Prostate Flashcards
AJCC T1 scores for prostate cancer:
There is no cT1
pT1 is either incidental:
<5% sampled tissue = pT1a
or >5% sampled tissue = pT1b
Or Focal Bx found on investigation of e.g. PSA = pT1b
AJCC T2 scores for prostate cancer:
T2 = Organ confined
a. Palpable ≤½ of
one lobe or less
b. Palpable >½ of
one lobe, but
not both lobes
c. Palpable both
lobes
What is T3 prostate cancer?
How bout T4?
T3 = Early extension beyond the date:
a) EPE
b) SV invasion
T4 = invasion - into bladder, external sphincter, rectum, levator muscles, pelvic wall.
Low risk prostate cancer is defined as:
Both D’amico and NCCN defines as:
T1–T2a, and
GS ≤ 6/grade (ISUP1), and
PSA < 10 ng/mL
Very low risk prostate cancer is defined as:
Note the very low risk group comes from NCCN. The D’amico staging just defines low risk which is the same as the NCCN. Similary D’amico does not divide int risk into fav/unfav…
T1
GS ≤ 6
PSA < 10 ng/mL
<3 positive biopsy cores
<50% cancer in any core
PSA density <0.15 ng/mL/g
Define a general criteria for int risk prostate cancer as a whole:
T2b, or
GS 7, or
PSA 10–20 ng/mL
Intermediate favourable prostate cancer:
T2b–T2c, or
GS 3 + 4 = 7/grade group 2, or
PSA 10–20 ng/mL, and
Percent of positive biopsy cores <
50%
Intermediate unfavourable prostate cancer:
2 or 3 intermediate risk factors:
GS 3 + 4
PSA 10–20 ng/mL
T2b–T2c
AND/OR
Grade group 3, and/or
>50% cores positive
The difference between fav and unfav intermediate PrCa:
the addition of:
Grade group 3, and/or
>50% cores positive
Low-risk prostate cancer includes organ-confined disease typically detected by:
Standard treatment options include:
Low-risk prostate cancer includes organ-confined disease typically detected by:
screening PSA or on DRE (T1-T2a), with a PSA < 10 ng/mL and GS ≤ 6.
Standard treatment options include:
Active surveillance, prostatectomy, EBRT, or brachytherapy.
For each standard treatment for low-risk prostate cancer, what is the cancer–specific survival?
Treatment selection is guided by:
Most guidelines recommend treatment only if:
Prostate cancer–specific survival is >95% for each.
Therefore, treatment selection is guided by: Side effect profiles and patient preference.
Most guidelines recommend treatment only if life expectancy is >10 years.
Is there a role for dose escalation in low-risk PrCa?
Dose escalation improves local control compared to conventional doses.
What is the watchful waiting approach? For which patient group is this most suited?
Watchful waiting:
No further testing = Tx only when
symptoms develop
Target audience:
Patients w/severe comorbidity
and/or limited life span
What is (and can be) involved in active surveillance?
Regimented follow up with routine PSA tests
and repeat biopsies;
Consider:
genomic testing
MRI guided biopsy
A healthy 60yro patient with low risk prostate cancer elects for definitive radiation. Name all the options (there are 5) and give an example dose for each:
Targeting the prostate:
1) IMRT/VMAT standard #s = 74Gy/35
2) Hypofractionation: 60Gy/20
3) SBRT (extreme hypofractionation): 35-40Gy/5
4) Brachy LDR (I-125/P-103): 125Gy to 145Gy
5) Brachy HDR (Ir-192): 27Gy/2. RCT evidence suggests 2#s better than 1
A healthy 60yro patient with low risk prostate cancer elects for definitive radiation. Name some possible patient concerns that may make this a good choice compared to prostatectomy:
In terms of functional outcomes there is no clear benefit of surgery vs radiation. Motivated toward nonoperative intervention - e.g. adverse to operative procedure/anaesthetic risk
Or specific concerns:
Erectile dysfunction 30-90% surgery
Versus 70% radiation (brachytherapy has lower rates)
Incontinence from prostatectomy. Around 5-10% risk.
