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MANAGEMENT OF EARLY PROSTATE CANCER

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Title: MANAGEMENT OF EARLY PROSTATE CANCER


1
MANAGEMENT OF EARLY PROSTATE CANCER
  • BY
  • EHAB ESMAT FAWZY
  • M.D. ONCOLOGY
  • FACULTY OF MEDICINE
  • CAIRO UNIVRSITY

2
INTRODUCTION
  • Prostate cancer represents 4.9 of all cancer
    incidences , and its average incidence all over
    the world is about 3.4 /100000 population.
  • It ranks 9th among all cancers all over the
    world.
  • The median age of patients with prostate cancer
    is 72 years .
  • North America and Europe represent the highest
    regions of prostate cancer incidence all over the
    world with almost 189,000 newly diagnosed cases
    and 30200 mortality for the year 2002 in USA
    (Cancer statistics 2002).

3
DIAGNOSIS
  • Early ( preclinical diagnosis)
  • This represented the basis of screening program
    for early detection of prostate cancer and it
    consists of 3 modalities
  • 1- Digital rectal examination (DRE) it is
    subjected to personal clinical experience ,so it
    is less sensitive than other modalities (Thompson
    et al 1984) however , it is required as many
    cases of prostate cancer are not PSA ( prostate
    specific antigen) positive (Lodding et al 1998).

4
DIAGNOSIS
  • 2- Serum level of PSA it is both sensitive and
    specific ( it has a positive predictive value
    PPV of 20 -30 for PSA 4-8 ng/ml and PPV of
    42-71.4 for PSA gt 10ng/ml) (Brawer et al
    1999).So it had been used for screening of
    prostate cancer

5
DIAGNOSIS
  • 3- Transrectal ultrasound (TRUS) /- biopsy
  • Indications for biopsy
  • Palpable mass on DRE.
  • Elevated PSA.
  • Both high PSA palpable mass.

6
DIAGNOSIS
  • Pathology
  • - Location Majority (75) in peripheral
  • zone , 15 in the central zone , and 10-15 in
    the periurethral zone.

7
DIAGNOSIS
  • - Grade the most commonly adopted system is
    the Gleason score (based on the fact that
    prostate cancer is a multifocal disease with
    heterogeneous glandular pattern ), patients with
    a score 2-4 represent well differentiated cancers
    , 5-7 moderately differentiated , and 8-10 poorly
    differentiated ( Gleason , 1992).

8
Diagnosis
  • Radiology
  • TRUS Is the earliest modality , and helps for
    doing biopsy from suspicious lesions , for
    screening purposes and target volume
    determination for prostate brachytherapy .
    Improvement in resolution power improved its
    sensitivity a lot ( like the use of contrast
    ultrasonography ( Sedelaar 1999) , and Gleason et
    al (2003). .

9
DIAGNOSIS
  • Bone scan is indicated if there is a high risk
    factors (PSA gt 10ng/ml Gleason score gt 8 ), or
    if the patient is symptomatic ( Scherr et al
    2003).
  • Pelvic CT scan and MRI are essential for local
    staging and localization of prostate lesions and
    targeting for conformal external beam radiation
    therapy or brachytherapy ( Berthelet et al 2003).

10
DIAGNOSIS
  • Preoperative CT scan of the prostate is
    recommended to draw the planning target volume(
    PTV) if post operative radiation therapy is
    indicated as shown by Hocht et al ( 2002) who
    showed in their study that almost 93 of patients
    who had postoperative PTV without looking to
    their preoperative CT scans required an increase
    in their PTV to cover the tumor properly.

11
DIAGNOSIS
  • MRI had a great addition to CT scan for initial
    staging , and target localization for radiation
    therapy ( Mah et al 2002).

12
DIAGNOSIS
  • Radioisotopes can be used for imaging and staging
    of prostate carcinoma , as shown by Feneley et
    al (2000) , who used immunoscintigraphy with
    radiolabelled antibody to prostatic- specific
    membrane antigen (PSMA) the radioactive
    material was Indium-111. The high sensitivity
    was shown as they noted that 36 patients of the
    whole study group(49) who were classified before
    as having localized cancer , 7 of them (19) had
    radiotracer uptake in regional and distant lymph
    nodes.

