1. Data from The Johns Hopkins Renal Mass Registry
Michael A. Gorin, M.D.
The James Buchanan Brady Urological Institute
Johns Hopkins University School of Medicine

2. Kidney Cancer Basics
Kidney cancer (also known as renal cell carcinoma) is an epithelial malignancy arising from the renal parenchyma
Approximately 62,000 new cases are diagnosed annually in the United States
Nearly 80% of cases will be clinically localized at the time of diagnosis
The incidence/prevalence of RCC has risen steadily in recent decades due to a marked increase in the number of incidentally detected clinical T1 tumors
There are several histologic variants of RCC, each with a unique prognosis

3. Epidemiology
SEER.cancer.gov

4. Epidemiology
Cooperberg et al., J Urol 2008; 179: 2131.

5. Kidney Cancer Staging T1a ≤4 cm T1b 4.1−7 cm T2a 7.1−10 cm T2b
Invades perinephric or sinus fat and/or the renal vein
T3b
Invades the IVC below the diaphragm
T3c
Invades the IVC above the diaphragm T4
Invades beyond Gerota’s fascia N1
Involves regional lymph nodes M1
Distant spread

6. Common Renal Tumor Histologies
Renal Cell Carcinoma Benign
Clear Cell Papillary Chromophobe Oncocytoma AML
55% % % % %
*Remaining 5% of tumors include translocation RCC, clear cell papillary RCC, unclassified RCC, mixed epithelial stromal tumors and cysts.

7. Prognosis by Tumor Histology
Tumor Size
Time
Death from
Other Causes
Size at which
Cancer Causes
Symptoms
Death
Clear Cell
Type II Papillary
Chromophobe
Type I Papillary
Oncocytoma
AML
Adapted from Smaldone et al., Nat Rev Urol 2013; 10: 266.

8. Management Active Surveillance cT1 Renal Mass Thermoablation Surgery
NCCN Kidney Cancer Guideline, 2015

9. Risk-adapted approach for the management of the cT1 renal mass….

10. Renal Mass Biopsy Benign Indeterminate Favorable Intermediate
Unfavorable
Follow-up
Repeat
Biopsy
<2 cm ≥2 cm
ACTIVE
SURVEILLANCE
ABLATION or
SURGERY
Ada[ted from Halverson et al., J Urol 2013; 189: 441.

11. Limitations of Renal Mass Biopsy
Invasive procedure with associated pain, discomfort and inconvenience
Requires sedation or anesthesia
Non-diagnostic rate of 10-20%
Major complication rate of 1%
Inability to accurately determine tumor grade
Molecular heterogeneity
The “oncocytic neoplasm” conundrum

12. Tumor Grade Heterogeneity
Ball et al., J Urol 2015; 193: 36.

13. Limitations of Renal Mass Biopsy
Invasive procedure with associated pain, discomfort and inconvenience
Requires sedation or anesthesia
Non-diagnostic rate of 10-20%
Major complication rate of 1%
Inability to accurately determine tumor grade
Molecular heterogeneity
The “oncocytic neoplasm” conundrum

14. “Oncocytic Neoplasm”
Lane et al., J Urol 2008; 179: 20.

15. Eosinophilic Clear Cell Eosinophilic Chromophobe
“Oncocytic Neoplasm”
Eosinophilic Clear Cell
Type II Papillary
Eosinophilic Chromophobe
Oncocytoma
Lane et al., J Urol 2008; 179: 20.

16. Can we eliminate the need for renal mass biopsy?

17. Johns Hopkins Renal Mass Registry
SKCCC Cancer Registry
National Death Index
Anesthesia Data System
Billing/Case Mix Office
OR Schedule
Urology Biorepository

18. JH Renal Mass Registry Stats
Complete annotated data on all patients who have undergone surgery for a renal mass at JHH or JHBMC from 2003 – Present
2,705 patients
2,733 procedures
Partial nephrectomy – 1,377
Radical nephrectomy – 1,232
Cryoablation – 121
Radiofrequency ablation – 3

19. Core Data Points Demographics Past Medical History Family History
Smoking Status
Clinical and Pathologic Staging
Operative Data
Hospital Charges
Medical Complexity / Mortality Group
Recurrence and Death Data
Biospecimen Availability

