Renal cell carcinoma case-based scenarios

1. RCC – case based scenarios
Dr.K.Priyatham
MCh Urology, Fellowship in Uro-oncology(RGCI)
Prashanth Hospital

2. 1) Small renal mass
2) Localised RCC
3) Locally advanced RCC
4) Metastatic RCC

3. Para-neoplastic syndrome
A. Anaemia
B. Blood pressure (HTN)
C. Cachexia
D. Deranged LFT
E. Elevated ESR
F. Fever
G. Glucose intolerance
H. Hyperglycaemia
I. Icterus & Jaundice

4. Case 1

5. • 48 yr old male, who is a professor in the engineering college with no
comorbidities presented to us with incidental left renal complex cyst
on ultrasound in the general health check up
• No comorbidities, non smoker, ECOG – 0
• Physical examination & labs - normal

7. Ultrasound
• Left renal complex cyst 3x2 cms
• Bosnaik cyst?

9. CT
• No evidence of mass in the left
kidney
• Essentially normal

10. CT REPORT GIVEN BY THE RADIOLOGIST
• Well defined isodense lesion of size 3x2 cms in the interpolar region
of the left kidney with peripheral puddlling of the contrast on arterial
phase and homogenous enhancement on venous phase and iso
dense to kidney on delayed phase - ? Haemangioma

12. CT

14. MRI
T2 weighted images T1 weighted image

15. Prospective performance of clear cell likelihood
scores (ccLS) in renal masses evaluated with
multiparametric magnetic resonance imaging
Clear cell likelihood score (ccLS)
• They confirm the good accuracy and
diagnostic performance of mpMRI to classify
a renal mass as ccRCC in a cohort of patients
with solid renal masses in a bi-institutional
study.
• While ccLS does not provide reliable
information about the likelihood of malignant
histology or oncologic aggressiveness in a
renal mass, it provides valuable information
for management decision making.
• The high PPV of ccLS≥4 and high NPV of
ccLS≤2 for ccRCC can help inform more
selective use of invasive biopsies in patients
with renal masses of any stage.
• 1-very unlikely,
• 2-unlikely,
• 3-equivocal,
• 4-likely
• 5-very likely

18. Diagnostic accuracy of 99mTc-sestamibi
SPECT/CT for detecting renal
oncocytomas and other benign renal
lesions: a systematic review and meta-
analysis
• 99mTc-sestamibi SPECT/CT
demonstrates a high
sensitivity and specificity for
characterizing benign and
low-grade renal lesions.
• This test can help improve the
diagnostic confidence for
patients with indeterminate
renal masses being
considered for active
surveillance.

19. 20%
20%
60%
Solid renal mass
Benign Aggressive cancer
Indolent Cancer

20. Metastatic work up

21. Management
• Active surveillance
• Renal Biopsy
• Focal therapy
• Partial Nephrectomy

23. Size does matter

26. Nephrometry scoring
1. Renal score
2. PADUA scoring
3. Centrality index
4. DAP (diameter axial polar) nephrometry
5. ZONAL nephron score
6. ABC (Arterial based complexity) scoring
7. MAP (mayo adhesive probability score)
8. Rosco score

27. score of 4-6: low
complexity
score of 7-9: moderate
complexity
score of 10-12: high
complexity

28. score of 6-7: low
complexity
score of 8-9: moderate
complexity
score of >10: high
complexity

29. Partial Nephrectomy

30. Only perform partial nephrectomy

31. Ideal partial nephrectomy
Trifecta
1. Negative surgical margins
2. Minimal renal function
decrease
3. No Urological complications
Pentafecta
1. Negative surgical margins
2. Minimal renal function
decrease
3. No Urological complications
4. Ischemia time <25 mins
5. No CKD stage progression 1
year after surgery

32. HPE
• Clear cell carcinoma
• Grade 1 (ISUP WHO grading)
• No evidence of sarcomatoid variant
• Margins – negative for tumor
• LVI & PI not seen
• Pathological staging pT1a

