MANAGEMENT OF EARLY PROSTATE CANCER

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MANAGEMENT OF EARLY PROSTATE CANCER

• BY
• EHAB ESMAT FAWZY
• M.D. ONCOLOGY
• FACULTY OF MEDICINE
• CAIRO UNIVRSITY

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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).

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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).

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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

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DIAGNOSIS

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

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DIAGNOSIS

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

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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).

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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). .

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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).

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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.

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DIAGNOSIS

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

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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.

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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)

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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.

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Treatment options for prostate cancer

• Observation alone.
• Radical prostatectomy.
• Radiation therapy.
• Hormonal treatment.

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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.

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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.

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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.

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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.

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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.

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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).

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RADIACAL PROSTATECTOMY

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

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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 ) .

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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) .

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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).

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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.

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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 .

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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).

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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
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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.

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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) .

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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.

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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.

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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.

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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 .

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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.

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• THANK YOU