Prostate cancer is the second most common cancers among men after skin cancer. In the UK alone about 10,000 people die from prostate cancer every year and 25,000 new cases are discovered (Mason & Moffat 2003). The prostate is a gland below the bladder and found only in men. It is responsible for providing the seminal fluid (Mason & Moffat 2003). The causes of prostate cancer is not fully known
Radiotherapy or radiation treatment is defined as the treatment of cancer (mostly malignant) with ionizing radiation. The radiation treatment works by destroying the DNA of the tumour. Sometimes, the radiotherapy treats the cancer by making it difficult for the cancerous cells to reproduce and spread further. However, in destroying the cancerous cells, some normal body cells are usually affected too. Despite this, the overall benefits of radiation treatment override its downside effects. It is a relatively safe treatment for most patients regardless of age. Radiotherapy is the second major treatment for prostate cancer (Picard et al 2009).
Principles of Radiotherapy:
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There are some basic principles to radiotherapy and they include:
Larger cancers require larger doses of radiation.
Higher doses increase the ability to control the cancer.
Higher doses can increase the damage to the normal cells surrounding the tumour.
This refers to a radiation dose given over a number of times instead of at the same time. Treatment spans days or weeks.
There benefits of fractionated radiotherapy include:
Spacing out the treatment allows the cells to repair some of the sub-lethal damage before the next treatment.
Cells undergo a cycle at different times and depending on the phase they are in, they can be more resistant to the radiation treatment. If the radiation treatment is given over a period of time, then there is a good chance that the dangerous cells that were in the resistance phase might be out of it and become sensitive to the treatment.
Some cancerous cells might be acutely or chronically hypoxic i.e. temporarily or chronically deprived of oxygen supply. Hypoxic cells are resistant to radiotherapy and spreading the treatment over a period of time gives the chance for them to come out of the hypoxic stage and become more sensitive to treatment.
Types of Radiotherapy for Prostate Cancer
The discovery of prostate-specific antigen (PSA) has made it easier to diagnose prostate cancer at stages where it can be more easily treated. It is therefore easier to localise the radiation therapy to reduce the side effects while effectively treating the cancer.
The advent of better radiation techniques has made it possible to increase radiation dose which increase survival rate without increasing the side effects of the treatment. Hanks et al 2008 (cited in Ash 2005) demonstrated that 5 year local recurrence rate could be reduced from 37% for patients who received less than 60 Gy to 19% in those who received more than 70 Gy (figure 1). Radiation techniques include:
Three-dimensional conformal radiation (3D- CRT): this makes it easier to identify the exact location of the tumour and the location of the normal cells surrounding it. This information is passes on to the linear accelerators which configures the radiation to the exact location of the tumour.
Intensity-modulated radiation (IMRT): this is a more sophisticated version of the previous technique that allows even better conformality.
External Beam Therapy (EBT): this delivers radiation from outside the body towards the tumour usually through the use of a linear accelerator.
Brachytherapy: this involves placing the radioactive sources directly inside the tumour.
Damage to normal cell tissue during fractionated radiotherapy
During radiation treatment, normal cells are also damaged. Radiation affects the atoms that make up the cells. It affects them directly and indirectly. Directly when it alters or destroys the DNA molecule thereby resulting in the inability of the cell to reproduce accurately (mutate) or not at all and dies. Indirectly, when the DNA of the cell is not affected but the radiation interacts with water in the cell thereby breaking the H2O into hydrogen and hydroxyls. These elements can combine with other toxins to form compounds such as hydrogen peroxide (H2O2), which ultimately destroys the cell.
2.0 Effects of Radiotherapy
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There are two types of effects of Radiotherapy; the early effects and the late effects.
In the treatment of prostate cancer, early effects have appeared to be moderate. Studies carried out by Soete et al (2006) showed that the patients only showed mild gastro-intestinal, genitor-urinary toxicity and these were all resolved two months after treatment. Nuyttens et al (2002) also carried a research to test for the early effects of radiotherapy on prostate cancer and reported that even though the doses given to the patients totalled 80 Gy, no severe effects were found; only mild early effects and the patients did not need to be hospitalised.
Late side effects/chronic:
Other side effects of treating prostate cancer are not seen immediately and may only appear months or years after treatment. The adverse late effects have been seen as expressions of a continuous sequence of events that have been initiated since the injury during treatment and continue until much later (Halperin et al 2007).
It appears that most of the late effects of radiotherapy for treating prostate cancer are on the rectum and bladder; the organs closest to the prostate. Goldner et al (2006) studied 298 prostate cancer patients who were treated using 3D-CRT between the years 1999 to 2002. They were divided into three risk groups; low, intermediate and high risk groups. The first two groups were treated with a total dose of 70Â Gy; the third group was treated using a total dose of 74Â Gy.
