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Genitourinary neoplasam

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					Genitourinary
 neoplasam
 Prof. Zhou-Jun Shen (沈周俊)
Cancer of the Bladder
Cancer of the Bladder
      Anatomy



             Kidneys:
                l   Make urine
             Ureters:
                l   Bring urine from
                    kidneys to bladder
             Great Vessels:
                l   Bring blood to kidneys
             Bladder:
                l   Stores urine


                                         3
               Cancer of the Bladder
                      Anatomy



                     Bladder
                     Prostate
       Urine
                       Vas
                      Uterus     Urine


                     Vagina
                     Urethra
                     Testicle
                      Penis




Male                               Female
                                            4
             Cancer of the Bladder
                                   Stages
                               Stages of Bladder Cancer



                              Ta
                                          Superficial Disease (non-invasive)
Bladder
 Bladder                           Tis
                                              Does not invade muscle layer
                                              of the bladder wall
                                   T1


                                     T2



                                   T3a
                                            Invasive Disease
                                                 Invades muscle layer of the
                                   T3b           bladder wall
    Bladder Wall:
         Mucosa
         Basement Membrane
         Superficial Muscle
         Deep Muscle
         Peritoneum
                                                                        5
         Cancer of the Bladder
           Superficial vs. Invasive Disease


                                           Tumor Progression
Superficial Disease:
   •80% of patients at presentation
                                                 10-50%
   •Good prognosis (85% survival at 5 years)
   •Easily treatable without major surgery


  Invasive Disease:
     •20% of patients at presentation
     •Poor prognosis (45% survival at 5 years)
     •Treatable by major surgery or radiation



                                                           6
                    Cancer of the Bladder
                                  Incidence

Overall
      l   52,900 cases/year ® 5th most common tumor
Sex
      l   M:F Ratio  3:1
      l   males 4th (prostate, lung, GI, TCC) 10% of male
          cancers
      l   females 8th 4% of all female cancers
Race
      l   caucasian > african american (27 vs. 14 /100,000)


                                                              7
                      Cancer of the Bladder
                                    Incidence


Regional                                            Age
   l incidence 30%-50% higher                250
     in the north
                                             200




                                 Incidence
National                                     150

   l incidence: US and GB high
                                             100
   l Japan and Finland low
   l Hawaii: Caucasians >                    50
     Japanese
                                              0
                                                   <35   40-49 50-59 60-69 70-79 80-89

                                                                   Age (years)      8
          Cancer of the Bladder
                 Risk Factors
Environmental:
   l Smoking/Chewing Tobacco

   l Pollution/Smog

Industrial:
   l Textile dye and leather

     tanning
   l Petrochemical

Medications:
   l Phenacetin

   l Cyclophosphamide

Radiation:
   l Cervical and rectal cancer   9
                               Cancer of the Bladder
                                Signs and Symptoms



        Signs and Symptoms           Percent of All Bladder Cancer Patients

Painless Hematuria                                       85
Vesical Irritability                                     40
Flank pain or Kidney Failure                             20
Lower extremity swelling                                 10
Pelvic Mass                                              10
Weight Loss                                              8
Abdominal or Bone Pain                                   5



                                                                              10
                        Cancer of the Bladder
                                 Diagnosis
Cystoscopy
   l  Looking through a
      telescope into bladder                  Urologist performing
   l  Office procedure                       Cystoscopy in the office

IVP/Ultrasound
   l  detects abnormalities of
      the kidneys and ureters
   l  blockage, other cancers
Urine Cytology
      Detects cancer cells
  in the urine
Urine Tumor Markers
   l  Fibronectin, FN
   l  MNP22                                                        11
Cancer of the Bladder
      Treatment




                        12
                               Cancer of the Bladder
                    Treatment of Suprficial Disease-The TUR


The Trans Urethral Resection (TUR)
   • Electrical scraping of tumor
   • General or spinal anaestesia
   • Same day or overnight surgery
   • Bladder catheter in place for 0-5 days


