Medical Students 2011 - G. Pentheroudakis - UROGENITAL CANCER SESSION - Prostate CancerPresentation 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
decreased force of stream
Irritative voiding symptoms
Hematospermia, decreased ejaculate volume
PRESENTATION OF PROSTATE CANCER (I)
Bone pain or anemia
Lower extremity edema
Disseminated intravascular coagulation
PRESENTATION OF PROSTATE CANCER (II)
Digital rectal examination (DRE)
( 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)
Serum PSA levels are affected by prostatic maneuvers
Affected by ejaculation
INTERPRETATION OF SERUM PSA LEVELS
PSA is the single test with the highest positive predictive value for cancer
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
Obturator nerve injury
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
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
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)
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
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
Very practical . One im injection every month or 3-monthly
Side effects : impotence, hot flashes, gynecomastia, peripheral edema
Nilutamide, flutamide and biclutamide
Mode of Action: Block androgen receptors by acting directly on prostatic cells.
They achieve also high responses and palliation
Avoid loss of sexual potency
Can be combined with LHRH agonists as first line treatment
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