The treatment of prostate cancer by external beam radiotherapy
- could it be better?
Professor Les Bradbury

2. The basics of external beam radiotherapy
and the 'standard' prostate cancer treatment.

They sought it with thimbles, they sought it with care; They pursued it with forks and hope;
They threatened its life with a railway share; They charmed it with smiles and soap.
(The Hunting of the Snark - Lewis Carroll)

SUMMARY.
This web page describes the general principles of external beam radiotherapy and, in particular, the forms of EBRT most commonly in use - namely three-dimensional conformal radiotherapy and, increasingly, intensity modulated radiotherapy (IMRT). Conventional EBRT uses high energy photons as the form of radiation. There are other forms of radiation therapy using protons and neutrons but these are not routinely available in the UK and so 'conventional' EBRT will remain an important mainstay therapy for some time to come.

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SUITABILITY FOR EXTERNAL BEAM RADIOTHERAPY.
The essential requirement to be a suitable candidate for radiotherapy of the prostate is that the disease has not spread from the prostate or the area immediately around it to sites remote from the prostate - i.e. the disease has not metastasized.This is established from a bone and CT scan carried out soon after a biopsy confirming the presence of prostate cancer.

The earlier prostate cancer is diagnosed, the better the chances of successfully treating the disease. From the diagnostic parameters, a level of risk can be defined. A patient at 'low' risk would have the following parameters; PSA less than 10, Gleason score less than 7 and a T-staging less than T2a. If any one of these was exceeded, the patient would be described as being at an 'intermediate' stage of risk and, if two parameters were exceeded, the risk would be assessed as 'high'. Using the Partin tables for a 'low' risk patient, there would only be a small probability (less than 5%) of the cancer having spread outside of the prostate to the seminal vesicles or the lymph nodes. This is referred to as 'locally confined' prostate cancer although this is a sort of statistical definition. For an 'intermediate' risk patient, the probability of seminal vesicle or lymph node involvement is higher at around the 15% to 20% level and for a 'high' risk patient, say, with a PSA of 20, Gleason 4+3 and a t-staging of T2b, the probability rises to around the 40% level. The disease is then referred to as 'locally advanced'. For low risk patients, external beam radiotherapy would be one of several treatment options that were available - others being surgery, brachytherapy on its own, cryosurgery and, more recently, high intensity focused ultrasound (HIFU). However, for patients at an 'intermediate' or 'high' level of risk, the options are fewer and EBRT along with brachytherapy (either low dose rate permanent seeds or high dose rate temporary seeds) combined with EBRT become almost the only options because, with EBRT, it is possible to extend the field of radiation to treat the region beyond the prostate in ways that are not possible with some of the other therapies. Of course, as will be shown in web page 4 on dose escalation, the probability of remaining disease free is diminished as the level of risk rises.

UNITS OF RADIATION AND THE 'STANDARD' RADIATION DOSE.
The unit in which radiation dose is most commonly measured is the Gray (abbreviated to Gy) after the British radiation physicist Louis Harold Gray. Its precise definition is not particularly important for present purposes but, for completeness, one Gray is the absorption of one joule of radiation energy by one kilogram of matter. In the case of prostate cancer, the most common dose given in external beam radiotherapy is 70 Gy delivered in short duration doses of 2 Gy per day. These short doses are given over a period of tens of seconds only and are called acute fractions. Treatment lasts 35 days but because no treatment is given at the weekends, the overall period of treatment is 7 weeks. Prostate cancer is generally a slowly developing cancer where the number of cancer cells doubles only over a period of months possibly even years. As a result, missing treatment at the weekends is not of any great importance. For other cancers where the doubling time can be measured in days, this is more problematic.

The choice of 70 Gy given in 2 Gy fractions seems to have emerged over time as a reasonable compromise between achieving good tumour control (i.e. destroying the cancerous tissue) and avoiding serious short or long term side effects. However, the technology of the era from which it emerged has been superseded by better technologies and this 'standard' treatment now needs to be carefully re-evaluated. One of the aims of this website is to draw patients attention to these changes so that they can discuss their treatment with their consultant more knowledgeably.

