Contemporary Outline Management of Renal • Epidemiology Masses • Differential Diagnosis • Evaluation • Imaging Geoffrey N. Box, MD • Role for Biopsy Vice Chair of Educational Affairs Assistant Professor • Treatment Direct, Laparoscopic Urologic Surgery • Surveillance Department of Urology • Surgery The Ohio State University Wexner Medical Center • Ablation James Cancer Hospital and Solove Research Institute • Follow-up • Cases Renal Mass • Increasing incidence with widespread use of cross-sectional imaging • Renal lesions are seen in 15-25% of abdominal imaging studies ‒ Most are benign cysts • Majority are detected incidentally. ● = <2 cm, ▲ = 2 – 4 cm, ○ = >4 – 7 cm, and ∆ = >7 cm 1 Renal Mass- Differential Diagnosis Renal Mass- Differential Diagnosis Malignant Benign Inflammatory Renal Cell Carcinoma Simple cyst Abscess -Clear Cell Angiomyolipoma Focal pyelonephritis Malignant Benign -Papillary Oncocytoma Xanthogranulomatous -Chromophobe Metanephric adenoma pyelonephritis Renal Cell Carcinoma Simple cyst -Collecting duct Cystic Nephroma Tuberculosis -Clear Cell Angiomyolipoma Urothelial Based Mixed epithelial/stromal -Urothelial tumor -Papillary Oncocytoma carcinoma Reninoma -Chromophobe -Squamous cell Leimyoma -Adenocarcinoma Pseudotumor Sarcoma Wilms tumor Carcinoid Lymphoma Leukemia Metastasis Is it Benign or Radiographic Assessment Malignant? • Ultrasound • The question at hand. • CT • This can frequently determined by • MRI radiographic assessment. • Size Matters • Key Point: • Current trend is to biopsy more renal masses ‒ Need to determine enhancement <4cm. 2 Ultrasound CT Scan • Triple Phase (Renal Protocol) • Reliable for ‒ Pre-contrast differentiation of ‒ Post-contrast (venous phase) a solid lesion Cyst ‒ Delayed (10 min) Tissue HU from fluid. Bone +1000 Blood 40 • Can establish Kidney 30 the diagnosis of Water 0 a simple cyst. • Hounsfield Units (HU) Fat -50 Solid Mass ‒ Represents the density of Air -1000 tissue Enhancement CT-Enhancement • Can only be determined if a contrast agent is used ‒ CT – iodonated contrast • Enhancing Lesion = Pre-contrast to Post-contrast change in HU >15-20 ‒ MRI – Gadolinium Pre-contrast HU: 15 • Slightly more subjective Post-contrast HU: 55 3 MRI Risk of Contrast Agents • Pre and Post Gadolinium • IV Contrast (CT) ‒ Contrast Allergy ‒ Nephrotoxicity • Avoid with severe renal impairment • Risk reduction: Hydration • Gadolinium (MRI) ‒ No nephrotoxicity ‒ Risk of Nephrogenic Systemic Fibrosis in those with severe renal impairment (EGFR<30). cG250 PET/CT: Radiolabeled Antibody Fat • 124I-cG250 • Solid masses with areas (REDECTANE®) of negative HU (<-20) ‒ Binds carbonic indicate the presence of anhydrase IX fat and are diagnostic of ‒ Clear cell RCC AMLs. ‒ Radiographic diagnosis • AML = Angiomyolipoma • No role for CT PET- • AML is a benign tumor. FDG with renal 18F-FDG tumors. 124I-cG250 Wilex AG, Munich, Germany 4 Renal Cysts: Bosniak Renal Cysts Classification Bosniak Class Description Cancer Risk Management • The kidney is one of the most common locations in the body for cyst formation. No enhancement Smooth Wall I No Septa 0% None • Renal cysts are cavities derived from renal tubules. No Calcifications No enhancement • Composed of a layer of epithelial II Hairline Septa Minimal None cells enclosing a cavity filled with Fine Calcifications urine-like liquid or semi-solid No enhancement material. Hyperdense lesion IIF Multiple Septa <10% Surveillance Thicker Calcifications • 20% by age 40 Thickened Wall with • 50% by age 60 III Enhancement 50% Surgery IV Enhancing Nodule 90% Surgery Adapted from Campbell-Walsh Urology 10th Ed. Renal Cysts – Bosniak Classification Case- Simple Renal Cyst I II • Pictures of each III IV 5 Imaging Interpretation Role for Biopsy • Enhancing renal masses are most likely malignant. • Historically, renal masses have not been biopsied. • Simple Cysts (Bosniak Type I): ‒ Most are malignant ‒ Can be diagnosed by U/S or CT. ‒ Do not need follow-up. ‒ Issues with accuracy/non-diagnostic rates • AMLs are benign and can be followed ‒ Fear of needle tract seeding ‒ >4cm = greater risk for spontaneous ‒ High reported complication rates bleeding • Selective angioembolization vs. surgery AML = Angiomyolipoma Role for Biopsy Role for Biopsy • Contemporary results of renal mass • Current role for biopsy is expanding biopsy: ‒ Especially for masses <4cm ‒ Diagnostic rate: 92%. • RCC Subtype Concordance: 80-100% • Updated date on biopsy results are much • Fuhrman Grade Concordance: 50-70% improved. ‒ Complications: <5% • Hematoma most common Marconi et al. Eur Urol 2015 6 Indications: Indications: Renal Mass Biopsy Renal Mass Biopsy • R/o non-renal primary (mets or lymphoma) • R/o non-renal primary (mets or lymphoma) • +/- R/o benign lesions • +/- R/o benign lesions • Confirm diagnosis and histologic subtype in • Confirm diagnosis and histologic subtype in patients with metastases or unresectable patients with metastases or unresectable lesions lesions • Confirm diagnosis: • Confirm diagnosis: ‒ Prior to ablative therapy ‒ Prior to ablative therapy ‒ In patients considering observation when ‒ In patients considering observation when surgery is high risk surgery is high risk Indications: Renal Mass Biopsy Tumor Size and Pathology • R/o non-renal primary (mets or lymphoma) Tumor Size RCC Benign* High Grade • +/- R/o benign lesions ≤2.0 75% 25% 4% Biopsy only if it will change management • Confirm diagnosis and histologic subtype in 2.1-3.0 80% 20% 5% patients with metastases or unresectable lesions 3.1-4.0 84% 16% 25% • Confirm diagnosis: ‒ Prior to ablative therapy *Oncocytoma and AML – 75% ‒ In patients considering observation when surgery is high risk J Urol 2006; 176:896 7 Renal Cancer 2015 Renal Cell Carcinoma – • Incidence Risk Factors ‒ 61,560 new cases • Tobacco Exposure ‒ 14,080 deaths ‒ May account for ~20% of cases • Obesity • Peak incidence 5th-7th decades ‒ May account for ~40% of cases in US ‒ Risk increases ~30% for every 5kg/m2 increase in BMI • Men > Women • Hypertension • Lifetime Probability of Developing Renal Cancer: • Low socioeconomic status and urban background ►1 in 49 male (#7) • More than 100 chemicals have been investigated ►1 in 84 female (#10) but none have been definitively established as American Cancer Society. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015 causative in RCC Renal Cancer – Mortality Renal Cancer – Presentation and Survival Site Incidence/yr Deaths 2015 Stage at Prostate Cancer 220,800 27,540 (12%) Diagnosis Distribution 5-yr Survival Localized 61% 91% Bladder Cancer 74,000 16,000 (22%) Regional 17% 63% Kidney Cancer 61,560 14,080 (23%) (lymph nodes) Distant 18% 11% (metastatic) American Cancer Society. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015 Seer Database 8 Clinical Presentation Paraneoplastic syndromes • 80% incidental • “Internist’s Tumor” • Elevated ESR 55% • HTN 38% • Flank pain • Anemia 36% • Gross hematuria • Cachexia 35% “Classic Triad” <10% • Pyrexia 17% • Palpable mass • Elevated LFTs 14% • Microhematuria • Hypercalcemia 5% • Polycythemia 4% • Paraneoplastic syndromes (10-20%) • Neuromyopathy 3% Campbell-Walsh Urology 10th Ed. Clinical Presentation - RCC Renal Cell Carcinoma: Histologic Subtypes • Local Tumor Growth ‒ Hematuria ‒ Flank Pain ‒ Abdominal Mass • Metastasis ‒ Persistent Cough ‒ Bone Pain ‒ Cervical Lymphadenopathy ‒ Constitutional Symptoms Type: Clear cell Papillary Chromophobe Oncocytoma • Obstruction of IVC ‒ Bilateral Lower Extremity Edema Freq (%): 75 15 5 5 ‒ Right-sided Varicocele (or nonreducing Varicocele) 9 Hereditary RCC VHL: Renal Cell Carcinoma Gene • RCC occurs in 50% of VHL Disease (chromosome) Histology Frequency patients von Hippel-Lindau VHL (3) Clear Cell 75% ‒ Males=females in VHL ‒ 4th to 5th decade (39) HLRCC* FH (1) Papillary Type 2 10% ‒ Now most common cause of death Multiple Renal Cysts Chromophobe/Onc Containing RCC Birt-Hogg-Dube BHD (17) 10% ocytoma Hereditary Met (7) Papillary Type 1 5% papillary RCC *HLRCC = Hereditary Leiomyomatosis Renal Cell Carcinoma Sporadic Inherited Clear Cell RCC Renal Cell Carcinoma: Treatment Options Staging • Surveillance Stage Tumor Lymph Nodes Metastasis • Surgical Excision I T1 (<7cm) N0 M0 Gold Standard ‒ Radical Nephrectomy ‒ Partial Nephrectomy II T2 (>7cm) N0 M0 T1 or T2 N1 • Needle Ablation III M0 T3 (vein/fat) N0 or N1 ‒ Cryoablation or Radiofrequency Ablation T4 (outside Any N Any M IV Gerota’s) Any N M1 • RCC does NOT respond to chemotherapy or Any T radiation 10 Decision Making Active Surveillance (AS) • Tumor Characteristics: • Incidentally detected tumors: ‒ Size ‒ Small size (<4cm) ‒ Location ‒ Elderly ‒ Appearance ‒ Patients with significant comorbidity unfit for surgery • Patient Characteristics ‒ Comorbid disease ‒ Life expectancy • Opportunity to observe the natural history ‒ Patient desire of these small tumors. Tumor Size and Pathology Active Surveillance • Tumors <3cm Tumor Size RCC Benign* High Grade ‒ Risk of developing metastasis in 3 ≤2.0 75% 25% 4% years is ~1% • Average growth rate ~0.3cm/yr 2.1-3.0 80% 20% 5% • Most studies only have limited follow-up 3.1-4.0 84% 16% 25% • Follow-up protocol is not defined *Oncocytoma and AML – 75% ‒ Repeat imaging every 6-12 months J Urol 2006; 176:896 11 Active Surveillance Risk-adapted Management • Biopsy can be helpful • AUA Guidelines: ‒ “AS is a reasonable option for • More favorable histology: patients with a limited life ‒ Papillary type 1 expectancy or for those who are ‒ Chromophobe unfit for or do not desire intervention.”