                                                     Tumor

                                                           Bladder wall




                                                Excised area

                                                                    13
                              Cancer of the Bladder
                Treatment of Invasive Disease-Radiotherapy
l   Improved 3-dimensional computer reconstruction from CT
l   Improved 3-dimensional computational dose calculations
l   Multileaf collimators “Designer Radiation Beam”
l   180º rotation of gantry

                                              Radiation Source




                                                     Beam




                                         Bladder
     Multileaf Collimator Assembly                               14
           Cancer of the Bladder
Treatment of Invasive Disease-The Ileal Conduit




 Stoma




             Ileum
                            Ureters implanted
                            into ileum

     Pro’s: Simpler operation
     Con’s: Need for bag (ostomy)
                                                  15
           Cancer of the Bladder
Treatment of Invasive Disease-The Indiana Pouch




           Colon
                   Appendix
                   or Ileum

 Pro’s: Small ostomy but no need for bag
 Con’s: Complex operation
         Need to do intermittent cath
                                              16
          Cancer of the Bladder
Treatment of Invasive Disease-The Neobladder




                 Ileum




 Pro’s: No ostomy
 Con’s: Complex operation
         Increased complication rate
                                               17
Renal Cell Carcinoma
• Background:
• Renal cell carcinoma accounts for approximately
  3% of adult malignancies and 90-95% of
  neoplasms arising from the kidney.

• It is characterized by a lack of early warning
  signs,
• diverse clinical manifestations,
• resistance to radiation and chemotherapy,
• infrequent but reproducible responses to
  immunotherapy agents such as interferon alpha,
  interleukin (IL)-2
• New agents, such as sorafenib and
  sunitinib, having anti-angiogenic effects
  through targeting multiple receptor kinases,
  have activity in patients failing
  immunotherapy.

• In the past, these tumors were believed to
  derive from the adrenal gland;
             Pathophysiology
• The tissue of origin for renal cell carcinoma is
  the proximal renal tubular epithelium.

• Renal cancer occurs in both a sporadic
  (nonhereditary) and a hereditary form, and
  both forms are associated with structural
  alterations of the short arm of chromosome 3
  (3p).
At least 4 hereditary syndromes associated
with renal cell carcinoma are recognized:
(1) von Hippel-Lindau (VHL) syndrome,
(2) hereditary papillary renal carcinoma (HPRC),
(3) familial renal oncocytoma (FRO) associated with
    Birt-Hogg-Dube syndrome (BHDS),
(4) hereditary renal carcinoma (HRC).
                  Frequency
• In the US: The age-adjusted incidence of renal cell
  carcinoma has been rising by 3% per year.

• 36,160 new cases of renal cell carcinoma in 2005,
  and more than 12,660 died. The greatest increase
  in incidence currently is observed in African
  Americans.

• Internationally: Number of deaths worldwide from
  kidney cancer was expected to exceed 100,000 in
  2001.
           Mortality/Morbidity

• Renal cell carcinoma is the sixth leading cause of cancer
  death.

• The 5-year survival rates initially reported by Robson in
  1969 were
  66% for stage I renal carcinoma,
  64% for stage II,
  42% for stage III,
  only 11% for stage IV.

• Except for stage I, these survival statistics have remained
  essentially unchanged for several decades.
                   Race

• Renal cell carcinoma is more common in
  people of Northern European ancestry
  (Scandinavians) and North Americans than
  in those of Asian or African descent.

• In the United States, its incidence has been
  equivalent among whites and African
  Americans, but incidence among African
  Americans is increasing rapidly.
• Sex: The male-to-female ratio is 2:1.

• Age: This condition occurs most commonly
  in the fourth to sixth decades of life, but the
  disease has been reported in younger
  people who belong to family clusters.
                   History
• Renal cell carcinoma may remain clinically
  occult for most of its course.
•
• The classic triad of flank pain, hematuria, and
  flank mass is uncommon (10%) and is indicative
  of advanced disease.

