Chapter 65 Low Risk Prostate Cancer Flashcards by Navin Bajracharya

Extension of prostatic urethra

Verumontanum to GUD

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Where does ejaculatory ducts join urethra in prostate

Verumontanum

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Which fascia separate prostate from rectum posteriorly?

Denonvilliers’ fascia

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Arterial blood supply of prostate

Branches of internal pudendal, inferior vesical, middle hemorrhoid arteries

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How many zones of prostate are there and what are they?

4 zones

Peripheral zone(PZ)
Transition zone(TZ)
Central zone
Anterior fibromuscular stroma zone

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Which zone is palpated on rectal examination?

Peripheral zone

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Which zone of prostate is the location of most prostate cancers(>70%)

Peripheral zone

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Which zone of prostate is the location of benign prostatic hyper trophy(>90%)

Transition zone

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Describe the prostate physiology by its histologic constituent

Prostate is Fibromusculo-glandular organ
Fibromuscular stroma functions both to control micturition by acting as a sphincter of urethra and to express acidic prostatic secretion into urethra by contracting during ejaculation
Glandular function contributes 30% seminal fluid

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Which structures secrete majority(70%) of seminal fluid?

Seminal vesicles, testicles, Bulbo-urethral gland

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What is the function of PSA?

PSA is serine protease involved in liquefaction of seminal coagulum.

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What is the active and most potent form of testosterone

alpha-dihydrotestosterone

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What is the enzyme involved in conversion of testosterone to its active form?

5-alpha-reductase

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What is the most important risk factor for prostate cancer?

Age

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Name 2 conclusive large randomized trials supporting harmonal influence in development of prostatic cancer

Prostate Cancer Prevention Trial

2. REDUCE trial(Reduction by Dutasteride of Prostate Cancer Event)

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Describe Prostate Cancer Prevention Trial

18,882 men
>=55 years
Normal DRE, PSA level

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Describe REDUCE trial in prostate cancer

8231 men
Age 50-60 years
PSA 2.5 - 10 
Dutasteride 0.5mg daily vs placebo
Result : at 4 years, relative risk reduction in diagnosis or subsequent prostate cancer of 22.8% noted in men taking Dutasteride vs placebo

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Male urethra is composed of how many segments and what are they?

5 segments

Pre-prostatic urethra
Prostatic urethra
Membranous urethra
Bulbar urethra
Penile urethra

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Describe characteristics of tumor arising from TZ in prostate

Lower frequency of ECE
May harbor large volume of disease with relatively high PSA level but remain confined to prostate
Despite high PSA >= 10ng/mL considered to have favorable prognosis

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Describe characteristics of tumor arising from PZ of prostate

Tend to spread along capsular surface of gland and may extend through capsule of gland, invade seminal vesicles, periprostatic tissues and involve bladder neck and rectum

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Pre treatment serum PSA is predictive of extraprostatic extension and seminal vesicle. With PSA level of 4-10ng/mL, what percentage are confined to prostate only?

53-67%

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Pre treatment serum PSA is predictive of extraprostatic extension and seminal vesicle. With PSA level of 10-20 ng/mL, what percentage are confined to prostate only?

31-56%

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Name 3 factors associated with involvement of seminal vesicle

PSA level
Gleason score
Clinical stage

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Roach formula to estimate probability of ECE+ in prostate cancer

ECE = 3/2 PSA + (Gleason score - 3) x 10

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Roach formula to estimate probability of SV+ in prostate cancer

SV+ = PSA + (Gleason score - 6) x 10

What is the percentage of lymph node involvement in low risk prostate cancer?

Partin et al generated nomogram for predicting nodal metastasis based in 3 factors, what are they?

Clinical stage Preoperative PSA Tumor biopsy grade

According to Bluestein et, patients with clinical stage T1a to T2c would have spared pelvic lymphadenectomy with what rate of missed nodal metastasis?

According to Bishoff et al, what percentage of patient with prostate cancer could be spared with pelvic lymphadenectomy with what percentage risk for missed nodal metastasis

20-63% | 2-10%

Roach formula based on pathological findings in prostatectomy specimens to estimate incidence of metastatic pelvic lymph nodes

Nodes+ = 2/3 PSA + (Gleason score - 6) x 10

What percentage has significantly greater probability of development of distant metastasis with positive pelvic nodes in prostate cancer?

>85% at 10 years

What percentage of abnormal DRE have cancer on biopsy of prostate cancer?

25-50%

What percentage of cancers detected by PSA screening are confined to prostate?