Australian prostate Ca epidemiology:
1) median age at Dx
2) Most common stage at Dx:
3) Chance of being Dx w/prostate cancer before age 86?
1) median age 69 (Australia)
2) 46% are Stage II, 36% s are Stage I , 11% are detected at Stage III
3) 1 in 6 chance of Dx before 86
The two most significant risk factors for prostate cancer?
Most significant:
1) Age (significant increase in risk > 50)
2) Family Hx
Risk factors for prostate cancer?
1) Age (signif increased risk>50)
2) fam Hx
3) Race (highest rates in Scandinavia)
4) Mutations in genes responsible for DNA repair (e.g., germline BRCA2 mutation) associated with higher GS and worse prognosis.
5) Syndromes associated with
increased risk:
Lynch syndrome,
BRCA2,
Fanconi’s anemia
HOXB13.
Syndromes associated with
increased PrCa risk:
Syndromes associated with
increased risk:
Lynch syndrome,
BRCA2,
Fanconi’s anemia
HOXB13.
Describe the fibromuscular and glandular anatomy of the prostate:
Composed of 2/3 glandular elements (divided into 3 zones) and 1/3 fibromuscular.
Glandular divided into 3 zones: peripheral zone (70% of
volume) with the majority of prostate cancer arising from it.
Central zone (25% of
volume) only 5% of cancers.
Transition zone (5% of volumes) rarely site of Ca BUT the site of benign prostatic hyperplasia.
Relate the glandular zones to the occurences of cancer and other common pathologies.
Glandular divided into 3 zones: peripheral zone (70% of
volume) with the majority of prostate cancer arising from it.
Central zone (25% of
volume) only 5% of cancers.
Transition zone (5% of volumes) rarely site of Ca BUT the site of benign prostatic hyperplasia.
Describe the anterior zone of the prostate:
Where are the neurovascular bundles located?
1) The fibromuscular stroma (or anterior zone) extends superiorly from the smooth muscle of the bladder neck and inferiorly to the urethra, prostate apex, and external sphincter.
2) Neurovascular bundles located posteriolaterally (thats why they often get invaded from the perif zone).
Anatomical relation of the seminal vesicles to the prostate:
Position of the pr and SVs varies w/ filling of the rectum and bladder.
SVs are coaxial with the prostate, positioned superiorly and adjacent to the posterolateral aspect of the It.
SV joins the vas deferens to the ejaculatory duct and open into prostatic urethra at the verumontanum.
Lymphatic drainage of the
prostate and SVs:
Drainage of prostate:
internal iliac, external iliac, obturator, and presacral lymph nodes, with occasional
drainage directly to the common iliac nodes.
SV lymphatics:
typically to external iliac nodes.
What percent of prostate cancers are adenocarcinomas?
Name some of the other histologies and very broadly make a statement about their prognosis:
1) 95%
2) Other histologies (worse prognosis):
- Small cell (neuroendocrine) carcinoma,
- Ductal adenocarcinoma,
- Transitional cell carcinoma,
- Sarcomatoid carcinoma,
- Sarcoma
The Gleeson Score is based on:
The most prevalent and highest grade are summed together for the GS since:
The GS is based on the
architectural structure of the malignant cells. Specifically the range from normal small uniform glands (Gleeson 1) to only occasional glands observed.
The most prevalent and highest grade are summed together for the GS since any amount of high-grade
tumor may indicate a more significant amount within the prostate.
When may a tertiary grade be given for a prostate cancer - E.g beyond Gleeson = x + y?
Tertiary grades are given
only in RP specimens if there is a component (< 5%) of higher grade tumor than the two predominant
patterns.
How common is:
1) ECE
2) SV invasion in setting of risk group
ECE is seen in ~45% of clinically localized disease and is
within 2.5 mm in 96% of cases.
