: Prostate Cancer : Prostate Cancer Dr Muhammad Ishfaq
SCW,Khyber Teaching Hospital,Peshawar,Pakistan,
March 2009 Prostate anatomy : Prostate anatomy Slide 4: Prostate Anatomy Prostate Anatomy : Prostate Anatomy Prostate weights ~20g
Measures ~3 by 4 by 2 cm
Apex = inferior portion of prostate, continuous with striated sphincter. Base = superior portion and continuous with bladder neck.
Covered by transitional epithelium
Hugs anterior portion of gland
Makes a ~30 degree bend in its mid portion (degree of angulation can vary from 0 to 90 degrees)
just distal to urethral angulation's.
ejaculatory ducts (union of seminal vesicles and each vas deferens) drain to each side of prostatic utricle (vestigial Mullerian duct structure) Lobes of the Prostate : Lobes of the Prostate Anterior lobe
Posterior lobe Image Source: SEER Training Website Zones of the Prostate : Zones of the Prostate Peripheral
Transitional Image Source: SEER Training Website Prostate zones : Prostate zones Central zone (CZ)
Cone shaped region that surround the ejaculatory ducts (extends from bladder base to the veru)
Likely stems from Wolffian ducts
25% of glandular tissue in young adults
Only 1-5% of prostate cancer from this region (likely because of Wolffian duct embryologic origin)
Peripheral zone (PZ)
Mesodermal in origin
Majority of prostatic glandular tissue
Origin of up to 70% of prostate adenocarcinoma
Transitional zone (TZ)
Surrounds the prostatic urethra proximal to the veru ( preprostatic urethra)
Endodermal in origin
In young men, accounts for only 5-10% of prostatic glandular tissue.
Only ~20% of prostate cancer Prostate Cancer Facts : Prostate Cancer Facts Most common tumor (non.cutaneous) in male
1/6 men diagnosed
1/34 men die of prostate cancer
70% over 65 y.o. at diagnosis
90% diagnosed at early stage
Over past 20 years, survival 67% to 97%
More diagnosis due to PSA Some facts : Some facts Most frequently diagnosed tumor.
10% deaths due to malignancies .
With PSA earlier diagnosis.
More die with disease then of the disease.
commonest in USA then Europe.
Least common in south and east Asia. Risk Factors : Risk Factors Environmental factors
Genetic factors(family history)
2.4 times increased risk9first degree relative)
Geography/race Risk factors : Risk factors Genetics
5-10% of cases
chromosome 1,17, HPC1 on ch 1
6-7 years earlier presentation
African-American have higher incidence and more aggressive disease course.
There serum testosterones level is 15% higher then Asians. Risk factors : Risk factors Diet
high fat diet is a risk factor.
diet rich in soy may be protective.
Omega 6 are positive stimulants while omega 3 are negative stimuli for Carcinoma.
vit E & selenium has protective effect.vit A,D deficiency is risk factor.
Androgen ablation & those using finisteride has decrease incidence. Age wise risk : Age wise risk AGE RISK
0 - 39: 1 per 10149
40 – 59 : 1 per 38
60 – 69 : 1 per 14
70 – 79 : 1 per 7
0 - Death : 1 per 6
Source: ACS 2000 to 2002 Presentations of Ca Prostate : Presentations of Ca Prostate Asymptomatic.
Incidental pathological finding
BOO/abnormal DRE/raised PSA level(47%)
Urinary irritative and obstructive symptoms.
bone pain,Pathological fractures,anorexia ,spinal cord compression etc.
