The document discusses prostate cancer including its anatomy, epidemiology, diagnosis, staging, treatment and outcomes. Key points include: - Prostate cancer is the most commonly diagnosed cancer in men. Risk factors include age, family history, and ethnicity. Screening includes PSA testing and biopsy. - Treatment depends on risk classification based on PSA, Gleason score, and stage. Options include active surveillance, surgery, radiation therapy and hormone therapy. - Studies show dose escalation radiation therapy and use of IMRT/3D conformal radiation improve biochemical control rates with acceptable toxicity compared to conventional radiation. Adjuvant hormone therapy with radiation improves outcomes for intermediate-high risk disease.

1. PROSTATE CANCER
DR:-OMAR HASHIM

2. Anatomy of the prostate
Prostate is a fibro-muscular gland. It lie between the base
of Bladder and deep transverse perineal muscles.behind
The pubic symphysis and front of the rectum .prostate is
Perforated by the prostatic part of the urethra and by the
Two ejaculatory ducts.the prostate is divide into five
Lobes .anterior lobe in front of the urethra. middle lobe
Is situated between the urethra and ejaculatory ducts. the
Upper surface is related to the trigone.the posterior lobe
Is situated behind the urethra and below the ejaculatory
Ducts .the right and lift lateral lobe lie on either side of
Urethra .

6. The 1ry lymphatic derange of the prostate is to the regional
LN s the distant LNs .75% of the cancer is or
Regional LN s:-
Internal iliac (hypo-gastric) .
Obturator
Persacral
Perivesical
External iliac.
Distant LNs:-
Deep and superficial inguinal .
Common iliac
Retroperitoneal
Supraclavicular
Cervical
scalene

7. EPIDEMIOLOGY & ETIOLOGY
Prostate cancer is the most commonly diagnosed cancer .
New case in the 2010 an estimated 217,730 .these is wide
Geographical variation .
Risk factors for ca prostate ;-
a) ↑ life expectancy .
b) Routine adoption of PSA .
c) Ethnicity .
d) Family history .
Less common risk factors ;- genetic /hormonal /obesity
/dietary habits /prostate inflammation/infection

8. Screening for prostate cancer ;-
PSA screening is impact in the incidence and mortality
of ca prostate .
In USA as example ;-
The percentage of low risk disease is ↑ and the
Age-adjusted death rate is↓ .
* ERSPC trial is demonstrated that PSA screening in
the general population show 20% ↓in the prostate
cancer with the screening .

9. Pathology of ca cancer
the most common histological type of the cancer is
adenocarcinoma .the International Society of Urological
Pathology Consensus Statement divide the histological
type into Gleason scoring system that show 5 basic
Tissue pattern referred as tumor grade. The classification
Is depend on the loss of normal glandular structure

10. DIAGNOSIS OF CA PROSTATE
most of the ca prostate is diagnosis due to the screening
Of the PSA with out symptoms .but advanced tumors
May invade the adjacent structure or regional lymph nodes
Such case may presented by bladder out let obstruction
Symptoms which include (heamaturia, hematospermia,
Erectile dysfunction, change in bowel function or bone pain
Examination :- be side BR examination include LNs,
Examination of the skeleton . and neurological examination
For sign of metastasis.

11. Deferential diagnosis for enlarged prostate:-
Acute prostatitia .
Chronic granulomatous prostate.
Nodular hyperplasia

12. Physical 1) Digital rectal examination noting rectal tone /presence of
examination Hemorrhiod or anorectal mass ,prostate size presence of nodules
Involvement of lateral sulci and seminal vesicles.
DRE is cornestone for staging although unsensitive for extracapsular
Extension .
TRUS- the procedure can miss
guaded
biopsy

