PROSTATE  CANCER  George Pentheroudakis Assistant Professor in Medical Oncology UNIVERSITY  OF  IOANNINA  GREECE ESO  COUR...
CANCER  OF  THE  URINARY  TRACT  IN  USA  FOR  1996-2000 Primary  site Incidence Mortality Kidney  Cancer (men) 15.9 6.1 B...
<ul><li>Prostate cancer  rarely causes symptoms  early in the course of the disease because most of the adenocarcinomas ar...
<ul><li>Obstructive voiding symptoms </li></ul><ul><ul><ul><li>hesitancy  </li></ul></ul></ul><ul><ul><ul><li>decreased  f...
<ul><li>Bone  pain  or anemia  </li></ul><ul><li>Lower  extremity edema  </li></ul><ul><li>Paraneoplastic syndromes  </li>...
<ul><li>Digital  rectal  examination (DRE) </li></ul><ul><li>PSA  </li></ul><ul><li>(  Transrectal ultrasonography  is not...
<ul><li>In the lack of malignancy, serum  PSA  levels  vary  with  age,  race, and prostatic volume  </li></ul><ul><li>PSA...
<ul><li>PSA is the single test with the  highest  positive predictive value for cancer  </li></ul><ul><li>Values: </li></u...
 
 
<ul><li>G 1 Gleason 2-4 (well differentiated) </li></ul>HISTOLOGIC  GRADE G 2 Gleason 5-6 (moderately differentiated) G 3 ...
 
Extent of Risk Clinical/Pathologic Features Estimated 5-y PSA failure-free survival Low Stage       T1c or T2a        85% ...
<ul><li>Radical  prostatectomy  is  the appropriate treatment  of  T 1 N 0 M 0  or  T 2 N 0  M 0  stages  in relatively  y...
<ul><li>EARLY </li></ul><ul><li>Hemorrhage  </li></ul><ul><li>Obturator nerve injury  </li></ul><ul><li>Rectal injury  </l...
<ul><li>When a cancer extends palpably beyond the prostate,  </li></ul><ul><li>lymph node metastases  are present in 30% t...
<ul><li>Brachytherapy  is  the placement  of  radioactive  sources  into  or  near  tumors  for  therapeutic  purposes.  <...
<ul><li>Lack of studies  comparing  radical prostatectomy  versus  radiation  treatment  with proper stratification for cl...
 
<ul><li>Initial spread to local lymph nodes </li></ul><ul><li>Followed by extensive bone  metastases </li></ul><ul><li>Vis...
<ul><li>How  do  you  restage  a  patient with suspected  metastases ? </li></ul><ul><li>CT-of the abdomen/pelvis </li></u...
<ul><li>Are the most common distant  metastatic  sites </li></ul><ul><li>Characteristically  are osteosclerotic lesions </...
<ul><li>It is a  sensitive  and  specific  tumour marker for disease relapse and for response to treatment  </li></ul><ul>...
<ul><li>Hormone – naive disease </li></ul><ul><li>Hormone – sensitive  disease (90%) </li></ul><ul><li>Hormone refractory ...
<ul><li>The  main  goal  of  therapy  is  androgen  deprivation   (ablation) </li></ul><ul><li>It is a  palliative  rather...
<ul><li>Surgical  castration (orchiectomy) </li></ul><ul><li>Oestrogens </li></ul><ul><li>Medical castration with LHRH ago...
<ul><li>It has been the  gold standard  as the best endocrine therapy for years. </li></ul><ul><li>Equally  effective   in...
<ul><li>Diethylstilbestrol,  Ethinyl Estradiol </li></ul><ul><li>No longer used because of cardiovascular toxicity </li></...
<ul><li> Luteinizing  hormone-releasing  hormone  (LHRH)  agonists or  analogues :  goserelin   or  leuprolide </li></ul>...
<ul><li>   Nilutamide,  flutamide  and  biclutamide </li></ul><ul><li>   Mode  of  Action:  Block androgen receptors by ...
<ul><li>Suppression of testicular androgens: orchiectomy or LHRH-agonists. </li></ul><ul><li>Block effects of adrenal andr...
<ul><li>   RESPONSES  :     Up  to 80%  of cases </li></ul><ul><li>     Normalization  of  PSA  in  70% </li></ul><ul><...
<ul><li>Second – line  Hormonal  Therapy   </li></ul><ul><li>Anti-androgen withdrawal  </li></ul><ul><li>Adrenal inhibitor...
