ca prostate

GUIDELINES FOR MANAGEMENT

Dr ANKITA SINGH PATELMBBS,MD(KGMU)

CONSULTANT

Apex Hospital Cancer Institute

TRAINING AND FELLOWSHIPFortis Research Institute ,New Delhi

Tata Memorial Hospital,MUMBAI

Mob. 8765845035,9305421547Email: dr.ankitapatel.onco@gmail.com

WEBSITE: www.apexhospitalvaranasi.com

INCIDENCE

Prostate cancer (PCa) is the second most common

cause of cancer and the sixth leading cause of cancer

death among men worldwide.

RISK FACTORS: Age ,Race , Family history/age of

onset , Diet / fat , Cadmium, cigarette

PROSTATE CANCER Tumor distribution

% of glandular tissue in prostate % of cancersin 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

Lung

Bone

Liver

Epidural space

PROSTATE CANCER Distant metastatic spread

PSA (Prostate Specific

Antigen)

DRE ( Digital Rectal

Examination)

GLEASON GRADE AND SCORE

FREE AND BOUND PSA

AGE NORMAL (ng/Ml)

40-49 0-2.5

50-59 3.5

60-69 4.5

70-79 6.5

AGE SPECIFIC PSA CUTOFF

DIGITAL RECTAL EXAMINATION

Histopathological Grading

GLEASON SCORE PRIMARY GRADE – Most predominant pattern. SECONDARY GRADE – Highest grade in all the samples. When these two grades are added together, the total is called the Gleason score.

EXAMPLE if the biopsy samples show that: most of the cancer seen is grade 3 the highest grade of any other cancer seen is grade 4, then the Gleason score will be 7 (3+4).

A Gleason score of 4+3 shows that the cancer is slightly more aggressive than a score of 3+4, as there is more grade 4 cancer.

Pathology Classification

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

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

PATHO-PHYSIOLOGY

Androgen Deprivation Therapy

degarelix (Firmagon)

•enzalutamide(MDV3100)

• ketoconazole

•Abiraterone (Zytiga)

•Goserlin (Zoladex)•Histerlin (Vantas)• leuprolide (Lupron)• triptorelin (Trelstar).

HYPOTHALAMUS

PITUITARY

TESTESS

PROSTATE / TUMOR megestrol

bicalutamide

flutamid

ilutamide 

American Society Prostate Cancer Screening Guidelines

Average risk: annually beginning age 50 years with 10+ year life expectancy

Age 45 if high risk: High risk includes African-American men or those with first-degree relative with prostate cancer <65 years of age

Age 40 if very high risk: Very high risk includes multiple family members with prostate cancer at early age

If testing performed, PSA with or without DRE

2009 guidelines reaffirmed in 2013

PSA Cutpoints for Biopsy

Recommendations

PSA RANGE RECOMMENDATION

0-3.9ng/mL

“normal “ range;

biopsy not generally recommended

4-9 ng/mL

Biopsy recommended ;

probability of detecting cancer ranges from 25% to 30%.

>10 ng/mLBiopsy recommended ;

high probability of detecting cancer (>=50%)

SYMPTOMS

PROSTATE CANCER SUSPECTED(PSA/Screening)

COMPLETE HISTORY AND PHYSICAL EXAMINATION INCLUDING DRE

TRUS GUIDED BIOPSY

Life expectancy <=5 yrs and AsymptomaticNo further workup or treatment until symptomatic except in high or very high risk group.

Life expectancy >5 yrs OR symptomatic

Risk classificationWORK UP depends on Risk Classification

BONE SCAN IF1. T1 and PSA>202. T2 and PSA>103. Gleason score >=84. T3,T45. Symptomatic

1. T3,T42. T1-T2 and normogram indicated

probability of lymph node involvment>10%

Pelvic CT or MRI or PETCT

MULTIDISCIPLINARY TREATMENT DEPENDING ON RISK STRATIFICATION

VERY LOW RISK GROUPEXPECTED SURVIVAL INITIAL THERAPY ADJUVANT

THERAPYACTIVE SURVEILLANCE•PSA 6 monthly and SOS•DRE 12 monthly and SOS•repeat prostate biopgy 12 monthly and SOS

>=20yrs EBRT OR Brachytherapy

Radical Prostatectomy(RP)+PLND if predicted probability of LN mets is >=2%

Roach formulaLN metastasis (%) = 2/3 PSA + 10× (Gleason-6)

ADVERSE FEATURES (Detectable PSA,positive margin,seminal vesicle invasion,ECE)EBRT

LYMPH NODE METASTASISADT+EBRT

10-20YRS ACTIVE SURVEILLANCE

<10 YRS OBSERVATION

•T1c•Gleason score<=6•PSA<10 ng/ML•Fewer than 3 prostate biopsy cores

positive,<=50% cancer in each core

LOW RISKEXPECTED SURVIVAL INITIAL THERAPY ADJUVANT THERAPY

>=10YRS ACTIVE SURVEILLANCE

EBRT OR Brachytherapy

RADICAL PROSTATECTOMY(RP)+PLND if predicted probability of LN mets is >=2%

ADVERSE FEATURES (Detectable PSA, positive margin, seminal vesicle invasion, ECE)EBRT