13. Serum 1) PSA screening is leading the majority of prostate cancer diagnosis
PSA 2) PSA is sensitive but not specific these false +ve .
3) PSA is↑ with age .
4) PSA of ≥ 4 ng/ml(atypical clinical threshold ) range 31—54%
Specificity ↑ with age and DRE is considered .
5)Another laboratory value include (free PSA/PSA density/PSAvel-
Ocity) .
6) Persistent ↑PSA and presence of palpable prostate indication
To transrectal U/S guide needle biopsy (TRUS)

14. Prostate cancer suspected (↑pSA) .
Algorithm for
Diagnosis and stag- Complete history &exam (DRE) .
Ing of prostate
cancer Trans-rectal U/S guided prostate biopsy .
If life expectancy >5yrs or symptomatic
treatment is recommend . If life expect-
Ancy <5yrs and asymptomatic no further
treatment .
Risk classification based on PSA,DRE&Gleason .
Work up depend on risk classification .
Bone scan;-1)T1,T2 and PSA >20ng/ml 2)Gleason
score≥8 3)T3/T4 4)sypmtomic..
Abdominal pelvic CT/MRI ;- 1)T3/T4 . 2)T1-T2
&nomogram probability of Lns involvement
Multidisciplinary treatment based on risk
classification

15. Tumor node .and metastasis (TNM) staging system of Amer-
Ican Joint Committee on Cancer (AJCC) is presented in the
Table blew ;-
Primary tumor;-
Stage Description
TX Primary tumor can not assessed
T0 No evidence of primary tumor .
T1a tumor finding in 5% or less of tissue resected
T1b Tumor finding in more than 5% of tissue resected
T1c tumor is find by needle biopsy because of elevated PSA .
T2a/pT2a Unilateral ,one half of one side or less
T2b/pT2b Unilateral involving more than one half of side but not both sides .
T2c/pT2c tumor involve both side
T3a/pT3a Extra prostatic extension or microscopic invasion /microscopic bladder
neck invasion
T3b/pT3b Tumor invade the seminal vesicle
T4/pT4 Tumor invade structure other than seminal vesicle (rectum /external

16. -Regional lymph nodes ;-
NX Regional lymph nodes cannot be assessed
N0 No regional lymph nodes metastasis
N1 Regional lymph nodes metastasis
Distant metastasis ;-
MX Distant metastasis can not be assessed .
M0 No distant metastasis
M1a distant metastasis to non regional L Ns
M1b Distant metastasis to the skeletal system
M1c Distant metastasis to the additional sites with or without skeletal
metastasis

17. T N M PSA Gleason
score
T1a-c 0 0 < 10 ≤6
1 T2a 0 0 <10 ≤6
T1-2a 0 0 -- --
T1a-c 0 0 <20 7
T1a-c 0 0 10--20 ≤6
11A T2a 0 0 <20 <7
T2b 0 0 -- --
T2c 0 0 any any
T1-2 0 0 ≥20 any
11B
T1-2 0 0 any ≥8
111 T3a-b 0 0 any any
T4 N1 M1 any any
1V

18. prognosis
Factors affecting the prognosis of ca prostate ;-
A. Gleason score .
B. Pretreatment serum PSA .
C. Stage at diagnosis
D. Additional pathological factors include percent
+ve biopsy cores,PSA density,and
Velocity length of core involvement and present
Of per neural invasion / age

19. TREATMENT
Treatment of localized prostate cancer ;-
The treatment option for localized disease include
Surveillance versus active treatment with radiotherapy,
Surgical, and systemic modalities of treatment .
A) Active surveillance ;- indicated in patients with very low
Disease if life expectancy <20 yrs or low risk disease
(if life expectancy <10yrs) .
Active surveillance include PSA, DRE,and repeat
Needle biopsy .
Definitive treatment recommended if clinical PSA↑,
Or pathological (higher Gleason score,↑number of

20. Advantage of active surveillance include avoidance
Of unnecessary treatment and potential side effects .
Disadvantages of surveillance include tumor prog-
Gression and need for more aggressive treatment .
Radical prostatectomy ;- indicated for patients with
Clinically localized prostate cancer with life expectancy
exceeds 10 yrs . PR is considered as the standard
surgical treatment .
The only local treatment that reduce mortality (RR=0.56)
Local progression (RR=0.33),metastasis (RR=0.6) over

