RENAL CELL CARCINOMA

CLINICAL PROGRESS AND CURRENT

MANAGEMENT
DR KALYAN K SARKAR MS
FRCSEd
RCC : SURGICAL OR MEDICAL
DISEASE ?

Early initial diagnosis and
advent of laparoscopic surgery
has provided different
treatment options.

Molecular pathology of these
lesions is better understood

Advanced lesions remain
difficult to treat by conventional
cytoreductive surgery or
biological response modifier
therapy
INCIDENCE
Incidence
There are approximately 30,000 new cases per year
and 12,000 cancer related deaths
Incidence is rising 6.1 to 9.3 per 100,000 over 20
years
Mortality rate has not decreased even with greater
detection of small tumors
Lead time bias
Short follow up
Less aggressive?
25% of tumors present with advanced disease
PREVALENCE IN INDIA

cases prev1yr prev5yr mort

M 4738 2685 9783 3425
F 2129 1247 4685 1459
EPIDEMIOLOGY
Equal racial distribution
2:1 male to female distribution
Occurs in 5th to 7th decade of life
Tobacco greatest risk factor
Obesity may be a risk factor
Most cases sporadic, yet also occurs with
Von Hippel-Lindau disease (VHL) [45%],
and less commonly with tuberous
sclerosis, and in rare familial distributions

PATHOLOGY
RENAL CELL CARCINOMA

Clear cell renal cell carcinoma
Papillary renal cell carcinoma
Oncocytoma
Chromophobe renal cell carcinoma
Collecting duct renal cell carcinoma
Other parenchymal renal tumours



PATHOLOGY
Clear cell carcinoma: comprises >70% of renal
lesions
VHL gene mutation principAL event. Recent
association between VHL protein and hypoxia
inducing factor [HIF] protein ties pathology into
angiogenesis cascade pathway.
Papillary renal cell carcinoma: comprises 10-
15% of renal lesions
Sporadic and hereditary forms
Associated with alterations in chromosomes 7, 17,
and Y
Generally better survival

PATHOLOGY
Chromophobe tumors: 5 % of cases
Loss on chromosome 1
Collecting duct carcinoma: one percent or less of cases
Can mimic transitional cell Ca
Generally poor outcome

Oncocytoma: 5 % of renal tumors
Generally localized and encapsulated. 5% bilaterality
Mahogany brown color, acidophilic cells secondary to dense
mitochondrial hyperplasia
Distinction from renal cell cancer difficult on imaging or needle
biopsy. Best treated with surgical removal


PATHOLOGY
Angiomyolipoma: Renal Hamartomas comprised
of fat, muscle and blood vessels. Tissue
signature on CT by demonstration of negative
Hounsfield units.
Sporadic, isolated lesions present age 35-50 with a
4:1 female ratio
Tuberous Sclerosis patients demonstrate multiple and
bilateral lesions. 80% of patients will develop AML.
Tumours <4 cm are observed, those >4cm undergo
selective angioembolization or partial nephrectomy



PATHOLOGY
Renal Sarcoma
Pure sarcoma is rare and usually lieomyosarcoma
All tumor types can degenerate towards sarcoma
Generally poorer outcome
Rare Renal lesions
Adult Wilms tumor
Lymphoma
Xanthogranulomatous Pyelonephritis [XPG]
Haemangiopericytoma




GRADING

Fuhrman grading system
Grade is an important variable
Fuhrman system has issues with
interobserver variability
STAGING
UICC-AJCC system is generally
accepted
Currently T1 lesion is 7 cm or less in size,
yet 4.0 cm associated with very low
recurrence rate
T1a category of <4.0 cm suggested
PROGNOSIS
STAGE 5 YR 10 YR
I 90% 80%
II 80% 70%
III 50% 35%
IV 10% 3%
RECURRENCE
PULMONARY,
HEPATIC OR BONE
FEW ARE LOCAL

MSKCC
NOMOGRAM

PARTIAL NEPH IN
TUMOURS < 4 CM
HAS SURVIVAL OF
100% AT 5 YRS
FOLLOW-UP
Traditionally, most patients with sporadic RCC are followed every 6
months or yearly with a history and physical examination (H&P), liver
function studies, serum chemistry (including alkaline phosphatase),
CXR, and abdominal cross-sectional imaging.

T1: H&P, serum chemistry, and CXR yearly for 5 years
T2: H&P, serum chemistry, and CXR every 6 months;
abdominal CT scan at 2 and 5 years for 5 years
T3: H&P, serum chemistry, and CXR at 3 months, then every
6 months; abdominal CT scan at 2 and 5 years

