Kidney Cancer: Epidemiology and Pathogenesis

Epidemiology

• Incidence & Mortality
  • Many databases include upper tract urothelial carcinoma with kidney cancer and therefore independent incidence of kidney cancer cannot be assessed
    • GLOBOCAN includes ICD-9 C65 - "Malignant neoplasm of renal pelvis" with kidney cancer
  • Incidence rates are higher in developed countries
    • Likely due to increased use of diagnostic imaging
  • USA (2021[1])
    • Includes renal pelvis cancers
    • Estimated mortality 13,780
    • Estimated incidence 76,080
  • Canada (2020[2])
    • Includes renal pelvis cancers
    • Estimated incidence 7,500
      • 10th most commonly diagnosed cancer in Canada
  • Incidence has been increasing due to (2):
    1. Increased use of diagnostic imaging
       • Greatest increase has been in small, clinically localized renal amsses which now represent > 40% of incident tumours.
    2. Increased prevalence of risk factors (e.g. obesity), see below
• Survival
  • 5-year relative survival (survival relative to population without disease) based on disease stage at diagnosis[3]:
    • Localized: 93%
    • Regional: 70%
    • Distant: 13%
    • All stages: 75%
  • Most lethal of all GU malignancies
    • 5-year relative survival all stages for[4]:
      • Prostate cancer: 98%
      • Bladder: 77%
  • Survival has been increasing (≈1% year since 2004)
• Gender
  • M:F 3:2
    • Overall mortality worse in males
• Age
  • Typical presentation between age 50-70; median age at diagnosis: 64
    • RCC in children and young adults is more likely to be symptomatic, locally advanced, high grade, and of unfavorable histologic subtypes.
      • Children and young adults may respond better to surgical therapy and aggressive approach and formal lymphadenectomy has been recommended at the time of radical nephrectomy
• Race
  • More common in African Americans, American Indian, and Alaska Native populations than Caucasians

Pathogenesis

• Majority of cases are believed to be sporadic
• Established risk factors (5):
  1. Obesity
     • Accounts for ≈30% of incident cases
     • Obese patients are more likely to develop RCC but these tumours are more likely to be low-grade, early stage tumours
  2. Smoking
     • Accounts for ≈20% of incident cases
  3. Hypertension
  4. Familial syndromes
     • Accounts for ≈4-6% of incident cases§
  5. Chronic renal failure
     • Controversial; however, patients on maintenance dialysis also are reported to have an increased risk
       • It has been suggested to delay screening for kidney cancer in patients on dialysis and without other major comorbidities until the 3rd year on dialysis.
• Other risk factors (5):
  1. Family history of renal malignancy (without familial syndrome)
  2. Exposure to chlorinated solvents
  3. Retroperitoneal radiation
  4. Diet
     • Moderate alcohol intake, consumption of fruits and (cruciferous) vegetables, and a diet rich in fatty fish are believed to reduce the risk of RCC
  5. Acquired cystic renal disease
• No increased risk of RCC in patients with autosomal dominant polycystic kidney disease

Questions

1. What proportion of RCCs are familial?
2. What are the risk factors for RCC?

Answers

1. What proportion of RCCs are familial?
   • ≈4-6%
2. What are the established risk factors for RCC?

1. 1. Obesity
   2. Hypertension
   3. Smoking
   4. Acquired cystic disease
   5. Familial syndrome

References

• Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 57
• Campbell, Steven C., et al. "Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline Part I." The Journal of urology (2021): 10-1097.