Cancers of the Urinary Tract

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Cancers of the Urinary Tract
2009 Annual M.U.D. Conference January 26, 2009
Cathy Percival, RN, BSN, MBA Vice President,
Medical Director
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Cell Proliferation

• A physiological process that occurs in almost
  all tissues
• Normally the balance between proliferation and
  cell death is tightly regulated to ensure the
  integrity of organs and tissues
• Apoptosis
• A type of programmed cell death that occurs in
  an orderly manner for the benefit of the entire
  system
• As cells become damaged, the immune system is
  triggered to engulf and destroy the cells
• DNA mutations can disrupt this orderly process
  and lead to the uncontrolled and often rapid
  proliferation of cells

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Cancer

• A complex disease characterized by
• Deregulation of cell proliferation and apoptotic
  mechanisms
• Stromal cell changes
• Connective tissue cells of an organ found in the
  loose connective tissue
• Make up the support structure of biological
  tissues and support parenchyma
• The interaction between stromal cells and tumor
  cells is known to play a major role in cancer
  growth and progression
• Angiogenesis
• Cell metastasis
• Occurs as a result of alterations in the genes
  which regulate cell growth and differentiation
• Genetic changes can occur at many levels, from
  gain or loss of entire chromosomes to a mutation
  affecting a single DNA nucleotide
• Two types of genes affected by these changes
• Oncogenes
• May be normal genes which are expressed at
  inappropriately high levels, or altered genes
  which have novel properties
• Expression of these genes promotes the malignant
  transformation of cells
• Tumor Suppressor Genes
• Genes which inhibit cell division, survival, or
  other properties of cancer cells
• Tumor suppressor genes are often disabled by
  cancer-promoting genetic changes

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Carcinogen

• Any substance or agent that causes cancer
• Changes blueprint of DNA
• Increases rate of cell division, which may cause
  DNA mutations
• Agents and groups of agents
• Arsenic
• Asbestos
• Chemotherapeutic agents
• Human Immunodeficiency Virus (HIV) type 1
• Hepatitis B C viruses
• Radiation
• Human papilloma virus (HPV)certain types
• Estrogens
• Mixtures
• Alcoholic beverages
• Analgesics containing phenacetin
• Tobacco products
• Coal tars
• Exposure circumstances
• Aluminum production

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Classification of Carcinogens

• International Agency for Research on Cancer
  (IARC)
• Part of the World Health Organization (WHO)
• Major goal is to identify causes of cancer
• Over the past 30 years, IARC has evaluated the
  cancer-causing potential of more than 900 likely
  carcinogens
• Developed the most widely used system for
  classifying carcinogens
• IARC Classification System
• Group 1 Carcinogenic to humans
• Group 2A Probably carcinogenic to humans
• Group 2B Possibly carcinogenic to humans
• Group 3 Unclassifiable as to carcinogenicity in
  humans
• Group 4 Probably not carcinogenic to humans
• Given the ethical limitations of testing
  potential carcinogens on humans, only 100
  substances are classified as known carcinogens

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Cancer

• Benign tumors
• Do not spread to other parts of the body or
  invade other tissues
• Only dangerous if they become large enough to
  compress surrounding tissues
• Brain tumors
• Malignant tumors
• Invade adjacent organs
• Metastasize to distant organs

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Malignant Tumors

• Characteristics
• Evade apoptosis
• Unlimited growth potential
• Self-sufficiency of growth factors
• Insensitivity to anti-growth factors
• Increased cell division rate
• Altered ability to differentiate
• Ability to invade neighboring tissues
• Ability to build metastasis at distant sites
• Ability to promote blood vessel growth

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Malignant Cells

• Microscopic findings
• Large number of dividing cells
• Variation in nuclear size and shape
• Variation in cell size and shape
• Loss of specialized cell features
• Loss of normal tissue organization
• Poorly defined tumor boundary

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Progression of Normal Cells to Cancer Cells
Normal
HyperplasiaExcessive rate of cell
divisionleading to a largerthan normal
ofcells, but cells are normal
MildDysplasia
Carcinoma in-situSevere Dysplasia
An abnormal type of excessive cellproliferation
characterized by loss ofnormal tissue
arrangement and cellstructure
InvasiveCancer
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Prognosis

• Tumor type
• Histological characteristics
• Extent of growth
• Presence of spread
• Lymph node involvement
• Metastasis
• Response to treatment

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Cancers

• Classified in 2 ways
• Primary Site
• Location in the body where the cancer first
  develops
• Histological type
• The type of tissue in which the cancer originates
• Grouped into 5 major categories
• Carcinoma
• Sarcoma
• Myeloma
• Leukemia
• Lymphoma
• There are also some cancers of mixed types

