By Dr Ahmed Rehman

FCPS (URO)Assistant Professor UROLOGY

CA prostate Incidence and EpidemiologyMost common cancer diagnosed in males

>65

second commonest cause of death from cancer in the western world

1 in 6 men (FUNCTIONING TESTIS) will get prostate cancer

Role of ethnicity & geography

PSA testing has had a major impact

Mo among Men in the United States

Cancer Incidence Rates* for Men, US, 1975-2000

0

50

100

150

200

250

1975

1976

1977

1978

1979

1980

1981

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

CA prostate mortality

Risk Factors AgeRaceFamily history/age of onsetDiet / fatCadmium, cigaretteSuspected but Not confirmed

Vasectomy Infections sex

Etiology Oncogene

Familial CAP ----chromosome 1Suppresser gene

8p,10p,13p,16q,17p, 18p, p53Epithelial stromal interactions/growth factors

PathologyClassification

>95%------------------ adenocarcinoma 5%------------------

90%--------------TCC 10%--------------neuroendocrine (small cell) CA --------------sarcomas

PROSTATE CANCER Tumor distribution

% of glandular % of glandular tissue in tissue in prostateprostate

% of cancers% of cancersin zonein zone

10% 25% 65%

5-10% 70%20%

Oesterling J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1322-1386.

Transition zone Central zone Peripheral zone

Histopathological Grading Gleason grading system

Grade 1-5Score = primary + secondary grade

Well diffentiated (G1) 2-4 Mod diff (G2) 5-6 ??? 7(primary ?) Poorly dif (G3-4) 8-10

Prognosis

Early Disease : asymtomaticEarly Disease : asymtomatic• Peripheral zone: none• Transition zone: LUTS / UTIs / retention

Progressive DiseaseProgressive Disease• Hematuria, Hematospermia, Decreased ejaculate

volume• Impotence

Advanced DiseaseAdvanced Disease• Bone pain (back) & pathological #• Cord compression / nerve involvement

» Paraesthesias / weakness» Urinary / fecal incontinence

• Constitutional symptoms • Obstructive uropathy• Bleeding tendencies / DIC, anemia, pancytopenia• Limb edema, Intestinal obstruction,

Lymphadenopathy• Other manifestations of distant mets

SIGNS AND SYMPTOMS / PRESENTATIONS

Detection of cancer: the challengeDRE----- s/s-----------????????PSA------s/s-----------?/////////

Prostate specific but not cancer specificOther causes

BPH size of prosate Acute & CH prostatitis(TB), prostatic abscess Manipulation, instrumentation, biopsy

Poorly diff CA --- not raised

Detection of Prostate Cancer ; The Challenge

• DRE

• PSA

Currently, clinical practice guidelines recommend the use of both PSA and

DRE in asymptomatic men

Establishing the diagnosis----- TRUS & Biopsy

Staging Local

DRE, serum acid phosphatase, TRUS,CT / MRI / Endorectal MRI -pelvis

Skeletal & visceral mets (bone, lung, liver) Bone scan, Alkaline phosphatase (asymptomatic,PSA <10, >30) CXR, CT scan abdomen

Nodal (high risk----surgery /radiotherapy) Involvement <10% Sensitivity as low as 22-36% CT /MRI (FNA), sampling / frozen sections

Negative bone scan,PSA>20, T3, gleason ggade (p) 4/5

PROSTATE CANCER Stage I

T1 Clinically inapparent tumor not palpable nor visible by imaging

G1 Well differentiated (slight anaplasia) T1a No MO G1

T1a Tumor incidental histologic finding in 5% or less of tissue resected

N0 No regional lymph node metastasis

M0 No distant metastasis

T1a N0 M0 G2, 3-4 T1b N0 M0 Any G

T1a Tumor incidental histologic finding in 5% or less of tissue resected

T1b Tumor incidental histologic finding in more than 5% of tissue resected

N0 No regional lymph node metastasis

M0 No distant metastasis

T1c N0 M0 Any G

T1c Tumor identified by needle biopsy (e.g., because of elevated PSA)

T1 clinically inapparent tumor not palpable nor visible by imaging

PROSTATE CANCER Stage II

T2a N0 M0 Any GT2b N0 M0 Any G T2c N0 M0 Any G

T2a Tumor involves one lobe

T2b Tumor involves both lobes

N0 No regional lymph node metastasis

M0 No distant metastasis

T2 Tumor confined within prostate*

*Note: Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, classified as T1c.

PROSTATE CANCER Stage II ( Cont’d)

T3a N0 M0 Any GT3b N0 M0 Any G

T3c N0 M0 Any G

T3a Extracapsular extension(unilateral or bilateral)

T3b Tumor invades seminal vesicle(s)

N0 No regional lymph node metastasis

M0 No distant metastasis

T3 Tumor extends through the prostate capsule*

*Note: Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2.

