Prostate cancer arises in a small, relatively inaccessible organ located deep in the pelvis, surrounded by sensitive structures like the bladder, rectum and nerves that control erectile function. Any treatment that could locate and eradicate the cancer and still protect surrounding tissue from injury would be of incredible value to tens of thousands of men diagnosed with prostate cancer each year. While we’re not completely there yet, we’re closer than we’ve ever been to reaching that point.
Prostate cancer has been a particular beneficiary of recent progress in diagnostic, imaging and radiotherapy technologies. This article describes some of the most important advances in external beam radiotherapy for localized disease.
Radiation dose: “more is better”
The most important goal of cancer therapy is to eradicate the tumour. While eliminating side effects is also important, many cancer sufferers willingly accept some level of temporary or permanent discomfort in exchange for a high chance of cure. Large North American and European clinical trials have recently confirmed that giving higher radiation doses improves prostate cancer control. However, these studies did not reveal the ideal dose.
Unfortunately, the higher the dose, the worse the potential side effects. Most Canadian centres now use external beam radiotherapy doses of 74 to 78 Gy to treat localized prostate cancer, as a reasonable balance between safety and efficacy. Brachytherapy (implanted radiotherapy) can safely attain higher doses, but medical factors or the extent of the tumour limit the number of men who are eligible for this treatment.
Much research has also been devoted to reducing the risks of treatment. This generally means limiting the radiation to just where it is needed, and making sure that it actually gets there.
Finding and hitting the mark
In radiotherapy, precision refers to the ability to identify the correct target within a small margin of error; accuracy is the capacity to hit (or avoid) that mark, also with a small error margin. By improving both precision and accuracy, new technology is leading to better cancer control and fewer, less severe side effects.
The important target that prostate radiotherapy must strike is the cancer within the prostate gland; targets to avoid include the bladder, rectum and nerves that control erections. Computed tomography (CT) scanning is an imaging technique that is very successful at locating the bladder and rectum, but rather poor at situating the nerves. Also, in most men, it cannot pinpoint the cancer within the prostate at all. The entire gland must be targeted and treated with the same dose — this may not be the most effective way of planning treatments.
Modern MRI (magnetic resonance imaging) is better than CT scanning at identifying the erectile nerves and can now reliably reveal small tumours within the prostate. Early evidence shows that these tumours are located where the cancer is most likely to recur. If this is confirmed, more radiation to these areas rather than to the whole prostate may improve cancer control without increasing side effects. It may also become possible to reduce the radiation dose to one or both erectile nerves. MRI is still being tested for prostate cancer diagnosis and radiation treatment planning and is not standard of care, but we will likely see more of it in the future.
Better delivery techniques
The use of powerful, high-speed computers for radiation planning and delivery has allowed radiation treatment plans to become very complex and very effective at concentrating the dose on the target of interest, while avoiding the bladder, rectum and nerves. The following are some of the new technologies that have evolved.
IMRT (intensity-modulated radiation therapy) is a way of breaking radiation beams into hundreds of tiny beamlets under individual control. Just like photographic clarity improves with more pixels, radiation treatment plans improve conformality (tailoring to a specified size and shape) with more beamlets. IMRT is well established; it was recently enhanced with a technique called VMAT (volume-modulated arc therapy), which increases the number of beamlets by continuously rotating the treatment unit while modulating the radiation beam. VMAT provides better conformality than standard IMRT, and less time is spent on the treatment couch.
Tomotherapy is highly specialized radiotherapy that borrows from some other techniques. As in CT scans, the radiation rotates continually around the patient while the couch moves through the radiation beam. Like IMRT, tomotherapy breaks the radiation into beamlets, and it produces highly conformal treatments similar to those produced by VMAT.
Cyberknife represents a blend of robotics and radiotherapy. A compact radiation treatment unit mounted onto a robotic arm can be programmed to move very precisely in any direction. The disadvantage is that many separate movements are required to produce the 200 or so beamlets necessary, and treatments can become very long. Cyberknife was developed to treat irregularly shaped tumours deep in the brain and has only recently been adapted for prostate cancer. The prostate has a regular shape, and we’re not sure whether Cyberknife offers an advantage over VMAT or tomotherapy. One possibility might be to use Cyberknife to deliver extra radiation to parts of the prostate, but studies are needed to determine if this is useful and if it can be done better with Cyberknife than with existing technology.
Proton therapy has been in use since the 1980s and is the oldest form of conformal radiotherapy. It gained prominence for prostate cancer treatment because it was used in one of the trials of radiation dose escalation. (The importance of this study was actually to show that a higher radiation dose was effective, not that proton therapy was effective.) Proton therapy is a good way — and was once the only way — to deliver a higher dose of radiotherapy safely to the prostate. Newer radiation treatments have caught up to protons, and at much lower costs. Unless proton therapy becomes more economical, it’s unlikely to compete with technology already available in Canada.
Advances in image guidance
A highly conformal treatment plan is only as good as the ability to deliver the radiation to the correct location. Prostate cancer radiotherapy is complicated by the fact that the prostate is located deep in the pelvis and moves with the filling and emptying of the bladder and rectum. Accuracy requires tracking the position of the prostate before each treatment, which is done through a process called image guidance.
Image guidance has been done for many years with ultrasound scanning or with x-rays of gold marker seeds implanted in the prostate. Seed markers remain the most accurate way to track the prostate, but an exciting new development is the ability to scan the pelvis just before each daily treatment with cone-beam CT or tomotherapy CT (combining CT imaging and radiation). Accuracy is only slightly lower than with implanted markers, but there is a great advantage to seeing the prostate, bladder and rectum at the same time. Also, no invasive procedure is required.
Stay tuned for more developments
Image-guided, high-precision, dose-escalated radiotherapy is the gold standard of external beam treatment for localized prostate cancer, whatever equipment is used for the purpose. Side effects have been reduced, and cancer control improved.
The next step will test the best way to use the precision and accuracy of new technology to give even higher radiation doses to all or part of the prostate, or to reduce the number of weeks it takes to give the treatment. As technology improves, so will radiation therapy.
Dr. Charles Catton is a Radiation Oncologist at Princess Margaret Hospital in Toronto, Ontario, and Associate Professor in the Department of Radiation Oncology at the University of Toronto.