This document provides an overview of radical radiotherapy for prostate cancer. It discusses the aims of radiotherapy to maximize dose to the tumor while minimizing dose to surrounding organs. External beam radiotherapy techniques like IMRT precisely shape radiation doses. Image guidance ensures accurate dose delivery. Hypofractionated schedules may improve outcomes while shortening treatment time. Brachytherapy can deliver a highly conformal dose but is best for localized disease. Overall the document outlines the key stages and techniques used in radiotherapy planning and treatment to effectively treat prostate cancer while limiting side effects.

1. Part of the “Enhancing Prostate Cancer Care” MOOC
Catherine Holborn
Senior Lecturer in Radiotherapy & Oncology
Sheffield Hallam University

2. Aim of the presentation
To provide an overview of the key aspects of
radical radiotherapy in the radical treatment of
localised and locally advanced prostate cancer
This supplements the information already
provided on the overall management of prostate
cancer and the role of the main radical treatment
options (surgery and radiotherapy)

3. What is Radiotherapy?
Radiotherapy is the use of ionising radiation to primarily treat
cancer.
Ionising radiation causes breaks in a cell’s DNA. This affects
the cell’s function and ability to divide, causing cell death.
There are two main types.
External Beam Radiotherapy (EBRT)
Uses high energy x-rays (photons). A series of carefully planned
photon beams, of varying sizes and multiple angles, are directed
from an external source into the patient
Brachytherapy (internal treatment)
A radioactive source is placed inside the body (temporarily or
permanently). Sources used for prostate brachytherapy emit
gamma rays that go on to damage the cell’s DNA

4. Aim of Radiotherapy
The main aim of radiotherapy is to maximise the ‘therapeutic
ratio’.
To deliver a high dose to the ‘target’ and maximise disease
control, whilst still keeping the dose to the normal tissue and
surrounding organs at risk(OAR) as low as possible, minimising
treatment related side effects and complications.
The main OAR during prostate radiotherapy are the rectum
and bladder . For external beam the dose to the femoral heads
is also assessed. The penile bulb may also be identified during
the planning stage. For brachytherapy, the urethra is an OAR
to which the dose must be minimised.

5. Considerations
For men with localised prostate cancer, surgery is a treatment
option alongside radiotherapy. A number of factors may
influence their final decision
Side effects are covered in a separate presentation. What else
may be a consideration?
General health/suitability for general anaesthetic (brachytherapy)
Avoid risks of major operation
PSA levels fall gradually (for up to 2 years). Some men may experience
PSA 'bounce' which can be worrying (increased amounts leak into
bloodstream as a result of prostate cell death and altered vascular
permeability)
Daily treatments (usually Mon-Fri) for approx. 6-8 weeks are required
Inflammatory bowel disease is a contraindication (external beam)
Salvage surgery is difficult after RT.
RT may not be possible if previous radical RT has been received e.g. for
another pelvic cancer

6. • There are a number of steps that are taken as part of the
radiotherapy process, that help to maximise the therapeutic
ratio
• The key stages of the radiotherapy process are:
• Localisation
• Planning
• Treatment delivery and verification
• The next few slides provide an overview of these stages

7. Localisation
A CT scan is taken with the man in the intended treatment
position
The pelvic CT slices/cross sectional images are later viewed by
the clinician
They outline the intended target and OAR on each of these
slices
An advance in this area is the additional use of an MRI scan, to
improve the visualisation of these structures and the accuracy
of the outline
CT alone tends to cause an overestimation of the true
prostate gland size, meaning the target may encompass more
normal tissue than necessary, potentially increasing side
effects
The target outlined will depend on the risk/stage of the
prostate cancer

8. Prostate Outlining (CT left, MRI right)
Rectum = red Prostate = blue Base of bladder = yellow

9. The prostate target volume
Low risk disease = prostate gland only (low risk of spread to the seminal
vesicles)
Although, the prostate outline (especially with a safety margin applied)
may include some of the proximal half of the seminal vesicles anyway
Intermediate and high risk disease = very likely to include the prostate +
seminal vesicles
The proximal half should always be included. It is debateable whether the
whole seminal vesicle volume needs to be included. Doing this increases
the amount of rectal volume in close proximity to the target/high dose
region
Inclusion of pelvic lymph nodes is more debateable. The benefits of
treating any cancer that may be present within these, must be weighed
against the potential increased risk of toxicity from treating a larger
radiation field
In the recent PRO7 trial, which demonstrated the benefits of adding
androgen deprivation to radical radiotherapy for men with high risk
localised and locally advanced disease, the pelvic lymph nodes were
treated