70%

What percentage of cancers detected by PSA are not palpable?

40%

What are other organs besides prostate that secretes PSA?

Pancreas | Salivary gland

Name 2 landmark screening trials for prostate cancer, that come into question after its publication

1. ERSPC - European Randomized Study of Screening for Prostate Cancer 2. PLCO - Contemporaneous US based Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial

As of August 2008, what is the recommendation of PSA screening test, U.S Preventive Services Task Force American Urological Association

U.S Preventive Services Task Force recommend screening in men age 75 years or older American Urological Association recommend annual DRE and PSA screening for men older than 40 years if their life expectancy >10 years

What is the sensitivity and specificity of PAP(Prostatic Acid Phosphatase)

Sensitivity 10% | Specificity 90%

How is Prostate-Specific Antigen Density calculated?

Divide serum PSA concentration by volume of prostate gland measured by TRUS

What does higher PSA density signifies?

Malignancy

What is Prostate Specific Antigen Velocity?

Serial PSA measurement and calculate rate of rise in PSA in year

How much rate of rise of PSA per year is associated with higher frequency of prostate cancer?

>0.75 ng/mL

How much rate of rise of PSA per year prior to diagnosis is correlated with greater prostate cancer specific mortality following RT and RP?

>2ng/mL

What clinical situation warrants for biopsy to establish pathologic diagnosis?

Combination of Abnormal DRE result and consistently elevated PSA

Describe tissue biopsy of prostate

TRUS guided needle biopsy most common method 10-18 cores are taken including cores from bilateral Base Mid Apex Midline Lateral peripheral zone Transition zone if obstructive symptoms Pathology report includes Length of each core Length of each core that contains tumor

What stage is tumor incidental histologic findings in > 5% tissue resected in prostate?

T1b

What stage is tumor involves both lobes of prostate?

T2c

What is the stage with invasion of seminal vesicles in prostate?

T3b

What is the stage with tumor invades lavatory muscles in prostate?

T4b

Describe N2 stage in prostate?

Mets in single node >2 cm but

What stage is mets to non regional nodes in prostate?

M1a

What location of prostate can be reliably detected by USG?

Roach et al what percentage of prostate volume was increased when compared by MRI and noncontrast CT?

32%

Positive yield of CT scan with PSA 4-20ng/mL PSA >20 and GS 6 or more PSA >50 and high GS

PSA 4-20 : 20 and GS 6 : >10%(+) extra capsular or metastatic disease PSA >50 and higher GS : 62%

American college of radiology appropriateness criteria recommendation for bone scan

>20ng/mL T3-4 GS>=8 Bone pain

According to most common NCCN prognostic risk grouping, | What is low risk?

PSA

According to most common NCCN prognostic risk grouping, | What is Intermediate risk?

PSA 10-20 | GS 7

According to most common NCCN prognostic risk grouping, | What is high risk?

GS 8-10 | T3

What is the most common tumor in prostate?

Adenocarcinoma

Gleason score is one of the strongest predictors of biologic behavior in prostate for?

Invasiveness | Metastatic potential

State overall undergrading and overgrading percentage of GS from 18 gauge needle biopsies compared with radical retropublic prostatectomy specimens in MSKCC study.

Undergraded 54% | Overgraded 15%

What is the 5-year biochemical control rate for patient with biopsy GS 2-6, 3+4, 4+3, 8-10?

GS 2-6 : 79% 3+4 : 81% 4+3 : 62% 8-10 : 18%

In John Hopkins study, whether GS 3+4 vs 4+3 cancers behave differently.what was the conclusion?

Postoperative GS and pathologic stage significantly correlated with preoperative PSA and preoperative GS of 4+3 vs 3+4 on biopsy.

What were the 4 most powerful predictors of biochemical failure in prostate cancer from Stanford experience

Cancer location in PZ Percentage Gleason Grade 4/5 Tumor volume >=6cm3 Tumor contained in prostatic capsule

University of Michigan, what 3 factors were highly predictive of PSA relapse free survival on multi variate analysis?

PSA GS Greatest percentage of biopsy core involved by cancer

Mayo Clinic experience, what were 3 factors in needle biopsy were only parameters that jointly predicted pathologic stage T2 vs T3 disease?

Percentage of positive cores Initial serum PSA GS

SEER-Medicare linked database, 85,088 men diagnosed with prostate cancer at age 65 years and above, what was the common modality of treatment received?