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Medical Students 2011 - G. Pentheroudakis - UROGENITAL CANCER SESSION - Prostate Cancer

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Medical Students 2011 - G. Pentheroudakis - UROGENITAL CANCER SESSION - Prostate Cancer

  1. 1. PROSTATE CANCER George Pentheroudakis Assistant Professor in Medical Oncology UNIVERSITY OF IOANNINA GREECE ESO COURSE IOANNINA, JULY 20 1 1
  2. 2. CANCER OF THE URINARY TRACT IN USA FOR 1996-2000 Primary site Incidence Mortality Kidney Cancer (men) 15.9 6.1 Bladder Cancer (men) 37.4 7.7 Prostate Cancer 90-150 32.9 Cases per 100.000 population
  3. 3. <ul><li>Prostate cancer rarely causes symptoms early in the course of the disease because most of the adenocarcinomas arise in the periphery of the gland distant from the urethra </li></ul><ul><li>The presence of symptoms suggests locally advanced or metastatic disease </li></ul>PRESENTATION OF PROSTATE CANCER
  4. 4. <ul><li>Obstructive voiding symptoms </li></ul><ul><ul><ul><li>hesitancy </li></ul></ul></ul><ul><ul><ul><li>decreased force of stream </li></ul></ul></ul><ul><ul><ul><li>intermittency </li></ul></ul></ul><ul><li>Irritative voiding symptoms </li></ul><ul><ul><ul><li>frequency </li></ul></ul></ul><ul><ul><ul><li>nocturia </li></ul></ul></ul><ul><ul><ul><li>urgency </li></ul></ul></ul><ul><ul><ul><li>urge incontinence </li></ul></ul></ul><ul><li>Hematospermia, decreased ejaculate volume </li></ul><ul><li>Impotence </li></ul>PRESENTATION OF PROSTATE CANCER (I)
  5. 5. <ul><li>Bone pain or anemia </li></ul><ul><li>Lower extremity edema </li></ul><ul><li>Paraneoplastic syndromes </li></ul><ul><li>Disseminated intravascular coagulation </li></ul>PRESENTATION OF PROSTATE CANCER (II)
  6. 6. <ul><li>Digital rectal examination (DRE) </li></ul><ul><li>PSA </li></ul><ul><li>( Transrectal ultrasonography is not recommended as a first line screening test because of its low predictive value) </li></ul>FIRST LINE SCREENING TEST
  7. 7. <ul><li>In the lack of malignancy, serum PSA levels vary with age, race, and prostatic volume </li></ul><ul><li>PSA expression is strongly affected by androgens </li></ul><ul><li>Serum PSA levels are affected by prostatic disease </li></ul><ul><ul><ul><li>BPH (benign prostate hyperplasia) </li></ul></ul></ul><ul><ul><ul><li>prostatitis </li></ul></ul></ul><ul><ul><ul><li>cancer </li></ul></ul></ul><ul><li>Serum PSA levels are affected by prostatic maneuvers </li></ul><ul><ul><ul><li>prostate massage </li></ul></ul></ul><ul><ul><ul><li>prostatic biopsy </li></ul></ul></ul><ul><li>Affected by ejaculation </li></ul>INTERPRETATION OF SERUM PSA LEVELS
  8. 8. <ul><li>PSA is the single test with the highest positive predictive value for cancer </li></ul><ul><li>Values: </li></ul><ul><ul><ul><li>PSA < 4  Risk = 1/50 </li></ul></ul></ul><ul><ul><ul><li>4 < PSA < 10  Risk = 1/4 </li></ul></ul></ul><ul><ul><ul><li>PSA > 10  Risk = 1/2 - 2/3 </li></ul></ul></ul><ul><li>Although PSA has the highest positive predictive values for prostatic cancer, use of PSA without DRE is not recommended because 25% of men with prostate cancers have PSA levels less than 4 ng/ml </li></ul>PSA AND PROSTATE CANCER
  9. 11. <ul><li>G 1 Gleason 2-4 (well differentiated) </li></ul>HISTOLOGIC GRADE G 2 Gleason 5-6 (moderately differentiated) G 3 Gleason 7-10 (poorly differentiated)
  10. 13. Extent of Risk Clinical/Pathologic Features Estimated 5-y PSA failure-free survival Low Stage      T1c or T2a       85% PSA     10 ng/mL Gleason score     6 Intermediate Stage T2b or 50% PSA 11-20 ng/mL or Gleason score of 7 High Stage    T2c or       30% PSA    20 ng/mL Gleason score    7
