Anatomy of the prostateProstate is a fibro-muscular gland. It lie between the base of Bladder and deep transverse perineal muscles.behindThe pubic symphysis and front of the rectum .prostate isPerforated by the prostatic part of the urethra and by theTwo ejaculatory ducts.the prostate is divide into fiveLobes .anterior lobe in front of the urethra. middle lobeIs situated between the urethra and ejaculatory ducts. theUpper surface is related to the trigone.the posterior lobeIs situated behind the urethra and below the ejaculatoryDucts .the right and lift lateral lobe lie on either side ofUrethra .
The 1ry lymphatic derange of the prostate is to the regionalLN s the distant LNs .75% of the cancer is orRegional LN s:-Internal iliac (hypo-gastric) .ObturatorPersacralPerivesicalExternal iliac.Distant LNs:-Deep and superficial inguinal .Common iliacRetroperitonealSupraclavicularCervicalscalene
EPIDEMIOLOGY & ETIOLOGYProstate cancer is the most commonly diagnosed cancer .New case in the 2010 an estimated 217,730 .these is wideGeographical 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
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 theAge-adjusted death rate is↓ .* ERSPC trial is demonstrated that PSA screening in the general population show 20% ↓in the prostate cancer with the screening .
Pathology of ca cancer the most common histological type of the cancer is adenocarcinoma .the International Society of UrologicalPathology Consensus Statement divide the histological type into Gleason scoring system that show 5 basicTissue pattern referred as tumor grade. The classificationIs depend on the loss of normal glandular structure
DIAGNOSIS OF CA PROSTATEmost of the ca prostate is diagnosis due to the screeningOf the PSA with out symptoms .but advanced tumorsMay invade the adjacent structure or regional lymph nodesSuch case may presented by bladder out let obstructionSymptoms which include (heamaturia, hematospermia,Erectile dysfunction, change in bowel function or bone painExamination :- be side BR examination include LNs,Examination of the skeleton . and neurological examinationFor sign of metastasis.
Physical 1) Digital rectal examination noting rectal tone /presence ofexamination 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 missguadedbiopsy
Serum 1) PSA screening is leading the majority of prostate cancer diagnosisPSA 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)
Prostate cancer suspected (↑pSA) .Algorithm forDiagnosis and stag- Complete history &exam (DRE) .Ing of prostatecancer 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
Tumor node .and metastasis (TNM) staging system of Amer-Ican Joint Committee on Cancer (AJCC) is presented in theTable 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 sideT3a/pT3a Extra prostatic extension or microscopic invasion /microscopic bladder neck invasionT3b/pT3b Tumor invade the seminal vesicleT4/pT4 Tumor invade structure other than seminal vesicle (rectum /external
-Regional lymph nodes ;- NX Regional lymph nodes cannot be assessed N0 No regional lymph nodes metastasis N1 Regional lymph nodes metastasisDistant metastasis ;-MX Distant metastasis can not be assessed .M0 No distant metastasisM1a distant metastasis to non regional L NsM1b Distant metastasis to the skeletal systemM1c Distant metastasis to the additional sites with or without skeletal metastasis
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 ≤611A 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 ≥8111 T3a-b 0 0 any any T4 N1 M1 any any 1V
prognosisFactors affecting the prognosis of ca prostate ;-A. Gleason score .B. Pretreatment serum PSA .C. Stage at diagnosisD. Additional pathological factors include percent +ve biopsy cores,PSA density,andVelocity length of core involvement and presentOf per neural invasion / age
TREATMENTTreatment of localized prostate cancer ;-The treatment option for localized disease includeSurveillance versus active treatment with radiotherapy,Surgical, and systemic modalities of treatment .A) Active surveillance ;- indicated in patients with very lowDisease if life expectancy <20 yrs or low risk disease(if life expectancy <10yrs) .Active surveillance include PSA, DRE,and repeatNeedle biopsy .Definitive treatment recommended if clinical PSA↑,Or pathological (higher Gleason score,↑number of
Advantage of active surveillance include avoidanceOf unnecessary treatment and potential side effects .Disadvantages of surveillance include tumor prog-Gression and need for more aggressive treatment .Radical prostatectomy ;- indicated for patients withClinically 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
The procedure is done by perineal to retro pubic,Retroubic nerve sparing, laparoscopic, and robotAssisted approaches .Side effects include ;- intra-operative bleeding,urinaryIncontinence and erectile dysfunction .Overall prostate-cancer-specific mortality of 12%(range5—38) at 15 yrs after surgeryExternal beam radiation therapy (EBRT) ;-As monotherapy for low-risk and selected intermediateRisk patients
In concurrent for low-risk and selected intermediateRisk patients .Adjuvant post prostatectomy treatment for high-riskPatients .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 controlTo prostatectomy and seed implant .