Difficult errection and ejaculation Prostate specific antigen : Prostate specific antigen Prostate specific antigen : Prostate specific antigen Total psa
Psa transitional zone density Average rate of rise in prostate-specific antigen levels with and without prostate cancer : Average rate of rise in prostate-specific antigen levels with and without prostate cancer Prostate Specific Antigen : Prostate Specific Antigen Protein produced by cells of prostate gland
Test introduced in 1986
40 - 49 / 2.550 - 59 / 3.560 - 69 / 4.570 - 79 / 6.5
Elevated indicates possible Carcinoma prostate
PSA 4 – 10 indicates 25-35% risk of cancer diagnosis
PSA 10 – 20 indicates 65% risk of cancer diagnosis
PSA > 20 indicates possible metastatic disease PSA : PSA It is not a diagnostic but help to identify in whom biopsy should be taken.
PSA velocity or doubling time is more specific to give indication for biopsy.
No identifiable PSA level give guarantee for normalcy.
Assist in response to therapy.
Most PSA is produced in TZ of prostate.
In About 30% CA ,PSA is in normal range.
Higher grade cancers cells produce less PSA.
However PSA per gram of prostatic tissue is more in carcinoma. PSA : PSA PSA level is increased with DRE , cystoscopy,catheter, trus.
2-3 days for normal level and 3-4 wks in case of biopsy. PSA density; : PSA density; Total PSA divided by prostate volume.
helps to differentiate b/w BPH and Ca in 4_10 PSA range.
PSA tranzitional zone density. Free PSA : Free PSA Free PSA : Free PSA PSA that circulates in blood w/o carrier protein
The lower the % of free PSA, the greater the risk of CaP
Free PSA > 24% probably benign www.marinurology.com Free PSA : Free PSA Indication for free PSA testing is PSA b/w 4____10 ng/ml and normal DRE.
Can be lower in prostatitits
However 95% cancer are detected. PSA velocity (PSA-V) : PSA velocity (PSA-V) Rate of Change in PSA over time.
PSA-V of greater then 0.75ng/ml over one year ,suggestive of Carcinoma.
(PSA2 – PSA1)/time + (PSA4 – PSA3)/time DRE : DRE PSA can be falsely elevated
DRE does not palpate entire prostate gland
Abnormal: nodules, hard spots, soft spots, enlarged Triad of diagnosis,--(PSA_DRE_BIOPSY) : Triad of diagnosis,--(PSA_DRE_BIOPSY) Screening ;Recommendations: : Screening ;Recommendations: AUA:
Annual PSA, DRE Caucasians > 50 y.o.
Annual PSA Af-Am males > 40 OR men w/+ FH
Annual tests men > 50 y.o. IF 10 years of life expected (earlier AA men, + FH) American College of
routine screening tests (PSA/DRE)
Men over 50 w/10 years
life should be told about
benefits & harms of
screening Biopsy : Biopsy Traditional indication for Prostate Biopsy:Usually with Life Expectancy >10yrs : Traditional indication for Prostate Biopsy:Usually with Life Expectancy >10yrs Abnormal DRE regardless of PSA
Abnormal PSA velocity (.75 ng/dL/yr)
PSA > 4.0 or age appropriate range
Consider decreasing in men in 40’s, 50’s or with risk factors (FH/American)
Elevated PSA does not mean prostate cancer Prostate biopsy : Prostate biopsy Performed during TRUS
Random biopsy 6-10 are taken to get a representative sample of prostate.
Abnormal hypoechoic areas on u/s are also biopsied.
Possibility of infection,give prophylactic antibiotic. Biopsy (TRUSP) : kidney.niddk.nih.gov/kudiseases Biopsy (TRUSP) Hypoechoic shows abnormal area needing biopsy Slide 40: Transrectal sonogram of the prostate. Looking up from the feet of a patient toward his head. Flow chart : Flow chart 1-PSA + DRE-----?results-------?if both results normal-?consider regular DRE and PSA
2-PSA + DRE ---?one or both result abnormal-----? possible causes BPH,Prostatitis,Carcinoma.---?consider Free PSA, if low ,--Ca suspected--?biopsy----?Gleason's scoring----? treatment options.