• 25 to 30 percent of patients are asymptomatic,
  and their renal cell carcinomas are found on
  incidental radiologic study.
• Most common presentations
  – Hematuria (40%)
  – Flank pain (40%)
  – Palpable mass in the flank or abdomen (25%)
• Other signs and symptoms
  – Weight loss (33%)
  – Fever (20%)
  – Hypertension (20%)
  – Hypercalcemia (5%)
  – Night sweats
  – Malaise
  – Varicocele, usually left sided, due to
    obstruction of the testicular vein (2% of males)
• unique and challenging, frequent occurrence
  of paraneoplastic syndromes,

• including hypercalcemia, erythrocytosis, and
  nonmetastatic hepatic dysfunction (ie, Stauffer
  syndrome).amyloidosis, anemia, fever,
  cachexia, weight loss, dermatomyositis,
  increased erythrocyte sedimentation rate, and
  hypertension also are associated with renal
  cell carcinoma.
– Cytokine release by tumor (eg, IL-6,
  erythropoietin, nitric oxide) causes these
  paraneoplastic conditions.

– Resolution of symptoms or biochemical
  abnormalities frequently follows successful
  treatment of the primary tumor or metastatic foci.
                             Physical
• Gross hematuria with vermiform clots suggests upper urinary tract
  bleeding.

• Look for hypertension, supraclavicular adenopathy, and flank or
  abdominal mass with bruit.

• Approximately 30% of patients with renal carcinoma present with
  metastatic disease. Physical examination should include thorough
  evaluation for metastatic disease. Organs involved include:
   – Lung (75%)
   – Soft tissues (36%)
   – Bone (20%)
   – Liver (18%)
   – Cutaneous sites (8%)
   – Central nervous system (8%)

• Varicocele and findings of paraneoplastic syndromes raise clinical
  suspicion for this diagnosis.
                      Causes
• A number of cellular, environmental, genetic, and
  hormonal factors have been studied as possible causal
  factors for renal cell carcinoma.

• Cigarette smoking doubles the risk of renal cell carcinoma
  and contributes to as many as one third of all cases.

• Obesity is another risk factor, particularly in women;
  increasing body weight has a linear relationship with
  increasing risk.
• Additional factors associated with
  development of the disease include the
  following:
  – Hypertension
  – Treatment for hypertension
  – Unopposed estrogen therapy
  – Occupational exposure to petroleum products,
    heavy metals, solvents, coke-oven emissions,
    or asbestos
• The risk of renal cell carcinoma is increased with
  the following:
  – Abuse of phenacetin-containing analgesics
  – Acquired cystic kidney disease associated with
    chronic renal insufficiency
  – Renal dialysis
  – Tuberous sclerosis
  – Renal transplantation: With its associated
    immunosuppression, renal transplantation confers an
    80-fold increase in the risk of renal cell cancer.
  – VHL disease: This inherited disease is associated
    with renal cell carcinoma.
          Other Problems

Abscess
Angiomyolipoma (benign neoplasm)
Oncocytoma (benign neoplasm)
Metastasis from distant primary
Metastatic melanoma
Renal adenoma (benign neoplasm)
Renal cyst
Renal infarct
Sarcoma
Transitional cell carcinoma of renal pelvis
                         Lab Studies
• Laboratory studies in the evaluation of renal cell carcinoma
  should include a workup for paraneoplastic syndromes. Initial
  studies are as follows:
    –   Urine analysis
    –   CBC count with differential
    –   Electrolytes
    –   Renal profile
•   Liver function tests (AST and ALT)
•   Calcium
•   Erythrocyte sedimentation rate
•   Prothrombin time
•   Activated partial thromboplastin time
•   Other tests indicated by presenting symptoms
             Imaging Studies
A large proportion of patients diagnosed with renal
  cancer have small tumors discovered
  incidentally on imaging studies. A number of
  diagnostic modalities are used to evaluate and
  stage renal masses, including the following:
  –   Excretory urography
  –   CT scan
  –   Ultrasonography
  –   Arteriography
  –   Venography
  –   MRI
  –   PET
Radiologic studies should be tailored to
 enable further characterization of renal
 masses, so that nonmalignant tumors can
 be differentiated from malignant ones.

