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RENAL CELL CARCINOMA CLINICAL PROGRESS AND CURRENT MANAGEMENT

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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 ... – PowerPoint PPT presentation

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Title: RENAL CELL CARCINOMA CLINICAL PROGRESS AND CURRENT MANAGEMENT


1
RENAL CELL CARCINOMACLINICAL PROGRESS AND
CURRENT MANAGEMENT
  • DR KALYAN K SARKAR MS FRCSEd

2
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

3
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

4
PREVALENCE IN INDIA
  • cases prev1yr prev5yr mort
  • M 4738 2685 9783 3425
  • F 2129 1247 4685 1459

5
EPIDEMIOLOGY
  • Equal racial distribution
  • 21 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

6
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

7
PATHOLOGY
  • Clear cell carcinoma comprises gt70 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

8
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

9
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 41 female ratio
  • Tuberous Sclerosis patients demonstrate multiple
    and bilateral lesions. 80 of patients will
    develop AML.
  • Tumours lt4 cm are observed, those gt4cm undergo
    selective angioembolization or partial
    nephrectomy

10
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

11
GRADING
  • Fuhrman grading system
  • Grade is an important variable
  • Fuhrman system has issues with interobserver
    variability

12
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 lt4.0 cm suggested

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14
PROGNOSIS
RECURRENCE PULMONARY, HEPATIC OR BONE FEW ARE
LOCAL MSKCC NOMOGRAM PARTIAL NEPH IN TUMOURS lt
4 CM HAS SURVIVAL OF 100 AT 5 YRS
15
FOLLOW-UP
  • Traditionally, most patients with sporadic RCC
    are followed every 6 months or yearly with a
    history and physical examination (HP), liver
    function studies, serum chemistry (including
    alkaline phosphatase), CXR, and abdominal
    cross-sectional imaging.
  • T1 HP, serum chemistry, and CXR yearly for 5
    years
  • T2 HP, serum chemistry, and CXR every 6 months
    abdominal CT scan at 2 and 5 years for 5 years
  • T3 HP, serum chemistry, and CXR at 3 months,
    then every 6 months abdominal CT scan at 2 and 5
    years

16
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

17
CLINICAL PRESENTATION
  • THE CLASSIC TRIAD lt10
  • INCIDENTAL DETECTION ALMOST 50
  • SYSTEMIC SYNDROMES
  • ANAEMIA, FATIGUE, CACHEXIA, WEIGHT LOSS,
    HYPERCALCEMIA, HEPATIC DYSFUNCTION
  • RARE SYNDROMES
  • ERYTHROCYTOSIS, ENtEROPATHY, NEUROPATHY,
    AMYLOIDOSIS

18
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.

19
Imaging
  • Ultrasonagraphy
  • Excellent in distinguishing cystic from solid
    masses.
  • 30-50 of patients gt50 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

20
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

21
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

22
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

23
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

24
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.

25
SURGICAL TREATMENT OPTIONS IN RCC
  • CLASSICAL RADICAL NEPHRECTOMY
  • OPEN PARTIAL NEPHRECTOMY
  • LAPAROSCOPIC PARTIAL NEPHRECTOMY
  • ENERGY APPLICATIONS PERCUTANEOUS, EXTRACORPOREAL,
    LAPAROSCOPIC
  • EXPECTANT TREATMENT

26
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27
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.

28
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29
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30
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 .

31
TREATMENT
  • Expectant management
  • Small lesions lt3.0 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

32
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.

33
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34
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 lt4cm, 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.

35
TREATMENT
  • Laparoscopic nephrectomy
  • Pure laparoscopic and "hand-assisted" techniques
    available. Hand- assisted approach has
    promulgated the technique, feasible for most
    tumors lt8-10 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.

36
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

37
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

38
  • THANK YOU
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