Temporal trends of the disease burden of renal cell carcinoma from 1992 to 2019 in the US: A population-based analysis

doi:10.21203/rs.3.rs-4113494/v1

Purpose

Significant advances in the management, in particular the treatment, of renal cell carcinoma (RCC) has have been made over the years. However, it is not clear whether these advances reduce the disease burden of RCC at the population level.

Methods

Using data from the Surveillance, Epidemiology, and End Results database, we estimated the temporal trends of RCC incidence, incidence-based mortality (IBM), and survival rates in the United States (US) from 1992 to through 2019.

Results

From 2008 to 2019, the incidence increased slowly at 1.1% annually (95% CI: 0.6–1.5%). The overall IBM rate of RCC increased by 6.8% per year (95% CI: -1.1–15.3%) between 1994 and 1997, plateaued between 1997 and 2015, and then decreased nonsignificantly after 2015. During the study period, the overall 5-year survival rate of RCC continuously increased from 53.69% in 1992 to 72.90% in 2014, with the best improvement observed for RCC patients with distant disease. However, we projected that, given the current trends, the incidence of RCC in the US will continue to increase from 6.92 per 100,000 in 2015–2019 to 9.59 per 100,000 in 2040–2044.

Conclusion

Over the years, the mortality of RCC has been decreased reducing at the US populational level mainly because the considerably significantly improved survival of RCC patients at all stages through the advances in treatment. However, the overall incidence of RCC is continuously increasing, indicating that more effective preventive strategies should be developed to reduce the disease burden of RCC.

Kidney cancer

Trends

Incidence-based mortality (IBM)

Surveillance

Epidemiology and End Results (SEER)

age-period-cohort analysis

In 2023, kidney cancer was the seventh most common cancer and the eleventh leading cause of cancer deaths, with an estimated 81,800 new cases and 14,890 deaths in the United States (US) [1]. Renal cell carcinoma (RCC), originating from the renal parenchymal epithelium, accounts for more than 90% of kidney cancers [2]. Globally, RCC mortality began to plateau or decline in many countries until the mid-1990s, after rising for more than two consecutive decades from the late 1970s [3]. It was reported that the incidence of RCC in US has increased continuously since 1990, especially for early disease [4]. However, it is not clear whether the increase in early-stage RCC is driven by a real increase in the overall RCC incidence or by stage migration through advances in early diagnosis [5, 6].

Over the years, the promotion of abdominal imaging has led to more RCC patients being diagnosed at an earlier stage [4]. Based on the Surveillance, Epidemiology, and End Results (SEER) database, Sun et al. reported that the prevalence of localized disease increased (51.2 to 70.8%), and the prevalence of both regional stage (20.9 to 13.6%) and distant stage (27.9 to 15.6%) declined from 1988 to 2006 [6]. In addition, the median tumor size decreased between 2001 and 2016 (from 50 mm to 45 mm in men and from 49 mm to 40 mm in women; p < 0.001) [5]. The observed stage migration at the population level may reflect an upward trend in the increased incidence of early-stage RCC. However, Saad et al. found an increase in the incidence of all stages of RCC between 1992 and 2015, except for unclassified disease [7]. The study by Palumbo et al. further supported an increase in the incidence of both early-stage and late-stage RCC between 2001 and 2016 [5], which suggested that the increased incidence of RCC might also be attributed to the prevalence of RCC risk factors, such as smoking, obesity, hypertension, and a history of chronic kidney disease [3, 5, 7].

In recent decades, the prevalence of risk factors for RCC has changed considerably in the US because of smoking cessation and better management of hypertension in the general population [8–12]. However, overweight and metabolic disorders are currently more prevalent in the US population [13–16]. These changing factors also influence the current and future incidence of RCC. On the other hand, continuous advances in the diagnosis and treatment of RCC further improve the survival and thus reduce the mortality of RCC [17]. To gain insight into RCC prevention and treatment, it is necessary to evaluate the latest trends in the RCC burden at the US population level. Therefore, we analyzed the incidence, mortality, and survival of patients with kidney cancer in the US from 1992 to 2019 based on the SEER database.