10. The Planning Target Volume (PTV)
A small ‘safety’ margin is added to the clinical target volume to
create the PTV.
The margin accounts for any movement of the patient, or internal
organs, that might occur and change the position of the target, from
when it was originally planned.
The size will vary across institutions, depending on local techniques
used that help to minimise any changes in position; it tends to be 3-
8mm (3-5mm posteriorly where it overlaps with the rectum)
The margin ensures that the high dose planned to the target, is still
delivered to the target; HOWEVER, this is essentially a margin of
normal tissue and so should be minimised as much as possible.
This means that we must keep the patient and the internal organs as
stationary as possible.
Immobilisation and image guidance are very important!

11. EBRT dose prescribed
Conventional treatment is delivered in a series of daily
doses (called fractions #), usually Monday to Friday, until
the prescribed total dose is reached.
It is well documented that EBRT as a definitive/primary
treatment should deliver a minimum dose of 74Gy in 37 #
to the prostate.
Rectal dose/toxicity is a concern though, given it’s
relatively low tolerance dose and close proximity to the
prostate gland. The anterior rectal wall will be included in,
or very close to, the PTV. The dose to this region needs to
be minimised as much as possible.

12. Minimising rectal dose
Using MR images as well as CT to outline the target will help to avoid an
over-estimation of prostate gland size.
With 3D planning techniques (considered the minimum standard), the
whole target volume can be viewed in all directions and radiation beams
can be created that closely match it’s size and shape.
Intensity Modulated Radiotherapy (IMRT) is a more advanced planning
technique which varies the radiation intensity across each beam, and can
shape the dose delivered even more precisely to the target.
When treating the seminal vesicles, more of the rectal volume is at risk. A
phased technique (sequential delivery of different plans) can be used to
limit the dose to the rectum. The prostate + seminal vesicles are treated
first to a slightly lower dose, and then a second plan focuses on the
prostate only, boosting the dose to 74Gy or possibly higher.
An advantage of IMRT is that this variation in dose across the prostate
and seminal vesicles, can be delivered simultaneously. Only one plan is
required

13. IMRT basic illustration: varying beam intensities build up the dose
to the prostate/seminal vesicles, as the machine moves around
the patient to differing positions, intensity is always lowest (blue)
in the path of the rectum

14. Different types of IMRT
Static IMRT
Uses a fixed number of intensity modulated beams, delivering
treatment from a series of specific angles/ directions
VMAT
Volumetric Intensity Modulated Arc Therapy
No fixed beam angles. The beam intensity changes as the machine
moves/arcs around the patient (at a fixed or variable speed)
Tomotherapy
Treatment is delivered in intensity modulated ‘slices’ across the
planned volume
Most common form Helical Tomotherapy. The slices are delivered
as the couch moves continuously through the machine (looks like a
CT scanner)

15. Minimising rectal dose cont…
Good immobilisation and image guidance techniques
on the treatment unit ensure the treatment plan is
delivered as intended
The PTV margin can also be kept small, encroaching
less on the rectum, if daily accuracy is high

16. Patient immobilisation
As much as possible, the patient and internal target
position should be the same each day for treatment,
and the same as when the treatment was originally
planned
To immobilise the patient, external positioning
devices are used to stabilise the legs and/or pelvis
(used at both the planning and treatment
appointments)
See next slides (other centres might use a device that
attaches over the pelvis)

17. Treatment room (conventional linear
accelerator) with leg immobilisation devices
Image courtesy of Radiotherapy Centre at Nottingham City Hospital

18. Treatment room (Tomotherapy) with leg
immobilisation devices

19. Stabilising the prostate position
Changes in rectal and bladder volume can also alter the
position of the prostate
To reproduce the same internal position, men may be
asked to empty their bowels prior to each treatment
and ensure they have a full bladder
Some departments may ask for an empty bladder but
this is less common. The full bladder is thought to keep
areas of normal tissue e.g. the small bowel, further
away from the higher target dose
Some centres (not common in the UK) might use a
'rectal balloon' to stabilise the position of the prostate

