What is the diagnostic and treatment approach for a patient with suspected renal cancer and abnormal lab results?

Renal Cancer: Clinical Presentation and Laboratory Findings

For suspected renal cancer, obtain a comprehensive metabolic panel (including serum calcium, liver function tests, and LDH), complete blood count, urinalysis, and high-quality multiphase cross-sectional imaging (CT or MRI with contrast) of the abdomen/pelvis plus chest imaging—these are the essential diagnostic studies that guide staging and treatment decisions. 1, 2

Clinical Presentation

Classic Symptoms (Now Uncommon)

• The classic triad of flank pain, palpable abdominal mass, and gross hematuria now occurs in less than 10% of patients and typically indicates locally advanced or metastatic disease 1, 3
• Over 50% of renal cell carcinomas are now detected incidentally on abdominal imaging performed for unrelated reasons 1, 3, 4
• 70% of patients present with stage I disease at diagnosis 1, 3

Warning Signs Requiring Urgent Evaluation

• Gross hematuria (visible blood in urine) or persistent microscopic hematuria on urinalysis 1, 5, 4
• Unexplained flank or abdominal pain with or without a palpable mass 1, 5
• Constitutional symptoms: unexplained weight loss, persistent fever without infection, or night sweats 1, 5, 6

Paraneoplastic Manifestations

• Hypercalcemia (elevated serum calcium) 1
• Erythrocytosis (elevated red blood cell count) 1, 7
• Hepatic dysfunction without liver metastases (Stauffer's syndrome) 7
• Unexplained fever 1, 5

Essential Laboratory Evaluation

Mandatory Initial Tests

Every patient with suspected renal malignancy requires: 1, 2

• Complete blood count (CBC): assess for anemia from bleeding, erythrocytosis (paraneoplastic), or thrombocytopenia 1
• Comprehensive metabolic panel including:
  • Serum creatinine and estimated GFR (assess baseline renal function) 1
  • Serum calcium (corrected for albumin—hypercalcemia is a poor prognostic sign) 1
  • Liver function tests (AST, ALT, alkaline phosphatase, bilirubin) 1
  • Lactate dehydrogenase (LDH—elevated levels indicate poor prognosis) 1
• Urinalysis: document hematuria (microscopic or gross) and assess for proteinuria 1, 2, 5
• Coagulation profile (PT/INR, PTT) 1

Additional Prognostic Laboratory Markers

• C-reactive protein (CRP) and erythrocyte sedimentation rate (inflammatory markers associated with worse outcomes) 1
• Serum alkaline phosphatase (if elevated, consider bone scan for skeletal metastases) 1

Chronic Kidney Disease Staging

Classify CKD stage based on eGFR and degree of proteinuria using KDIGO guidelines—this directly impacts surgical candidacy and treatment options 1, 2, 7

Critical Imaging Studies

Primary Diagnostic Imaging

• Multiphase CT of abdomen/pelvis with and without IV contrast (gold standard for characterization and staging) 1, 2
• Chest imaging (CT chest preferred over plain radiograph) to evaluate for pulmonary metastases—the most common metastatic site 1, 2, 5
• Abdominal MRI is an alternative when contrast cannot be administered due to allergy or severe renal insufficiency, or to evaluate inferior vena cava tumor thrombus 1

Conditional Imaging (Not Routine)

• Bone scan: only if elevated alkaline phosphatase or bone pain present 1
• Brain CT or MRI: only if neurological symptoms or signs suggest brain metastases 1
• PET scan is NOT routinely indicated in initial workup 1

Role of Renal Mass Biopsy

Needle biopsy should be considered in specific scenarios: 1, 2

• Before ablative therapies (cryoablation, radiofrequency ablation) to confirm malignancy 1, 2
• In patients with metastatic disease before starting systemic therapy 1
• To guide active surveillance strategies for small renal masses 1, 2
• When imaging remains indeterminate after optimal cross-sectional studies 1, 2

Biopsy provides high sensitivity and specificity for histopathological confirmation but has limited role when surgical resection is planned 1

Physical Examination Priorities

Focus the examination on detecting: 1

• Supraclavicular lymphadenopathy (suggests advanced disease)
• Palpable abdominal or flank mass (indicates larger tumor)
• Varicocele (especially left-sided, non-reducible—suggests renal vein involvement)
• Lower extremity edema (may indicate IVC obstruction)
• Subcutaneous nodules (cutaneous metastases)

Common Pitfalls to Avoid

• Do not assume all enhancing renal masses are malignant—approximately 20% of surgically resected small renal masses are benign 2
• Do not overlook proteinuria assessment—it reflects underlying CKD and independently predicts outcomes, though it is not caused by RCC itself 1, 2, 7
• Do not order bone scan, brain imaging, or PET scan routinely—these are only indicated when specific clinical or laboratory findings suggest metastases 1
• Do not delay urologic referral when a solid or complex cystic renal mass is identified on imaging 1, 3
• Dropping hemoglobin on serial CBCs indicates ongoing hemorrhage and requires urgent cross-sectional imaging 5

Prognostic Implications

Five-year survival rates by stage: 1

• Stage I: 96%
• Stage II: 82%
• Stage III: 64%
• Stage IV: 23%

Poor prognostic laboratory findings include: 1

• Elevated LDH
• Hypercalcemia
• Anemia
• Elevated CRP
• Thrombocytosis
• Elevated alkaline phosphatase