RT 42% RP 21% ADT 17% Observation 20%

Scandinavian Prostate Cancer Group, Phase III trial, 695 men, early stage T1-T2, 12.8 years follow up, primary end point death attributed to prostate cancer, secondary end point overall survival. What was the conclusion?

Primary end point in favor of surgery 14.6% Observation 20.7% Benefit limited to younger patients below 65 years

Name 2 approach of radical prostatectomy

Retropubic | Perineal

Which is the common approach of radical prostatectomy and what is its advantage?

Retropubic approach | It also facilitate access for performing bilateral Pelvic LND

Describe radical prostatectomy

Complete removal of prostate and its surrounding capsule Seminal vesicles Ampulla Vas deferens

Is there a significant difference between open vs laparoscopic and robot assisted RP in recent comparison?

No significant difference

Define treatment isocenter for prostate cancer

Near the center of prostate gland, midline, at caudad aspect, approx 5 cm posterior to symphysis pubis.

Define CTV and PTV margin

At MSKCC CTV=prostate + seminal vesicles PTV=Add 1 cm to CTV except 0.6cm posteriorly

What is PTV margin in IGRT

6mm circumferentially

What are OARs during high dose IMRT planning in prostate cancer?

Inner and outer wall of rectum and bladder Femoral heads Outer skin surface Portion of small bowel and sigmoid within 1 cm of PTV Central 1 cm diameter portion of prostate encompassing prostatic urethra

Roach et al. What is difference in prostate volume between noncontrast CT and MR?

CT image is 32% larger than MR

What are 3 areas of disagreement between CT and MR images of prostate?

Posterior and posteroinferior apical portion of prostate Apex Regions corresponding to neurovascular bundle

Rash et al. What is the difference between CT and MR defined volume of prostate?

CT defined prostate is 8mm larger at base of seminal vesicles and 6mm larger at prostatic apex.

What are the common contouring errors during prostate cancer?

Overestimation of prostatic apex | Underestimation of prostatic base

Movement of prostate during treatment, what direction has been consistently reported?

Antero-Posterior | Supero-Inferior

Zelefsky et al. What is the mean prostate motion in anteroposterior superoinferior and left-right directions?

AnteroPosterior 1.2mm Superoinferior 0.5mm Left-right 0.6mm

MSKCC, describe the margins for prostate cancer

``` 1 cm around CTV 6 mm around prostate rectal interface Posterior aspect of CTV 90% coverage Anterior 100% Superoinferior 99% Left-Right 100% ```

What is dose prescription for 125 Iodine interstitial seed implantation for prostate cancer?

144Gy

125 Iodine Half life Mean photon energy Initial dose rate

Half life 60 days Mean photon energy 27KeV Initial dose rate 7cGy/hour

Outcome of Radical Prostatectomy Bianco et al.(1963 pts) 5 and 10 years biochemical tumor control 10 years PSA relapse free survival

``` 82% and 77% PSA level 4-10 : 83% 10-20 : 64% >20 : 47% ```

Outcome of radical prostatectomy Roehl et al.(3478 pts) 10 years overall biochemical recurrence rate 10 years PSA relapse free survival 10 year cancer specific and overall survival 10 year biochemical relapse free survival GS 3+4 GS 4+3

``` 32% Preoperative PSA level 10 : 49% 97% and 83% 64% and 33% ```

``` Outcome of radical prostatectomy University Hospital Hamburg, Germany Median follow up more than 10 years 10 year PSA relapse free survival pT2 pT3a pT3b pT4 GS =8 10 year PSA control rate + margin - margin ```

``` T stage 87% 53% 28% 6% GS 90% 58% 21% 11% Margin 24% 68% ```

Amling et al. What is the time of highest risk of biochemical relapse noted after surgery in prostate cancer?

2 years

ASTRO definition of PSA failure

3 consecutive rising PSA value above nadir value

``` Outcome with conventional EBRT for low risk disease Kuban et al. (4839 pts) Overall 8 year PSA control rates with pretreatment PSA 0-4 4-9.9 10-20 20-30 Overall 8 years PSA control rates with post treatment nadir PSA 0-0.49 0.5-0.99 1-1.99 >=2 ```

``` Pretreatment 80% 60% 46% 34% Post treatment 93% 88% 86% 72% ```

What prescription dose in conventional EBRT associated with significant decrease in PSA relapse rate with intermediate and higher risk prostate cancer?

>=72Gy

Dose escalation low risk disease MD Anderson Hospital Phase III trial T1-T3 prostate cancer 70Gy conventional dose vs 78Gy with boost What is the 8 year biochemical control?

63% vs 88%

Zelefsky et al. MSKCC T1-T3 prostate cancer Follow up beyond 20 years Low dose, =75.6Gy 10 year PSA relapse free survival

Low dose 70% vs High dose 84%

RTOG 94-06 dose escalation 3D-CRT low risk prostate cancer 5 year PSA relapse free survival with dose prescribed 68.4Gy 73.8Gy 79.2Gy 74Gy 78Gy