Data source

The SEER database of the National Cancer Institute (NCI) is a public cancer registry database that covers approximately 26% of the US population [18]. Cancer cases are collected by the SEER program from health service unit records and death certificates of residents when cancer is listed as a cause of death. The population at risk for the incidence and incidence-based mortality (IBM) was the exposed population in the SEER area during the same period. We used SEER*Stat software (version 8.4.1) to select patients (aged at least 20 years) diagnosed with RCC from the SEER-13 registry database from 1992 to 2019. RCC cases were defined according to the third revision of the International Classification of Diseases for Oncology and were classified as papillary adenocarcinoma (8260/3), clear cell adenocarcinoma (8310/3), renal cell carcinoma (8312/3), renal cell carcinoma, chromophobe type (8317/3), and collecting duct carcinoma (8319/3) [19]. Patients diagnosed by death certificate or autopsy only were excluded due to incomplete histology information. Patients with multiple primary cancers or kidney cancer as a secondary cancer were also excluded from this study.

Joinpoint regression

Joinpoint regression analysis was performed using the NCI Joinpoint Regression Program (version 4.9.1.0), which describes piecewise log-linear calendar trends in age-adjusted rates by sex, histology, and stage. We used a best-fitting log-linear regression model to calculate the annual percent change (APC) and the corresponding 95% confidence interval (CI) for each calendar period and to identify the joinpoints for significant changes in the APC (P < 0.05).

Age-period-cohort model

Age-period-cohort analysis assesses and estimates the influence of age, calendar year (period), and year of birth (cohort) on disease incidence or mortality rates. Using the age-period-cohort model provided by the NCI web tools [20], we assessed the relationship between the observed rates and age, period, and cohort effects. The incidence and IBM of RCC were calculated using thirteen 5-year age groups (20–24, 25–29, …, 80–84) and five corresponding calendar periods. We calculated the rate ratio (RR) of the incidence and IBM for each calendar period (or birth cohort) to the reference period (or birth cohort), adjusting for age and nonlinear cohort (or birth cohort) effects. A P value ≤ 0.05 (two-tailed) was considered statistically significant.

Future projections

We employed the nordpred package in R language (version 3.5.1) to predict the incidence and IBM rates of RCC in US from 2019 to 2044 [21]. The pertinent future population projection data was sourced from the World Population Prospects published by the United Nations [22].

Trends in RCC incidence in the US

From 1992 to 2019, the incidence of RCC increased consistently regardless of sex or age group (Table 1). The overall incidence of RCC increased from 8.90 per 100,000 in 1992 to 14.53 per 100,000 in 2019 (Fig. 1A). The incidence of clear-cell RCC increased from 1.27 per 100,000 in 1992 to 9.31 per 100,000 in 2019 (average annual percent change [AAPC] = 7.9%, 95% CI: 6.2–9.6%) (Fig. 1B). Temporal trends in the incidence were significantly different by stage (Fig. 1C). The incidence of localized disease increased from 4.54 per 100,000 in 1992 to 9.96 per 100,000 in 2019 (AAPC = 3.5%, 95% CI: 3.1–3.9%). The incidence of regional disease increased from 1.88 per 100,000 in 1992 to 2.50 per 100,000 in 2019 (APC = 1.0%, 95% CI: 0.7–1.4%).