• Excretory urography is not used frequently
  in the initial evaluation of renal masses
  because of its low sensitivity and specificity.

• A small- to medium-sized tumor may be
  missed by excretory urography.
• Contrast-enhanced CT scanning has become the imaging
  procedure of choice for diagnosis and staging of renal cell
  cancer and has virtually replaced excretory urography and
  renal ultrasound.

• In most cases, CT imaging can differentiate cystic masses
  from solid masses and supplies information about lymph
  node, renal vein, and inferior vena cava involvement.

• Ultrasound examination can be useful in evaluating
  questionable cystic renal lesions if CT imaging is
  inconclusive.

• Large papillary renal tumors are frequently undetectable
  by renal ultrasound.
• Renal arteriography is not used in the evaluation of a
  suspected renal mass as frequently now as it was in the
  past. When inferior vena cava involvement is suspected,
  either inferior venacavography or MRI angiography is used.

• Knowledge of inferior vena cava involvement is important
  in planning the vascular aspect of the operative procedure.

• A bone scan is recommended for bony symptoms with
  elevated alkaline phosphatase level.

• PET imaging remains controversial in kidney cancer. Its
  sensitivity for detecting metastatic lesions is better than for
  determining the presence of cancer in the renal primary
  site.
         Histologic Findings
• Renal cell carcinoma has 5 histologic subtypes,
  as follows: clear cell (75%), chromophilic (15%),
  chromophobic (5%), oncocytoma (3%), and
  collecting duct (2%).
Renal oncocytoma consists predominantly of
eosinophilic cells, in a characteristic nested
or organoid pattern, that rarely metastasize
and do not exhibit 3p deletion or trisomy 7 or
17.
Table 1. Pathologic Classification of Renal Cell Carcinoma
                      Staging
The Robson staging system is as follows:
  – Stage I - Tumor confined within capsule of kidney
  – Stage II - Tumor invading perinephric fat but still
    contained within the Gerota fascia
  – Stage III - Tumor invading the renal vein or inferior
    vena cava (A), or regional lymph-node
    involvement (B), or both (C)
  – Stage IV - Tumor invading adjacent viscera
    (excluding ipsilateral adrenal) or distant
    metastases
                   The TNM classification system :
                         Primary tumor (T)
•   TX - Primary tumor cannot be assessed
•   T0 - No evidence of primary tumor
•   T1 - Tumor 7 cm or smaller in greatest dimension, limited to the kidney

•   T2 - Tumor larger than 7 cm in greatest dimension, limited to the kidney

•   T3 - Tumor extends into major veins or invades adrenal gland or perinephric
    tissues but not beyond the Gerota fascia

•   T3a - Tumor invades adrenal gland or perinephric tissues but not beyond the
    Gerota fascia
•   T3b - Tumor grossly extends into the renal vein(s) or vena cava below the
    diaphragm
•   T3c - Tumor grossly extends into the renal vein(s) or vena cava above the
    diaphragm
•
•   T4 - Tumor invading beyond the Gerota fascia
– Regional lymph nodes (N) - Laterality does not
  affect the N classification
  •   NX - Regional lymph nodes cannot be assessed
  •   N0 - No regional lymph node metastasis
  •   N1 - Metastasis in a single regional lymph node
  •   N2 - Metastasis in more than 1 regional lymph node


– Distant metastasis (M)
  • MX - Distant metastasis cannot be assessed
  • M0 - No distant metastasis
  • M1 - Distant metastasis
                 Medical Care
• More than 50% of patients with renal cell carcinoma
  are cured in early stages, but outcome for stage IV
  disease is poor.

• The probability of cure is related directly to the stage
  or degree of tumor dissemination, so the approach
  is curative for early stage disease.

