ca prostate
TRANSCRIPT
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: [email protected]
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