Table 1

Joinpoint trends of RCC incidence rates, SEER-13 registries^a, 1992–2019.
	Joinpoint trends for incidence rates
	Trend 1			Trend 2			Trend 3			1992–2019 AAPC
Characteristic	Years	APC (95% CI)	p	Years	APC (95% CI)	p	Years	APC (95% CI)	p	AAPC (95% CI)	p
Overall	1992–2008	2.8* (2.4 to 3.1)	< 0.001	2008–2019	1.1*(0.6 to 1.5)	< 0.001	—	—	—	2.1*(1.8–2.3)	< 0.001
Male	1992–2008	2.5* (2.1 to 2.9)	< 0.001	2008–2019	1.2*(0.7 to 1.7)	< 0.001	—	—	—	2.0*(1.7–2.3)	< 0.001
Female	1992–2007	3.1* (2.5 to 3.7)	< 0.001	2007–2019	0.8*(0.1 to 1.4)	0.020	—	—	—	2.1*(1.6–2.5)	< 0.001
Age groups
20-24^b	—	—	—	—	—	—	—	—	—	—	—
25–29	1992–1996	-14.0(-33.3 to 10.8)	0.228	1996–2011	9.9* (6.2 to 13.8)	< 0.001	2011–2019	-2.3(-7.3 to 3.0)	0.373	2.4(-1.9 to 6.8)	0.279
30–34	1992–2015	6.4*(5.1 to 7.6)	< 0.001	2015–2019	-7.9(-18.5 to 4.0)	0.175				4.1*(2.1 to 6.2)	< 0.001
35–39	1992–2019	4.6*(4.1 to 5.2)	< 0.001	—	—	—	—	—	—	4.6*(4.1 to 5.2)	< 0.001
40–44	1992–2019	4.0*(3.6 to 4.4)	< 0.001	—	—	—	—	—	—	4.0*(3.6 to 4.4)	< 0.001
45–49	1992–2009	3.5*(2.7 to 4.2)	< 0.001	2009–2019	1.3*(0.0 to 2.5)	0.049	—	—	—	2.6*(2.0 to 3.3)	< 0.001
50–54	1992–2019	2.0*(1.6 to 2.4)	< 0.001	—	—	—	—	—	—	2.0*(1.6 to 2.4)	< 0.001
55–59	1992–2019	1.6*(1.3 to 1.9)	< 0.001	—	—	—	—	—	—	1.6*(1.3 to 1.9)	< 0.001
60–64	1992–2008	2.8*(2.4 to 3.2)	< 0.001	2008–2011	-2.8(-9.6 to 4.6)	0.430	2011–2019	1.7*(1.0 to 2.5)	< 0.001	1.8*(1.0 to 2.7)	< 0.001
65–69	1992–2007	2.9*(2.3 to 3.6)	< 0.001	2007–2019	0.7(0.1 to 1.3)	0.031	—	—	—	1.9*(1.5 to 2.3)	< 0.001
70–74	1992–2019	1.5*(1.2 to 1.9)	< 0.001	—	—	—	—	—	—	1.5*(1.2 to 1.9)	< 0.001
75–79	1992–2007	2.7*(2.0 to 3.5)	< 0.001	2007–2019	0.8(0.0 to 1.7)	0.057	—	—	—	1.9*(1.3 to 2.4)	< 0.001
80–84	1992–2008	1.5*(0.9 to 2.0)	< 0.001	—	—	—	—	—	—	1.5*(0.9 to 2.0)	< 0.001

^a SEER-13 Registry areas: San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, Atlanta, San Jose, Los Angeles, Georgia.

^b Because zero new cases occurred in the 20–24 age group in 2003, the trend of incidence was not available.

* The trend was statistically different from zero (P < 0.05).

Abbreviations: AAPC: average annual percent change; APC: annual percent change; CI: confidence interval; RCC: renal cell carcinoma; SEER: Surveillance, Epidemiology and End Results;