SV involvement increases with risk group:
Low risk ~1%,
Intermediate risk ~15%,
High risk ~30%, with a median 1 cm length of involvement and ~1% risk of SV involvement beyond 2 cm
Probability of SV invasion in setting of risk group (just like the last card):
SV involvement increases with risk group:
Low risk ~1%,
Intermediate risk ~15%,
High risk ~30%, with a median 1 cm length of involvement and ~1% risk of SV involvement beyond 2 cm
Outline PSA screening approach in Australia and NZ:
Lower grd (C) evidence suggests mortality benefit from early Dx of PrCa due to PSA testing is not seen within less than 6–7 yrs from testing. Therefore PSA testing not recommended for men who are unlikely to live> 7 yrs.
In NZ: men aged 50 and over should discuss testing w/GP or doctor. For Pts w/a FamHx of prCa this discussion should begin at 40.
Australia: Men >50 should be made aware of PSA testing and informed about the pros and cons.
The Australian cancer council advice is supported by RANZCR
50yro man elects to have a screening PSA test. At what PSA value should further investigation be discussed?
> =3ng/ml
For men without a dx or sx of pr.cancer who wish to undergo regular PSA testing, the following strategy is recommended:
Why is it recommended?
For men without a dx or sx of pr.cancer who wish to undergo regular PSA testing, the following strategy is recommended because it is associated with reduced risk of death from prostate cancer:
PSA testing every 2–4 years from age 50 to age 69, and offer further investigation if the PSA is greater than 3.0 ng/mL
Key questions in the Hx of a patient w/low risk Prostate:
1) Life limiting co-morbidities
2) Baseline:
- Urinary function - With IPSS
- Sexual function - E.g IEFS or SHIM score
- Bowel function
3) Fam Hx - may denote higher risk
Any benefit to MRI guided prostate Bx?
May decrease the number of cores compared to random. Otherwise same outcomes.
Can see how would be good in setting of active surveillance.
Role of imaging in Low-Risk Pr Ca?
No role for routine staging scans in low-risk prostate cancer. Multi-parametric MRI may be
used in patients considering active surveillance as it may detect lesions concerning for GS >7 cancer or ECE.
Natural Hx of low-risk prostate cancer:
The risk of death from early-stage, low-risk disease is ~1% at 10 years (active monitoring arm of the ProtecT trial).
Many tumors follow an indolent course for the first 10 to 15
yrs post Dx, but beyond 15 yrs, the PrCa specific mortality rate triples (15/1000 person-years to 44/1000).
BUT recent 15yr ProtecT seems inconsistent with this (active monitoring seems the same).
Outcomes for biochemically recurrent PrCa post RRP:
Per the Pound study of pts w/ biochemical failure post RRP:
Mets at a median of 8 yrs after biochemical failure.
Death occurred at a median of 5
years from the development of mets.
Is there a role for systemic therapies in patients under active surveillance for low-risk Pr Ca?
use of 5-α-reductase inhibitors to prevent cancer progression in the setting of AS is debatable.
The REDEEM trial shows lower 3-year rates of prCa progression with dutasteride vs placebo (38 vs 48%).
Which approach to prostatectomy has the worst outcomes? Which appear equivalent?
A perineal approach omits lymphadenectomy and SV removal, and has with higher rates of biochemical failure/+margins, and
rectal injury. open is 2nd worst. Lapro and robotic are about the same in RCTs.
The +margin rates for open, laparo, and robotic are around
23%, 15%, and 14%, respectively.
The most common post prostatectomy adverse side effects?
Impotence and incontinence are the most common (impotence 50-75%, total incontinence 1-2%, ~50% some degree of poor control):
Bilateral nerve-sparing procedure is associated with an estimated ~50%
rate of impotence.
Unilateral nerve-sparing procedure is associated with impotence rate of ~75%.
Around 30% of patients reported have total urinary control,
40% occasional leakage,
7% frequent leakage,
1%–2% no urinary control
A standard lymph node dissection involves?
Can outcome be improved with a more aggressive approach?
A standard lymph node dissection involves “sampling” of the obturator and external iliac lymph nodes.