``` 68% 73% 67% 84% 80% ```

Outcome comparison EBRT vs Sx low risk disease Kupelian et al Cleveland Clinic 8 year PSA relapse free survival

72Gy or more vs Sx similar outcome | Sx has better outcome when compared to

PSA relapse free survival after permanent seed implantation in prostate cancer depends on which prognostic variables?

Pretreatment PSA Biopsy GS Clinical stage Implant dose delivered to target volume

What is the indication of permanent seed implantation in prostate cancer associated with excellent biochemical outcome and comparable with local intervention?

Pretreatment PSA

PSA relapse free survival with permanent seed implantation in prostate cancer for Favorable risk Intermediate risk High risk

86% 80% 62%

Sylvester et al permanent seed implantation for low risk prostate cancer 7 year biochemical tumor control Cause specific survival Overall survival

98.6% 99% 77.5%

Permanent seed implantation in prostate cancer 8 year PSA relapse free survival D90>130Gy D90

90% | 73%

Permanent seed implantation in prostate cancer 8 years PSA relapse free survival, PSA nadir value 0-0.49 0.5-0.99 1-1.99 >2

92% 86% 79% 67%

When is most complications attributed to RT observed in prostate cancer?

Within first 3-4 years after treatment | Likelihood of complications developing after 5 years is low

What are the 4 factors associated with increased bowel or rectal toxicity after EBRT in prostate cancer?

Volume of rectum exposed to high dose RT Increasing age of patient Concomitant use of androgen deprivation therapy Presence of diabetes and inflammatory bowel disease

Zelefsky et al. What is the predictor of 6 times more likely to experience late GI toxicities in prostate cancer?

Acute GI toxicities during treatment

Zelefsky et al. What is the predictor of late GU toxicities in prostate cancer?

Acute GU toxicities during treatment | Higher radiation dose

Peeters et al. What are the predictors of late GI toxicities in prostate cancer?

History of abdominal surgery | Pretreatment GI symptoms

Peeters et al. What are the predictors of late Gu toxicities in prostate cancer?

Pretreatment urinary symptoms Use of neoadjuvant ADT Prior TURP

What is the percentage of urethral stricture observed with 3DCRT in prostate cancer?

1.5%

What is the percentage of urethral stricture observed with 3DCRT in prostate cancer after TURP?

What is the percentage of urethral incontinence observed with 3DCRT in prostate cancer?

Prostate cancer treatment with RT, most studies showed wide range of erectile dysfunction from 6-84% observed in aging population with what comorbidities?

``` Anti-hypertensive drugs Atherosclerotic Heart Disease Diabetes Baseline erectile function Use of neoadjuvant and concurrent hormonal therapy ```

Name the drug that showed significant improvement in erectile dysfunction after 3DCRT for prostate cancer?

Sildenafil

What is the known risk that occur immediately after prostate brachytherapy?

Acute urinary retention

Roeloffzen et al name 2 variables which give higher likelihood of developing urinary retention in prostate brachytherapy?

Prostate volume > 35cm3 | Higher International Prostate Symptom Scores(IPSS)

Keyes et al what are the 5 year likelihood of developing late grade 2,3 and 4 urinary toxicities in prostate cancer?

24%, 6% and 1%

Zelefsky et al what is the incidence of grade 2,3 and 4 rectal toxicities after prostate brachytherapy?

G2 : 4-12% | G3-4 :

Snyder et al. What is the variable that gives higher likelihood of developing rectal toxicities in prostate brachytherapy?

Rectal volume in cm3 exposed to prescription dose of 160Gy correlated with G2 proctitis 1.8 cm3 : 25% proctitis

What is PSA bounce in prostate cancer?

PSA fluctuation in follow up period of prostate cancer

What percentage of patients experience PSA bounce after EBRT and interstitial implantation in prostate cancer?

35% Median time for bounce effect 18 months 92% fluctuating levels observed during 1st 26 months after EBRT

What is the PSA bounce range in prostate cancer?

0.11-15.8ng/mL

Chapter 65 Low Risk Prostate Cancer Flashcards

(121 cards)