25. Is there a distinguishing feature among the histologic types that we can exploit with advanced imaging techniques?

26. Oncocytoma

27. Clear Cell RCC
Rajasekaran et al., Histol Histopathol 2005; 20: 35.

28. 99mTc-Sestamibi

29. Sestamibi Mechanism of Action

30. Oxyphilc Cell of the Parathyoid
Cytoplasm
Packed with
Mitochondria

31. Sestamibi Imaging of a Parathyroid Adenoma
Neumann et al., JNM 2008; 12: 2012.

32. Pilot Study

33. Pilot Study Design
Aims: To determine the feasibility of 99mTc-sestamibi SPECT/CT imaging of renal tumors.
Inclusion criteria:
≥1 solid cT1 renal mass
Age ≥18 years
Biopsy proven oncocytoma (n=3)
No biopsy, but scheduled to undergo surgery (n=3)
Exclusion criteria:
Pregnancy
Other malignancy with concern for renal metastasis
Allergy to sestamibi or technecium

34. Biopsy-Proven OncocytomasA B C D E I F G H J K L
Standard CT/MRI SPECT SPECT/CT Histology
Patient Patient Patient 1

35. Resected RCCs A B C D E I F G H J K L
Standard CT/MRI SPECT SPECT/CT Histology
Patient Patient Patient 4
Clear Cell RCC
Unclassified RCC
Translocation RCC

36. Prospective Diagnostic Trial

37. Study Design Solid cT1 Renal Mass Electing for Surgery
Preoperative 99mTc-MIBI SPECT/CT
Surgery with Either Partial or Radical Nephrectomy
Blinded Radiology and Pathology Review
Solid cT1 Renal Mass Electing for Surgery

38. Study Design
Primary endpoints: sensitivity and specificity of sestamibi SPECT/CT for the diagnosis of oncocytoma or hybrid oncocytic tumors (HOCT).
Sample Size: 50
Inclusion criteria:
≥1 solid cT1 renal mass
Scheduled to undergo surgery
eGFR ≥45 mL/min/1.73 m2
Exclusion criteria:
Pregnancy
Other malignancy with concern for renal metastasis
Allergy to sestamibi or technecium

39. Study Design Centralized blinded pathology and radiology review
Funding: Mini Grant from the National Kidney Foundation of Maryland and private philanthropy
Regulatory: Johns Hopkins CRC and IRB approved with an IND waiver, registered with ClinicalTrials.gov (NCT )

40. Prospective Trial Data
n = 50

41. Preoperative Characteristics
Variable
n (%) / median (range)
Age, years
62 (40-80)
Sex
Male
37 (74)
Female
13 (26)
Race
White
42 (84)
Black
5 (10)
Other
7 (6)
Tumor Diameter, cm
3.0 ( )
Clinical T Stage
cT1a
33 (66)
cT1b
17 (34)

42. Tumor Histology Data Histologic Type n (%) Clear Cell RCC 26 (52)
Papillary RCC
8 (16)
Chromophobe RCC
4 (8)
Clear Cell Papillary RCC
2 (4)
Unclassified RCC
1 (2)
AML
Oncocytoma
6 (12)
HOCT

43. Imaging Read Design
Two fellowship trained nuclear medicine attendings served as blinded readers.
Each reader was provided with the pilot study cases as a training set.
To avoid potential bias from cross-sectional imaging findings suggestive of tumor histology, readers were not provided access to preoperative CT or MRI scans. Instead, line diagrams were used to aid in lesion localization.

44. Imaging Read Design

45. Imaging Read Design
In one sitting, each reader reviewed all 50 studies in a prescribed random order.
Readers were asked to quantify the highest tumor and parenchymal uptake as well as to categorize a given tumor as either “hot” or “cold.”
On a separate day, each reader re-reviewed all 50 studies in a second random order.

46. Intra- and Inter-observer Agreement
Intra-observer
κ-value
Reader 1
0.92
Reader 2
1.0
Inter-observer
Read 1
Read 2

47. Results
p = 0.001

48. Results
p = 0.001

49. - Sensitivity and Specificity Oncocytoma/HOCT + - SPECT/CT + 7 2 1 40
SPECT/CT + 7 2 1 40 -
Sensitivity = 87.5% (95% CI 52.9−97.9%)
Specificity = 95.2% (95% CI 84.2−98.7%)

50. Gorin et al., Nat Rev Urol 2015 12; 445.
18F-DCFPyL
Gorin et al., Nat Rev Urol ; 445.

51. Conclusions
RCC is relatively common malignancy, the incidence of which is rising
Not all RCCs are lethal and therefore a risk-adapted approach to is needed to avoid overtreatment
Although renal mass biopsy can aid in a risk-adapted approach, this procedure has many shortcomings
Clinical information alone is insufficient for replacing renal mass biopsy
Nuclear imaging offers a potential invasive means to accurately risk stratify patients presenting with a cT1 renal mass

52. An improved risk-adapted approach for the management of the cT1 renal mass….

53. Gorin et al., Nat Rev Urol 2015 12; 445.

54. Thank you!