Trends of incidence-based mortality in the US

Contradictory to the consistently increasing incidence rates, the IBM of RCC patients were stable from 1997 to 2015 and started to decrease at -2.9% (95% CI: -7.8% to 2.4%) per year thereafter (Figure 2A, Table 2). The IBM of clear cell RCC increased from 0.29 per 100,000 in 1994 to 1.65 per 100,000 in 2015 and decreased at an annual rate of -4.9% (95% CI: -9.2% to -0.4%) after 2015 (Figure 2B). However, the IBM for nonclear cell RCC continuously increased from 1996 to 2019 (0.01 per 100,000 to 0.20 per 100,000, AAPC=15.0%, p < 0.001). In contrast, the IBM for unclassified RCC declined from 2.18 per 100,000 in 1994 to 1.00 per 100,000 in 2019, with a peak of 2.70 per 100,000 in 1998. The IBM for both localized RCC and regional RCC showed an increasing or stable trend from 1994 to 2019 (Figure 2C). However, the IBM for distant RCC patients dropped from 1.85 per 100,000 in 1998 to 1.27 per 100,000 in 2019. From 1998 to 2004, the IBM of distant RCC decreased at a rate of -4.2% per year (95% CI: -7.8% to -0.5%), and after a plateau period of 11 years, it began to decline again in 2015 with an APC of -5.2% (95% CI: -9.9% to -0.3%).

Table 2. Joinpoint trends of RCC IBM rates, SEER-13^a, 1992–2019.

	Joinpoint trends for IBM raresb
	Trend 1			Trend 2			Trend 3			1992-2019 AAPC
Characteristic	Years	APC (95% CI)	p	Years	APC (95% CI)	p	Years	APC (95% CI)	p	AAPC (95% CI)	p
Overall	1994-1997	6.8(-1.1 to 12.3)	0.088	1997-2015	-0.2(-0.6 to 0.3)	0.404	2015-2019	-2.9( -6.6 to 0.9)	0.124	0.2(-0.9 to 1.3)	0.742
Male	1994-1998	4.8(-2.2 to 12.3)	0.171	1998-2015	0.0(-0.7 to 0.7)	0.980	2015-2019	-2.8(-7.8 to 2.4)	0.265	0.3(-1.1 to 1.7)	0.684
Female	1994-1997	6.5(-1.3 to 14.9)	0.100	1997-2015	-0.8*(-1.2 to -0.4)	< 0.001	2017-2019	-8.3( -19.6 to 4.6)	0.183	-0.6(-1.9 to 0.7)	0.378
Age groups
20-24c	—	—	—	—	—	—	—	—	—	—	—
25-29c	—	—	—	—	—	—	—	—	—	—	—
30-34c	—	—	—	—	—	—	—	—	—	—	—
35-39	1994-2019	0.7(-1.4 to 2.7)	0.510	—	—	—	—	—	—	0.7(-1.4 to 2.7)	0.510
40-44	1994-2019	-1.6*(-2.9 to -0.3)	0.019	—	—	—	—	—	—	-1.6*(-2.9 to -0.3)	0.019
45-49	1994-2019	-1.8*(-2.9 to -0.6)	0.004	—	—	—	—	—	—	-1.8*(-2.9 to -0.6)	0.004
50-54	1994-2019	-1.7*(-2.5 to -0.9)	< 0.001	—	—	—	—	—	—	-1.7*(-2.0 to -0.6)	0.001
55-59	1994-2019	-1.5*(-2.2 to -1.1)	< 0.001	—	—	—	—	—	—	-1.5*(-2.2 to -1.1)	< 0.001
60-64	1994-1998	13.3*(0.8 to 27.3)	0.037	1998-2019	-2.4*(-3.1 to -1.6)	< 0.001	—	—	—	0.0(-1.8 to 1.9)	0.992
65-69	1994-2019	-0.1(-0.7 to 0.4)	0. 026	—	—	—	—	—	—	-0.1(-0.7 to 0.4)	0.602
70-74	1994-2017	0.8* (0.2 to 1.4)	0.011	2017-2019	-12.5(-30.6 to 10.2)	0.241	—	—	—	-0.3(-2.1 to 1.5)	0.708
75-79	1994-2019	0.5(-0.3 to 1.2)	0.189	—	—	—	—	—	—	0.5(-0.3 to 1.2)	0.189
80-84	1994-2014	2.5*(1.5 to 3.5)	< 0.001	2014-2019	-5.0(-11.3 to 1.7)	0.133	—	—	—	0.9(-0.6 to 2.5)	0.219

^a SEER-13 Registry areas: San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, Atlanta, San Jose, Los Angeles, Georgia.

