Renal Cell Carcinoma: 5 Things to Know for Primary Care

Renal cell carcinoma (RCC) represents up to 85% of kidney cancers. It is considered the deadliest urologic cancer in the United States, with a 5-year survival rate of 76% overall, going down to only 12% for patients with late-stage disease.

Here are five things that primary care clinicians should know about the epidemiology, risk factors, and comorbidities of RCC.

1. The incidence of kidney cancer has more than doubled in the past half century.

Kidney cancer accounts for 2.2% of the world's cancer diagnoses and 1.8% of cancer deaths, but this burden is projected to rise. The American Cancer Society estimates that approximately 81,800 new cases of kidney cancer will be diagnosed in the United States in 2023, which is up from 79,000 in 2022 and 76,080 in 2021.

Over the past half century, kidney cancer has been one of the fastest-growing cancer diagnoses in the United States, with RCC becoming the ninth most common neoplasm in the country. Its incidence has more than doubled from 7.1 cases per 100,000 population in 1975 at its first reporting to 16.5 cases per 100,000 population in 2019. Increased utilization of cross-sectional imaging, which enables the detection of cancers that might not have been identified in the past, has contributed to this rise in RCC diagnoses.

2. American Indian/Alaska Native persons are disproportionately affected.

The cumulative incidence of kidney and renal pelvis cancers was 17.3 cases per 100,000 population from 2015 to 2020. However, incidence varies widely by race and ethnicity, ranging from 8.1 cases per 100,000 population in Asian American/Pacific Islander persons to 31.0 cases per 100,000 population in American Indian/Alaska Native persons in the same 5-year period. In the middle lie the incidence rates among Hispanic/Latinx and White persons, both at 17.5 cases per 100,000 population, and Black persons, at 19.1 cases per 100,000 population. Hispanic American and Native American persons with RCC have been found to have different disease characteristics from European American persons, including younger age at diagnosis and a higher proportion of renal clear cell cancer.

There are also differences in the cumulative 5-year mortality rates of kidney and renal pelvis cancers across races and ethnicities, with an overall mortality rate of 3.5 per 100,000 population and ranging from 1.6 per 100,000 population in Asian American/Pacific Islander patients to 6.5 per 100,000 population in American Indian/Alaska Native patients. Again, Hispanic/Latinx, Black, and White patients comprise the middle rates, with mortality rates of 3.3 per 100,000 population, 3.4 per 100,000 population, and 3.6 per 100,000 population, respectively.

Survival rates are lower in Black patients than in White patients for every histologic disease subtype. Despite this, 5-year survival rates in kidney and renal pelvis cancers are similar between the two groups, at 76% in White patients and 77% in Black patients as of 2019. The similarity of the overall survival rates can be attributed to the higher proportion of cases of papillary and chromophobe RCC in Black than in White patients; these forms of disease have a favorable prognosis compared with other RCC types.

3. Men in their 60s are most commonly affected.

Although kidney and renal pelvis cancer affect both men and women, men are affected at a higher rate. Between 2015 and 2020, the cumulative incidence of kidney or renal pelvis cancer in men was nearly twice that of women (23.5 cases per 100,000 population vs 12.0 cases per 100,000 population). These cancers are projected to account for 5.2% of all estimated new cases of cancer in men and 3.1% in women in 2023. They also are projected to contribute to more deaths in men in 2023, leading to an estimated 3.1% of cancer deaths in men vs 1.7% in women.

In the United States, the average age at diagnosis of RCC is 64 years, even though a majority of patients receive a diagnosis between the ages of 65 and 74 years.