21. The procedure is done by perineal to retro pubic,
Retroubic nerve sparing, laparoscopic, and robot
Assisted approaches .
Side effects include ;- intra-operative bleeding,urinary
Incontinence and erectile dysfunction .
Overall prostate-cancer-specific mortality of 12%(range
5—38) at 15 yrs after surgery
External beam radiation therapy (EBRT) ;-
As monotherapy for low-risk and selected intermediate
Risk patients

22. In concurrent for low-risk and selected intermediate
Risk patients .
Adjuvant post prostatectomy treatment for high-risk
Patients .
Palliative treatment to primary or metastatic foci .
Intensity modulated radiation therapy (IMRT) .
Represents the current standard of care of EBRT .
If the dose>72 GY IMRT is similar in disease control
To prostatectomy and seed implant .

23.  Interstitial brachytherapy ;-
 Is used to curative treatment of localized prostate
 Cancer .
 Advantage ;-
Highly conformal dosimetry
Moderate invasiveness ,out patient nature .
Minimal number of treatment visits

24.  Androgen ablation ;-
 Short term ADT in intermediate-risk prostate cancer .
 Long term and adjuvant ADT in high to very high-risk
Prostate cancer .
Mainstary treatment for palliative therapy in metastatic
Disease .
Unproven role as a component of salvage therapy
Although it is utilized empirically in selected high risk-
Patients .
Orchiectomy or LHRH agonists (90-95% of testosterone)

25. TAB utilized orchiectomy or LHRH agonist +anti-andro-
Gen for complete testosterone blockade .
Estrogen as a second-line hormonal therapy

26. Diagnosis of prostate cancer
Risk classification
Interm.risk/T2d-c
Low risk/t1-2a High risk/Tt3a.G= Very high risk
G=7, or PSA
Or PSA<10 8-10 or PSA>20 T3b-t4n0 m0
10-20
Definitive
Active IG-IMRT±BT IG-IMRT±BT treatment as
surveillance/I Boost/±short Boost/±long high risk or
G-IMRTor BT Term ADT Term ADT palliative
4-6months 2—3YRS ADT
or
or
or
Radical Radical
prostatectomy prostatectomy
+PLND±adjRT Active follow upc

27. EBRT(dose
escalation&treatment outcome
EBRT IS one of the most important definitive treat-
Ment modality for localized prostate cancer of all
Stages .IMRT is represent the current standard of care
For prostate EBRT .
The study show that 3D and IMRT improve the
biochemical control and reduce toxicity rate as
Compared to the 2D .

28. studies description
hanks number of patients 232. with prostate cancer treated using 3D-CRT
For out come of radiation dose escalation.
The dose response was observed for patients with pretreatment
PSA = >10 ng/ml based on 5yrs BNED results .
5 yrs bbNED rate of 35% at 70 GY and 75% at 76 GY (p=0.0049) .
No response was observed for patients with pretreatment PSA<10
ng/ml .
dose response was observed for FL-LENT grade 2 and grade
3,4 GI sequelae and LENT grade 2GU sequelae .
The improvement in 5 yrs bNED for patients with PSA =>10 ng/ml
suggested benefit of radiation dose escalation

29. studies description
RTOG 9406 phase 1/11 study for radiation dose escalation in treatment of stage
T1 and T2 prostate adenocarcinoma .
Patients number=225 . Treated to 78 GY to prostate alone if
probability of seminal vesicles involvement < 15% or 78 GY to
Prostate and 54GY to seminal vesicle lf the involvement of
SV probability more than 15%
Acute toxicity at dose of 78GY was low grade3 acute effects
In 4% of patients to prostate alone and 2% of patients treated
To both prostate and SV .NO grade 4 or 5 acute toxicity
reported

