1. Management of Incidentally Detected Small Renal Masses: A Primary Care Guide
Alon Z. Weizer, MD, MS
Associate Professor of Urology
University of Michigan

2. Disclosures
Advisory Board for Summus eConsult platform

3. 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

4. Outline Case presentation Definition small renal mass
Epidemiology of renal masses
Determining management of small renal masses
Treatment options/outcomes
Surveillance/survivorship

5. 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….

6. 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

7. 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

8. 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)

9. Epidemiology: Risk Factors
Clinical observations from UM
Median BMI 38
Trend toward decreasing age at diagnosis (17 years old youngest primary RCC)
Association with Hepatitis C
Chow et al, Nat Rev Urol, 2010

10. Epidemiology: Familial Syndromes

11. 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)

12. 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

13. 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

14. Cystic Lesions/Bosniak Classification

15. Cystic Lesions/Bosniak Classification

16. Size Matters in SRM Mgmt
Kunkle, J Urol, 2008
N=2770
Frank, J Urol, 2003

17. Location/Complexity of tumors: Nephrometry Score
Nephrometry.com

18. 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

19. Management: Patient Factors
Medical comorbidities
Age
Prior surgical history
Family history
Symptoms

20. Chronic Kidney Disease is an Important Consideration in How We Manage Small Renal Masses

21. 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

22. Health Implications of Chronic Kidney Disease
Adverse CV Events
Death
An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, communitybased population. These findings highlight the clinical and public health importance
of chronic renal insufficiency.
Go et al, NEJM, 2004

23. Quantifying competing risks in RCC
Age-specific mortality from kidney cancer showed relative stability within size strata; cancer-specific mortality varied inversely with tumor size.: 5.3% at 5 years for patients with tumors <= 4cm vs 18.1% for patients with tumors > 4 cm. Competing cause mortality increased with patient age, estimated at 28% at 5 years for patients 7 and older at the time of diagnosis.
Hollingsworth et al, CANCER, 2007

24. Even Nephron Sparing approaches have potential side effects
IMPORTANCE
Even Nephron Sparing approaches have potential side effects

25. Types of Complications: Ablation
Collecting system / Ureteral injury
Hemorrhage
Adjacent organ injury
Pain/Neuromuscular injury
Tumor seeding
Grounding pad burns
Infection
Pneumothorax
Cryoshock (theoretical)

26. Complications- Nephron Sparing Surgery
Variable
Partial Nephrectomy Approach
Mean % (range)
Laparoscopic
Laparoscopic-RP
Robotic
Open N
11505
255
1055
9947
Acute Kidney Injury
0.7 ( )
Not reported
3.5 (0.5-13)
Death
0.3*
0.5*
Nephrectomy
1.8 (0.5-4)
3.6 ( )
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*
Urine leak
3.4 (1-8)
0-1.8
3.9 (1-16.8)**
2.5 ( )
Blood transfusion
6.3 ( )
4.2 (0-7.1)
8.2 (5.1-11)
Readmission
11 ( )*
11.9*

27. How Do We Balance Tumor, Patient Factors, and Risks to Help Patients Make Informed Decisions About Management of SRMs?

28. 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?

29. Results: most grow slowly
Combined
Uzzo J Urol 2005

30. Renal Mass Biopsy- A Christmas Carol Remix
Renal Mass Biopsy at UM
Past
Present
Future

31. Renal Mass Biopsy: Past
The ancient past: no renal mass biopsy
The more recent past at UM…

32. 78/204 patients underwent RMB Patient factors predicting biopsy:
Patient factors predicting biopsy:
Non-Caucasian
Family history
Anatomic factors:
Juxta-hilar tumors
Increasing BMI
High complexity Nephrometry score

33. Biopsy directed management
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

34. Renal Mass Biopsy-Present
What drives active surveillance?

35. 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

36. Renal Mass Biopsy-Future
OR the Death of Unecessary Surgery?

37. 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
Exclusion
Hereditary syndrome
ECOG > 2
Concerns over compliance
Unable to obtain adequate imaging to perform surveillance

38. 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

39. Individualizing SRM Management
Renal Mass Biopsy
Indeterminate
Treat per histology
Repeat Biopsy
F/u per MD
Benign
F/u per MD
Treat
Unfavorable
Intermediate
Favorable

40. 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

41. 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%

42. How Many People Remain on AS?.2 .4 .6 .8 1
Cum. Survival 6 12 18 24 30 36
Time
How Many People Remain on AS?

43. 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?

44. Small Renal Masses: Treatment Strategies

45. Small Renal Masses: Treatment Strategies

46. Take Home Message
Discuss imaging with Urologist prior to referral (minimize unnecessary/unhelpful imaging)
Help Urologist understand the competing medical co-morbidities 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