• Selected patients with metastatic disease respond
  to immunotherapy, but many patients can be offered
  only palliative therapy for advanced disease.
The treatment options for renal cell cancer are
• surgery,
• radiation therapy,
• chemotherapy,
• hormonal therapy,
• immunotherapy,
• Targeted inhibitors
• or combinations of these.
            Multi-kinase inhibitors
Sorafenib
  – On December 20, 2005, the US Food and Drug
    Administration granted approval for sorafenib (Nexavar),
    a small molecule Raf kinase and VEGF multi-receptor
    kinase inhibitor, for the treatment of patients with
    advanced renal cell carcinoma.

  – This indication is based on the demonstration of
    improved progression-free survival in a large,
    multinational, randomized double-blind, placebo-
    controlled phase 3 study and a supportive phase 2 study.

  – Overall survival results from the phase 3 study are
    preliminary at this time.
• Sorafenib targets serine/threonine and receptor
  tyrosine kinases, including those of RAF,
  VEGFR-2,3, PDGFR-b, KIT, FLT-3, and RET.

• Further clinical studies evaluating the role of
  sorafenib in the first-line setting, in combination
  with other immunomodulators, are underway.
  Preliminary results appear promising.
           Sunitinib (Sutent)
• Sunitinib is another multi-kinase inhibitor
  approved by the FDA in January 2006 for the
  treatment of metastatic kidney cancer that has
  progressed after a trial of immunotherapy.

• The approval was based on the high response
  rate (40% partial responses) and a median time
  to progression of 8.7 months and an overall
  survival of 16.4 months.
• The receptor tyrosine kinases inhibited by
  sunitinib include VEGFR 1-3 and PDGFR a
  and b.

• Major toxicities (grade II or higher) include
  fatigue (38%), diarrhea (24%), nausea (19%),
  dyspepsia (16%), stomatitis (19%), and
  decline in cardiac ejection fraction (11%).

• Dermatitis occurred in 8%, and hypertension
  occurred in 5% of patients.
           Chemotherapy
A recent phase 2 trial of weekly intravenous
  gemcitabine (600 mg/m2 on days 1, 8, and
  15) with continuous infusion fluorouracil
  (150 mg/m2/d for 21 d in 28-d cycle) in
  patients with metastatic renal cell cancer
  produced a partial response rate of 17%.
No complete responses were noted.
             Surgical Care
• Surgical resection remains the only known
  effective treatment for localized renal cell
  carcinoma, and it also is used for palliation
  in metastatic disease.
• Radical nephrectomy, which remains the
  most commonly performed standard
  surgical procedure today for treatment of
  localized renal carcinoma,

• involves complete removal of the Gerota
  fascia and its contents, including a
  resection of kidney, perirenal fat, and
  ipsilateral adrenal gland, with or without
  ipsilateral lymph node dissection.
• Laparoscopic nephrectomy is a less invasive
  procedure, incurs less morbidity, and is
  associated with shorter recovery time and less
  blood loss.

• Disadvantages include concerns about spillage
  and technical difficulties in defining surgical
  margins.

• Laparoscopic partial nephrectomy can be
  considered at centers with experience in this
  procedure for early stage renal cell cancer.
• Radiation therapy may be considered as
  the primary therapy for palliation in
  patients whose clinical condition precludes
  surgery, either because of extensive
  disease or poor overall condition.
   PROATATE
ADENOCARCINOMA
• Prostate cancer is usually adenocarcinoma.

• Symptoms are rare until urethral obstruction
  occurs.

• Diagnosis is suggested by digital rectal
  examination or prostate-specific
  antigen(PSA) measurement and confirmed
  by biopsy.
• Prognosis, localized or regional, is very
  good; more men die with prostate cancer
  than of it.

• Treatment is with prostatectomy, radiation
  therapy, or, for some elderly patients,
  watchful waiting.
• Adenocarcinoma of the prostate is the most
  common nondermatologic cancer in men >
  50 in the US. In the US, about 230,100 new
  cases and about 29,900 deaths (in 2004)
  occur each year.

• Incidence increases with each decade of life;
  autopsy studies show prostate cancer in 15
  to 60% of men age 60 to 90 yr, with
  incidence increasing with age.
• Median age at diagnosis is 72, and > 75% of
  prostate cancers are diagnosed in men > 65.