33. Positive surgical margins on histopathological
specimens
• 2–8% of PNs
• Most trials showed that intra-operative frozen section analysis had no
influence on the risk of definite positive surgical margins
• A positive surgical margin status occurs more frequently in cases in which
surgery is imperative (solitary kidneys and bilateral tumours) and in
patients with adverse pathological features (pT2a, pT3a, grade III-IV)
• The potential negative impact of a positive margin status on the oncologic
outcome is still controversial

34. • Diffuse or global/focal
• Local tumour bed recurrences were found in 16% in patients with
positive surgical margins compared with 3% in those with negative
margins
• Therefore, RN or re-resection of margins can result in over-treatment
in many cases.
• Patients with positive surgical margins should be informed that they
will need a more intense surveillance (imaging) follow-up and that
they are at increased risk of secondary local therapies

36. Virtual 3d models to aid in partial
nephrectomy

37. Follow up

38. Case 2

39. • 55 yr old male, presented to us with haematuria since 10 days
• Hypertensive, smoker, ECOG – 1
• Physical examination - normal

40. Ultrasound

42. • A well defined soft tissue density lesion of size 10x8 cms with central
hypodensities involving upper and mid cortical regions with exophytic
component with heterogenous enhancement with central necrotic areas
• Multiple prominent vessels surrounding the lesion
• Lesion causing mass effect on PCS
• Superiorly abutting the liver
• Renal vein & IVC – normal
• Mass abutting psoas
• Rest - normal

43. Blood investigations
• CBC - Normal
• LFT: Normal
• Serum Calcium: Normal
• CXR: WNL

45. Treatment
• Radical nephrectomy – open, laparoscopic, robotic

46. • Histological type – Papillary RCC
• Grade 2 (WHO/ISUP)
• Extent – involves capsule, perinephric fat, PCS, renal sinus
• Margins – negative
• Stage – pT3aN0

47. Ipsilateral adrenalectomy
• Patients without radiographic adrenal involvement - Level 2 evidence
demonstrates no oncological benefit to adrenalectomy
• No change in OS
• Patient with radiographic abnormality – if patient is N0 & M0, then
adrenalectomy might be beneficial
• If patient has N+ & M+ disease, adrenalectomy is unlikely to benefit

48. Embolization
• In patients unfit for surgery with massive hematuria or flank pain,
embolization can be a beneficial palliative approach

50. Prognostic models
for localised RCC

51. Follow up

52. Case 3

53. Chief Complaints
• Seventy two year old male presented to OPD with complaints
of passing blood in urine, 2-3 episodes for 1 day

54. History of presenting illness
• Passing of clots +, tubular in nature, painless
• No h/o burning micturition, LUTS
• No h/o of trauma or fever
• History of loss of weight 8-9 kgs in last 1 year

55. Past & Family History
• No h/o of similar complaints in the past
• No h/o of previous surgery, no h/o bony pains
• Non smoker nor tobacco chewer
• Hypertensive on Rx, no other co morbidities
• Family history: Nothing significant

56. Physical Examination
• O/E
Patient conscious, oriented, afebrile
No pallor, icterus, lymphadenopathy, edema
BP: 144/88 mm Hg, PR: 82/min
• Systemic Examination
P/A: Soft, non tender

57. • 7 x 6 cm mass palpable in the left lumbar region, firm in consistency,
bimanually palpable, moves with respiration, irregular surface,
fingers can be insinuated beneath costal margins, BS +
Genital examination: Meatus N, left irreducible varicocele +, grade 2
prostatomegaly, firm, smooth surface, anal tone good
RS,CVS & CNS: Normal