PROSTATE CANCER Stage III

T4 N0 M0 Any GAny T N1 M0 Any GAny T Any N M1 Any G

T4 Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall

M1 Distant metastases

M1a Nonregional lymph node(s)

M1b Bone(s)

M1c Other site(s)

N1 Metastasis in regional lymph node or nodes

PROSTATE CANCER Stage IV

Lung

Bone

Liver

Epidural space

PROSTATE CANCER Distant metastatic spread

Natural History of Disease Latent / indolent CAVirulent

Clinically manifested disease Time of onset & doagnosis

Localized Locally advanced Metastatic Hormone refractory (HRCAP/ AICP)

Clinicallylocalized

Hormonerefractory

Local treatment Endocrine Chemotherapy

Relapsedand

newly diagnosed M+

Treatment: Localized DiseaseT1-2Options

Watchful waitingRadical prostatectomy ( Young/ Millon /

Walsh) Margin +ve adjuvent radiation radiation at relapse

Neoadjuvent hormone therapy + surgeryRadiation

External beam Brachytherapy

cryosurgery

Treatment: Locally Advance DiseaseT3-4Options

RadiatonNeoadjuvent hormone therapyradiation

2months before & during

Treatment: Recurrent DiseaseFollowing RP

Radiation

Following RXT Salvage RP cryosurgery

Treatment: Metastatic DiseaseAny T,M+N+

Options Hormone therapy (70-80%)

Testosterone Pituitary gonadal axis 95% testes 2% Free

cellDHTRECEPTORnucleus/transcription Surgical ablation

Bilateral Total orchidectomy Bilateral Subcapsular orchidectomy /

prosthesis Medical ablation

Treatment: Metastatic Disease/ Medical ablationPituitary -------Diethylstilbesterol (Hanovan)

LHRH Agonists Goserelin (zolladex) Leuoprolid Leuprorelin (Lucrin)

Adrenals------- Ketoconazole (DIC /cord compression) Aminoglutithemide

Prostate --------Antiandrogens Pure Antiandrogens Flutamide

(Eulexin/Flutamida) Nilutamide Bicalutamide (Casodex) Steridal / Progestational

Antiandrogens Ceproterone

Acetate (Androcur) Mesesterol acetate

Treatment: Metastatic DiseaseComplete androgen blockade

Testicular +adrenalLHRH/ orchedectomy + antiandrogensBetter initial & prolong response but not

confirmed by others. Intermittent androgen blockade

?delays refractory stateEarly versus late blockade

Veteran’s ----- no survival benefitMRC -----better survival + less

complication rate

Treatment: HRPC ChemotherapyWhy refractory incomplete blockade / resistant cells

Responsiveness time 18 months-3years

Logivity 6-9 / 12 months

No standard chemotherapy regimen has been defined

Early Management of Endocrine Failure:discontinution / addition of antiandrogrns

No single agent or combination had improved survival in randomised trials

Complete remissions were rare

Physicians were reluctant to use chemotherapy in prostate cancer

Androgen-independent prostate cancer may respond toWithdrawal of anti-androgensKetoconazoleCorticosteroids prednisoloneAminoglutethimideAnti-androgensOestrogensProgestational agentsChemotherapy estramustine,mitoxantrone,

vinblastine etoposide, cyclophosphamideNovel agents paclitoxel, Docetaxel

Clinicallylocalized

Hormonerefractory

Local treatment Endocrine Mitoxantrone+Pfor symptoms

Relapsedand

newly diagnosed M+

PROSTATE CANCER Treatment Paradigms

No survivalbenefit

Clinicallylocalized

Hormonerefractory

Local treatment EndocrineTaxotere + P

q3 wks

Relapsedand

newly diagnosed M+

PROSTATE CANCER Treatment Paradigms

Improves SurvivalImproves SurvivalImproves SurvivalImproves Survival

A multimodal approach to evaluating and treating a patient with androgen – insensitive prostate cancer

VOL. 5 SUPPL. 3 2003 REVIEWS IN UROLOGY

PROSTATE CANCER (HRPC / AIPC) Multi-modality Team

VOL. 5 SUPPL. 3 2003 REVIEWS IN UROLOGY

Prostate cancer: algorithm

(DRE, TRUS, CT + bone scan)

• Surgery• Radiotherapy • Adjuvant

hormones

Presentation

Diagnosis

MetastaticLocalised Locally advanced

• Hormone therapy

• Surgery + neoadjuvant hormone therapy

• Radiotherapy ± hormone therapy

• Hormone therapy

Local control PalliativeCurative Observation

(symptoms/PSA)

(biopsy)

Staging

CT = computed tomography; DRE = digital rectal examination; PSA = prostate-specific antigen; TRUS = transrectal ultrasound