MANAGEMENT OF EARLY PROSTATE CANCER by elma3rad

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									MANAGEMENT OF EARLY
  PROSTATE CANCER

           BY:
    EHAB ESMAT FAWZY
      M.D. ONCOLOGY
    FACULTY OF MEDICINE
      CAIRO UNIVRSITY
           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).
                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).
              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 > 10ng/ml)
  (Brawer et al 1999).So it had been used for
  screening of prostate cancer
             DIAGNOSIS
3- Transrectal ultrasound (TRUS) +/- biopsy :
  *Indications for biopsy:
• Palpable mass on DRE.
• Elevated PSA.
• Both high PSA & palpable mass.
             DIAGNOSIS


• Pathology :
- Location : Majority (75%) in peripheral
zone , 15% in the central zone , and 10-15 %
  in the periurethral zone.
             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).
                  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). .
                DIAGNOSIS
• Bone scan is indicated if there is a high risk
  factors (PSA > 10ng/ml ; Gleason score > 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).
              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.
               DIAGNOSIS

• MRI had a great addition to CT scan for
  initial staging , and target localization for
  radiation therapy ( Mah et al 2002).
               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.
                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 > 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)
           NCCN RISK
         STRATIFICATION
• Low risk: T1-T2a , and Gleason score 2-6 ,
  and PSA < 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 > 20ng/ml.
  Treatment options for prostate
             cancer
• Observation alone.

• Radical prostatectomy.

• Radiation therapy.

• Hormonal treatment.
     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.
     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 <6, and , PSA <
  10 ng/ml , and PSA doubling time >
  10years are more suitable for observation
  alone.
     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.
    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.
     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.
           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 >20 ng/ml. + Gleason score
  5-6.
Or- PSA 15 –20ng/ml + Gleason score >7.
(Bishoff et al 1995).
          RADIACAL
       PROSTATECTOMY

• Types:
• Radical retropubic prostatectomy(RRP).

• Radical Perineal prostatectomy(RPP).

• Radical Laparoscopic prostatectomy(RLP)
  RADICAL PROSTATECTOMY
       PROS & 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 ) .
         EXTERNAL BEAM RT
   I-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) .
               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) .
             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).
    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.
 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)
 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 .
          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).
        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)
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.




                                       •
                               .
MODALITY        10 YEARS DISEASE FREE              10 YEAR OVERALL
                SURVIVAL                           SURVIVAL

SURGERY         82% Sciarra et al (2003)           76%(Do LV et al 2002 ).
                72%(Han et al 2003)                75%((Hanks 1988)
                88%(D'Amico et al 2002)            78%(Lu, Yao , 1997).
CEBRT           78%(D'Amico et al 2002)            68% (Hahn et al 1996).
                78%(Nguyen et al 2002).            69%(Hank 1988).
                76%(Zimmermann 2001)               65%(Lee et al 1994).
                                                   63%(Lu, Yao , 1997).
                                                   69%(Gray et al 2000).
3D-CRT          73% (3 years Geinizet aal 2002).
                78%(3 years , Dearnaley et al
                1999).


BRACHYTHERAPY   77% Ragde et al 2001               66%(Stamey et al 2000).
                96%(Koutrouvelis et al 2003)
                80%(5 years Nag S. 1985).
EBRT+BOOST      78%Puthawala et al (2001)          79%(Stamey et al 2000).
BRACHYTHERAPY

IMRT            92% Zelefsky et al
                (2002)(3YEARS)
        SEQUELAE OF DIFFERENT TREATMENT MODALITIES

MODALITY         RECTAL TOXICITY                INCONTINENCE                 IMPOTENCE

SURGERY          1%(Catalona et al 1999).       80%(.post surgery)           66%(neve spring)
                 1.1% (Guillonneau 1999)        6%(.late ; 1 year later)     75%%(standard RP)
                                                Schaefffer et al 1998).      Robinson et al   (2002).
                                                53%(Schwartz et al 2002)
                                                25%((Guillonneau 1999) (6
                                                months).


CEBRT            29.6%(Scwartz et al 2002).     19.2%(Scharwz et al 2002).   45%(Robinson et al 2002).
                 14%(Storey et al 2000).        20%(Storey et al 2000).      50%((Bagshawet al 1988).
                 15% (Dearnaley et al 1999).    10%(Lawton et al 1991).      35%(Schroder et l 2000).


3D-CRT           21%(Storey et al 2000).        9%(Strorey et al 2000).      40%(Robinson et al 2002)
                 5%( (Dearnaley et al 1999).

BRACHYTHERAPY    1%(Koutrouvelis et al 2003).   1% (Koutrouvelis et al       24%(Robinson etal).
                 1%(Kang et al 2002).           2003).                       7%(Nag S. 1985).
                 2% (Syed et al 2001            2%(Syed et al 2001)          10% (Sharkey et al(1998).
                 3%( Schroder et al 2000).      3%(Sharkey et al(1998).
                                                3%(Schroder et al 2000).


IMRT             17%((Teh et al 2002).          9%(Zelefsky et al 2002)      10%(Zelefsky et al 2002)
                 4.5%(Zelefsky et al 2002)
           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.
   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%.
 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).
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) .
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.
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.
             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.
            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 .
            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.
THANK YOU

								
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