  11. 14. <ul><li>Radical prostatectomy is the appropriate treatment of T 1 N 0 M 0 or T 2 N 0 M 0 stages in relatively young patients </li></ul>RADICAL PROSTATECTOMY FOR STAGES T 1 , T 2
  12. 15. <ul><li>EARLY </li></ul><ul><li>Hemorrhage </li></ul><ul><li>Obturator nerve injury </li></ul><ul><li>Rectal injury </li></ul><ul><li>Ureteral injury </li></ul><ul><li>LATE </li></ul><ul><li>Anastomotic stricture </li></ul><ul><li>Urinary incontinence </li></ul><ul><li>Erectile dysfunction </li></ul>COMPLICATIONS OF RADICAL PROSTATECTOMY
  13. 16. <ul><li>When a cancer extends palpably beyond the prostate, </li></ul><ul><li>lymph node metastases are present in 30% to 50% of patients </li></ul><ul><li>The purpose of employing radical prostatectomy in these patients is to control local tumor progression with its associated improvement in quality of life </li></ul><ul><li>Surgical treatment of patients with clinical stage T 3 prostate cancer has not been widely accepted because of the potential for incomplete excision of the primary tumor and the high incidence of lymph node metastasis </li></ul>T 3 STAGE
  14. 17. <ul><li>Brachytherapy is the placement of radioactive sources into or near tumors for therapeutic purposes. </li></ul><ul><li>Appropriate as monotherapy for localised low-risk prostate cancer </li></ul><ul><li>Used in conjunction to external beam RT as a boost </li></ul>BRACHYTHERAPY
  15. 18. <ul><li>Lack of studies comparing radical prostatectomy versus radiation treatment with proper stratification for clinical stage, baseline PSA and Gleason score </li></ul><ul><li>The D`Amico series reported equivalent outcomes with surgery and RT, the Cleveland series superiority of surgery in high-risk prostate cancer. </li></ul><ul><li>Neoadjuvant or adjuvant androgen blockade coupled to RT was shown to improve PFS in locally advanced prostate cancer in 3 RCT. </li></ul>RADICAL PROSTATECTOMY VS RADIATION TREATMENT
  16. 20. <ul><li>Initial spread to local lymph nodes </li></ul><ul><li>Followed by extensive bone metastases </li></ul><ul><li>Visceral metastatic sites during the course of the disease can be found. </li></ul><ul><li>About 30-35% of patients will present with regional or metastatic tumours </li></ul><ul><li>An additional 25% will develop metastases in the course of the disease </li></ul>NATURAL HISTORY OF METASTATIC PROSTATE CANCER
  17. 21. <ul><li>How do you restage a patient with suspected metastases ? </li></ul><ul><li>CT-of the abdomen/pelvis </li></ul><ul><li>Chest X-ray of the thorax </li></ul><ul><li>Bone scintigraphy </li></ul><ul><li>Plain X-ray of affected bones </li></ul><ul><li>Serum PSA levels </li></ul><ul><li>Full blood count and biochemistry (ALP, Ca ++ ,..) </li></ul>STAGING PROCEDURES FOR METASTATIC PROSTATE CANCER
  18. 22. <ul><li>Are the most common distant metastatic sites </li></ul><ul><li>Characteristically are osteosclerotic lesions </li></ul><ul><li>Affect mainly the pelvic bones, the spine and the ribs </li></ul><ul><li>Can produce bone pain, fractures or compression </li></ul>BONE METASTASES IN PROSTATE CANCER
  19. 23. <ul><li>It is a sensitive and specific tumour marker for disease relapse and for response to treatment </li></ul><ul><li>Almost 90% of patients with metastatic disease will have raised serum levels of PSA </li></ul><ul><li>Decrease in PSA after systemic treatment of more than 50% to 80% is associated with prolong ed survival . </li></ul>SERUM PROSTATIC SPECIFIC ANTIGEN (PSA)
  20. 24. <ul><li>Hormone – naive disease </li></ul><ul><li>Hormone – sensitive disease (90%) </li></ul><ul><li>Hormone refractory disease </li></ul>HORMONAL TREATMENT OF ADVANCED PROSTATE CANCER primarily (10%) secondarily