3- if biopsy negative then go for regular DRE and PSA. Other Workup : Other Workup Bone scan
Chest x-ray Carcinoma prostate staging : Carcinoma prostate staging TNM system Staging ,TNM system : Staging ,TNM system T1
Clinical inapparent tumor not palpable or visible by imaging
Tumor confined to prostate(palpable or visible by imaging)
Tumor extending through prostatic capsule
Tumor fixed or invading adjacent structure other then seminal vesical Lymph node staging : Lymph node staging NX-cant be assessed
N0-no lymph node involved
N1-lymph node involved
MX- Cant be assessed
M0- no mets
M1-distant mets present Tumor staging : Tumor staging T1
T1a-incidental findings at TURP(<5% of resected tissue)
T1b-incidental findings at TURP(>5% of resected tissue)
T1c-identified by needle biopsy(eg because of raised PSA)
T2a-Involving half of one lobe or less
T2b-Involving more then half of one lobe,but not both lobes.
T2c-Involving both lobes
T3a – extracapsular extension
T3b- extension into seminal vesicle(s)
T4a-Fixed or invading other structures apart from s.v,like bladder,ext sphincter.
T4b-invasion of levator muscles,pelvic floor. Localized and advance disease : Localized and advance disease Natural history of carcinoma prostate : Natural history of carcinoma prostate Slide 53: Death from Other Causes Death from Other Causes Symptomatic Phase Detectable Presymptomatic Phase Disease Not Detectable Remaining Expected Lifetime Progression of Disease Patient 2 Patient 3 Patient 1 Death From Prostate Cancer Death From Other Causes Patient 4 Histology : Histology Histology : Histology 99% Adenocarcinoma
Sarcoma, small cell, other
PIN –(prostate intraepithelial neoplasia)
30% men will go on to develop CaP
Close follow-up recommended for 2 years visualsonline.cancer.gov Gleason's scoring system : Gleason's scoring system Gleason's scoring system : Gleason's scoring system Dr Donald Gleason 1976
Based on microscopic tumor pattern assessed by pathologist while examining biopsy,when carcinoma is present GS is based on degree of loss of normal architecture of gland.
Technically it is tumor grade. Gleason's scoring system : Gleason's scoring system Gleason's grade GG
Gleason's score or GS/also called Gleason's sum
Gleason's differential GD Gleason's grades , a histolopathological specimen into 5 grades. : Gleason's grades , a histolopathological specimen into 5 grades. Gleason's sum : Gleason's sum Primary histological grade
Secondary histological grade
More then 50% of total pattern seen is primary ,Less then 50% but more then 5% of total pattern seen in a histopathological slide
Suppose a specimen has loss of architecture of gland more then 50 % in grade 3 and the next pattern seen is grade 4 that is less then 50 %but more then 5%.
Gleason's sum is 3+4=7
More the score ,worse the prognosis
However 4+3 is not equal to 3+4 Gleason's differential : Gleason's differential The percentage make up of any Gleason score
Suppose a GS ,3+4=7 this means that
More then 50% are in histological grade 3.its amount can vary from 51% to 95%.
Gleason,s differential is this exact percentage eg it is 75 %,so Gleason's score can be shown as
Gleason's sum 3+4=7(75/25) Data based tables : Data based tables Partin table
Developed by dr Alan W.Partin
Developed by dr Misop Han
These tables are used to predict pathology preoperatively (Partin)and recurrence post operatively(Han) Partin nonogram : Partin nonogram Doctors need PSA, Gleason score, and estimated clinical staging
Can determine probability of:
Seminal vesical invasion
Lymph node involvement Han table : Han table Shows probability of prostate cancer recurrence up to 10 years following surgery.
Based on accumulated data from patients.