THE BASIC PROBLEM.
The sketch below shows a simplified but roughly to scale diagram of the prostate in relation to the bladder and the rectum. One sketch shows a side view and the other is a transverse slice through the body. The basic problem in external beam radiotherapy is to be able to subject the prostate to beams of radiation consisting of streams of high energy particles (photons) so that the prostate receives a sufficiently high dose of radiation to destroy the cancerous tissue without serious damage being inflicted on the surrounding organs - the rectum being the most sensitive to damage. It is clear that this cannot be achieved with a single beam because the organs in front of and behind the prostate would receive more or less the same level of radiation as the prostate.
3-D CONFORMAL RADIOTHERAPY.
To avoid this problem, beams are directed at the prostate from several angles and the second sketch shows a simple 3-beam arrangement with a frontal beam and two lateral beams. Where the beams intersect is the region of highest radiation intensity and this is centred on the prostate. To improve the concentration of radiation further, the beam cross-sectional shapes are conformed to the outline of the prostate (with some margin around it typically of about 10mm) by passing the beam through a multileaf collimator. Below is shown a sketch of such a device which consists of 20 to 40 pairs of Tungsten leaves that can be individually positioned to the outline shape of the prostate seen from the direction of the beam. Information about the three-dimensional shape of the prostate is obtained from a CT scan taken just prior to the radiation treatment. The photograph below shows a linear accelerator (linac) used to deliver a beam of radiation. The patient lies on the couch and the beam of radiation is directed at the prostate gland from the head of the linac which also contains the multileaf collimator. The whole head unit can be rotated so that beams can be directed at the prostate from different angles. The process of optimising and calculating the radiation that is delivered by the linac is a complex one and is carried out by specialised computer software. In the example above, only three beam angles were used but four and five beam angles are also common. The final output from the whole process is a so-called planning chart which shows the contours of equal strength radiation that occur in and around the prostate and the aim is to maximise the radiation level directed at the prostate gland whilst minimising the radiation to which the surrounding organs are subjected. In optimising the radiation pattern, the beams may have different intensities. The figure below is an example of a planning chart showing the target area for the highest levels of radiation and the contours of radiation at lower levels. The position of the rectum is also shown. Even with 3-D conformal radiotherapy, it is impossible to avoid some part of the rectum being subjected to high levels of radiation and this is the source of rectal bleeding that sometimes occurs after treatment. However, at radiation levels between 70 and 80 Gy, it is quite rare and only affects about one or two percent of patients. By the same token, serious urinary problems are equally rare although around 40% of men will experience temporary urinary urgency or stinging either during or soon after treatment.



INTENSITY MODULATED RADIOTHERAPY (IMRT)
One of the weaknesses of 3-D conformal radiotherapy is that it is not possible to have three dimensional indentations in the surfaces of equal radiation dose. This is because the intensity of the radiation across the beam is constant. A refinement in technique that allows these three dimensional concave surfaces to be developed is intensity modulated radiotherapy - IMRT. In IMRT, there is an additional freedom to control the intensity distribution across the beam. This is achieved by dynamically adjusting the collimator during the exposure time and this is equivalent to producing a variable intensity beam. The addition of this extra freedom allows the radiation contours to be fitted more closely around the prostate and, in particular, to curve them inwards around the rectum thus reducing the extraneous radiation to which the rectum would otherwise be subjected. As a result, for a given radiation dose, the damage to adjacent organs will be lower or, more importantly, higher radiation doses can be delivered to the prostate without adversely affecting the damage to the rectum and bladder.

The sketch below is an illustration of the sort of intensity profiles that would produce a closer fitting of the radiation contours to the prostate. Intuitively, it is clear that beams of constant intensity could not achieve the same sort of 'fit' as beams of variable intensity.


Although IMRT can be thought of as an incremental improvement on 3-D conformal radiotherapy, it involves substantially more computing to produce the optimum beam angles and intensity profiles. As a result, the number of beam angles tends to be greater than is the case with 3-D conformal radiotherapy and as many as 7 beam angles are used with IMRT. The linear accelerator also has to be capable of dynamically controlling the positions of the Tungsten leaves in the collimator. Nevertheless, an increasing number of NHS Trusts are being equipped with both the hardware and the software for undertaking intensity modulated radiotherapy.

MONITORING THE MOVEMENT OF THE PROSTATE.
There have been a number of studies of the movement of the prostate over the period of radiotherapy treatment. Generally, this movement is just a few millimetres but occasionally it can be larger than this with movements of around 10mm or more being reported. Generally, a margin in the targeted field of 10mm around the prostate is sufficient to ensure that the prostate remains within the high intensity radiation pattern. However, with the increasing accuracy of dose delivery that can be achieved with techniques like IMRT, it begins to be important to monitor the movement of the prostate during the treatment period. There are a variety of techniques for doing this and some are already commercially available like the ultrasonic technique referred to as the BAT system. With this system, ultrasonic images of the prostate are obtained prior to each treatment session and movements of the prostate are compensated for on every daily radiation treatment.

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