Transcript PROGRESS IN RENAL CELL CARCINOMA

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
M
F
cases
prev1yr
prev5yr
mort
4738
2129
2685
1247
9783
4685
3425
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 1015% 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
RECURRENCE
PULMONARY,
HEPATIC OR BONE
STAGE
5 YR
10 YR
I
90%
80%
II
80%
70%
III
IV
50%
10%
35%
3%
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
INCIDENTAL DETECTION
<10 %
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
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–
–
–
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