• Risk is highest for black men.

• Sarcoma of the prostate is rare, occurring
  primarily in children.
• Undifferentiated prostate cancer, squamous
  cell carcinoma, and ductal transitional
  carcinoma also occur.

• Hormonal influences contribute to
  adenocarcinoma but almost certainly not to
  other types of prostate cancer.
• Prostatic intraepithelial neoplasia (PIN) is
  precancerous histologic change.

• It may be low- or high-grade; high-grade is
  considered a precursor of invasive cancer.
        Symptoms and Signs

• Prostate cancer usually progresses slowly and
  rarely causes symptoms until advanced.

• In advanced disease, hematuria and symptoms
  of bladder outlet obstruction (eg, straining,
  hesitancy, weak or intermittent urine stream, a
  sense of incomplete emptying, terminal dribbling)
  may appear.
• Bone pain may result from osteoblastic
  metastases to bone (commonly pelvis,
  ribs, vertebral bodies).
                Diagnosis
• Sometimes stony hard induration or nodules
  are palpable on digital rectal examination
  (DRE), but the examination is often normal;
  induration and nodularity suggest cancer but
  must be differentiated from granulomatous
  prostatitis, prostatic calculi, and other
  prostate disorders.
• Extension of induration to the seminal
  vesicles and lateral fixation of the gland
  suggest locally advanced prostate cancer.

• Prostate cancers detected by DRE tend
  to be large, and > 50% extend through
  the capsule.
                 Screening

• Most cases are detected by screening with DRE
  and serum prostate-specific antigen (PSA) levels,
  which is commonly performed annually in men >
  50 yr.

• Abnormal findings require histologic confirmation,
  most commonly by transrectal ultrasound
  (TRUS)–guided transrectal needle biopsy, which
  can be done in a clinic without general
  anesthesia. Hypoechoic areas are more likely to
  represent cancer.
Occasionally, prostate cancer is diagnosed
incidentally in tissue removed during surgery
for benign prostatic hyperplasia (BPH).
Staging
• TRUS may provide information for staging,
  particularly about capsular penetration and
  seminal vesicle invasion.

• Elevated serum acid phosphatase—
  especially the enzymatic assay—correlates
  well with the presence of metastases,
  particularly in lymph nodes.
• However, this enzyme may also be elevated
  in BPH (slightly after vigorous prostatic
  massage), multiple myeloma, Gaucher's
  disease, and hemolytic anemia.

• Radionuclide bone scanning is done to
  check for metastases to bone (sometimes
  detected by x-rays).
• Reverse transcriptase–PCR assays for
  circulating prostate cancer cells are being
  studied as a staging and prognostic tool.
                Grading
• Grading, based on the resemblance of
  tumor architecture to normal glandular
  structure, helps define the aggressiveness
  of the tumor.

• Grading takes into account histologic
  heterogeneity in the tumor.
• The Gleason score :
• The most prevalent pattern and the next most
  prevalent pattern are each assigned a grade of 1 to
  5, and the 2 grades are added (total score:
• 2 to 4 = well differentiated,
• 5 to 7 = moderately differentiated,
• 8 to 10 = undifferentiated);
• another scaling system ≤ 6 is considered well
  differentiated, 7 moderately, and 8 to 10 poorly
  differentiated.
• Gleason score, clinical stage, and PSA
  together (using tables or nomograms)
  predict pathologic stage and prognosis
  better than any of them alone.
• Both acid phosphatase and PSA levels
  decrease after treatment and increase
  with recurrence,

• but PSA is the most sensitive marker for
  monitoring cancer progression and
  response to treatment.
               Prognosis
• Prognosis for most patients with prostate
  cancer, especially when it is localized or
  regional, is very good.

• Prognosis for elderly men with prostate
  cancer differs little from age-matched men
  without prostate cancer.
• For many patients, long-term local control,
  even cure, is possible.

• Potential for cure, even when cancer is
  clinically localized, depends on the tumor's
  grade and stage.