  21. 25. <ul><li>The main goal of therapy is androgen deprivation (ablation) </li></ul><ul><li>It is a palliative rather than curative treatment. </li></ul>RATIONAL OF TREATMENT OF HORMONE – NAÏVE DISEASE
  22. 26. <ul><li>Surgical castration (orchiectomy) </li></ul><ul><li>Oestrogens </li></ul><ul><li>Medical castration with LHRH agonists </li></ul><ul><li>Non-steroidal anti-androgens (i.e. bicalutamide) </li></ul><ul><li>Steroidal anti-androgens (cyproterone) </li></ul>ANDROGEN DEPRIVATION TREATMENTS
  23. 27. <ul><li>It has been the gold standard as the best endocrine therapy for years. </li></ul><ul><li>Equally effective in producing castrate levels of testosterone (< 50 ng/ml). </li></ul><ul><li>Gives high responses and palliation to the patients. </li></ul><ul><li>It is less expensive and without drug side effects. </li></ul><ul><li>However, it has been abandoned in many parts of the world, for psychological and cultural reasons. </li></ul>SURGICAL CASTRATION (ORCHIECTOMY)
  24. 28. <ul><li>Diethylstilbestrol, Ethinyl Estradiol </li></ul><ul><li>No longer used because of cardiovascular toxicity </li></ul>OESTROGENS
  25. 29. <ul><li> Luteinizing hormone-releasing hormone (LHRH) agonists or analogues : goserelin or leuprolide </li></ul><ul><li> Mode of Action: Inhibit gonadotrophin release from the pituitary causing testosterone reduction </li></ul><ul><li> Achieve s responses up to 80% of patients </li></ul><ul><li> More expensive. </li></ul><ul><li> Very practical . One im injection every month or 3-monthly </li></ul><ul><li> Side effects : impotence, hot flashes, gynecomastia, peripheral edema </li></ul>MEDICAL CASTRATION
  26. 30. <ul><li> Nilutamide, flutamide and biclutamide </li></ul><ul><li> Mode of Action: Block androgen receptors by acting directly on prostatic cells. </li></ul><ul><li> They achieve also high responses and palliation </li></ul><ul><li> Toxicities: Hepatotoxicity </li></ul><ul><li> Avoid loss of sexual potency </li></ul><ul><li> Can be combined with LHRH agonists as first line treatment </li></ul>NON-STEROIDAL ANTI-ANDROGENS
  27. 31. <ul><li>Suppression of testicular androgens: orchiectomy or LHRH-agonists. </li></ul><ul><li>Block effects of adrenal androgens: anti-androgen drugs. </li></ul><ul><li>The treatment of choice in some centers </li></ul><ul><li>One RCT and meta-analysis showed no statistical difference for response rate or survival. </li></ul><ul><li>One RCT and meta-analysis of non-steroidal anti-androgens showed a modest survival benefit for CAB. </li></ul><ul><li>It adds more toxicity (i.e GI side effects) </li></ul><ul><li>The combination is very expensive </li></ul>COMBINED ANDROGEN BLOCKADE (CAB)
  28. 32. <ul><li> RESPONSES :  Up to 80% of cases </li></ul><ul><li>  Normalization of PSA in 70% </li></ul><ul><li>  Improvement in bone scan in 30-50% </li></ul><ul><li> MEDIAN RESPONSE DURATION : 12 – 18 months </li></ul><ul><li> MEDIAN SURVIVAL : 2 ½ years </li></ul>RESULTS OF FIRST LINE TREATMENT IN HORMONE – NAÏVE PATIENTS
  29. 33. <ul><li>Second – line Hormonal Therapy </li></ul><ul><li>Anti-androgen withdrawal </li></ul><ul><li>Adrenal inhibitors (ketoconazole) </li></ul><ul><li>Megestrol or steroids </li></ul><ul><li>Response Rates = 10-30% </li></ul><ul><li>Chemotherapy </li></ul><ul><li>1) Estramustine (nitrogen mustard + estradiol) </li></ul><ul><li>3) Mitoxantrone </li></ul><ul><li>4) Docetaxel </li></ul><ul><li>Response Rates = 10-40% </li></ul><ul><li>S URVIVAL B ENEFIT = ? or minimal </li></ul>TREATMENT OF HORMONE - REFRACTORY DISEASE

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