ena ors

Earnest John B. Tenorio, MD

Fellow, Phil. College of Surgeons
Fellow, Phil. Society of General Surgeons
 Renal Tumors
•

; • 51,000 cases diagnosed and more

than 12,900 deaths annually in the US
• Accounts for 3°/o of adult malignancy
 • BENIGN
• Oncocytoma

Renal • Papillary Adenoma

• Angiomyolipoma
Tumors
• MALIGNANT
• Renal Cell Carcinoma
RENAL CELL CARCINOMA
• First described by Konig in 1826
• In 1883, Grawitz noted the fatty content of cancer cells similar to
the adrenal glands
• Arises from the Renal tubular epithelium
• Accounts for 80-85°/o of kidney cancer
• 2°/o to 4°/o increase in incidence per year
RENAL CELL CARCINOMA
EPIDEMIOLOGY
• 1.6:1.0 M:F
• 7°/o diagnosed incidentally
• Highest incidence between age 50-75 years old
• Median age of diagnosis - 66 years old
• Median age of death - 70 years old
• Majority occurs sporadically
• Highest incidence in Scandanavia and North America, lowest in
Africa
 • RISK FACTORS
• Smoking contributes to 24-30°/o of RCC
cases
• Tobacco results in 2-fold increased
risk
• Environmental
• Cadmium, thorium-dioxide,
RENAL CELL petroleum, phenacetin analgesics
• Occupational
CARCINOMA • Leather tanners, shoe workers,
asbestos workers
• Hormonal
• Diethylstilbestrol
• Obesity, hypertension
• 35-47°/o on long term dialysis patients
develop Adult Polycystic Kidney
Disease
• Out of which, 5.8°/o develop RCC
RENAL CELL
CARCINOMA
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Type Papillary type 1 Papillary type 2 Chromophobe Oncocytoma

Incidence (%) 75% 5% 10% 5% 5%

Associated VHL c-Met FH BHD BHD
mutations

A sarcomatoid variant represents 1% to 6% of renal cell carcinoma and these tumors are
associated with a significantly poorer prognosis.
BHD=Birt-Hogg-Dube; FH=fumarate hydratase; VHL=von Hippel-Lindau.
RENAL CELL CARCINOMA
NATURAL HISTORY
• 45o/o with localized disease, 25°/o with locally advanced disease, 30o/o
with metastatic disease
• Lymph node metastasis- 9°/o to 27°/o (renal hilar, para-aortic, paracaval)
• Locally advanced disease
• Renal Vein - 21 °/o
• IVC-4°/o
• Distant metastasis - lung (75°/o}, soft tissue (36°/o}, bone (20°/o}, liver
(18°/o}, skin (8o/o}, CNS (8°/o}
RENAL CELL CARCINOMA
CLINICAL PRESENTATION
• Clinically occult for most cases
• Classic Triad (occur in 5-10°/o of cases)
• Flank pain
• Hematuria
• Palpable mass
• Hematuria - 40o/o of patients
• Systemic symptoms - anemia, fatigue, cachexia, weight loss
• Para neoplastic Syndromes
• Parathyroid like hormones, EPO, renin, gonadotropins, prolactin
DIAGNOSTICS
• General - History and PE
• Laboratory
• CBC, LFT, Alk. Phosphatase, BUN, creatinine, urinalysis
• Radiographic Studies
• Xray- KUB region
• Ultrasound - solid vs cystic mass
• IV Urography- initial tests for hematuria evaluation and kidney
function
• CT scan - excellent assessment of the parenchyma and lymph
nodes
• MRI - imaging test of choice to demonstrate locally advanced
tumors. Useful in patients with renal insufficiency
Metastatic Work up
• Chest Xray or Chest CT
• CT/MRI of abdomen or pelvis
• Bone Scan with plain films
 Robson Modification of the Flocks & Kadesky
Staging
Tumor
,...__
Stage] Description
I ___ Renal cell carcinoma is confined to the kidneys
II Renal cell carcinoma extends through the renal capsule but is
confined to Gerota's fascia
III Renal cell carcinoma involves the renal vein or inferior vena cava
(IIIA) or the renal hilar lymph nodes (IIIB)
IV I Renal cell carcinoma has spread to local adjacent organs (other -
------
I than adrenal gland) or to distant sites
 TNM Staging
T- primary tumour
TX j Primary tumour cannot be assessed
No evidence of primary tumour
Tu1nour confined to kidney, <7cm
~4cm, confined to kidney
>4cm but <7cm, confined to kidney
J Tumour >7cm, con fined to kidney
T3 Tumour extends into major veins or ad1·enal or pe rinephric tissue but not beyond Gerota's fascia
T3a Direct invasion of adrenal gland, perirenal and/ or sinus fat
T3b Gross extension into renal vein or lVC
T3c Extends into IVC above diaphragm or wall of JVC
IT4__ l Invasion b':)'ond Gerota's fascia
 TNM Staging
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N - regional lymph nodes
_ NX __ Nodes cannot be assessed
~ No ~ Regional lymph node s not involved
Metastasis in a single regional lymph node
Metastases in >1 regio nal lymph node
M - distant metastases
MX Metastases cann.o t be assessed
Mo J No d istant metastases
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M1 Distant m etastases
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II T2
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• Stage 1-111: Localized Disease