The probability of being diagnosed with kidney cancer increases with age. Men aged ≤ 49 years have a 1 in 389 (0.3%) probability of developing kidney or renal pelvis cancer. This increases to 1 in 250 (0.4%) for men aged 50-59 years, 1 in 144 (0.7%) for men aged 60-69 years, and 1 in 69 (1.4%) for men aged ≥ 70 years. Likewise, the chance of kidney or renal pelvis cancer in women increases with age, from 1 in 609 (0.2%) in women aged ≤ 49 years, 1 in 504 (0.2%) in those aged 50-59 years, 1 in 292 (0.3%) in those aged 60-69 years, and 1 in 124 (0.8%) among those aged ≥ 70 years. Overall, men have a 1 in 44 (2.3%) lifetime probability of developing kidney or renal pelvis cancer, whereas the probability for women is lower, at 1 in 75 (1.3%).

4. Among other significant risk factors, kidney cancer risk increases with smoking even a few cigarettes per day.

The most significant modifiable risk factor for RCC is tobacco smoking. A systematic review and meta-analysis found that compared with never-smokers, the relative risk (RR) for kidney cancer among current smokers is 1.39 (95% CI, 1.28-1.51) and among former smokers is 1.20 (95% CI, 1.14-1.27). Smoking intensity increased this risk, albeit in a nonlinear manner, with a RR of 1.18 (95% CI, 1.11-1.26) for individuals who smoke five cigarettes a day and 1.72 (95% CI, 1.52-1.95) for those who smoke 30 cigarettes a day. The risk for kidney cancer increased linearly with smoking duration, with an RR of 1.70 (95% CI, 1.10-2.64) after 25 years of smoking. The risk decreased in a linear manner as more time passed since quitting smoking.

Obesity is another modifiable risk factor for RCC. According to a meta-analysis, the risk for kidney cancer was increased in men with a body mass index (BMI) ≥ 30 compared with men with a BMI between 18.5 and 24.99 (RR, 1.57; 95% CI, 1.38-1.77). Similarly, a higher BMI in women conferred increased risk for kidney cancer compared with women in the lower BMI group (RR, 1.72; 95% CI, 1.58-1.88).

An additional 11 lb (5 kg) in body weight may increase the risk for RCC by 25% in men and 35% in women. On the other hand, a cohort study in Japan demonstrated that low BMI (< 21) in Asian men may also increase the risk for kidney cancer (hazard ratio [HR], 1.86; 95% CI, 1.01-3.45) compared with a BMI between 23.0 and 24.9.

Hypertension has also been associated with an increased risk for kidney cancer. A meta-analysis showed that each 10-mm Hg increase in systolic blood pressure (SBP) increased the risk for RCC by 5% (95% CI, 1.03-1.06), and each 10-mm Hg increase in diastolic BP (DBP) increased it by 7% (95% CI, 1.04-1.10). When BP is extremely high (SBP > 150 mm Hg or DBP > 100 mm Hg), the incidence of RCC rises rapidly. Even BPs that are high-normal (SBP, 130-140 mm Hg; DBP, 80-90 mm Hg) may increase the risk for RCC.

5. Comorbid dementia can increase mortality in patients with RCC.

RCC prognosis can be affected by comorbidities present at diagnosis. A nationwide cohort study in Denmark found that patients with RCC with Charlson Comorbidity Index scores of 1-2 and ≥ 3 had higher mortality rates than patients without comorbidities (HR, 1.15 [95% CI, 1.06-1.24] and 1.56 [95% CI, 1.40-1.73], respectively). The comorbidities with the greatest effect on mortality were mild liver disease (HR, 2.09; 95% CI, 1.53-2.84), moderate to severe liver disease (HR, 4.01; 95% CI, 2.44-6.56), and dementia (HR, 2.16; 95% CI, 1.34-3.48). Congestive heart failure, peripheral vascular and cerebrovascular disease, chronic pulmonary disease, preexisting renal disease, diabetes, and lymphoma also increased mortality.

A study conducted in the United States in patients aged > 65 years with localized RCC found similar results, except its highest HRs were for patients with congestive heart failure and chronic kidney disease. Other comorbidities associated with decreased overall survival in this study were peripheral vascular disease, chronic obstructive pulmonary disease, diabetes, and cerebrovascular disease.

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