• Without early treatment, patients with high-
  grade, poorly differentiated cancer have a
  poor prognosis.
• Undifferentiated prostate cancer,
  squamous cell carcinoma, and ductal
  transitional carcinoma respond poorly to
  the usual control measures.

• Metastatic cancer has no cure; median life
  expectancy is 1 to 3 yr, although some
  patients live for many years.
               Treatment
• Treatment is guided by PSA, grade and
  extent of tumor, patient age, coexisting
  disorders, and life expectancy.
• Most patients, regardless of age, prefer definitive
  therapy.

• However, watchful waiting may be appropriate for
  asymptomatic patients > 70 with localized prostate
  cancer, particularly if it is well or moderately well
  differentiated and low volume or if life-limiting
  disorders coexist;

• in these patients, risk of death due to other causes
  is greater than that due to prostate cancer.
• This approach requires periodic DRE, PSA
  measurement, and monitoring of symptoms.
•
• If symptoms worsen, treatment is required.

• In elderly men, watchful waiting results in the
  same overall survival rate as prostatectomy;

• however, patients who had surgery had a
  significantly lower risk of distant metastases and
  disease-specific mortality.
• Radical prostatectomy (removal of prostate
  with adnexal structures and regional lymph
  nodes) is probably best for patients < 70
  with a tumor confined to the prostate.

• Prostatectomy is appropriate for some
  elderly patients, based on life expectancy,
  coexisting disorders, and ability to tolerate
  surgery and anesthesia.
• Complications include urinary incontinence
  (about 5 to 10%), bladder neck contracture
  or urethral stricture (about 7 to 20%),
  erectile dysfunction (about 30 to 100%—
  heavily dependent on age and current
  function), and fecal incontinence (1 to 2%).
• Major complications occur in > 25%, more
  often in elderly patients.

• Nerve-sparing radical prostatectomy
  reduces the likelihood of erectile dysfunction
  but cannot always be done, depending on
  tumor stage and location.
• Surgery ablation of androgen: orchiectomy
• Cryotherapy (destruction of prostate cancer
  cells by freezing with cryoprobes, followed
  by thawing) is less well established; long-
  term outcomes are unknown.

• Adverse effects include bladder outlet
  obstruction, urinary incontinence, erectile
  dysfunction, and rectal pain or injury.
• Results with radiation therapy and prostatectomy
  may be comparable, especially for patients with
  low pretreatment PSA levels.

• Standard external beam radiotherapy usually
  delivers 70 Gy in 7 wk. Conformal 3-dimensional
  radiation therapy or intensity modulated radiation
  therapy (IMRT) safely deliver doses approaching
  80 Gy to the prostate;

• data indicate that the rate of local control is higher,
  especially for high-risk patients.
• For most patients, some decrease in
  erectile function occurs in at least 40%.

• Other adverse effects include radiation
  proctitis, cystitis, diarrhea, fatigue, and,
  possibly urethral strictures, particularly in
  patients with a prior history of transurethral
  resection of the prostate.
• Whether brachytherapy (radioactive seed
  implants) can produce equivalent results is being
  studied; results appear to be comparable for
  patients with low PSA levels and low-grade
  localized tumors.

• Brachytherapy also decreases erectile function,
  although it may be delayed and patients may be
  more responsive to phosphodiesterase type 5
  (PDE5) inhibitors than patients whose
  neurovascular bundles are resected or injured
  during surgery.
• Urinary frequency, urgency, and, less often,
  retention are common but usually subside
  over time.

• Other adverse effects include increased
  bowel movements; rectal urgency, bleeding,
  or ulceration; and prostatorectal fistulas.
• For short-term palliation, one or more drugs
  may be used, including antiandrogens,
  chemotherapy drugs (eg, mitoxantrone,
  estramustine, taxanes), corticosteroids, and
  ketoconazole.
           Drug Information
• Patients with a locally advanced tumor or
  metastases may benefit from androgen
  deprivation by
• castration, either surgically with bilateral
  orchiectomy or
• medically with luteinizing hormone-
  releasing hormone (LHRH) agonists, such
  as leuprolide

				
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