30. Randomize description
d
trial
Dearnaley Pts number =225 . Clinical trial compared 3D-CRT versus conventional
Et al RT to 64GY . The primary end point was the development of late radiation
Complication (>3 months after treatment) .
Reduced grade 1-2 late radiation proctitis in patients received 3D-CRT comp-
Ared with conventional treatment
Koper al randomized clinical trial reported anorectal morbidity with the use of 3D-
(dutch rand- CRT versus conventional RT to 66GY . Number of patients 266 withT1—4
Omized N0M0 prostate cancer .
trial) Reduction in the GIT toxicity was observed in the arm of 3D-CRT(32and
19% p=0.02) mostly due to the reduced grade 2 rectum,sigmoid and anal
Toxicity .
No difference in urological toxicity was observed

31. Randomized description
trial
MD Anderson Comparing clinical trial 78GY versus 70 GY of the EBRT using
3D-CRT .number of patient s=301 stage T1b to T3 ca prostate .
Significant 8 yrs biochemical DFS improvement in patients
Received 78GY (78 versus 59% p=0.004) .
The largest benefit amonge patients with pretreatment
PSA>10ng/ml .
No different in GIT or GU toxicity was observed
Dutch mutlicenter Randomized trial compared 78GY versus 68GY using 3D-CRT
Randomizes trial For prostate cancer . Pts number =669 with T1B—T4 .
The primary end point freedom from failure (FFF) .other end
Point were freedom from clinical failure (FFCF) ,overall survival
(OS), and toxicity .with follow up of 51 months ,5 yrs FFF was
Significantly better after 78 GY3D-CRT (64 versus 54%) .
No significant difference in FFCF or OS .
No difference in late GU or GI toxicity .

32. PROG/ACR Randomized trial compared 70.2 GY conventional or 70.2 GY proton
95--09 In the early stage prostate cancer .
Number of patients =393 with T1b—T2b and PSA <5 with out
Androgen suppression .
End point include local failure (LF) biochemical failure .
Proton beam therapy reduced LF with HR of 0.57 .
The 10 yrs ASTRO BF rate were 32.4 versus 16.7% favored
high dose (p=0.0001) .
The difference was due to largely to difference in the low
And probably intermediate- risk disease .
There was strong trend in the same direction for inter-
Mediate –risk disease (n=144,37% of total 42 versus30.4%
P=0.06) .
11 versus 6% of patients required ADT for recurrence
After conventional –versus high dose RT ( p=0.047) .
No difference in OS (78.4 versus 83.4% . P=0.41)
Toxicity rate (1—3% of grade 3—4) between tow arm .

33. mo
Hormonal therapy for local advanced ca prostate ;-
Androgen deprivation therapy ;-
Consisting of a combination of luteinizing-hormone
-releasing hormone (LHRH) suppression and anti-
Androgen . Used as adjuvant therapy to EBRT to
Improve outcome in intermediate and high risk
Patients .the supportive trial show significant
Improvement in local control and disease free
Survival with inconsistent improvement in overall survival

34. Adjuvant radiation therapy ;- prostatectomy provide
Good control when the cancer is confined to the
Prostate while failure rate is high when cancer exten-
Sion beyond the capsule specially in patients with
High Gleason grade and +ve margin.
Study show that strong benefit of EBRT of patients
With pathological high-risk disease (T3N0 and /or+ve
Margin)

35. Metastatic prostate cancer ;-
Advanced prostate cancer include those of distant
Metastasis or non regional LNs metastasis(1vb-1vc )
Pts usually required ADT and palliative radiation
Therapy for symptomatic foci

36. Radiation therapy techniques
;-
IMRT ;-represent the current standard of care for
Prostatic EBRT .
PTs set up and planning for prostate cancer IMRT ;-
1) PTs preparation ;-
Pts should instructed to present with empty rectum
And full bladder .

