Prostate Flashcards by Sam O'Boy

What is the commonest prostate cancer histology
What are the others and how are they broadly managed

Adenocarcinoma
Small cell - manage as per small cell lung
TCC - typically of prostatic urethra - manage as bladder

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Does renal function affect PSA

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What are the 2WW referral limits for PSA, by age

40–49yrs: 0 - 2.5
50–59yrs: 0 - 3.5
60–69yrs: 0 - 4.5
70–79yrs: 0 – 6.5

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When is staging (CT & bone scan) done for prostate cancer

High risk cases - Gleason 8, PSA >20, T2c

CPG1-2 - no staging needed
CPG 3 - Bone scan +/- CTCAP
CPG 4-5 - bone scan, CTCAP +/- PSMA PET

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When is a PSMA PET scan indicated

HIgh risk pts ahead of radical tx - Gl 8, T2c, PSA >20

Suspected recurrence in patients with a rapidly rising PSA and negative or equivocal imaging where results would directly influence pt management

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What are the treatment options split by risk for localised prostate cancer

Low risk - active surveillance, radical prostatectomy, EBRT only, or LDR brachytherapy

Intermediate risk - radical prostatectomy, LDR brachytherapy, 6/12 ADT with EBRT, HDR brachytherapy followed by EBRT

High risk - 3yr ADT with EBRT, HDR brachytherapy followed by EBRT

Very high risk - up front docetaxel

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What are the treatment options for relapsed prostate cancer after radical treatment

Relapse following RT - observation with delayed ADT, or local salvage - radical prostatectomy, HDR brachy

Relapse following surgery - prostate bed RT, consider 6-24mths ADT

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What does active surveillance consist of

Yr1:
3-4mthly PSA
12mth dre
12-18mth MRI

Yr2:
6mthly PSA
12mth dre

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What are advantages and disadvantages of a radical prostatectomy

Advantages
Immediate treatment
No androgen deprivation
Full histology
Easier to monitor PSA (should be undetectable)

Disadvantages
Higher rates of erectile dysfunction and incontinence
Erectile dysfunction (50%): can do nerve sparing operation
Urinary morbidity: 80% continent by 3 months
Likely to need adjuvant RT if T3 disease
25% risk of +ve margins: lack of tissue around prostate, esp at apex to allow wide margins

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What are the side effects of ADT

Hot flushes
Erectile dysfunction and loss of libido
Osteoporosis
Mood change
Fatigue
Gynaecomastia

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What can be given to treat hot flushes as a side effect

1st line: medroxyprogesterone 20mg OD for 10 weeks initially
2nd line: cyproterone acetate 50mg BD for 4 weeks then review

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What formula determines whether to treat the SV or not

And at what thresholds

= PSA + [(Gl -6) x10]

Low risk: <15% - base of SV only;
High risk: >15% or pathologically involved – whole SVs

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What RT dose is given to the prostate, nodes (if treated), and SV

Prostate - 60Gy/20#
SV - 48Gy/20#
Pelvic nodes - 44Gy/20# (47Gy within pivotal boost)

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What is the dose regime for HDR brachy followed by EBRT

Brachy boost - 15Gy/1# (brachy) followed by 37Gy/15# (EBRT) over 3 weeks (prostate only) or 46Gy/23# (prostate and nodes) IMRT

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What RT volumes are included for a low or intermediate risk prostate cancer, and how are these defined

Low - int risk: ≤T2c, Gl 6-7, PSA ≤20

Volumes:
GTVp- prostate only
GTVpsv - prostate & SVs
<15% Roach -> prox 2cm of SV
15-30% Roach -> whole SVs

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What is the hypofractionated dose for prostate SABR

36.25Gy/5#/2wks

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What is the rate of erectile dysfunction after radical prostate RT
And bladder/bowel toxicity

40%
10-15% Urinary and bowel changes
Bowel and bladder - 95% minimal & 5% moderate-severe s/e

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What are the indications for adjuvant RT for prostate cancer

T3 disease, Gleason 8+, Positive margins

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What are the three options for inclusion of brachytherapy & what dose

