Clinical Division of Oncology Department of Medicine I

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Prostate CancerProstate Cancer



PROSTATE CANCER

Incidence Incidence

*Incidence per 100,000 population.

Parkin DM, et al. CA Cancer J Clin. 1999;49:53.

39.5539.55

16.7516.75

8.518.51

49.7049.70

1.081.08

5.135.13

31.0331.03

92.3992.39

Eastern Eastern EuropeEurope

JapanJapan

AustraliaAustraliaNew ZealandNew Zealand

ChinaChina

North North AfricaAfrica

South South AfricaAfrica

North North AmericaAmerica

WesternWestern Europe Europe



PROSTATE CANCER

5-year survival rates5-year survival rates49%49%

22%22%

52%52%

63%63%

40%40%

40%40%

41%41%

79%79%

SouthSouthEuropeEurope

JapanJapan

AustraliaAustraliaNew ZealandNew Zealand

ChinaChina

North North AfricaAfrica

Sub-Saharan Sub-Saharan AfricaAfrica

North North AmericaAmerica

NorthwesternNorthwestern Europe Europe

Parkin DM, et al. CA Cancer J Clin. 1999;49:37.

Estimated 5-Year Survival (%).



PROSTATE CANCER

5-year survival by stage5-year survival by stage

30

98

87

32

100

94

0 20 40 60 80 100

Distant

Localized & Regional

All Stages

Percent

White

African American

Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.



PROSTATE CANCERGenetic events in prostate Genetic events in prostate

carcinogenesiscarcinogenesis

Abeloff M, et al. Clinical Oncology. 1995;1439.

Normal prostate

Histologic prostate cancer

Localized prostate cancer

Metastatic prostate cancer

Androgen-independent prostate cancer

Tumor suppressor gene inactivation

p53 gene inactivation H-ras oncogene overexpression

bcl-2 oncogene overexpression

Metastasis gene suppressor inactivation

Decreased adhesion molecule expression

Retinoblastoma gene loss



PROSTATE CANCER

Risk factorsRisk factors

• Age

• Diet

• Family history

• Race

• Environmental factors

Parkin DM, et al. CA Cancer J Clin. 1999;49:33-64.Carroll PR, et al. Cancer: Principles & Practice of Oncology.

6th ed. 2001;1418-1479.



PROSTATE CANCER

ScreeningScreeningAdvantages• Early disease highly curable;

advanced disease generally incurable

• Screening relatively simple

Routine PSA and DRE

Disadvantages

Value of screening not proven

Suboptimal sensitivity, specificity, predictive value of tests (DRE, PSA, TRUS)

Not all prostate cancers clinically significant:

Psychological and economic burden of diagnosisMorbidity of potentially unnecessary treatment

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

Carroll PR, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1418-1479.

Rimer BK, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;.627-640.



PROSTATE CANCER

Screening toolsScreening tools

Rimer BK, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;627-640.

MethodMethodSensitivitySensitivity

(%)(%)SpecificitySpecificity

(%)(%)

PositivePositivePredictivePredictiveValue (%)Value (%)

DRE 45-84 45-97 21-43

PSA 67-82 48-82 32-48

TRUS 77-92 27-94 15-54



PROSTATE CANCERProstate specific antigen (PSA)Prostate specific antigen (PSA)

• Single-chain glycoprotein

• Produced by prostate epithelial cells; secreted into prostatic lumen

• Blood level of <4 ng/mL considered normal

• PSA 4-10 ng/mL associated with 22% positive biopsy rate

• PSA >10 ng/mL associated with 66% positive biopsy rate

• Elevated by any prostate disease, prostate manipulation, medication

• Used for staging, monitoring, prognosis


Kelly WK, Dodd PM. The American Cancer Society Textbook of Clinical Oncology. 3rd ed. 2001;427-435.

Brawer MK. CA Cancer J Clin. 1999;49:264-281.



PROSTATE CANCER

Improving accuracy of PSAImproving accuracy of PSA

• PSA density– Serum PSA level/prostate volume

• PSA velocity– Change in serum PSA over time

• Age-adjusted PSA– Different cutoff levels for different age groups

• Prostate-specific–membrane antigen (PSMA)• Free-to-total PSA

– Measurement of free and complexed circulating PSA

• None of these tests has a role in routine management

Brawer MK. CA Cancer J Clin. 1999;49:264-281.



PROSTATE CANCER

Free-to-total PSA*Free-to-total PSA*

PSAPSA Probability of CancerProbability of Cancer

2 ng/mL 1%

2-4 ng/mL 15%

4-10 ng/mL 25%

>10 ng/mL >50%

Brawer MK. Prostate-specific antigen: Current status. CA Cancer J Clin. 1999;49(5):264-281.

% FPSA% FPSA Probability of CancerProbability of Cancer

0-10% 56%

10-15% 28%

15-20% 20%

20-25% 16%

>25% 8%

*Men with non-suspicious DRE results, regardless of patient age.



