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Management of Incidentally Detected Small Renal Masses: A Primary Care Guide Alon Z. Weizer, MD, MS Associate Professor of Urology University of Michigan Disclosures • Advisory Board for Summus eConsult platform Learning Objectives • Define Small Renal Mass • Determine when referral is needed • Understand How Management is determined based on patient and tumor factors • Understand the role of the primary care physician in longitudinal management Outline • • • • • • Case presentation Definition small renal mass Epidemiology of renal masses Determining management of small renal masses Treatment options/outcomes Surveillance/survivorship Case presentation • • • • • • • • • 53 yo man incidentally discovered 4 cm renal mass on CT obtained for elevated LFTs PMH: Type 2 diabetes, hypertension, treated hepatitis C, obesity (BMI 38) PSH: knee arthroscopy Social history: married, employed, 2 adult children, works at water treatment facility FH: no kidney disease or masses Medications: lisinopril, HCTZ, metformin, OTC ibuprofen, MVI All: none Labs, CXR normal Next steps…. What is a small renal mass? • Cystic or solid lesion of the kidney measuring less than 4 cm • Refers to primary kidney tumors, not urothelial or metastases • Usually incidentally detected • Certain patients should be managed differently: – Multiple masses in one or both kidneys – Family history of kidney tumors Epidemiology • Incidence: 63,000 new cases; 14,000 deaths • 2:1 ratio (men: women) • Occurs most frequently in 6th to 8th decade of life (rare < 40 yo) • Racial differences exist with increasing incidence in AA Epidemiology: RCC is increasing • Largely attributed to increased use of cross-sectional imaging • Mortality decline subtle • Most renal masses detected are small with good outcomes • Patients with locally advanced/metastatic disease continue to have poor survival (although TKIs have improved outcomes) Epidemiology: Risk Factors • Clinical observations from UM Chow et al, Nat Rev Urol, 2010 – Median BMI 38 – Trend toward decreasing age at diagnosis (17 years old youngest primary RCC) – Association with Hepatitis C Epidemiology: Familial Syndromes Appropriate Management of SRMs? • Historically all SRMs are treated (biopsy considered non-informative) • Arguments to avoid intervention: – many tumors are benign – Will not affect survival of patient – Our treatments have side effect (“Do no harm”) – We have tools that can give us information about how to manage SRMs (biopsy) Management Considerations • Understanding the tumor: – Character (Cystic versus solid) – Size – Location – Number of lesions – Extent of disease • Understanding the patient: – – – – – Medical comorbidities Age Prior surgical history Family history Symptoms • Understanding Risk of Interventions Management: Tumor Characteristics • Imaging goals: – Determine whether the tumor is cystic or solid – Size of tumor – Location of tumor in reference to vascular, collecting system anatomy – Assess for loco-regional disease/metastases Cystic Lesions/Bosniak Classification Cystic Lesions/Bosniak Classification Size Matters in SRM Mgmt Kunkle, J Urol, 2008 N=2770 Frank, J Urol, 2003 Location/Complexity of tumors: Nephrometry Score Nephrometry.com Number of lesions/Extent of Disease • Multifocal disease warrants different evaluation – Referral to tertiary center with Urologic Oncology and genetic evaluation – All patients with renal masses/cysts < 40 years old are recommended to be evaluated by genetics • Staging work-up can include: – – – – – Labs: CBC/comp Chest imaging Abd/pelvis imaging Bone scan not indicated unless Ca, Alkaline phosphatase elevated or symptoms Brain imaging not indicated unless symptoms • Risk of metastasis rare with tumors < 2 cm so imaging work-up should also be influenced by diagnosis and management Management: Patient Factors • • • • • Medical comorbidities Age Prior surgical history Family history Symptoms Chronic Kidney Disease is an Important Consideration in How We Manage Small Renal Masses Why does this matter for our patients with kidney cancer? • CKD is actually more common than we think among patients with renal cortical tumors • Baseline GFR may be associated with long-term survival • Nephron sparing approaches (partial/ablation) associated with a decreased risk of post-operative chronic kidney disease and adverse renal health outcomes – BUT STILL RISK WITH NS approaches Health Implications of Chronic Kidney Disease Adverse CV Events Go et al, NEJM, 2004 Death Quantifying competing risks in RCC Hollingsworth et al, CANCER, 2007 IMPORTANCE Even Nephron Sparing approaches have potential side effects Types of Complications: Ablation • • • • Collecting system / Ureteral injury Hemorrhage Adjacent organ injury Pain/Neuromuscular injury • • • • • Tumor seeding Grounding pad burns Infection Pneumothorax Cryoshock (theoretical) Complications- Nephron Sparing Surgery Variable Mean % (range) Partial Nephrectomy Approach Laparoscopic Laparoscopic-RP Robotic Open 11505 255 1055 9947 0.7 (0.6-0.9) Not reported 0 3.5 (0.5-13) 0.3* Not reported 0 0.5* Nephrectomy 1.8 (0.5-4) Not reported 3.6 (1.6-7.7) 0 Clavien 3+ 11 (0-36) 4.5* 4.9 (0-8.2) 5 (4-6.7) Embolization 