13
DIAGNOSIS
  • Risk group stratification
  • A lot of prognostic factors affect the biological
    behavior of prostate cancer and its response to
    different treatment modalities so depending on
    TNM staging system to treat those patients may
    lead to under treatment of some patients ( eg T1/
    T2 lesions with PSA gt 20 ng/ml or with a Gleason
    score of 8 or more) , so the National
    Comprehensive Cancer Network( NCCN) has recently
    adopted a reasonable risk stratification for
    prostate cancer( Scherr et al 2003)

14
NCCN RISK STRATIFICATION
  • Low risk T1-T2a , and Gleason score 2-6 , and
    PSA lt 10 ng/ml( all the criteria should be
    present).
  • Intermediate risk T2b-T2c,or Gleason score 7 or
    PSA 10-20 ng/ml.
  • High risk T1/T2 , Gleason score 8-10 , or , PSA
    gt 20ng/ml.

15
Treatment options for prostate cancer
  • Observation alone.
  • Radical prostatectomy.
  • Radiation therapy.
  • Hormonal treatment.

16
OBSERVATION ALONE
  • Rationale
  • Most cases will not die of their disease.
  • A life expectancy of every patient should be
    taken into consideration trying to avoid the
    treatment related complications for those with
    relatively limited expected survival.
  • Patients are not left for just observation but
    a close monitoring of disease progression is
    done.
  • Patient preference should be considered.

17
OBSERVATION ALONE
  • WHICH PATIENTS BENEFIT FROM OBSERVATION ALONE?
  • - Choo et al (2001) suggested that those
    patients with T1-T2 , and age 70 years or more ,
    and , Gleason score lt6, and , PSA lt 10 ng/ml ,
    and PSA doubling time gt 10years are more suitable
    for observation alone.

18
OBSERVATION ALONE
  • Follow up regimen
  • - Scherr et al (2003) recommended to have a
    six monthly assessment of
  • PSA
  • DRE
  • -Repeat prostate biopsy after the 1st year ( to
    detect transformation to higher grades.

19
OBSERVATION ALONE
  • Signs of disease progression on observation
    modality
  • - Rise in PSA level.
  • - Clinical symptoms of disease progression.
  • -Increase in size as felt by DRE.
  • -Biologic transformation to higher grades.

20
OBSERVATION ALONE
  • Survival figures
  • Aldolfssen et al (2000) reviewed the survival of
    11, 500 cases of early prostate cancer treated
    with watchful waiting between 1965 1993 , had
    found that only 5 of these patients died , and
    this happened during the years 11-20 of follow up.

21
RADIACAL PROSTATECTOMY
  • Indications
  • Organ confined prostate cancer ie T1 or T2 ,
    pelvic lymph node dissection is indicated for
    any one of these features
  • -Either PSA gt20 ng/ml. Gleason score 5-6.
  • Or- PSA 15 20ng/ml Gleason score gt7.
  • (Bishoff et al 1995).

22
RADIACAL PROSTATECTOMY
  • Types
  • Radical retropubic prostatectomy(RRP).
  • Radical Perineal prostatectomy(RPP).
  • Radical Laparoscopic prostatectomy(RLP)

23
RADICAL PROSTATECTOMYPROS CONS
  • RP had the same overall and disease free survival
    figures as the other local control modalities (
    3D-CRT , IMRT , and brachytherapy ) however the
    sequelae are more with surgery ( higher incidence
    of urinary incontinence , impotence ) .

24
EXTERNAL BEAM RTI-conventional external beam
radiation therapy(CEBRT)
  • Main problem dose limitation usually radiation
    dose does not exceed 70GY in CEBRT ( dose
    limiting structures rectum and urinary bladder)
    and for early T1 / T2 lesions , the results of
    CEBRT are much inferior than 3D-CRT as shown by
    Catton et al (2002) .

25
3D-CRT
  • Three dimensional conformal radiation
    therapy(3DCRT) has a better localization of the
    target volume and less radiation dose to critical
    organs,as compared to CEBRT Ghilezan et al (2001)
    .

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ROLE OF PORT
  • Patients with high PSA , positive surgical
    margins , after RRP will benefit from adjuvant
    PORT in the form of better DFS and this is
    confirmed by Do LV etal (2002).

29
HYPOFRACTIONATION/EBRT
  • The use of higher radiation dose per fraction
    ( hypo fractionation) had been studied by many
    oncologists as Yeoh et al (2003) who found that ,
    biochemical relapse-free survival rate was did
    not differ significantly between the CEBRT and
    hypofractionation schedule as well the toxicity
    profile.

