzillet et al. found that genes associated with TNM stage were significant predictors of clear cell carcinoma, even after adjusting for multiple confounding factors (22). Similarly, we found that with an increase in tumor stage and grade, the prognosis worsened. Therefore, early identification of tumors and control of risk factors are crucial for tumor prognosis and reduction in disease burden.
In addition to the tumor stage and grade, several other factors are strongly associated with ccRCC prognosis. Age, sex, race, and marital status have been found to influence ccRCC progression and prognosis, with similar results obtained in our study (24). Among patients with clear cell carcinoma, women have a better prognosis than men, which is consistent with our findings (6, 25).
This study had some limitations. First, this was a retrospective study, and the clinical data and death situations were all from the SEER database, which is only representative of the general US population and cannot be extrapolated to the rest of the world. In addition, in terms of the treatment profile, although the most important treatment approach (surgery) was analyzed, the influence of some factors, such as immunotherapy and treatment of complications, was not considered. Larger databases and additional studies are required to confirm this hypothesis.