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Histological Types

• Carcinoma
• A cancer that arises from epithelial cells
• Line the cavities and surfaces of structures
  throughout the body
• Accounts for 80-90 of all cancers
• Most carcinomas affect organs or glands capable
  of secretion
• Breasts
• Lungs
• Colon
• Prostate
• Bladder
• Two major subtypes
• Adenocarcinoma
• Develops in an organ or gland
• Squamous Cell Carcinoma
• Found in the tissues that form the epidermis, the
  lining of the hollow organs of the body (such as
  the bladder, kidney, and uterus), and the
  passages of the respiratory and digestive tracts

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Histological Types

• Sarcoma
• Originates in supportive and connective tissues
• Bones, Tendons, Cartilage, Muscle, Fat
• Examples
• Osteosarcoma (Bone), Leiomyosarcoma (Smooth
  muscle), Rhabdomyosarcoma (Skeletal muscle),
  Angiosarcoma (Blood vessels)
• Myeloma
• Originates in antibody-forming plasma cells of
  the bone marrow
• Leukemia
• A malignancy of the blood or bone marrow
• Characterized by abnormal proliferation of white
  blood cells
• Lymphomas
• Develop in the glands or nodes of the lymphatic
  system
• May also occur in specific organs
• Stomach, breast, brain
• Mixed Types
• The components of the cancer cells may be within
  one category or from different categories
• Teratocarcinoma
• Carcinosarcoma
• Mixed mesodermal tumor

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Cancer Staging

• Describes extent of a cancer
• Takes into account
• Size of a tumor
• Depth of penetration
• Invasion of adjacent organs
• Lymph node involvement
• Distant metastasis
• Staging criteria vary with different cancers
• Stage at diagnosis is the biggest predictor of
  survival

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Staging

• Clinical stage
• Based on all available information obtained
  before a surgery to remove a tumor
• Biopsy path findings
• May underestimate the true stage of the cancer
• Used when non-surgical treatments are implemented
• Pathologic stage
• Based on microscopic findings after complete
  removal of tumor
• Provides true stage of entire tumor and
  surrounding tissue
• General Staging Criteria
• Stage I
• Localized to one part of the body
• Stage II and Stage III
• Locally advanced
• A stage II or III rating can depend on the
  specific type of cancer
• Criteria will vary according to type of cancer
• Stage IV
• Represents metastasis

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TNM System

• Used to stage solid tumors
• Each component is separately listed and paired
  with a number to further identify the stage
• Tumor (T)
• Refers to primary tumor
• Carries a number of 0-4
• Based on size of tumor and extent of invasion
• Criteria will vary slightly based on type of
  cancer
• Node (N)
• Represents regional lymph node involvement
• Ranked from 0-4
• Metastasis (M)
• Xunknown
• 0no metastasis
• 1metastasis

Example T1N0Mx T2N3M0
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Histological Grade

• Grade
• Based upon the degree of differentiation of tumor
  cells
• Differentiation
• Describes the degree or extent that cancer cells
  resemble normal cells
• Rated numerically or descriptively
• Grade 1- 4
• Low-grade to high-grade
• The higher the grade, the more poorly
  differentiated the cells
• More aggressive tumor
• Less favorable prognostic factor

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Genitourinary System

• Consists of
• Kidneys
• Ureters
• Bladder
• Urethra
• Cancers most commonly occur in the kidneys and
  bladder

Kidneys
Ureters
Bladder
Urethra
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Kidney Cancer Statistics
American Cancer Society National Cancer Institute

• 2008 estimates for cancers of the kidney
• 54,390 new cases
• 46,232 renal cell carcinomas
• 13,010 U.S. deaths
• 9th most common cause of cancer deaths
• Incidence is highest between ages 55 and 84
• Average age at time of diagnosis is 65
• Risk is higher in men than women
• Among the 10 most common cancers

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Cancer of the Kidneys

• Renal Cell Carcinoma (RCC)
• Most common primary cancer of the kidneys
• Accounts for 90-95 of kidney cancers
• Occurs primarily in the proximal renal tubular
  epithelium in the renal cortex
• Tumors of the renal pelvis ureters account for
  smallnumber of kidney tumors

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Other Kidney Cancers

• Transitional Cell Carcinoma (TCC)
• About 5 to 10 of cancers in the kidney are
  transitional cell carcinomas
• Begins in the renal pelvis
• Transitional cells are present throughout the
  lining of the urinary tract
• TCC has been shown to be linked to cigarette
  smoking and workplace exposure to certain
  carcinogenic chemicals
• Wilms Tumor
• About 5 of all kidney cancers
• Almost always found in children
• Extremely rare in adults
• Renal Sarcoma
• Very rare
• Less than 1 of all kidney tumors
• Occurs in the kidney's connective tissue

