What are the findings that support a diagnosis of renal cell carcinoma (RCC)?

From the Guidelines

Renal cell carcinoma (RCC) diagnosis is primarily supported by imaging studies, such as CT scans with contrast, MRI, or ultrasound, showing a solid renal mass with enhancement, particularly in the cortical phase, as well as histopathological examination of tissue samples revealing characteristic clear cells 1. The diagnosis of RCC is a complex process that involves various diagnostic modalities. Key findings that support the diagnosis of RCC include:

• A solid renal mass on imaging studies, such as CT scans with contrast, MRI, or ultrasound, showing enhancement with contrast, particularly in the cortical phase
• Histopathological examination of tissue samples revealing characteristic clear cells with abundant cytoplasm, distinct cell membranes, and hyperchromatic nuclei in the most common clear cell RCC subtype
• Laboratory findings, such as hematuria, elevated erythrocyte sedimentation rate, anemia, and occasionally elevated calcium levels (paraneoplastic syndrome)
• Clinical presentations, including the classic triad of flank pain, hematuria, and palpable abdominal mass, though this complete triad is present in less than 10% of cases
• Additional findings, such as constitutional symptoms like weight loss, fatigue, and fever
• Genetic testing, which may reveal mutations in the VHL gene (von Hippel-Lindau) in hereditary cases or sporadic clear cell RCC
• Imaging studies, which may also show evidence of local invasion, lymphadenopathy, or distant metastases, particularly to lungs, bone, liver, or brain, indicating advanced disease. According to the most recent study 1, the American Cancer Society estimates that approximately 73,750 new cases of kidney and renal pelvis cancer will be diagnosed in the United States, and approximately 14,830 people will die of this disease. RCC accounts for 85% of all malignant renal tumors and represents approximately 2% to 3% of all malignancies in adults. The staging of RCC is crucial for determining the prognosis and treatment plan. The stage of RCC reflects the tumor size, extent of invasion outside of the kidney, the involvement of lymph nodes, and whether the tumor has metastasized, and CT imaging with contrast enhancement of the chest, abdominal cavity, and pelvis is required for optimal staging 1. In terms of treatment, surgical resection with curative intent, including radical nephrectomy or partial nephrectomy, continues to be the standard of care for clinically localized RCC 1. Ablative therapies, such as radiofrequency ablation, microwave ablation, and cryoablation, have been shown to be effective and safe alternatives for the treatment of small localized RCCs 1. Active surveillance protocols may also be considered for some patients with small localized RCCs 1. The AUA guideline 1 focuses primarily on the evaluation and management of clinically localized renal masses suspicious for RCC in adults, including solid enhancing renal tumors and Bosniak 3/4 complex cystic masses. The guideline reflects significant advances in the field of kidney cancer since the initial AUA guideline on this topic was released in 2009. Recent cancer genomic studies have revealed an overt complexity of intra-tumor and inter-tumor heterogeneity in ccRCC, which could contribute to the heterogeneous clinical outcomes observed 1. Targeted therapy against vascular endothelial growth factor (VEGF) and mTOR pathways has been developed, but treatment response is varied, and most patients eventually progress 1. However, increased genomic and molecular understanding of metastatic ccRCC has contributed to an unprecedented number of drug approvals in the United States and European Union.

From the FDA Drug Label

The ORR was higher in the sunitinib arm (see Table 11). Table 11 Treatment-Naïve RCC Efficacy Results (Interim Analysis) from Study 3 Efficacy Parameter Sunitinib (N = 375) Interferon Alfa (N = 375) p-value (log-rank test) HR (95% CI) Progression-free survival a[median, weeks (95% CI)] 47.3 (42.6,50.7) 22.0 (16.4,24.0) < 0.000001 b 0.415 (0.320,0.539) Objective response rate a [%, (95% CI)] 27.5 (23.0,32.3) 5.3 (3.3,8.1) < 0. 001 c NA

The findings that support a diagnosis of renal cell carcinoma (RCC) include:

• High objective response rate (ORR): 27.5% of patients with RCC treated with sunitinib had a partial response, compared to 5.3% of patients treated with interferon alfa.
• Improved progression-free survival (PFS): The median PFS was 47.3 weeks for patients treated with sunitinib, compared to 22.0 weeks for patients treated with interferon alfa.
• Statistically significant advantage: Sunitinib had a statistically significant advantage over interferon alfa in terms of PFS and ORR. These findings suggest that sunitinib is effective in the treatment of RCC, and may be used to support a diagnosis of RCC in patients who respond to treatment with sunitinib 2.

From the Research

Diagnostic Imaging for Renal Cell Carcinoma

• Computed Tomography (CT) is the primary choice for imaging of renal masses due to its high resolution, reproducibility, and reasonable preparation and acquisition time 3.
• Magnetic Resonance Imaging (MRI) is considered an important alternative for patients requiring further imaging, or in cases of allergies, pregnancy, or surveillance, and its use has been increasing due to concerns over radiation exposure 3.
• Ultrasound is commonly used for renal imaging but is not the first choice for imaging of renal masses 3.

Incidental Diagnosis and Screening

• Many patients (37%-61%) are diagnosed with renal cell carcinoma incidentally on an abdominal imaging study such as ultrasound or computed tomographic scan 4.
• Screening for renal cell carcinoma is usually only carried out for patients who have been identified as having one of the known genetic lineages linked with specific RCC subtypes 5.

Diagnosis and Prognosis

• Renal masses, either cystic or solid, are best detected with contrast-enhanced, triple-phase computed tomography 6.
• Predictors of a poor prognosis include poor functional status and metastasis, but new therapies have improved the prognosis for patients with metastatic disease 6.
• MRI can clearly show venous invasion without the use of IV contrast medium and is superior to CT in differentiating lymphadenopathy from small vascular structures 7.

Treatment Options

• Treatment options for renal cell carcinoma confined to the kidney include surgical resection with partial or radical nephrectomy, ablative techniques, or active surveillance 4.
• For advanced or metastatic renal cell carcinoma, combinations of immune checkpoint inhibitors or the combination of immune checkpoint inhibitors with tyrosine kinase inhibitors are associated with tumor response and median overall survival 4.