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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

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

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