^b Joinpoint trends for IBM were analyzed during 1994-2019 after accounting for 2-year burn-in period to catch enough death cases in SEER-13 Registries.

^c Because deaths in the 20-24, 25-29 age grbaoups were not consecutive from 1994 to 2019, the trend of IBM was not available.

* The trend was statistically different from zero (P < 0.05).

Abbreviations: AAPC: average annual percent change; APC: annual percent change; CI: confidence interval; IBM: incidence-based mortality; RCC: renal cell carcinoma; SEER: Surveillance, Epidemiology and End Results;

Survival trends of RCC patients in the US

The 5-year survival rates for RCC patients in the US increased consistently from 53.69% in 1992 to 72.90% in 2014 (Figure 3A). The 5-year survival rates of clear cell RCC increased from 64.44% in 1992 to 78.11% in 2014, with an AAPC of 0.9% (95% CI: 0.6% to 1.2%) (Figure 3B). The 5-year survival rates of nonclear cell RCC increased from 63.64% in 1992 to 85.72% in 2014 at a rate of 0.6% per year (p = 0.002). The 5-year survival rates of unclassified RCC decreased slightly with an APC of -0.5% (p < 0.001). From 1992 to 2019, the proportion of unclassified RCC decreased significantly from 84.94% to 18.09%, while those of clear cell RCC (14.43% in 1992 to 64.04% in 2019) and nonclear cell RCC (0.63% in 1992 to 17.87% in 2019) both increased greatly. The survival rate of RCC patients increased consistently between 1998 and 2018 at all stages (Figure 3E-H). The 1-year survival of distant disease increased from 31.15% in 1992 to 52.87% in 2006 (APC = 2.5%, 95% CI: 1.3% to 3.8%), increasing rapidly by 6.4% (95% CI: -1.8% to 15.3%) from 2015 to 2018. From 1992 to 2019, the proportion of regional, distant, and unstaged disease decreased, except for localized disease (Figure 3D). The proportion of localized disease increased from 51.15% to 67.67%, with almost two-thirds of RCC patients in the localized stage. The proportion of distant disease decreased from 21.95% to 13.03%.

Age-period-cohort analysis and projections

The age-period-cohort analysis of the incidence and IBM of RCC patients in the US is shown in Figure 4. Incidence rates increased over time in all age groups (Figure 4A, B). IBM rates were stable or decreased in most age groups (Figure 4E, F). The incidence of RCC increased with the progression of the study period (Figure 4C). The period effect analysis showed that the rate ratio (RR) of IBM declined from 1999-2003 to 2014-2018 (Figure 4G). The incidence in the US increased with the aging of the birth cohorts (Figure 4D). The cohort effect analysis showed that the risk of death from RCC was the highest among patients born in 1939, and the risk of death gradually decreased with the aging of the birth cohort (Figure 4H). Compared with patients born in 1954, the cohort RR for patients born in 1994 was approximately 80% lower in terms of RCC IBM rates, with the lowest risk of death. Figure 5 shows the projections of future trends in the incidence and IBM of RCC in the US until 2044. Over the next 25 years, the incidence of RCC in the US will continue to increase from 6.92 per 100,000 in 2015-2019 to 9.59 per 100,000 in 2040-2044 (Figure 5A). The IBM of the RCC population in the US will decline slowly from 1.95 per 100,000 in 2015-2019 to 1.75 per 100,000 in 2040-2044 (Figure 5B). For most age groups, the incidence will continue to increase over the next 25 years, while the IBM will decline or remain stable (Figure 5C, D).

In this study, we found that the overall IBM rate of RCC has remained stable or decreased since 1997 because of the significantly improved survival of patients. This trend could be attributed mainly to treatment (tertiary prevention) advances, and to a lesser degree, better secondary prevention that detects more early-stage diseases. However, the incidence of RCC has not yet started to decrease. In contrast, the incidence is predicted to continue to increase over the next 25 years, unless more effective primary prevention strategies are implemented.