The Late effects assessed were as follows:
Increased number of vessels
Patients with pathological findings
The research concluded that it was not just the dose - volume effect that caused rectal problems in the patients. Other factors such as age and history of diabetes also influenced the late effects of radiation treatment and have to be considered before treatment.
Lievens et al (1996) carried out a retrospective research on past prostate cancer patients who had been treated with radiotherapy on a linear accelerator or a cobalt unit between 1980 and 1981. All the patients had received multiple fractions per day totally up to a dose of 60 Gy. It was discovered that there was a high frequency of late side effects. After a few months, the patients started to develop urological complications at a rate of 10%. The effects continued to appear after five years. The incidence of gastrointestinal problems was 14% and all happened within the first 3 years. They concluded that the incidence of late side effects was high because there was not enough time for cell repair between treatments.
Borghede et al (1997) followed up on 184 prostate cancer patients over a period of 24 to 96 months in order to assess the late side effects of radiotherapy. The patients had been treated using the radical external beam therapy with a total dose of 70 Gy. They discovered that 37% of the patients did not have any late side effects, 53% of them had mild complications (42% of which were gastrointestinal and 23% were urogenital). Only about 9% of the patients had moderate or severe complications.
It appears that even though the dose and the technique of radiation treatment can cause late side effects, these effects are not totally responsible for these effects. Pre-disposing factors such as age, pre-existing symptoms also contribute greatly to the incidence of late effects.
3.0 Advances made to reduce and prevent the late effects of Radiotherapy
A lot of technological improvement has occurred in the past few years to increase the efficacy of radiotherapy and reduce its effects (Bottke & Wiegel 2010). There are more realistic models used for predicting the required dose to increase tumour control while reducing normal tissue damage as can be seen from the "cube root law" to cumulative radiation effect (CRE) (Fowler 1984). In particular, emphasis has been made to be able to increase doses while keeping side effects the same or even reduced. The challenge is to be able to balance the dose and the side effects on normal cell tissues.
Improvement in image guided radiotherapy helps to increase safety of other organs by increasing precision thereby reducing late effects (Bottke & Wiegel 2010, Mangar 2005). It helps to corrects and track the movement of the prostate in real-time and provide smaller tumour margins. CT Scanning has been used for this purpose; however, MRI scanning is also currently being used and is proving to be an even more sensitive tool.
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There have also been more advances in the precision of external beam radiotherapy (EBRT) allowing for higher concentration of radiation on the tumour (Manger et al 2005).
Bekelman (2010) also discovered during their research that protest cancer patients that were treated with IMRT had fewer gastrointestinal problems compared to patients treated with 3D-CRT. This confirms that the IMRT is even more sophisticated than the 3D-CRT.
Using hormone therapy first for prostate cancer treatment might also reduce the side effects of radiotherapy. 80 - 90% of prostate cancer patients can be treated using hormonal therapy (Ash 2005). Therefore, using hormone therapy before radiotherapy might reduce the amount of radiotherapy needed for treatment. Bolla et al 2002 (cited in Ash 2005) discovered that there was increase in overall survival from 67% to 78% in cases where hormone therapy was combined with radiotherapy.
Surgically removing hypoxic cells that are more resistant to radiotherapy decreases the radiation dose required and increases the probability of the local control.
Recent research has also shown that melanin can be used to protect normal tissues from excessive radiation; an extension of the skin's use of melanin to protect itself from harmful sun radiation. At the moment, experimentation is still going on but it is expected that human beings might be able to benefit from this research within the next few years (Schweitzer et al 2010).
The importance of using radiotherapy for prostate cancer treatment cannot be under-estimated. It is the second major type of treatment. However, there are side effects to its use. Some of these effects occur early and some occur later. The late effects are usually more severe.
Advances in techniques and technology have made it possible to have less side effects and increase survival rates. The use of 3D- CRT, IMRT, improved External Beam therapy and Brachytherapy have resulted in fewer incidences of late effects. There are ongoing studies and research to further improve these techniques.
Using a combined and integrated approach to treat prostate cancer can result in the fewer incidences of late effects. The use of both hormone therapy and radiotherapy have proved to be very effective to cure and resulting in fewer side effects (Picard et al 2009). Also, the use of surgery with radiotherapy also reduces the amount of radiation the patient needs to have, thereby reducing the risks of late effects.
Other things that might also reduce the incidence of late effects, is checking the pre-disposition of the patients before radiotherapy, such as their ages, any organ problems and infection. In addition, the use of radiation protectant like amifostine and melanin might also reduce the occurrence of radiotherapy's late effects.