37. Cl inical evidance on combined EBRT with hormonal therapy for intermediate
Risk ca prostate .
Randomized trial description
D’Amino et al Phase 111 clinical trial to compare RT with or with out 6months of
Intermediate ADT . 80% of randomized patients had intermediate –risk ca
risk Prostate .
Conformal dose 79.35 in 36 fr to prostate and seminal vesicles with
Acone –down boost to the prostate .
Median follow upof 4.5 yrs revealed statistical improvement in
Prostate cancer –specific survival,survival free salvage androgen
Deprivation and OS rate .
Up dated results after a median follow up of 7.6 yrs all cause
Mortality was significant greater in the RT alone arm (HR 1.8
P=0.01) .
Sub group analysis show the significant different in pts with no or
Minimal comorbid

38. Randomized description
trial
RTOG Randomized trial of 977 patients to adjuvant goserelin versus
85--31 observation .
Eligible patients had advanced tumor characteristics (Ct3,N+ or pathol
Ogical penetration through the capsules to the resection margin
or SV involvement .
RT→regional lymphatic to an initial 44—46 GY in node +ve patients
followed by a prostate boost to 65—70 GY.
10 yrs up dated results demonstrated significant improvement
In local failure(23 versus 38%), disease specific mortality(16
Versus 22%) DM ( 24 versus 39%) . NED survival (37 versus
23%) and OS (49 versus29%)

39. Clinical evidence on combined EBRT with hormonal therapy for high-risk
Prostate cancer ;-
RTOG Randomized clinical trial to the effect of the androgen
86—10b Suppression .
1st arm → to neoadjuvant and concurrent goserelin
And flutamide for 2 months prior and 2 months
During RT treatment versus observation .
Selected pts have bulky 1ry tumor (≥5x5 cm) with or
Without LNs involvement .
Dose include treatment of the regional lymph nodes
(Except in LN-ve) .followed by broatatic boost to
65—70 GY .
Up date result at 10 yrs demonstrated significant
Improvement distant metastasis (35 versus 47%)
Disease-specific mortality (23 versus 36%) DFS (11
Versus 3%) and biochemical failure .non significant
Trend toward improved OS with also observed .
Non significant impact on the risk of fatal
Cardiac events was seen .

40. Clinical evidence on combined EBRTNwith hormonal therapy for high-risk ca prostate
EORTC Phase 111 study (103) compare EBRT with long term (concurrent
And adjuvant ) androgen suppression.
EBRT targeting initially the prostate and pelvic nodes to 50GY
Then boost prostate only to anadditonal 20 GY.
Hormonal therapy consisted of monthly goeserelin for 3 yrs from
The first day of the EBRT and 1month of cyproterone .
With median follow up of 66 months→ this result improvement
inDFS (40 versus 74%), DSS (79 versus 94%) and OS (62
versus 78%)

41. Study examined long-term toxicities of androgen suppression
Treatment used with EBRT .
RTOG Long-term pelvic toxicity does not appreciably worsen with
dataset Addition of androgen suppression .
analysis Pts treated with EBRT +short term hormonal therapy have > grade
3 GI ,GU and other toxicity as compared to RT .
Pts treated with long term hormonal therapy + EBRT had
Significant lower probability>grade 3 GU toxicity as compared to
RT alone .
Demonstrated no ↑ cardiovascular toxicity after hormonal
treatment

42. RTOG Analysis for the cardiovascular toxicity after hormonal
92—02b Therapy for prostate cancer .
Demonstrated no↑cardiovascular mortality after
Hormonal treatment from 24 versus 4 months

43. TROG Randomized clinical trial studies the optimal duration of short
96.01 of Course hormonal therapy .
(Australia) 3arm study compared prostate –only radiation to 66 GY versus
3 or 6 months of androgen deprivation before and during radiation
For intermediate –risk patients .
Result revealed a significant improvement in prostate cancer
Specific mortality with 6(HR=0.56) but not 3 (HR;0.95) months