History and exam
Key diagnostic factors
common
presence of risk factors
Risk factors include smoking, male sex, age over 55 years, obesity, hypertension, positive family history of renal cancer, and history of hereditary syndrome.
haematuria
uncommon
flank pain
Other diagnostic factors
uncommon
non-specific systemic symptoms
Included in a spectrum of paraneoplastic presentations of RCC, and occur in up to 20% of patients.[19] May include fever, weight loss, sweats, pallor, cachexia, myoneuropathy.
signs of hepatic dysfunction
Included in a spectrum of paraneoplastic presentations of RCC.[19] Includes ascites, hepatomegaly, and spider angiomata.
myoneuropathy
Included in a spectrum of paraneoplastic presentations of RCC.[19]
lower limb oedema
Often suggestive of inferior vena cava involvement, but not a common presentation.
scrotal varicocele
RCC is a cause of varicocele in a very small proportion of men.[70]
dermatological manifestation (hereditary syndromes)
Patients may present with dermatological signs of hereditary syndrome. Patients with Birt-Hogg-Dube syndrome may have dermatological papules; and hereditary leiomyomatous patients may have skin fibromas.
vision loss (von Hippel-Lindau)
Patients with the hereditary syndrome von Hippel-Lindau may present with vision loss and retinal angiomatosis detected on fundoscopy.
Risk factors
strong
smoking
Consistently shown to be a modifiable risk factor for RCC in both men and women.[26][28] It is implicated in 20% to 30% of renal cancers in men, and 10% to 20% in women.[25]
In one study, smokers with more than 22.5 pack-years of exposure had a greater than 50% increased risk of RCC, compared with those who never smoked.[39] The overall relative risk of RCC is 1.31 for all (current and former) smokers.[40]
male sex
Worldwide, the age-standardised incidence rate of kidney cancer is 5.9 per 100,000 males and 3.0 per 100,000 females.[22]
In the US, the incidence rate is 23.8 per 100,000 men and 12.0 per 100,000 women (2018-2022, age-adjusted).[20] Kidney cancer is the sixth most commonly diagnosed adult malignancy in men.[21]
age over 55 years
residence in developed countries
RCC incidence and prevalence is greater in Europe and North America than other continents.[26][41]
The following 5-year kidney cancer prevalences have been reported (2022 data): 54.9 per 100,000 population in very high human development index (HDI) countries; 12.9 per 100,000 population in high HDI countries; 3.7 per 100,000 population in medium HDI countries; 2.4 per 100,000 population in low HDI countries (1.8).[42]
non-Hispanic American Indian/Alaska Native ethnicity
In the US, the incidence and mortality rates for kidney cancer are highest among non-Hispanic American Indian/Alaska Native persons (39.2 new cases per 100,000 men and 20.2 per 100,000 women [2018-2022, age-adjusted]; 9.2 deaths per 100,000 men and 4.0 per 100,000 women [2019-2023 age-adjusted]).[20]
obesity
Associated with increased risk for RCC.[26][28] In one study, individuals with a BMI ≥35 had a 71% increased risk of RCC compared with normal weight individuals (BMI <25).[39]
There is some evidence to suggest that patients with RCC with obesity may have improved survival outcomes compared with patients with RCC without obesity.[43] The association of body composition with clinical outcomes is being evaluated in a multicentre prospective cohort study.[44]
hypertension
positive family history of RCC
A positive family history of renal cancer carries a 2.8- to 4.3-fold increased risk for RCC.[47]
Familial non-syndromic RCC is suspected when two or more relatives have RCC and there are no features to suggest an underlying 'syndromic cause'.[31] Early-onset tumours and/or multiple/bilateral tumours increase suspicion of familial RCC, and genetic testing is usually performed.[31] Cases without an identifiable genetic cause are likely to be genetically heterogeneous.[31]
history of hereditary syndromes
Familial RCC is usually inherited in an autosomal dominant manner and accounts for 3% to 5% of RCC.[48][49]
Several familial genetic syndromes have been identified, including Von Hippel-Lindau syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), hereditary papillary renal carcinoma (HPRC), and Birt-Hogg-Dubé Syndrome.[28]
Von Hippel-Lindau syndrome is the most common syndrome associated with clear cell RCC.[31] Type 1 papillary kidney cancers have mutations in the mesenchymal-epithelial transition factor (MET) gene and type 2 (as part of HLRCC) having mutations in the fumarate hydratase (FH) gene.[31] Chromophobe and oncocytic kidney cancers are predominantly associated with Birt-Hogg-Dubé syndrome, which has a folliculin (FLCN) mutation.[31] Tuberous sclerosis may be associated with early-onset RCC, but RCC is rare in this condition and renal lesions are most commonly angiomyolipomas.[31]
weak
asbestos/cadmium exposure
obstetric history/oestrogen exposure
Reproductive factors (e.g., parity, age at first birth) have been associated with risk for renal cell carcinoma; however, study findings are not universally consistent.[54][55][56][57]
There is evidence to suggest that hormone replacement therapy is inversely associated with risk for renal cell carcinoma in women.[58] One cohort study found that women who reported hysterectomy appeared to be at increased risk for renal cell carcinoma.[54]
pelvic radiation
A small increase in RCC has been found in patients who have received ionising radiotherapy.[25]
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