1.7 (0.5-4) 0.9* 1.7 (1-2.6) 3* 3.4 (1-8) 0-1.8 3.9 (1-16.8)** 2.5 (0.6-5.5) 6.3 (1.6-12.5) 2.7-5.1 4.2 (0-7.1) 8.2 (5.1-11) 11 (10.4-11.1)* Not reported 11.9* Not reported N Acute Kidney Injury Death Urine leak Blood transfusion Readmission How Do We Balance Tumor, Patient Factors, and Risks to Help Patients Make Informed Decisions About Management of SRMs? Observation of Renal Masses • Observation of small renal masses – Often used in elderly/multiple medical comorbidities – Advantages • Determine natural history of mass • Avoid unnecessary intervention – Disadvantage • Risk of disease progression? Results: most grow slowly Combined Uzzo J Urol 2005 Renal Mass Biopsy- A Christmas Carol Remix • Renal Mass Biopsy at UM – Past – Present – Future Renal Mass Biopsy: Past • The ancient past: no renal mass biopsy • The more recent past at UM… • 78/204 patients underwent RMB – 2009-10 • Patient factors predicting biopsy: – Non-Caucasian – Family history • Anatomic factors: – Juxta-hilar tumors – Increasing BMI – High complexity Nephrometry score • Biopsy performed in a greater proportion of patients undergoing radical nephrectomy (identification of aggressive pathology-papillary type II) • Biopsy directed management – Active surveillance more common in patients with benign or low risk histology – Intervention more frequent for aggressive histology • Take home message- biopsy was often used to avoid intervention for technically difficult surgeries Renal Mass Biopsy-Present • What drives active surveillance? • Similar population: – 73 of 204 patients underwent active surveillance – Patient factors: distance from the hospital, ECOG performance status – Tumor factors: tumor size, endophytic, multifocality – Surgeon factors: minimally invasive surgeons more likely to operate – Interestingly, biopsy did not play a major role in selecting active surveillance over treatment Renal Mass Biopsy-Future • OR the Death of Unecessary Surgery? SRM Active Surveillance Protocol Eligibility criteria • Inclusion – – – – – Incidental sporadic solid renal mass 2 kidneys < 4 cm mass Percutaneous renal mass core biopsy No lymphadenopathy or metastatic disease – – – – Hereditary syndrome ECOG > 2 Concerns over compliance Unable to obtain adequate imaging to perform surveillance • Exclusion SRM Active Surveillance Protocol Histology definitions • Benign – AML, adenoma, … • Favorable – oncocytic, chromophobe, gr 1 pap type 1 / • Intermediate – gr 2 pap type 1 / clear cell • Unfavorable – pap type 2, gr 3-4 clear cell, … • Indeterminate – any non-diagnostic histology Individualizing SRM Management Renal Mass Biopsy Benign Indeterminate Unfavorable Treat F/u per MD Treat per histology Favorable Intermediate Repeat Biopsy Indeterminate F/u per MD • 151 patients underwent renal mass biopsy and surgery over 10 years for mass < 4 cm • We used this data to see if RMB would help characterize the appropriate treatment based on algorithm • Biopsy diagnostic in 133 cases • 36 patients assigned to surveillance based on algorithm – 11 patients initially assigned to surveillance should have undergone treatment based on final pathology (issue with grade especially for clear cell) – No patients went from treatment to surveillance • After moving any clear cell to intermediate risk – Accuracy 97%, NPV 86%, PPV 100% How Many People Remain on AS? 1 .8 .6 .4 .2 0 0 6 12 18 Time 24 30 36 Renal Mass Biopsy: The Real Future? • Need to use Renal Mass Biopsy to better characterize risk – Grade continues to be difficult – Does biopsy represent true biology of tumor? – Can we learn more from RMB to refine algorithm? • IHC • Omics? Small Renal Masses: Treatment Strategies Renal Mass ≤ 7 cm (Page 1 of 2) University of Michigan Department of Urology No Medical condition and/or renal function poor, mass < 4 cm in all but most extreme cases Surveillance Nephron-sparing procedure Is treatment needed? Consider Biopsy if < 4 cm Yes Yes Active Treatment Should nephrons be spared? No Page 2 Mass unfavorable for partial nephrectomy, and/or good renal function Laparoscopic Radical Nephrectomy Adapted from: W olf, J.S., Jr. and Hollenbeck, B.K. Urologic Oncology, 24: 281-283, 2007. Small Renal Masses: Treatment Strategies Renal Mass ≤ 7 cm (Page 2 of 2) University of Michigan Department of Urology From Page 2 Excise How to spare nephrons? Mass ≤ 3 cm and not adjacent to renal hilum, and patient with less tolerance of complications and/or shorter life expectancy Excision Ablate Mass not technically amenable to laparoscopic excision Ablation Mass adjacent to bowel, psoas muscle, or ureter Percutaneous Ablation Lap/Robotic Partial Nephrectomy Open Surgical Partial Nephrectomy Laparoscopic Ablation Adapted from: W olf, J.S., Jr. and Hollenbeck, B.K. Urologic Oncology, 24: 281-283, 2007. Take Home Message • Discuss imaging with Urologist prior to referral (minimize unnecessary/unhelpful imaging) • Help Urologist understand the competing medical comorbidities of your patient • Discourage direct referral to radiology if they do not partner with a Urologist • Consider referral to tertiary center for young patients/multifocal disease • Re-assure patients that outcomes of SRMs are good and that they have time to understand options