LYMPH NODE METASTASISADT+EBRT

<10YRS OBSERVATION

•T1-T2a•Gleason score<=6•PSA<10 ng/ML

INTERMEDIATE RISKEXPECTED SURVIVAL INITIAL THERAPY ADJUVANT THERAPY

>=10 YearRADICAL PROSTATECTOMY(RP)+PLND if predicted probability of LN mets is >=2%

ADVERSE FEATURES (Detectable PSA, positive margin, seminal vesicle invasion, ECE)EBRT

LYMPH NODE METASTASISADT+EBRT

EBRT +- ADT(4-6 month) OR Brachytherapy alone

<10 yr EBRT +- ADT(4-6 month) OR Brachytherapy alone

Observation

•T2b-T2c or•Gleason score 7 or•PSA 10-20ng/mL

HIGH RISKINITIAL THERAPY ADJUVANT THERAPY

EBRT + ADT (2-3 YRS)

or

EBRT + + brachytherapy +ADT (2-3 YRS)

or

RP +PLND ADVERSE FEATURES (Detectable PSA, positive margin, seminal vesicle invasion, ECE)EBRT

LYMPH NODE METASTASISADT+EBRT

•T3a or•Gleason score 8-10 or•PSA>20 ng/mL

VERY HIGH GRADEINITIAL THERAPY ADJUVANT THERAPY

EBRT + ADT (2-3 YRS) or

EBRT + + brachytherapy +ADT (2-3 YRS) or

RP +PLND ADVERSE FEATURES (Detectable PSA, positive margin, seminal vesicle invasion, ECE)EBRT

LYMPH NODE METASTASISADT+EBRT

ADT in select patient

•T3b-T4 or•Primary Gleason pattern 5 or•>4 cores with Gleason score 8-10

METASTATIC

Any T , N1 ADT or

EBRT +ADT(2-3 YRS)

Any T , Any N , M1 ADT + EBRT to site of metastasis ,if in weight bearing bones , or symptomatic

•Any T,N1 or•Any T,Any N , M1

MONITERING AFTER INITIAL MANAGEMENT PSA every 6-12 months for 5 yr , then every year.

DRE every year, but may be omitted if PSA undetectable

N1 ,M1 - Physical examination +PSA every 3-6 month

POST RP Failure of PSA to fall to undetectable levels (PSA PERSISTENCE)

RADICAL PROSTATECTOMY BIOCHEMICAL FAILUREUndetectable PSA after RP with a subsequent

detectable PSA that increases on 2 or more determination (PSA RECURRENCE)

POST EBRT Biochemical failure (PSA increase by 2ng/mL or more above nadir)Or Positive DRE

RADIATION THERAPY RECURRENCE

RADICAL PROSTATECTOMY BIOCHEMICAL FAILURE

PSADT

+- CT/MRI TRUS

+- Bone Scan

+-PET CT

+-Prostate bed

biopsy (especially if

imaging suggests

local recurrence)

Studies negative for distant metastasis

EBRT +- ADT ORObservation

Studies positive for distant metastasis

ADT + EBRT to site of metastasis ,if in weight bearing bones , or symptomatic

RADIATION THERAPY RECURRENCECandidate for LOCAL THERAPY

•PSADT

•TRUS

Biopsy

• Bone Scan

•PET

CT/CT/MRI

•+Prostate

MRI

TRUS Biopsy + metastatic -

•Observation or

•RP or

•Cryosurgery or

•Brachytherapy

•ADVANCED DISEASE

TRUS Biopsy - metastatic -

•Observation or

•ADT or

•Clinical trial or

•More aggressive

workup for local

recurrence

ADVANCED DISEASE

metastatic + •ADVANCED

DISEASE

Not a candidate for LOCAL THERAPY

ADTOr observation

ADVANCED DISEASE

ADVANCED DISEASE :SYSTEMIC THERAPY

•Orchidectomy or PROGRESSION

•LHRH agonist +- antiandrogen >= 7 days to prevent testosterone flare or

•Castration

•LHRH agonist + antiandrogen or •Resistant

•LHRH antagonist or •Prostate

•Observation(for M0 disease) or •Cancer

•Continous ADT and Docetaxel 75mg/m2 w/o prednisolone for 6 cycles( for castration sensitive high volume M1 only)

Definition of Castration Resistant Prostate Cancer

Serum testosterone <50 ng/Ml

And one or more of the following:

• Rising PSA from nadir on androgen deprivation therapy(ADT)

• Radiographic progression on ADT.

• Clinical progression

APPROVED THERAPY FOR CRPCNAME DRUG TYPE APPROVAL INDICATION

Docetaxel (Taxotere)+Prednisolone

Chemotherapy FDA,EMA First line

Denosumab(Xygeva)

Targeted therapy( RANKL)

FDA Prevention of SREs in patients with bone metastasis

Cabazitaxel (Jevtana+ Prednisolone

Chemotherapy FDA,EMA Second line

Sipuleucel-T (Provenge)

Immunotherapy FDA First line asymptomatic or minimally symptomatic mCRPC

Abiraterone acetate(Zytiga)

Targetederapy(anti-androgen)

FDA,EMA First and second line

Enzalatumide (Xtandi)

Targeted THerapy(anti-androgen)

FDA Second line advanced mCRPC

PROGNOSISStage 5-year relative survival

ratelocal nearly 100%

regional nearly 100%

distant 28%

THANKYOU