Prostate Flashcards
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
Does renal function affect PSA
No
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
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
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
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
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
What does active surveillance consist of
Yr1:
3-4mthly PSA
12mth dre
12-18mth MRI
Yr2:
6mthly PSA
12mth dre
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
What are the side effects of ADT
Hot flushes
Erectile dysfunction and loss of libido
Osteoporosis
Mood change
Fatigue
Gynaecomastia
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
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
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)
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
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
What is the hypofractionated dose for prostate SABR
36.25Gy/5#/2wks
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
What are the indications for adjuvant RT for prostate cancer
T3 disease, Gleason 8+, Positive margins
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)
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
What isotope does LDR brachy use
I-125 - 50-70 seeds, T1/2 60days
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
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
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