CLINICAL PRESENTATION
A QUARTER PRESENT WITH ADVANCED
DISEASE, LOCALLY ADVANCED OR
METASTATIC

A THIRD OF PATIENTS POST SURGERY FOR
LOCALISED DISEASE WILL RELAPSE

WITH METASTATIC DISEASE THE MEDIAN
SURVIVAL IS 13 MONTHS

CLINICAL PRESENTATION
THE CLASSIC TRIAD <10 %

INCIDENTAL DETECTION ALMOST 50%

SYSTEMIC SYNDROMES
ANAEMIA, FATIGUE, CACHEXIA, WEIGHT LOSS,
HYPERCALCEMIA, HEPATIC DYSFUNCTION

RARE SYNDROMES
ERYTHROCYTOSIS, ENtEROPATHY, NEUROPATHY,
AMYLOIDOSIS




Imaging
Increased use of imaging has increased the
detection of renal lesions most of which are
simple cysts. Also a greater percentage of small
renal lesions have been noted which has
changed the therapeutic strategy towards renal
lesions. CT and MRI findings are fairly classical
for renal tumors. Initial diagnosis with IV
urography or ultrasound may require further
confirmatory testing.
Imaging
Ultrasonagraphy
Excellent in distinguishing cystic from solid
masses.
30-50% of patients >50 years will have renal
cysts
Bosniak classification provides guidelines.
I [Simple cyst] 0% cancer risk
II [Minimally complicated] 2-10% cancer risk
III [Indeterminate cyst] up to 50% cancer risk
IV [Cystic renal cell] up to 90% cancer risk
Imaging
Intravenous Urography
Starting point for hematuria evaluations
Abnormal findings require other imaging for
conformation
Calcification pattern suggestive
Speckled or mottled, 90% cancer
Rim calcification 10-20% cancer
Imaging
Computed tomography
Provides an excellent assessment of the
parenchyma and nodal status. Thin slice
images provide superior definition of smaller
lesions. Good assessment of nodal status is
provided. Tissue signature of fat allows
diagnosis of AML. 3-D reconstruction now
available
Imaging
Magnetic Resonance Imaging
Non ionizing radiation modality provides
excellent demonstration of solid renal masses
and is image test of choice to demonstrate
extent of vena caval involvement with tumor.
Useful in patients with renal insufficiency
Imaging
Angiography
Generally supplanted by MRI angiography
Used for embolization of large lesions preoperatively
Radionuclide Imaging
Most useful in detecting pseudo-masses
Tumors and cysts are photo-deficient areas
Percutaneous biopsy
Generally not useful due to the high [30-50 percent]
false positive rate
Some value in ruling out metastatic disease or
lymphoma
CLINICAL STAGING
Chest X-ray or Chest CT
CT/MRI scan of abdomen or pelvis
Bone scan with plan films (for elevated
alkaline phosphatase or bone pain).
Laboratory: CBC, LFT's, alkaline
phosphotase, BUN, creatinine.
SURGICAL TREATMENT
OPTIONS IN RCC
CLASSICAL RADICAL NEPHRECTOMY
OPEN PARTIAL NEPHRECTOMY
LAPAROSCOPIC PARTIAL
NEPHRECTOMY
ENERGY APPLICATIONS
PERCUTANEOUS, EXTRACORPOREAL,
LAPAROSCOPIC
EXPECTANT TREATMENT
TREATMENT
Classic Radical Nephrectomy
Gold standard of comparison. Performed
through several different flank or subcostal
approaches. Well tolerated.
Minimal role for aggressive
lymphadenectomy. Nodes generally removed
from ipsilateral great vessel.
Adrenalectomy not required if preoperative
imaging is normal or if the renal tumor is in
the mid or lower pole of the kidney.
TREATMENT
Inferior vena cava
extension
Sub classification based on
cranial extent of lesion
figure 1
Patient prognoses based
on stage of lesion and not
extent of thrombus
Complexity of surgery
ranges from partial
clamping of the vena cava
to cardiopulmonary bypass
with hypothermia and
circulatory arrest. Mortality
2-14 %.
TREATMENT
Expectant management
Small lesions [<3.0 cm] have a minimal risk of
metastasis and increase in size approximately
6 mm per year. In elderly and very ill patients
minimal intervention may be warranted
TREATMENT
Percutaneous or laparoscopic ablation
CT guided radiofrequency ablation - potential
minimally invasive therapy requiring further
follow-up
Laparoscopic cryosurgical ablation - less
invasive ablation technique will require further
follow-up
These and similar technologies promising and
suited to the higher incidence of smaller
lesions detected incidentally.
TREATMENT
Nephron-sparing surgery
Local recurrence rate 1-2%
15% of small lesions may not be renal cell Ca
Preservation of renal function is laudable
Indicated in small lesions [<4cm], patients with poor
renal function, bilateral disease, and solitary kidney
Renal cooling and intraoperative ultrasound required
in more difficult cases.
Open vs. laparoscopic approach based on tumor
location, size, and operator experience.
TREATMENT
Laparoscopic nephrectomy
Pure laparoscopic and "hand-assisted"
techniques available. Hand- assisted
approach has promulgated the technique,
feasible for most tumors <8-10 cm depending
on location.
Operative time longer, hospital stay and pain
requirement less, time to normal function
shorter than flank incision.
Learning curve associated with this approach.
TREATMENT
Metastatic disease - Surgery
Outcome with metastatic disease depends on
performance status
Low volume metastasis, especially pulmonary
involvement tend to respond best.
Recent data to suggest a slight but statistically
significant survival benefit if nephrectomy
performed in conjunction with immunotherapy.
Patients with significant disease burden and
poor performance status less likely to benefit
TREATMENT
Metastatic disease - Medical therapy
Few cytoreductive agents have any significant
impact on renal cell carcinoma
Radiation therapy has little proven effect on
renal cell carcinoma
Cytokine therapy [IL-2] demonstrates a
complete response in 4% of patients and a
partial response in 12-20% of patients
Antiangiogenesis agents have theoretical
promise for this disease



THANK YOU