PROGRESS IN RENAL CELL CARCINOMA

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PROGRESS IN RENAL CELL CARCINOMA Powered By Docstoc
					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
                       RECURRENCE
                       PULMONARY,
                       HEPATIC OR BONE
STAGE   5 YR   10 YR   FEW ARE LOCAL


I       90%    80%     MSKCC
                       NOMOGRAM
II      80%    70%
                       PARTIAL NEPH IN
III     50%    35%     TUMOURS < 4 CM
                       HAS SURVIVAL OF
IV      10%    3%      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