We found that the incidence of RCC has been increasing since 1992 in the US, especially among males. Two Global Burden of Disease (GBD) studies showed that since the 1990s, the RCC incidence has increased in most countries, including the US, and the increase is more marked among males than among females [3, 23]. Saad et al. found that the incidence of RCC among females began to decline after 2008, whereas the incidence of RCC among males increased [7]. Although we did not observe a downward trend in the RCC incidence for females, we did find that the incidence has remained stable. Furthermore, we project that the incidence of RCC will continue to increase through 2043. The increasing incidence of RCC calls for successful primary prevention of RCC, especially in controlling modifiable risk factors such as smoking, obesity, and hypertension [4]. The prevalence of hypertension among US adults has not changed substantially during the past two decades [9, 12]. Therefore, hypertension might not account for the increasing incidence of RCC in the US. Recent studies have shown that because of success in smoking cessation initiatives, the number of smokers in the US has decreased considerably in the last 20 years [8, 10-11]. A reduction in the smoking-related disease burden has already been seen in the US population [24]. Thus, the increasing RCC incidence in the US is not attributable to smoking.

Interestingly, we found that the RCC incidence among males was approximately twice as high as that among females in recent years. Since 2007, the increase in the incidence of overall RCC has been dominated by an increase in the incidence of RCC among males. Coincidentally, the age-adjusted prevalence of general obesity was reported to have increased more among males than among females in the US population from 2001 to 2018 [15]. Obesity is an independent risk factor for RCC [25] and is estimated to account for 26% of RCC cases worldwide [26]. The prevalence of obesity in the US remains high and has been increasing since 1999, with nearly half of US adults projected to be obese by 2030 [13-14, 16]. Therefore, the increasing prevalence and the same sex difference in obesity suggest that the increasing incidence of RCC is probably attributed to rising obesity rates in the US population, especially among males. Thus, to reduce the burden of RCC in the US, it is prudent to recommend that both individuals and society make a concerted effort to fight against obesity. Individuals should develop healthy behaviors and lifestyles and exercise and have a healthy diet [27, 28]. At the same time, we should further strengthen social health education and develop and implement stronger public policies, such as building more public sports venues [29]. We projected that the incidence of RCC will continue to increase over the next 25 years for most age groups; therefore, these strategies should be applied to people of all ages.

We found that the increasing incidence was predominantly for localized disease, with decreasing incidence in both regional stage and distant disease. Since 1992, the proportion of localized disease has increased substantially. Localized disease currently accounts for almost two-thirds of RCC cases. In contrast, the proportions of distant and unstaged disease both decreased by half from 1992 to 2019. This is obviously attributed to the more widespread application and advances in early diagnostic measures such as abdominal imaging and examinations [30-31], which allow more incidental detection and early diagnosis of small cancerous lesions [32-33]. Early diagnosis allows potential distant RCC patients to be diagnosed at an early stage and prevents stage migration for RCC. Secondary prevention (early detection and early diagnosis) and early treatment together can prolong the survival of RCC patients and improve their long-term quality of life. To achieve comprehensive secondary prevention, the main approach is to conduct disease screening [34]. For individuals, regular health checkups might help. Public health authorities should develop relevant policies, such as providing more available health management and even free regular health checkups for people over 65 years of age with a high prevalence of RCC.