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Renal Cell Carcinoma

• At least 4 hereditary syndromes are associated w/
  renal cell carcinoma

• von Hippel-Lindau (VHL) syndrome
• Renal cell carcinoma develops in nearly 40 of
  patients w/ VHL disease
• Hereditary papillary renal carcinoma (HPRC)
• Affected individuals develop bilateral,
  multifocal papillary renal carcinoma
• Familial renal oncocytoma (FRO) associated w/
  Birt-Hogg-Dube syndrome (BHDS)
• Hereditary renal carcinoma (HRC)

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Renal Cell Carcinoma

• Non-hereditary Risk Factors
• Smoking
• Obesity
• Age
• Hypertension
• Treatment for hypertension
• Use of phenacetin-containing analgesics
• Unopposed estrogen therapy
• Occupational exposure
• Petroleum products
• Heavy metals
• Solvents
• Emissions

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Renal Cell Carcinoma

• Renal cell carcinoma may remain clinically occult
  for most of its course
• Isolated location of kidney allows for
  asymptomatic tumor growth
• By the time symptoms develop, the disease is
  usually at an advanced stage
• Approximately 30 of patients presenting w/ renal
  carcinoma have metastatic disease
• Lung
• Soft tissues
• Bone
• Liver
• Cutaneous sites
• Central nervous system
• 25-30 of patients are asymptomatic
• Often diagnosis is made due to an incidental
  finding on a study done for another reason

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RCC Signs Symptoms

• Classic Triad of Symptoms
• Hematuria
• Flank pain
• Palpable mass in flank or abdomen
• Other Signs Symptoms
• Weight loss
• Fever
• Hypertension
• Hypercalcemia
• Night sweats
• Malaise

• Paraneoplastic Syndromes
• Occur as a result of cytokine release by renal
  cell tumors
• Erythrocytosis
• Nonmetastatic hepatic dysfunction
• Polyneuromyopathy
• Amyloidosis
• Anemia
• Cachexia
• Fever
• Weight loss

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RCC Treatment

• Nephrectomy
• The only known effective treatment for localized
  renal cell carcinoma
• Also used for palliation in metastatic disease
• Radical Nephrectomy
• Involves complete removal of kidney, peri-renal
  fat, adrenal gland, and lymph node dissection
• Provides a better surgical margin than simple
  removal of the kidney
• 20-30 of patients w/ clinically localized
  disease develop metastatic disease after
  nephrectomy
• Nephroureterectomy
• Transitional cell carcinomas

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RCC Histology

• Clear Cell RCC
• Most common form of renal cell carcinoma
• Under a microscope, the cells appear very pale or
  clear
• Papillary RCC
• Second most common subtype
• 10 to 15 of RCCs
• Form little finger-like projections (called
  papillae) in some, if not most, of the tumor
• Chromophobe RCC
• Accounts for about 5 of RCCs
• Collecting Duct RCC
• Very rare and aggressive
• Unclassified RCC
• Appearance doesn't fit into any of the other
  categories or there is more than one type of cell
  presentvery rare

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RCC Staging
Stage II
Stage I
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RCC Staging
Stage IV
Stage III
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Renal Cell Carcinoma Staging
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Renal Cell Carcinoma

• 5-Year Survival
• The percentage of patients who live at least 5
  years after being diagnosed

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Bladder Cancer

• 5th most common cancer overall
• 68,810 new cases and 14,100 deaths estimated for
  2008
• 4th most common cancer in menbehind prostate,
  lung, and colorectal cancers
• Men are 4x more likely to develop bladder cancer
• 90 occur in those over age 55
• Median age at diagnosis is 73 years
• Urothelium
• Multi-layer, specialized epithelium, made up of
  transitional cells
• Present in most of the urinary tract, including
  the renal pelvis, ureters, bladder, and part of
  urethra
• 90 of bladder cancers are transitional cell
  carcinomas
• 6-8 squamous cell carcinoma
• 2 adenocarcinoma

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Bladder Cancer

• 80 of bladder cancers are caused by
  environmental exposure
• Smoking (50)
• Aromatic amines in dyes
• Solvents
• Leather dust
• Inks
• Combustion products
• Rubber
• Textiles
• Other risk factors
• Prior exposure to radiation treatment of the
  pelvis
• Chemotherapeutic agents
• Cyclophosphamide
• Recurrent bladder infections
• Age
• Gender

• Signs and Symptoms
• Painless hematuria
• Change in bladder habits
• Dysuria
• Urgency
• Frequency
• Pelvic/flank pain

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Bladder Cancer Diagnosis

• Urinalysis
• Microscopy
• Hematuria
• Culture
• r/o infection
• Cytology
• Identify malignant cells
• High incidence of false negatives
• Exfoliated cells from low-grade tumors are
  sometimes hard to differentiate from normal
  epithelium
• CT scan of abdomen pelvis
• AUA Best Practice Policy
• Intravenous Pyelogram (IVP)
• Poor tool for evaluating parenchyma
• Renal Ultrasound
• Can miss urothelial tumors of the upper tract