Correlates PSA level ,Gleason's score and estimated stage D’Amico et al risk stratification for clinicallylocalized prostate cancer : D’Amico et al risk stratification for clinicallylocalized prostate cancer Low risk
Diagnostic PSA < 10.0 ng/mL and
Highest biopsy Gleason score < 6 and
Clinical stage T1c or T2a
Diagnostic PSA > 10 but < 20 ng/mL or
Highest biopsy Gleason score = 7 or
Clinical stage T2b
Diagnostic PSA > 20 ng/mL or
Highest biopsy Gleason score > 8 or
Clinical stage T2c/T3 Treatment : Treatment Treatment : Treatment Goal: Find clinically significant cancer at a point when a cure is possible
Goal: Avoid excessively aggressive treatment in clinically insignificant disease
Examine prognostic factors of diagnosed disease to predict if it will be significant
Consider patient medical issues, age, philosophy Prognostic indicators : Prognostic indicators PSA
#positive biopsy cores
%biopsy core positive
This helps us predict what cancer may be significant vs. insignificant Treatment : Treatment Surgery Beam RT Seed RT Hormone Experimental Observation Management : Management Management of localized cancer
Management of advance disease
T3 ,T4 Management of localized tumor : Management of localized tumor Pre cancerous lesions : Pre cancerous lesions High grade prostatic intraepithelial neoplasia
Look for con cumitant cancer.
Regular PSA, DRE, physical examinations.
30 % develop carcinoma in one year.
Atypical small acinar proliferations.
Repeat biopsy.40-50% chance of carcinoma in subsequent carcinoma.
Look for con concomitant cancer Management of localized disease (t1,t2) : Management of localized disease (t1,t2) Active monitoring
Radical radiotherapy+-neo- adjuvant therapy
Brachytherapy Active monitoring : Active monitoring Ideal for men with well differentiated tumor and relatively low PSA level.
Monitoring is regular PSA quarterly,biopsy yearly.
Offered to man with life expectancy of 10 years.
Morbidity associated with treatment is avoided.
Delay for other diseases to improve
Co-morbidities prevent other treatments. Radical prostatectomy : general anesthesia.
Begins just below navel and extends to pubic bone.
Remaining Urethra is sewn to bladder neck over a catheter. Pelvic
(Pubis) Urethra Prostate Rectum Bladder Radical prostatectomy Surgical Approach Laparascopic prostatectomy : Laparascopic prostatectomy Robotic prostatectomy : Robotic prostatectomy Surgeon operates from a console with a 3-D screen.
Grasp controls to manipulate surgical tools within the patient.
Robotic arms translate finger, hand, and wrist movements.
Shortens learning curve of surgeons
Cost, Benefit unclear Radiation therapy : Radiation therapy High-Powered X-Rays that damage DNA and kill prostate cancer cells.
External Beam Radiation Therapy (EBRT): X-rays aimed at prostate.
Brachytherapy: Radioactive seed implants into prostate. External beam radiation : External beam radiation Beam Radiation : Beam Radiation Prostate Brachytherapy : Prostate Brachytherapy www.prostate-cancer.org Image of Prostate With Radioactive Bead Implants : Image of Prostate With Radioactive Bead Implants Management of advance disease : Management of advance disease Management of advance disease : Management of advance disease Locally advance disease. (T3)
Radical prostatectomy is not usually indicated in this group.
Active monitoring in asymptomatic patient,
Palliative radiotherapy +/ - hormonal therapy Management of metastatic disease : Management of metastatic disease Systemic palliative treatment
Early institution of hormonal treatment Hormone Therapy : Hormone Therapy LHRH analogs
They are not as effective as LHRH analog www.upmccancercenters.com Bilateral orchidectomy : Bilateral orchidectomy Very effective
Avoids repeated inj Management of hormone escaped prostate cancer : Management of hormone escaped prostate cancer Initial response of hormone treatment is excellent but with time prostate cancer becomes androgen independent and it this time hormone treatment is ineffective,
Once this occur medial survival is 6 months.
Various chemotherapy regimes are used in this case
Di ethyl stilbestrol
Local radiotherapy to bone mets Experimental : Experimental Hyperthermia
Vaccines Treatment for Recurrence/Mets : Treatment for Recurrence/Mets Hormones
Radiation to mets
Chemotherapy Slide 94: Thank you