58. Investigations
• Urine Routine: RBC’s- 25-30, WBC’s- 10-12
• Urine C/S: No growth
• Blood
CBC: Hb- 13.3 gm/dl, TC- 9800, N- 79%, Platelets- 2.74 lacs, ESR- 40mm/hr
RFT: Sr Creatinine-0.96mg/dl, BUN- 14.1

59. Electrolytes: Na-137, K-3.53, Cl- 102
Coagulation: PT/INR/APTT- 14.2/1.07/29.3
Serology: Non Reactive

62. USG Abdomen Pelvis
• Exophytic hypoechoic to isoechoic mass noted in the lower pole of left
kidney measuring 6.5 x 6.2 cm
• 37 cc prostate
• Right kidney is normal
• Rest of the abdomen normal

69. CECT Abdomen Pelvis
• Large heterogenously enhancing mass arising from anterior aspect of interpolar
region of left kidney measuring 7.7 x 6.2 x7 cm
• Multiple non enhancing necrotic areas seen with in the lesion
• There is heterogeneously enhancing soft tissue density in the left renal vein
measuring 1.2 x 4 cm – likely tumour thrombus
• IVC is normal
• There are few heterogeneously enhancing necrotic lymphnodes in the left para
aortic region, largest measuring 2 x 3.2 cm
• Prostate gland is enlarged
• Left varicocele

70. • LFT: TB-0.59, DB- 0.2, TP- 7.2,
Alb-4.4, OT/PT-16/10, ALP-59
• Serum Calcium: Total 9.8 mg/dl,
Ionized 4.3mg/dl
• CXR: WNL

73. • Left Radical Nephrectomy
• Biopsy:
Diagnosis: High grade sarcomatoid renal clear cell
carcinoma with renal vein thrombus
a) Tumor size: 6.5 cm
b) Furhman’s nuclear grade: 4
c) Necrosis: Present 50%
d) Perinephric fat: Involved

74. e) Ureteric cut margin: Free of tumor
f) Gerotas fascia: Free of tumor
g) Hilar vessels cut margin: Free of tumor
h) Lymphovascular emboli: Present
i) Hilar LN: 4 nodes + for metastasis
j) Extra nodal extension: Present
k) Adrenal gland: Free of tumor
l) Hilar LN inclusive of para aortic nodes: 5/6 + for metastasis
m) 50% of sarcomatoid differentiation present
Pathology stage: pT3 N1 Mx, Stage III

75. • Three weeks after left radical nephrectomy he
presented with pain in left hip & thigh after
trivial injury
• He was diagnosed with subtrochantric fracture of
left femur
• Treated by open reduction & internal fixation
• Biopsy was sent from fracture site

77. HPE:
• Specimen: Bone specimen from fracture site ? Pathological fracture
• Report: Section showed sclerotic bone & fragments of compactly arranged
sheets of oval to round cells possessing hyperchromatic pleomorphic cells
with vesicular nuclei, areas of hemorrhage & necrosis seen
• IHC: Vimentin +, Pax 8 +, EMA +
• Diagnosis: Metastatic carcinoma in Femur ( Primary in kidney)

78. • Patient succumbed to death within 8 months from the date of
nephrectomy
• Any role of adjuvant therapy

79. • The potential role of sunitinib in combination with gemcitabine has
been investigated in a phase II trial of RCC with sarcomatoid
features.
• The results show that the combination was well tolerated and is
active, especially in patients with rapidly progressing disease.
• There are ongoing trials studying sunitinib in combination with
gemcitabine compared to sunitinib alone in patients with sarcomatoid
features.

80. • Sarcomatoid renal cell carcinoma (SRCC) is currently defined in the
2004 World Health Organization (WHO) classification of renal tumors
as any histologic type of renal cell carcinoma (RCC) containing foci of
high-grade malignant spindle cells.
• Sarcomatoid differentiation is reported in 5% of RCCs overall.
• The incidence rates according to RCC histologic subtypes are –
o5-13% for clear cell renal cell carcinoma (CCRCC),
o2-7% for papillary RCC,
o9-13% for chromophobe RCC, and
o11-26% for unclassified RCC.
o29% of carcinomas of the collecting duct of Bellini.