20. Why image guidance?
The PTV margin accounts for the typical errors/changes in
position that are known to occur, when using the specific set
up used locally for a particular patient group i.e. prostate
cancer patients
However, individual patients may display positional
errors/changes that are greater than this safety margin
In these instances, the treatment couch that the patient is
lying on, can be moved, thus altering the patient position and
bringing the target back in alignment with the treatment
beam
Image Guided Radiotherapy (IGRT) on the treatment unit is
used to assess how much a patient/target has moved, relative
to the original planned target position

21. Methods of image guidance
Image guidance protocols vary across radiotherapy departments
The type of imaging modality used
Images that show the position of the prostate directly, as opposed to
plain x-rays showing only bony anatomy, are considered the gold
standard
CT based imaging modalities are increasingly common
A few implanted markers in the prostate could also be used, which can
be visualised on plain x-rays or CT images
Ultrasound has been researched but not commonly used
The frequency of imaging
Daily imaging allows for all daily variations to be corrected, if needed
Imaging for the first 1-5 days, allows the ‘average’ positional change,
compared to the original planned position, to be calculated and
corrected if needed. It also allows assessment of the daily variation
around this. If this is large, daily imaging may continue. Alternatively, a
weekly imaging check may then occur.

22. Effect of an empty bladder (seen on cone beam CT images): the shift anteriorly would have moved the rectum into the higher dose region
planned for the prostate/seminal vesicles (planned blue/red outlines) and the seminal vesicles into the lower dose region where the bladder
originally was (planned green outline).
Rectum
and SVs
shifted
anteriorly

23. Hypo-fractionation
Conventional doses are delivered in 2Gy per fraction. The alpha-beta
(α/β) ratio is a measure of radio sensitivity to fraction size. In
comparison to many other cancers, prostate cancer is thought to
have a relatively low α/β ratio (1.5-3.0) and this implies that a larger
dose per fraction will increase its sensitivity/have a greater
radiobiological effect.
This is called hypo-fractionation
It’s use has gained momentum in the advent of IMRT and IGRT,
which can more effectively and accurately deliver these higher daily
doses to the target.
The CHHiP trial investigated the benefits of hypo-fractionation. As
you will see from the next slide. One obvious benefit for the man is
the reduction in overall treatment time!

24. Conventional or Hypo-fractionated High Dose Intensity
Modulated Radiotherapy (CHHiP) trial for Prostate Cancer
T1B - T3A N0 M0
Risk of SV involv ≤30%
PSA ≤30ng/ml
Conventional
74Gy 37F 7.5 wks
Hypofractionation
Schedule 1:
57Gy 19F 3.8 wks
Hypofractionation
Schedule 2:
60Gy 20F 4.0 wks

25. Stereotactic Ablative Radiotherapy
(SABR)
This is not a common/routine treatment as yet
Research is ongoing and long term outcome data is sparse
SABR involves the delivery of large, ablative doses per fraction, over
only a few fractions
For example: 35-36Gy in 5#
A very high degree of accuracy is required.
Robust immobilisation and daily image guidance essential.
This may involve an initial image to measure any error and make
corrections, a second image to verify this altered position and a
third image at the end of the treatment to monitor if any movement
is occurring during treatment.
Some centres may even use tracking software to monitor
movement of the target in real time, as the treatment is being
delivered. The ultimate form of image guidance would then involve
‘gating’ the treatment alongside this tracking.