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Bladder Cancer Diagnosis

• Cystoscopy
• Rigid or flexible cystoscope is inserted, via the
  urethra, into the bladder
• Allows direct visualization of the bladder
  epithelium and ability to obtain tissue biopsy
• Tumor staging
• In most cases, treatment can beprovided at time
  of cystoscopy
• Transurethral resection oftumor

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Superficial Bladder Cancers

• Transitional Cell Carcinoma (TCC)
• Urothelial cancer
• Accounts for 90 of bladder cancers
• Low-grade, non-invasive, superficial cancer
• Papillary tumor
• Frequent recurrence

• Carcinoma in-situ (CIS)
• Unlike other in-situ carcinomas, CIS of the
  bladder can become an aggressive, invasive cancer
• Recurrent CIS is associated w/ a 63 risk of
  progression to muscle-invasive bladder cancer

TCC
CIS
Lamina Propria
Urothelium
Muscle
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Invasive Bladder Cancers

• Adenocarcinoma
• Originates in glandular cells of the bladder
• Accounts for 2 of bladder cancers
• Squamous cell carcinoma
• Originates in epithelial cells
• Accounts for approximately 6-8 of bladder
  cancers
• Nonurothelial primary bladder tumors
• Extremely rare
• Small cell carcinoma
• Carcinosarcoma
• Primary lymphoma
• Sarcoma

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Bladder Cancer Staging

• Tis
• CIS, high grade dysplasia, confined to epithelium
• Ta
• Papillary tumor confined to epithelium
• T1
• Tumor invades lamina propria
• T2
• Tumor invades muscularis propria
• T3
• Tumor invades perivesical fat
• T3amicroscopic invasion
• T3bmacroscopic invasion
• T4
• Tumor involvement of invasive organs, such as
  prostate, rectum or pelvic sidewall

T2
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Bladder Cancer Treatment

• Transurethral Resection
• Endoscopic excision of tumor, adjacent muscle and
  tissue
• Preserves the bladder
• Only treatment necessary for non-invasive,
  low-grade tumors
• Intravesical Immunotherapy
• Bacillus Calmette-Guérin (BCG) immunotherapy
• An attenuated strain of the tuberculosis bacillus
• Stimulates the bodys immune system to fight the
  cancer
• Administered weekly for 6 weeks
• This course can be repeated if subsequent
  cystoscopy shows evidence of recurrence
• Maintenance therapy w/ a weekly treatment for 3
  weeks every 6 months for 1-3 years may provide
  more lasting results
• Side effects
• BCG sepsis
• Used as adjuvant treatment for patients w/ CIS,
  T1 and high risk Ta tumors, and those w/ multiple
  recurrent low-grade tumors

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Bladder Cancer Treatment

• Cystectomy
• Simple Cystectomy
• Removal of bladder
• Radical Cystectomy
• Includes removal of bladder and other pelvic
  organs
• MenProstate, seminal vesicles, lymph nodes
• WomenUterus, fallopian tubes, ovaries, anterior
  part of the vagina and pelvic lymph nodes
• Used to treat recurrent TCC, CIS or invasive
  tumors
• 35-50 of patients who undergo cystectomy for Ta,
  T1, or CIS are discovered to have muscle-invasive
  disease
• 10-15 have microscopic lymph node metastasis
• Chemotherapy/Radiation
• Used to treat advanced/metastatic tumors
• Palliative

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Urinary Diversion
Continent Diversion A pouch is constructed out of
portions of the small and large intestine. The
ureters are connected to the pouch and thestoma
is created through the abdominal wall.Urine is
removed by inserting a catheter into thestoma
when the pouch is full.
Ileal Conduit A piece of small intestine is
removed, cleaned, andtied at one end to form a
tube. The other end is used to form a stoma, an
opening through the abdominal wall to the outside
of the body. The ureters are then connected to
the tube.
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Bladder Cancer

• At presentation
• 55-60 have low-grade superficial disease
• 40-45 have high-grade disease
• 50 of those w/ high-grade tumors have muscle
  invasive disease
• The most significant prognostic factors
• Grade
• Depth of invasion
• Presence of CIS
• 5-Year Survival by Stage

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In Summary

• Staging is the most important prognostic
  indicator in determining mortality risk of GU
  tumors
• Both bladder and renal carcinomas have high risk
  of recurrence
• Regular surveillance screening is important
• Patients are generally asymptomatic
• Painless hematuria may be only sign
• May be intermittent
• By the time symptoms develop, disease may be
  advanced