Kidney Cancer – Diagnosis, Symptoms, and Treatment

What is Kidney Cancer?

Renal cell carcinoma (RCC) is the most common form of kidney cancer.  It is more frequently seen in men than women and usually affects individuals in the 6th to 8th decade.  Patients classically have flank pain, blood in the urine (hematuria), and an abdominal mass – although this triad is seen in a small percentage of individuals.  Patients are occasionally asymptomatic with microscopic blood in the urine.  Smoking and obesity are major risk factors for the condition.

Patients with advanced disease have a poor prognosis with high mortality.

What Causes Kidney Cancer?

The precise cause of renal cell carcinoma is not known.  It likely involves a combination of genetic and environmental factors.  Patients with a family history of renal cell carcinoma are at risk of developing the disease.  Studies indicate that most sporadic cases are related to a mutation in the von Hippel-Lindau tumor suppressor gene.  Most cases of renal cell carcinoma are of the clear cell type.

Risk factors associated with an increased incidence of RCC include:

• • Smoking
  • Obesity
  • Hypertension

• Genetic factors

How Common is Kidney Cancer?

In the United States, the incidence of renal cell carcinoma is about 64,000 new cases a year.  There are nearly 14,000 deaths related to renal cell cancer annually.  The condition is most frequently seen in the Czech Republic and North America.  Men are 50% more likely to have the disease than women.  The disease is rare in patients under age 40.  The condition typically requires referral to a urologist and occasionally an oncologist.

Signs and Symptoms

The classic features of renal cell carcinoma include:

• Flank pain
• Blood in the urine
• Abdominal renal mass felt on examination

The presence of all three of these findings suggests locally advanced cancer.  Patients may also develop symptoms related to local invasion or distant spread (metastasis) of the disease.  This typically includes back or flank pain on the same side of cancer.  Metastatic disease is often associated with decreased appetite and weight loss.

Occasionally, patients may develop dilated veins in the scrotum due to kidney cancer.  This occurs because veins of the left scrotum drain into the left renal vein.  When the renal vein becomes blocked off with a large kidney mass, this causes backup of blood into the scrotum.

Diagnosis

The diagnosis of renal cell carcinoma is suggested based on symptoms and physical examination but typically confirmed with laboratory and imaging studies.  Your doctor will usually obtain a urine analysis evaluating for blood or any other abnormalities.  They will also typically get a CT scan of the abdomen to visualize the kidneys and asses for any masses.

Small solitary kidney masses are not reliably characterized as benign versus malignant on CT scans - these often require surgical removal for a definitive diagnosis.  Renal cell carcinoma is staged based on the size of the tumor, presence of regional lymph node involvement, and whether or not there is distant metastasis (TNM staging system).  Patients with distant metastasis have a poor prognosis.

Additional blood tests that are commonly ordered include a CMP (comprehensive metabolic panel), CBC (complete blood cell count), and coagulation studies (PT/INR, PTT).

Kidney Cancer Medication and Treatment

The treatment of renal cell carcinoma typically depends on the disease stage and the presence of comorbidities.  Generally, healthy patients with small tumors involving one or both kidneys may be candidates for partial nephrectomy – only portions of the kidney affected by cancer will be removed.

Those with local invasion into the adrenal gland, renal vein, or surrounding fat frequently require radical nephrectomy - complete surgical removal of the kidney.

Patients with multiple comorbidities and those that are elderly may benefit from less invasive strategies such as cryoablation or radiofrequency ablation.

In patients with local renal cell carcinoma, complete resection of the tumor frequently leads to a cure.  Those with more advanced forms of the disease may require adjuvant therapy with either immunotherapy, vascular endothelial growth factor (VEGF) pathway inhibitors, or mechanistic target of rapamycin (mTOR) inhibitors.

First-line treatment for patients with the metastatic disease typically includes immunotherapy with high-dose interleukin-2 (IL-2).  An alternative includes vascular endothelial growth factor (VEGF) pathway inhibitors such as Votrient (pazopanib) or Sutent (sunitinib).

Other agents used in renal cell carcinoma include:

• Inlyta (axitinib)
• Nexavar (sorafenib)
• Opdivo (nivolumab)
• Cabometyx (cabozantinib)

References:

1. Santos Arrontes D, Fernández Aceñero MJ, García González JI, et al. Survival analysis of clear cell renal carcinoma according to the Charlson comorbidity index. J Urol 2008; 179:857. - https://www.ncbi.nlm.nih.gov/pubmed/18221956
2. Lamb GW, Bromwich EJ, Vasey P, Aitchison M. Management of renal masses in patients medically unsuitable for nephrectomy--natural history, complications, and outcome. Urology 2004; 64:909. - https://www.ncbi.nlm.nih.gov/pubmed/15533476
3. Rendon RA, Stanietzky N, Panzarella T, et al. The natural history of small renal masses. J Urol 2000; 164:1143. - https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20025