报告肾细胞癌的地理和时间趋势：为什么这很重要?

Reporting Geographic and Temporal Trends in Renal Cell Carcinoma: Why Is This Important?

A number of different factors influence cancer incidence and mortality among various geographic and ethnic regions of the world; these include rate of screening, incidental detection, presence of genetic risk factors and environmental exposures, and socioeconomic status. Renal cell carcinoma (RCC) is no exception. Previous epidemiologic studies have demonstrated that the incidence and mortality of RCC is increasing worldwide [1], and with an estimated 143 000 deaths in 2012, kidney cancer is the 16th most common cause of cancer-specific death worldwide [2]. Among the 338 000 new cases of kidney cancer — representing 2.4% of the total cancer incidence burden worldwide — the majority were estimated to arise from North America, Australia or New Zealand, and Europe, and 75,000 (52%) of the deaths from kidney cancer occurred in the more developed countries of the world [2]. Despite advances in image-guided detection of renal neoplasms, 25–30% of patients still present with metastatic disease because the majority of renal tumors are largely asymptomatic [3]. Because metastatic RCC is one of the most treatment-resistant malignancies, the outcomes for these patients are often poor, despite recent advances in systemic targeted therapies. Understanding the current state of total global disease burden and trends in incidence, mortality, and survival is paramount as we assess the impact of our current treatment strategies and future directions.

In this month’s issue of European Urology, Znaor et al present a comprehensive report on the incidence and mortality of RCC in the context of global geographic variations for 42 countries [4]. They achieved this by analyzingRCC incidence andmortality trends in 42countries from Cancer Incidence in Five Continents, an international databaseof population-based cancer registry data developed by the International Agency for Research on Cancer (IARC), along with the World Health Organisation Cancer Mortality Database,also maintained byIARC. For17countries,national incidence data were obtained using the country’s regional registries as a proxy. The authors showed a significant difference in RCC incidence rates worldwide, with >15-fold variation among the lowest population of incident cases of RCC in the African countries compared with the highest rates in eastern European countries, namely, the Czech Republic. Incidence of RCC has also been on the rise over the past 10 yr for men and for women (albeit at generally half the rate of men) in North America, parts of Europe, Asia, Oceania, and particularly Latin America. In comparison, RCC mortality trends have either stabilized or decreased in the developed world to 1–3%.

It is impossible to correlate the trends in geographic and temporal incidence and mortality of RCC seen in the study by Znaor et al [4] to definitive changes in the prevalence of risk factors, but one can speculate that they may play a role. Although not specifically correlated in this study, smoking, obesity, hypertension, and diet have all been associated with increased risk of RCC [5–7]. A global increase in these risk factors, in addition to the increasing use of modern imaging techniques in more developed countries, correlated with the rising incidence of RCC; however, the interplay among these factors is often complex. Are the lowest incidences of RCC observed, for example, in sub-Saharan Africa and India in the study by Znaor et al, the result of lower average body mass index in these areas or the result of under-registration due to relative lack of advanced imaging techniques and lack of liberal use of imaging in the general population?

Although comprehensive, these data need to be interpreted with some caution because few low- and middle-income countries are represented, as duly noted by the authors [4]. In addition, the use of regional and seminational registries adds to the heterogeneity of the data presented and could introduce falsely low rates as a result of under- registration. In addition, it is unclear whether the stabiliza- tion or decrease in mortality in the setting of rising trends in incidence reflects improved survival or is merely a consequence of increased incidental diagnosis. As reported by Welch and colleagues [8], an increase in cancer incidence with concomitant stability in mortality can represent either overdiagnosis (of mostly low-risk tumors) or a situation in which a true rise in the prevalence of cancer is counter- balanced by a concomitant substantial improvement in the diagnosis and treatments available. Given that there have been relatively moderate advances in the treatment of RCC over the past decade, the latter scenario becomes less likely. In addition, variations in coding or capturing the incidence of RCC will differ significantly not only from country to country but also from region to region. Because many countries may not have a central registry or participate in global registry initiatives, these data would be have to be extrapolated [9].

Despite the limitations, studies like the one by Znaor et al [4] reporting geographic and temporal trends are important in cancer care because they can be used to affect regional healthcare efforts; can point to potential etiologies of cancer [10]; and can be a proxy for demonstrating whether we, as a community, are having a meaningful impact on this disease. Ultimately, as new molecular diagnostic and treatment paradigms emerge for RCC, we will need to continue such observations to see if they truly have a positive effect on the incidence and mortality rates for this disease.

[1]   Weikert S, Ljungberg B. Contemporary epidemiology of renal cell carcinoma: perspectives of primary prevention. World J Urol 2010; 28:247–52.

[2]  Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–86.

[3]  Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemio- logic and socioeconomic burden of metastatic renal cell carcino- ma (mRCC): a literature review. Cancer Treat Rev 2008;34: 193–205.

[4]  Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray B. Interna- tional variations and trends in renal cell carcinoma incidence and mortality. Eur Urol 2015;67:519–30.

[5]  Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569–78.

[6]  Hunt JD, van der Hel OL, McMillan GP, Boffetta P, Brennan P. Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies. Int J Cancer 2005;114:101–8.

[7]  Weikert S, Boeing H, Pischon T, et al. Blood pressure and risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition. Am J Epidemiol 2008;167:438–46.

[8]  Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst 2010;102:605–13.

[9]  Forman D, Bray F, Brewster DH, et al. Cancer incidence in five continents, vol. X. International Agency for Research on Cancer Web site. http://ci5.iarc.fr.

[10]   Blot WJ, Fraumeni Jr JF, Mason TJ, Hoover RN. Developing clues to environmental cancer: a stepwise approach with the use of cancer mortality data. Environ Health Perspect 1979;32:53–8.

Reply from Authors re: Mehrad Adibi, Jose A. Karam, Christopher G. Wood. Reporting Geographic and Temporal Trends in Renal Cell Carcinoma: Why Is This Important?

The editorial [1] raises several important issues with regard to the respective roles of putative and known risk factors, under-registration, and overdiagnosis in explaining the geographic and temporal variations in global renal cell carcinoma (RCC) incidence [2]. The incidence burden from this and other (historically relatively rare) cancer types is clearly on the increase, and in countries undergoing rapid socioeconomic transition, this may be allied with increasing adoption of more Western lifestyles and habits [3]. Even in the absence of these observations, there is little doubt that the number of kidney cancer patients will steadily rise year over year in the next decades via the projected global phenomenon of population ageing and population growth. The demographic impact will be greater on countries in societal transition: Kidney cancer incidence is predicted to increase by 62% in low- and medium-income regions by 2030 compared with a 39% increase in high- and very high- income regions of the world [4].

The contrast remains stark according to the levels of human development previously and currently observed in countries and regions worldwide. The high-spendhealthcare