LDR only - approx 145Gy
HDR brachy (15Gy) followed by EBRT 37.5Gy/15#/3wks, (prostate only) or 46/23 (prostate + nodes) 2wks later
EBRT 46Gy/23# followed by LDR brachy boost (115Gy)

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When is brachytherapy contraindicated

Previous TURP - high risk of urinary incontinence
IPSS >15 ie urinary outflow restriction - more likely to have complications
Gland >50ml & likelihood of pubic arch interference
Inability to undergo anaesthesia

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What isotope does LDR brachy use

I-125 - 50-70 seeds, T1/2 60days

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When is LDR brachy indicated
What is the advantage
What are the disadvantages

Low and intermediate risk pts - up to T2b/c
(<T2a, Gleason ≤7, PSA ≤10)
IPSS score low, <10 ideally
Prostate volume <50ml

Advantage - lower risk of impotence and incontinence

Disadvantage - higher rate of acute urinary retention & dysuria
Radiation protection issues for 6mths post implant

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What are the side effects of LDR brachy

Urinary:
Urethritis - 50% have moderate urinary sx at 6mths
10% risk of acute urinary retention in first 2wks (higher risk for high IPSS and large prostate)
Urethral stenosis

Rectal - 5% proctitis, intermittent bleeding and discomfort. 0.1-0.2% risk of fistula

Erectile function - 30-40% risk of erectile dysfunction

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What is the indication for EBRT followed by an LDR brachy boost
What is the advantage demonstrated by what trial if ADT given or not

Int-high risk pts
Improved 7yr PFS benefit according to Ascende RT trial
Trial also gave 12mths ADT

What is the indication for HDR brachy +EBRT What is the dose used

Intermediate and high risk pts 46Gy/23# EBRT followed by 15Gy HDR boost as 2x 8.5Gy (although can be other way round)

What is the GTV-CTV and CTV-PTV margin for prostate EBRT

GTVp/psv - Prostate & SVs CTVp - GTVp + 5mm PTVp - CTVp + 10mm

What is the GTV-CTV and CTV-PTV margin for involved nodal EBRT

GTVn-CTVn - 1cm margin CTVn-PTVn - 0.7cm

What is the indication for breast bud irradiation And what dose and modality is used

Prophylaxis of gynaecomastia on bicalutamide (if planned for >6mths), or treatment of established symptoms Dose: 8Gy/1# by electrons or orthovoltage 15Gy/3#/1wk alternate days with photons

What histological marker is seen in prostate small cell carcinoma

TMP RSS2:ERG gene fusion seen by FISH

What is the definition of biochemical relapse after RT

Phoenix definition: rise of PSA nadir +2

What workup is considered for a relapsed prostate cancer

CTCAP, bone scan, and PET / PSMA PET, to determine extent of recurrence

What are the treatment options for a biochemical relapse of prostate cancer after RT

Consider restarting ADT (indications - symptomatic disease, proven mets, PSA doubling time <3mths) Prostatectomy HDR brachytherapy HIFU

What are the indications to restart ADT following biochemical relapse of prostate cancer

Symptomatic disease Proven mets PSA doubling time <3mths

What is the rate of biochemical relapse following prostatectomy, and how is it defined

20-40% 3 consecutive rises in PSA, or persistently rising PSA >0.2

What is the dose for salvage RT to the prostate bed, for biochemical relapse following prostatectomy What is the rate of biochemical control

55Gy/20# 5yr biochemical control with salvage RT 88% as per the Radicals-RT trial

When should ADT be considered after biochemical relapse following prostatectomy

Men with risk factors prior to salvage RT - PSA >0.7, Gl8-10, positive margins at surgery Spport trial randomised to prostate bed RT only, prostate bed RT & 6mths ADT, and prostate bed and pelvic nodes RT & 6mths ADT. There was an increasing rate of freedom from progression, and distant metastasis rates were significantly lower for the triple treatment approach

How is very high risk non-metastatic castrate-sensitive prostate cancer defined How are these patients treated

Node positive disease OR at least 2 of T3/4, PSA >40, Gleason 8-10 Tx: consider upfront docetaxel ADT (3yrs) Abiraterone and pred