PROSTATE CANCERScreening and DiagnosisScreening and Diagnosis


Initial Evaluation Screening Results Follow-up

DRE + total PSA DRE negative and Annual DRE/PSA PSA normal

Counseling for DRE negative with:prostate cancer - PSA >10 ng/mL - TRUS biopsyscreening - PSA 4-10 mg/mL - TRUS biopsy or % free PSA - Abnormal age- - Consider TRUS biopsy

referenced PSA

Family history DRE positive and TRUS biopsyHistory of prostate PSA normal or positive disease Medication/supplementsPrior PSA/DRE



PROSTATE CANCER

Stage at diagnosisStage at diagnosis

5%

35%

60%

0

10

20

30

40

50

60

70

Localized Regional Distant

Stage

% o

f C

ases

Kassabian VS, et al. The American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;311-318.Zinner NR, et al. Everyone’s Guide to Cancer Therapy.

1997;634-649.




PROSTATE CANCER

Signs and symptomsSigns and symptoms

Early DiseaseEarly Disease• Peripheral zone: none• Transition zone:

– Urinary hesitancy, frequency, urgency– Decreased force of urine stream– Nocturia

Progressive DiseaseProgressive Disease• Hematospermia• Decreased ejaculate volume• Impotence

Advanced DiseaseAdvanced Disease• Bone pain



PROSTATE CANCERPathological classificationPathological classification

Epithelial NeoplasmsEpithelial Neoplasms• Adenocarcinomas

– Pure ductal– Mucinous

• Small cell tumors• Transitional cell carcinomas• Carcinoma in situ (intraepithelial neoplasia)

and precursors of neoplasia

CarcinosarcomasCarcinosarcomas

Nonepithelial NeoplasmsNonepithelial Neoplasms• Mesenchymal—benign and malignant• Lymphoma

Germ Cell TumorsGerm Cell Tumors




PROSTATE CANCER

Tumor distributionTumor distribution




PROSTATE CANCERLocal extension



PROSTATE CANCER

Lymphatic spreadLymphatic spread



PROSTATE CANCER

Distant metastatic spreadDistant metastatic spread



PROSTATE CANCER

StagesStages

AJCC® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.

Stage I T1a N0 M0 G1

Stage II T1a N0 M0 G2,3-4T1b N0 M0 Any GT1c N0 M0 Any GT1 N0 M0 Any GT2 N0 M0 Any G

Stage III T3 N0 M0 Any G

Stage IV T4 N0 M0 Any GAny T N1 M0 Any GAny T N2 M0 Any GAny T N3 M0 Any GAny T Any N M1 Any G



PROSTATE CANCER

Stage IStage I




PROSTATE CANCER

Stage IIStage II




PROSTATE CANCER

Stage II (cont’d)Stage II (cont’d)


*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 IIIStage III

AJCC® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia,

Pennsylvania.

*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 IVStage IV

AJCC® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia,

Pennsylvania.



PROSTATE CANCERPrognostic factors for Prognostic factors for

advanced diseaseadvanced disease

• Presence of symptoms

• Performance status

• Location and extent of disease

• Number of lesions on bone scan

• Serum testosterone and alkaline phosphatase levels




PROSTATE CANCERCommonly used therapies

Disease Stage TreatmentStage I/II Radical prostatectomy (if <70 years old and healthy);

Radiation (if >70 years old and healthy); orWatchful waiting (if < 10 year life expectancy,significant comorbidity, or unfavorable tumor

characteristics)

Stage III Radiation therapy or surgery (in rare cases) plus adjuvant hormonal therapy

Stage IV Pharmacologic castration (LHRH analogues, antiandrogens)

HRPC Antiandrogen withdrawal or continued testicular androgen deprivation;

Second-line hormonal therapy;Chemotherapy; orRadiation therapy



PROSTATE CANCER

Response to surgeryResponse to surgery

Diagnosis of Stage I/II disease (45% to 55% of new prostate cancer diagnoses)

SURGERY

85% Respond Without Further Intervention and Achieve a Disease-Free Status

15% Fail to Respond, Developing Stage III/IV Disease

Within 1 Year



PROSTATE CANCER

Risk factors for Risk factors for biochemical failurebiochemical failure

• Rising serum PSA levels after definitive local therapy are indicative of recurrence

• Pretreatment disease characteristics predictive of poor outcome following curative-intent prostatectomy:

Clinical stage T3 or T4 disease

Serum PSA levels >20 ng/mL

Poorly differentiated histology (ie, biopsy Gleason score 8)

D’Amico AV, et al. JAMA. 1998;280:969-974.



PROSTATE CANCERResponse to hormonal therapyResponse to hormonal therapy

Enter Hormone-Refractory Status(Median Survival =

6 to 12 months from time of diagnosis)

20% Achieve a Disease-Free Status

and Terminate Therapy

Diagnosis of Stage III/IV disease (45% to 55% of new prostate cancer diagnoses)

HORMONAL THERAPY

85% Respond (ie, PSA decline 50%)

15% Fail to Respond

80% Respond While Continuing Therapy(Mean Response Duration =

3 Years)

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Clinical Division of Oncology Department of Medicine I

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