81. Prognosis
• 5 year survival rates –
1. clear cell RCC 44%–69%
2. papillary RCC 82%–92%
3. chromophobe RCC 78%–87%
4. Sarcomatoid variant – 15-27%
• Median survival is – 4-9 months
• If left untreated 3.8 months – 6.8 months

82. • Sarcomatoid variant of renal cell carcinoma is one of the aggressive
variants of RCC
• Once we get a tissue diagnosis, we should look for any evidence of
metastasis even in patients without any symptoms of metastasis
• A standardized therapy regime for sRCC is not yet available due to
the rarity of sRCC and the lack of information regarding its biology
but chemotherapy should be considered because of high chance of
recurrence & metastasis.
• Despite advances in surgery, chemotherapy for other variants of RCC,
sRCC has the worst prognosis & patients should be counselled
accordingly.

83. Case 4

84. Case Presentation
• Seventy five year old male presented to us with loss of appetite, Right
flank pain, loss of weight, dyspnea since 6 months
• Smoker, Diabetic, hypertensive, CAD – s/p PTCA
• ECOG - 3
• O/E – PR- 95/ min, BP – 130/90 mm of Hg

85. • P/a – Soft, no mass palpable
• U/s abdomen – Hetero echoic mass of size 6x4 cms present in the
lower pole of the right kidney
• Hb – 8 gm%, Ca2+ - 10 gm/dl, LDH – 500 IU/L, ALP - 160 IU/L
• Rest of the blood investigations – within normal limits

86. CT
• Ill defined heterogeneously dense
lesion of size 7.1 x 4.3 x 5.3cms noted
in lower pole region infiltrating mid
and lower pole calyces – Likely
Neoplastic.
• Few enlarged para caval and aorta
caval nodes noted, largest measuring
62 x 40mm at renal level on right side.
• Lytic sclerotic foci noted involving
multiple vertebral bodies and pelvic
bones.

87. Further metastatic workup
• When do you do Bone scan?
• When do you do MRI brain

88. FDG PET CT

89. FDG Pet CT
• PET CT don't play a major role in localised RCC as there is significant
background activity & prevent accurate diagnosis
• Renal parenchyma shows high FDG uptake itself & differentiation to
malignant lesion is difficult
• Positive PET CT results as a good predictive for evaluating metastatic
deposits – higher sensitivity in metastatic RCC (90%)

91. Renal biopsy indications
• Before ablation therapy
• Undetermined mass
• Before systemic therapy
• Active surveillance
• Suspicion of lymphoma
• Solitary kidney

93. HPE
• Clear cell carcinoma
• Grade 3 (ISUP WHO grading)
• No evidence of sarcomatoid variant
• LVI & PI - seen

94. ISUP RCC grading

95. Treatment

97. Purpose of risk stratification

98. Management
• Radical nephrectomy
• Radical nephrectomy followed by immunotherapy
• Immunotherapy

102. Carmena trial - 2018
• Sunitinib alone was not inferior to nephrectomy followed by sunitinib
in patients with metastatic renal-cell carcinoma who were classified
as having intermediate-risk or poor-risk disease.

103. Comparison of Immediate vs Deferred
Cytoreductive Nephrectomy in Patients
With Synchronous Metastatic Renal Cell
Carcinoma Receiving Sunitinib: The
SURTIME Randomized Clinical Trial
• Deferred CN did not improve the 28-week PFR.
• With the deferred approach, more patients received sunitinib
and OS results were higher. Pretreatment with sunitinib may
identify patients with inherent resistance to systemic therapy
before planned CN.
• This evidence complements recent data from randomized
clinical trials to inform treatment decisions in patients with
primary clear cell mRCC requiring sunitinib.

106. Genetic evaluation