26. Key principles and practice

27. Brachytherapy
The direct insertion of radioactive sources, either permanent
(low dose rate-LDR) or temporary (high dose rate-HDR), into
the prostate gland
Brachytherapy is known for it’s rapid dose fall off away from
the source and as such it is a highly conformal treatment,
minimising the dose to the surrounding normal tissue
Not currently recommended as a monotherapy for high risk,
bulkier disease. With the rapid dose fall off, the dose delivered
may not be sufficient to cover all areas of spread.
It could however be used as a boost (most likely HDR), in
combination with EBRT (this may be considered for men with
intermediate risk disease as well)

28. LDR and HDR
LDR (Low Dose Rate) involves the permanent
implantation of Iodine125 and Palladium103 seeds.
HDR (High Dose Rate) is delivered using a temporary
implant. Plastic or metal tube applicators are inserted
into the prostate and (when ready for treatment delivery)
are connected to a machine that remotely loads the
radioactive source into the prostate (via the applicators).
The source used is Iridium192, delivering the radiation in
a matter of a few seconds as it passes through the tube
within the prostate

29. LDR
Used for low and selected intermediate risk, localised prostate
cancer patients
Larger prostate volumes >50-60cc can be difficult to
treat/access due to pubic arch interference and also are at a
higher risk of acute urinary retention post implant
Men with existing urinary symptoms are also at risk of more
severe urinary morbidity.
An IPSS (International Prostate Symptom Score) of >20 is
associated with a 30-40% risk of acute urinary retention and
sustained urethritis. An IPSS of <15 is typical in terms of
eligibility for treatment
Previous TURP (trans-urethral resection of the prostate) e.g.
for benign disease, would also be a contraindication

30. HDR
Can also be used for intermediate or high risk localised
disease
For men with early T3a, the disease extension should be
minimal
As previously noted, HDR as a monotherapy may not be
recommended unless as part of a research trial
For higher risk disease it is likely to be combined with EBRT
(which also allows treatment of pelvic lymph nodes, as well as
extra prostatic extension, that brachytherapy may not
sufficiently treat)
Similar to LDR, men should have an IPSS ≤ 15 and shouldn’t
have had a TURP within 6 months
Prostate volume is less of an issue as the more flexible
catheters can more easily manoeuvre around the pubic arch
and they can be placed in the periphery of the prostate to
help treat larger glands, and also as indicated above extra-capsular
spread.

31. Precautions and preparation
Men may be asked to stop taking any blood
thinning or anti-coagulant medication such as
aspirin or warfarin.
Men may be given a bowel enema to improve the
ultrasound image and visibility of structures

32. Localisation and planning
A Trans-Rectal Ultrasound (TRUS) is taken to assess the prostate
volume, and in the case of HDR, guide the insertion of the catheters.
Other images may also be taken e.g. CT, to aid the planning.
Images are then sent to a specialist computer for planning
The program plans the number of seeds that will be needed and at
what locations (LDR), or how long the source needs to stay in each
catheter (HDR)
Clinicians generally aim to achieve a uniform distribution of dose
throughout the prostate. Some may place more seeds/dose nearer the
peripheral zone. Dose to the urethra must be limited as much as
possible
Localisation and planning may be completed at a separate visit for LDR,
or the seed/source insertion can be undertaken immediately after
planning (like with HDR). Intra-operative, real time planning, as the
seeds are inserted, is also possible.

33. LDR seed insertion
Done under TRUS guidance
Most commonly under general anaesthetic
Bowel prep may again be used
A urinary catheter may also be used to help to highlight the
position of the urethra
The position/shape of the prostate must be matched to that
achieved at the pre-implant Prostate Volume Study (PVS) if
this were conducted at a separate visit
A template attached on top of the ultrasound probe is used
to guide the needles through the perineum into the prostate.
The brachytherapy plan identifies where on the template, to
insert the needles and to what depth

34. Post-implant
A post implant CT/MRI is taken to verify the position of
the seeds (LDR) approx. 4-6 weeks after implant

35. Post-implant precautions
Because of the low dose rate from the LDR seeds, men
are not radioactive as such but should limit the time
spent sitting very close to pregnant women or young
children for the first two months
Sexual intercourse can resume approx. 1 month after
treatment. It is rare, but an individual seed could migrate
outside of the prostate and can be passed in the urine or
when they ejaculate. Men should wear a condom for the
first few weeks.
‘Stranded’ seeds reduce the chances of migration.
Research is ongoing regarding the dosimetry and
outcomes achievable with these

36. You may want to review the articles included in the journals
provided as part of the MOOC.
Many of these relate to issues/points highlighted in this
presentation and reading these may help to enhance your
knowledge of radiotherapy technique and the research being
carried out in this field.