It is uncertain whether an extended lymph node dissection improves outcomes.
For low-risk PrCa, give some:
1) Conventional doses:
2) Moderately hypofractionated doses:
2) SBRT/extreme hypofractionated:
1) 78 Gy/39 or 79.2 Gy/44
2) 70 Gy/28 fx or 60 Gy/20 fx
3) 30gy/5 to 40/5
Compared to other options, how good is Brachy (LDR or HDR) for low risk prCa?
Brachy is common for low-risk, with comparable outcomes to surg and EBRT, but no RCT has compared these head to head.
Dose for LDR brachytherapy is?
Dose for LDR:
144 to 145 Gy for I-125 (D90>145Gy)
125 Gy for Pd-103.
In low and favourable intermediate risk PrCa what is the role for combining EBRT with brachy boost or with ADT?
Monotherapy alone is sufficient.
For low-risk and favorable intermediate-risk there is no role for combining EBRT with brachy boost or ADT.
E.g. The ProtecT study suggests outcomes are so good in surveillance arm, would be difficult for any significant difference to be detected in mono vs combined arms.
The optimal dose, fractionation and scheduling for HDR brachytherapy?
The optimal dose, fractionation and brachytherapy scheduling has yet to be defined.
RCT data suggests at 5yrs 2 (13.5Gy/#) fractions is superior to 1 (19Gy) in terms of disease-free survival and cumulative incidence of local failure.
A suitable HDR dose for low risk PrCa?
Dose should cover?
24Gy, 12Gy/#, fractions at least 6 hours apart.
100% cover target volume, aiming for a minimum of 95% coverage as per ICRU 58
The definition of biochemical failure after curative intent radiation is:
As per who?
RTOG-ASTRO Phoenix
Consensus defines biochemical failure as:
A rise of 2 ng/mL above the post-treatment nadir PSA
What is a PSA bounce?
A PSA “bounce” may occur in some patients, especially post brachy.
It is not associated with worse outcomes.
Acute side effects of brachy:
Perineal bruising and swelling
Fatigue
Irritative or obstructive urinary Sx: Bladder spasms, dysuria, nocturia, frequency, incontinence, urgency.
Urinary retention +/- clots
Proctitis: diarrhoea, increased bowel frequency, rectal urgency, pain and bleeding.
late side effects of brachy:
Sexual dysfunction -eg. erectile dysfunction, impotence, dry and/or painful ejaculation, haematospermia and reduction in ejaculate.
Obstructive urinary SX and retention
Perineal discomfort
Rectal ulceration
Urethral stricture
Proctitis
Prostatorectal fistulas very rare, but increased risk in the setting of subsequent rectal biopsies which are contraindicated.
Urinary incontinence
Second malignancy
Common SBRT/hypofractionated prostate regime? How does it compare to IMRT?
For SBRT, 36.25 to 40 Gy in 5 fx delivered every second day is common.
Yet to be tested against IMRT in an RCT.
How many major PSA screening trials are there?
General themes?
In the PSA era there has been stage migration toward early localized disease and a decrease in metastatic rates.
3 major screening trials.
Methodology suggests that the magnitude of screening may be likely larger than represented.
The ERSPC and Swedish Trial shows a PCSM benefit for PSA screening, while PLCO did not.
It is difficult to keep people in the “observation” arm from being screened, which is one of the criticisms of the PLCO trial.
Is extreme hypofractionation via SBRT safe and effective?
Biochemical control and toxicity outcomes are comparable to historical outcomes of dose-escalated 3D/IMRT but longer follow-up is needed.
Patients should be aware of the shorter follow-up and lack of randomized data with SBRT.
Early experience from Stanford found that 2nd daily tx resulted in less toxicity than OD SBRT (nonrandomized) - why most have adopted QOD
The potential benefits of moderate hypofraction in low-risk PrCa:
1) Improved convenience
2) lower cost
3) Potentially improved outcomes (low α/β).
Longer follow-up will be helpful to establish noninferiority for clinical effectiveness and toxicity profiles.