How is non-metastatic castrate resistant prostate cancer defined And how is high risk NM-CRPC defined What treatment is indicated And based on what trials

No mets on conventional imaging (excluding PSMA PET) Rising PSA Suppressed testosterone <50 (castrate) High risk: Also Baseline PSA >2 Rising PSA with doubling time <10mths, taken from 3 readings at least one week apart Tx: ADT (3yrs), likely with EBRT ARTA - apalutamide, darolutamide, enzalutamide Based on Spartan / Prosper / Aramis trials Increase in time to progression

When is enzalutamide contraindicated What needs to be seen before prescribing it

Epilepsy - can lower seizure threshold Need to see that cancer is hormone responsive, ie falling PSA in response to ADT (castrate sensitive) before giving enzalutamide

When is apalutamide indicated

High risk non-metastatic castrate resistant PC, with ADT Metastatic hormone sensitive prostate cancer in combination with ADT

What are the indications for enzalutamide

Non-metastatic castrate-resistant prostate cancer Metastatic hormone sensitive prostate cancer Metastatic castrate resistant prostate cancer (before or after docetaxel)

What are the indications for darolutamide

Non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease In combination with docetaxel & ADT for newly diagnosed metastatic hormone-sensitive prostate cancer

What is the purpose of oligometastatic directed treatment in the hormone sensitive setting

To delay the start of ADT

What are the treatment options for a new presentation of metastatic hormone sensitive prostate cancer

If low vol disease - ADT + enza/apa + prostate only RT If high volume disease Fit - ADT + docetaxel +/- darolutamide Unfit for docetaxel - ADT + apa/enza

What is the prognostic benefit of docetaxel in the metastatic setting, based on what trial

17mths, vs ADT alone, for high volume disease Based on Chaarted trial 10mths as per Stampede trial

When is prostate RT beneficial in metastatic disease, and based on what trial And at what dose

Stampede trial Low volume disease only Prostate only RT - 36Gy/6#/6wks

What is the median time to progression on ADT alone in the metastatic hormone sensitive setting

18mths mOS 42mths

What is the benefit to enzalutamide in the castrate resistant metastatic setting

Pre-docetaxel: approx 10mth PFS benefit (prevail trial) Post-docetaxel: approx 5mth PFS benefit (Affirm trial)

What is the indication for Radium 223 What are the side effects? What is the survival benefit?

mCRPC with symptomatic bone mets & no visceral or nodal >30mm disease +/- docetaxel PS 0-1 SE: Diarrhoea, myelosuppression, thrombocytopaenia Survival benefit based on Alsympca trial: 2.8mth OS survival benefit and delayed time to skeletal events

What are the contraindications to radium treatment

cord compression PS 2 or worse LNs >3cm or visceral mets

When in 177-Lu indicated What is the benefit What are the side effects

Advanced metastatic prostate cancer, following chemotherapy, and if PSMA positive disease Based on Vision trial: prolonged PFS (median, 8.7 vs. 3.4 months) and OS (median, 15.3 vs. 11.3 months) SE: N/V, fatigue

What is the indication for use of a PARP inhibitor in metastatic CRPC What is the benefit Based on what trial

Monotherapy for pts who have progressed (prior therapy must include an ARTA) for mCRPC bearing germline and/or somatic BRCA 1/2 mutations and PS 0-2 Profound trial - longer PFS by approx 3mths Survival benefit

When is bone directed treatment indicated in metastatic prostate cancer

Osteoporosis Bone mets and bone pain

when is adjuvant RT needed post prostatectomy

PSA >0.2 at 6wks

what is the threshold to stage prostate cancer

CPG 3 Gl 3+4 with PSA 10-20 & T1-2 or Gl 4+3 and T1-2 stage

for radiotherapy to the prostate in metastatic disease, how is high volume disease defined

4 or more mets within the axial skeleton with one or more outside the vertebral bodies or pelvis, or visceral mets, or both. Patients with low metastatic burden disease, according to the CHAARTED definition, may have an unlimited number of metastases provided they are confined to lymph nodes and the axial skeleton. otherwise classified as low volume disease and Stampede demonstrates a benefit to prostate RT - 36/6