In the 1990s, distant RCC patients were treated with interferon-α (IFN-α) and interleukin-2 (IL-2) alone or in combination, with poor patient survival. The results of two prospective trials, EORTC 30947 and SWOG 8949, showed that IFN-α combined with nephrectomy significantly improved overall survival (OS) in advanced RCC, which established the use of nephrectomy for patients with advanced RCC [35-37]. The decrease in the IBM of distant RCC from 1998 to 2004 was associated with the introduction of this therapy. In the period analysis of IBM, the mortality risk for RCC began to decrease from 1999-2003, further illustrating that this treatment combination can reduce the risk of death from RCC. Our data also showed that the IBM among distant RCC patients started decreasing significantly in 2015. In 2015, the first immune checkpoint inhibitor (ICI), nivolumab, was used to treat RCC [38]. Subsequently, ICI-based immune combination therapies such as avelumab combined with axitinib, pembrolizumab combined with axitinib, and nivolumab combined with ipilimumab have shown significant clinical efficacy [39-41]. Immunotherapy has ushered in a new era in the treatment of RCC and improved the clinical outcomes of patients with advanced RCC [42]. Ongoing trials of combination therapy have provided potential for durable clinical benefit in the survival of RCC patients. For example, a recent trial (COSMIC-313) showed superior efficacy of the triple combination of cabozantinib, nivolumab, and ipilimumab in patients with metastatic RCC [43].

However, the SEER database lacks information on RCC risk factors, such as lifestyle factors, environmental exposures, and viral infection status, so we could not directly explain the direct association between individual exposure factors and RCC incidence. Thus, the association could only be inferred indirectly by investigating the trend of RCC risk factors. In addition, a large number of cases were described with unknown histology in SEER; thus, the incidence and IBM trends could not be reliably analyzed by histological subtype in this study. Nevertheless, the SEER database collects cancer diagnosis, treatment, and survival data for approximately 30% of the U.S. population, and population-based cancer registry reporting is considered the gold standard for reporting cancer rates in specific populations. Although descriptive studies cannot provide absolute evidence of causality, the findings of this study can help inform the prevention of RCC to guide the rational allocation of health resources and the targeted development of preventive intervention strategies.

Treatment advances have remarkably improved the survival and moderately reduced the mortality of RCC in the US at the population level. However, the overall incidence of RCC in the US is still increasing, likely due to the rising prevalence of obesity in the US population. We projected that over the next 25 years, the incidence of RCC in the US will continue to increase if no further strengthened strategies are taken. To significantly decrease the disease burden, effective approaches to control modifiable RCC risk factors such as obesity, hypertension and smoking must be further developed and implemented immediately.

AAPC

average annual percent change

APC

annual percent change

CI

confidence interval

GBD

Global Burden of Disease

IBM

incidence-based mortality

ICI

immune checkpoint inhibitor

IFN-α

interferon-α

IL-2

interleukin-2

NCI

National Cancer Institute

OS

overall survival

RCC

renal cell carcinoma

RR

rate ratio

SEER

Surveillance, Epidemiology and End Results

US

United States.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81773555).

Declarations of interest

The authors have no relevant financial or non-financial interests to disclose.

Acknowledgement

We sincerely thank the National Cancer Institute and the SEER staff for providing this invaluable database.

Author Contributions

Conceptualization: Z.F. Data curation: R.C and W.L. Formal analysis: W.L. Funding acquisition: Z.F. Investigation: S.L. H.D. and T.J. Methodology: J.H. Project administration: T.T. Resources: S.L. and W.L. Software: H.D. and T.J. Supervision: T.T. Validation: J.H. Visualization: R.C. and Si Li. Roles/Writing – original draft: R.C. Writing – review & editing: Z.F. and R.C. The work reported in the paper has been performed by the authors, unless clearly specified in the text.

Ethical approval and consent to participate

Patient consents were not required because the study is a retrospective database research in nature, there was no direct patient contact. Institutional Review Board approval was not required according to our institution policy.

Data Availability Statement

The data presented in this study are openly available in the Surveillance, Epidemiology, and End Results at https://seer.cancer.gov [18].

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No competing interests reported.

Temporal trends of the disease burden of renal cell carcinoma from 1992 to 2019 in the US: A population-based analysis

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Materials and methods

Data source

Joinpoint regression

Age-period-cohort model

Future projections

Results

Trends in RCC incidence in the US

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1