Prostate cancer is an extremely common condition. Studies indicate that at least a quarter of men over age 55 have prostate cancer. But we know that only a small proportion of these men will actually go on to have clinical problems with the disease, and the risk of dying from it is extremely low. By treating every man who is diagnosed with prostate cancer, are we subjecting a huge number of them to unnecessary treatments? This is a serious question, because it’s also well known that standard therapies have real long-term side effects that can decrease quality of life: for example, significant urinary frequency in men who have brachytherapy; damage to the rectum from external beam radiation therapy and brachytherapy; erectile dysfunction from surgery.
The problem is that currently, we’re not able to accurately predict how any individual man’s disease will progress over time or his likelihood of dying from prostate cancer rather than from another cause. For now, we can’t distinguish with certainty those patients who need aggressive treatment from those with early-stage, low-grade cancer who might benefit from an active surveillance approach — i.e. being closely monitored and undergoing treatment only if and when signs of progression occur. This dilemma will remain until we discover an effective biomarker that can separate indolent (slow-growing) from aggressive disease, and until then both patients and doctors often feel pressured to “do something” to cure the cancer.
Focal therapy seeks to establish a middle ground between active surveillance and radical treatment by using less invasive methods that control cancer without the devastating side effects. At the University of Toronto, we’re testing a new image-guided focal laser therapy technique that we hope will change prostate cancer treatment for men the way lumpectomy changed breast cancer surgery for women.
Theory behind focal therapy
The last 10 years have brought enormous progress in prostate imaging, the most important being with magnetic resonance imaging (MRI), which allows us to see 80% to 85% of tumours in the prostate. As our ability to see tumours improved, a question arose: why couldn’t we just eliminate the cancer as opposed to removing or destroying the entire gland and damaging the surrounding tissues?
Focal therapy isn’t a novel idea; lumpectomy has been done in women with breast cancer for 50 years. In people with low-grade bladder cancers, we also just remove the cancer and leave the bladder. But the closest model to the kind of focal therapy we’re proposing for prostate cancer is in people who have cancerous polyps of the colon. Until 25 or 30 years ago, these patients would have a portion of their colon removed in a big operation from which it would take months to fully recover. Now, polyps are removed in a relatively short outpatient procedure called a colonoscopy. If polyps recur, the operation can be repeated without any serious consequences.
The biggest obstacle to trying this approach in prostate cancer has been the thinking that it’s a multifocal disease, found in more than one area in the gland. But it’s also true that, in at least 20% of people, the cancer is restricted to one site. If the cancer starts off in only one site, it’s possible that it doesn’t appear all at once, but develops in a sequential manner over time.
The most interesting concept of how prostate cancer develops is that of the “dominant focus.” Dr. Peter Scardino, of the Memorial Sloan Kettering Cancer Center in New York, looked at tissue from almost 1000 men who had radical prostatectomies. He confirmed that prostate cancer was indeed multifocal, but that there was almost always something called a dominant focus, which was larger than the other areas and from where close to 90% of local cancer spread came. Even more exciting, a recent paper in Nature Medicine suggested that metastatic disease also comes from this dominant focus! While more research is needed in this area, we think it’s plausible that by destroying the dominant focus, we might not only decrease local extension, but also — and even more critical — prevent the cancer from spreading to other parts of the body.
MRI-guided focal laser therapy explained
With these optimistic visions in mind, we created a system based on MRI and laser ablation that is designed to eliminate only the tumour within the prostate. By leaving the uninvolved tissue intact, our aim is to minimize the risk of incontinence and erectile dysfunction and achieve the best possible balance between cancer control and maintenance of quality of life.
For now, this technique is only being done as part of clinical trials. To be eligible to join the trial, participants must fulfill the following criteria:
- Their tumour must be small in volume.
- They must fall into a low-risk or low-intermediate risk group (Gleason grade 3+3 or 3+4).
- Their cancer must be limited to only one site in the prostate, based on the biopsy and confirmed by MRI.
Selected patients are put into the MRI scanner and sedated, and we’re able to see exactly where the tumour is. We use software that tells us exactly where to insert the needle into the tumour. On the tip of the needle is a laser that generates heat. MRI is very temperature-sensitive, and we can watch in real time as the laser essentially burns the tumour without affecting anything around it. So we can destroy large volumes of the prostate without causing any side effects. Patients can go home the same day.
We’ve done this procedure both manually and using a special robot that we developed here. The robot arm with needle and laser attached can bend and angulate in multiple directions — up, down, right, left, tilt and rotate — to align itself precisely with the tumour.
We’ve been following people for up to four years now and we’re impressed with the early results. The vast majority (75%) of men have no tumour left in the area that we’ve burnt and — probably due to appropriate selection — we also find very little tumour on the other side. And the men have virtually no side effects. So far, only two patients have elected to have conventional treatment after focal laser therapy because of residual cancer or grade progression.
Our experimental study has included a total of 40 patients to date. To my knowledge, we’re the only ones doing MRI-guided focal laser therapy in Canada, but it’s being done elsewhere in the world. This approach is gaining traction because more people are questioning whether, given the serious quality-of-life consequences, radical treatment is the right choice for many very low-risk men.
Risks and follow-up
The risk of progression associated with focal therapy is certainly less than it is with active surveillance, because you’re at least knocking out one of the areas of cancer — the dominant lesion, which we believe causes most of the problems. Our idea is to get rid of the cancer and monitor men without cancer, as opposed to following them with cancer.
Most people have a biopsy four months after the laser treatment. If they have any tumour left, they have to consider what kind of standard therapy they want. If there’s no tumour anywhere in the prostate, they’re followed as for active surveillance. I tend to see patients every six months for a prostate-specific antigen (PSA) test and clinical exam, and we do a biopsy annually for a few years to make sure we haven’t missed any residual cancer. The fact that the men have had prostate cancer once may put them in a higher risk group, but there’s lots of evidence to suggest that their overall risk of recurrence is remarkably low.
Research directions
Research is looking at ways to improve the imaging of prostate tumours with MRI, as well as techniques for removing them. There’s a group that has developed an endorectal MRI-guided high-intensity focused ultrasound (HIFU) device to do the same thing as we’re doing with the laser: i.e. find and ablate only the tumour using a noninvasive energy source. Others are trying the same thing with cryotherapy (application of freezing temperatures to destroy diseased tissue), using ultrasound. The problem is that it’s very hard to see where the actual tumour is with ultrasound; you can only see where the prostate is. We’ve also done studies treating people with laser initially, then removing their whole prostate. We found that in the area treated with laser, there were no viable cancer cells. It gives us a lot of solace that in fact, if we get to the right place, we really can kill all the cancer.
With advances in breast cancer treatment, women went from having a whole mastectomy, which caused innumerable side effects and truly decreased their functioning, to something much more tolerable. Focal therapy might work even better in men, because if you select patients well, the risk of their disease ever progressing is very low. If you can get rid of the cancer, they’ll be even better off.
Talking as a surgeon, I’d say that no matter what the treatment, we don’t evaluate the quality-of-life outcomes enough, other than in clinical trials. We’re very good at following cancer control, but not so good at looking at the side effects men suffer on a day-to-day basis from prostate cancer treatment. And this is what we’re trying to change.
Dr. John Trachtenberg is Director of the Prostate Centre, University Health Network — Princess Margaret Hospital, and Professor in the Departments of Surgery and Medical Imaging at the University of Toronto.