Staging • Stage IV: Advanced, metastatic Disease
 Pathologic stage 5 yr survival
• T1 - 2 organ confined 70-90%

Prognosis • T3
• N+, M1
50-70%
5-3o%
Tumour size
• < 4cm > 90%
• 4-10 cm 50%
• > 10 cm 0%
Histological type
• Clear cell 70%
• Papillary, Chromophobe 85%
• Multilocular cystic 100%

• Medullary, Collecting duct 0%

Management
Localized disease

Surgery Radio Therapy

 • GOLD STANDARD for localized RCC with normal
Surgery contralateral kidney

Principles of Surgery- Early ligation of renal artery

and vein , removal of l<idney including Gerota's
fascia, removal of ipsilateral adrenal gland, regional
lymphadenectomy from crus of diaphragm to aortic
bifurcation.
Radiotherapy • Radiosensitivity of RCC is variable
• Animal experiments suggest a theoretical benefit
to preoperative RT(? Reduce intra-operative
seeding)
• Historically several series suggested clinical
benefit to adjuvant (post-op) RT
• Limited applicability because of long time span,
improvements in staging, surgery, changing RT
technology
Radiotherapy

• Neoadjuvant
• No overall survival or metastasis-free benefit
• Poorer survival

• Adjuvant
• Stage 11/111 disease
• No difference in RCC relapse
• More GI complications
• 19°/o of deaths attributed to RT complications
• Potential benefit in selected cases where there is a high ri sk local failure:
• Incomplete resection
• Lymph node involvement
 Metastatic
Disease

I I I I I
Radio Chemo Targeted Immuno
Therapy Therapy Therapy Therapy
 • Palliative Nephrectomy - Indicated in patients with

Surgery • Severe hemorrhage,

• Severe pain,
• Paraneoplastic syndrome
• or compression of adjacent viscera
• Solitary metastasis can be resected and may show some survival
advantage
• Therapeutic:
• Not curative but produce some long-term survivors.
• The possibility of disease-free survival increases after resection of
primary tumor and isolated metastasis excision.
• to decrease tumor burden in preparation for subsequent therapy
Surgery

• Resection of met's
• in pt. not relieved from palliative RT
• In solitary mets.
• Spontaneous regression of met's
• < 1 % of cases
• only 4 (0.8%) of 474 patients in 9 series who underwent
nephrectomy experienced regression of metastatic foci
Radiotherapy

• Palliation
• Used for local or symptomatic metastatic disease, such
as painful osseous lesions or brain metastasis.
• Treatment field encompasses metastatic deposit (or
local recurrence) with 2-3cm margins
• Higher doses (up to 35-40Gy) may be required to
overcome radioresistance
• Symptomatic relief in 64-84% of patients
Chemotherapy
• RCC is CHEMORESISTANT
• Conventional therapy has little to offer
• Response rate - 1Oo/o
Targeted Molecular Therapy

• New treatment approach that targets only the cancer.

• In renal cell carcinoma patients, this type of therapy
uses drugs that stop the new blood vessels from
growing, and targets certain factors that cause the cells
to grow.
• Tyrosine kinase (TK) inhibitors blocl< the
intracellular domain of the VGEF receptor
- Sunitinib (Sutent)
- Sorafenib (Nexavar)
lmmunotherapy
• Systemic type of treatment used to improve the body's
natural defenses.
• Boosts the immune system and slows down the cancer
growth
• Clinical response to immunotherapy seen in patients with
1. Good performance status
2. Had a prior nephrectomy
3. Non bulky pulmonary or soft tissue metastasis
4. Asymptomatic patient
• Interferon (IFN)
• Interleukin (IL -2}
 I
•

Long Exam tomorrow - 25 items