30
Intensity modulated radiation therapy (IMRT)
  • A major advantage of IMRT in comparison to
    three-dimensional conformal radiotherapy is the
    higher capability in providing dose distributions
    that conform very tightly to the target even for
    very complex shapes so sparing a lot of adjacent
    normal tissues( Francescon et al 2003)

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NEUTRON BEAM THERAPY
  • Lindsley et al (1996) in a prospective
    randomized study comparing the CEBRT and neutron
    beam therapy in localized prostate cancer , found
    a significant reduction in the number of 5 years
    local failures (11) as compared to that of CEBRT
    ( 32) ,, however the 5 years survival rate was
    not statistically different between the two study
    groups , and the toxicity profile of neutron beam
    therapy was acceptable .

33
STEREOTACTIC RADIOTHERAPY
  • There are no mature data on the results of
    stereotactic radiotherapy in prostate cancer
    however , methods for its optimization for
    treatment of early cases of prostate cancer are
    going on Herfarth(2000).

34
BRACHYTHERAPY
  • The basic principle of the use of interstitial
    brachytherapy in prostate carcinoma is the
    inverse square law which entails the fact that
    the deposition of radiation energy in tissues
    decreases exponentially as a square function of
    the distance from the radiation source , ( Blasko
    et al 1991)

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A) 3D reconstruction of the implant with dose
distribution, (B) 3D reconstruction, lateral view
with dose distribution, and (C) 3D
reconstruction, AP view with dose distribution.
 

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SEQUELAE OF DIFFERENT TREATMENT MODALITIES
43
CRYOTHERAPY
  • Mack ET AL(1997) had a study on the open
    perineal cryotherapy for 66 prostate cancer
    patients ( early stge ) .The mean survival was
    7.2 years. The mean follow-up period of survivors
    (38 patients) is 8.5 years. Complications were
    stress-incontinence in 10, impotence in 10 and
    temporary rectoperineal fistula in 8 . Donnelly
    etal (2002) reported 89 5 year overall survival
    rate , and 98 disease free survival rate after
    cryotherapy for early prostate cancer.

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NEOADJUVANT HORMONAL TREATMENT
  • Wachter et al(2002) in a study on 164 patients
    with early prostate carcinoma were randomized to
    either a total dose of 66 Gy (n 109) alone or
    in combination with a short-term hormonal
    treatment (n 55) . The 4-year rates of no
    biochemical evidence of disease for all patients
    was 58.

46
NEOADJUVANT HORMONAL TREATMENT
  • For the high-risk group the 4-year rates could be
    improved with borderline significance from 35 to
    66 (p 0.057) by additional neoadjuvant
    hormonal treatment. In contrast for the low-risk
    group no significant improvement was observed
    73 and 82, respectively (p 0.5).

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MANAGEMENT GIUDELINES
  • The choice of best treatment modality for early
    prostate cancer is controversial as several
    studies have suggested that expectant management
    provides similar 10-year survival rates and
    quality of life compared with radical
    prostatectomy or radiotherapy especially in low
    risk patients Klotz L., 2002) .

56
MANAGEMENT GIUDELINES
  • One of the principle factors in the management
    guidelines of prostate cancer is life expectancy
    of the patient which can be expected though
    different mathematical systems that used
    different variables to identify approximately the
    life expectancy of that patient.

57
MANAGEMENT GIUDELINES
  • Breuer et al 1998 formulated a method of life
    expectancy of 1145 elderly residents of nursing
    homes at the Jewish Home and Hospital they
    found that there was a significant, independent
    predictors of decreased survival with , increased
    age, increase in ADL index (dependencies in
    activities of daily living ), impairment of
    cardiac, respiratory, neurological, and
    endocrine/metabolic systems.

58
CONCLUSION
  • Management of early prostate cancer depends on
    multiple factors including expected survival of
    the patient , tumor grade , and PSA level . So
    in asymptomatic elderly patients with poor
    performance state and associated medical problems
    regardless of tumor characteristics , or PSA
    value watchful observation is advised . and if
    they start to show symptoms ( urinary symptoms)
    , they are given radiation therapy for symptom
    control.

59
CONCLUSION
  • In case of younger patients with good
    performance status and no major medical problems
    , the treatment decision depends on the risk
    status of the patient , so in case of low or
    intermediate risk , the patient can be treated
    with any local treatment modality( either
    prostatectomy , external beam radiation therapy
    or brachytherapy) , all of them had the same
    impact on disease free and overall survival and
    the patient will be informed about the
    complication of each modality before he start
    his treatment .

60
CONCLUSION
  • while if these patients are at a high risk
    category , it is better to give them a
    neoadjuvant hormonal treatment for 2-3 months
    before the local treatment ( surgery or
    radiation) as this will improve their disease
    free survival.

61
  • THANK YOU
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