Interstitial brachytherapy ;- Is used to curative treatment of localized prostate Cancer . Advantage ;-Highly conformal dosimetryModerate invasiveness ,out patient nature .Minimal number of treatment visits
Androgen ablation ;- Short term ADT in intermediate-risk prostate cancer . Long term and adjuvant ADT in high to very high-riskProstate cancer .Mainstary treatment for palliative therapy in metastaticDisease .Unproven role as a component of salvage therapyAlthough it is utilized empirically in selected high risk-Patients .Orchiectomy or LHRH agonists (90-95% of testosterone)
TAB utilized orchiectomy or LHRH agonist +anti-andro-Gen for complete testosterone blockade .Estrogen as a second-line hormonal therapy
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 Radicalprostatectomy prostatectomy +PLND±adjRT Active follow upc
EBRT(dose escalation&treatment outcomeEBRT IS one of the most important definitive treat-Ment modality for localized prostate cancer of allStages .IMRT is represent the current standard of careFor prostate EBRT .The study show that 3D and IMRT improve the biochemical control and reduce toxicity rate asCompared to the 2D .
studies descriptionhanks 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
studies descriptionRTOG 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
Randomize descriptiondtrialDearnaley Pts number =225 . Clinical trial compared 3D-CRT versus conventionalEt 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 treatmentKoper 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—4Omized 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
Randomized descriptiontrialMD 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 observedDutch mutlicenter Randomized trial compared 78GY versus 68GY using 3D-CRTRandomizes 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 .
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 .
moHormonal 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 toImprove outcome in intermediate and high riskPatients .the supportive trial show significantImprovement in local control and disease freeSurvival with inconsistent improvement in overall survival
Adjuvant radiation therapy ;- prostatectomy provideGood control when the cancer is confined to theProstate while failure rate is high when cancer exten-Sion beyond the capsule specially in patients withHigh Gleason grade and +ve margin.Study show that strong benefit of EBRT of patientsWith pathological high-risk disease (T3N0 and /or+veMargin)
Metastatic prostate cancer ;-Advanced prostate cancer include those of distantMetastasis or non regional LNs metastasis(1vb-1vc )Pts usually required ADT and palliative radiationTherapy for symptomatic foci
Radiation therapy techniques ;-IMRT ;-represent the current standard of care forProstatic EBRT .PTs set up and planning for prostate cancer IMRT ;-1) PTs preparation ;-Pts should instructed to present with empty rectumAnd full bladder .
Cl inical evidance on combined EBRT with hormonal therapy for intermediate Risk ca prostate .Randomized trial descriptionD’Amino et al Phase 111 clinical trial to compare RT with or with out 6months ofIntermediate ADT . 80% of randomized patients had intermediate –risk carisk 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
Randomized descriptiontrial 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%)
Clinical evidence on combined EBRT with hormonal therapy for high-riskProstate cancer ;-RTOG Randomized clinical trial to the effect of the androgen86—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 .
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%)
Study examined long-term toxicities of androgen suppression Treatment used with EBRT . RTOG Long-term pelvic toxicity does not appreciably worsen withdataset 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
RTOG Analysis for the cardiovascular toxicity after hormonal92—02b Therapy for prostate cancer . Demonstrated no↑cardiovascular mortality after Hormonal treatment from 24 versus 4 months
TROG Randomized clinical trial studies the optimal duration of short96.01 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