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Conversations With Prostate Cancer Experts


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Advanced Imaging + Prostate Cancer

Dr. Phillip Koo is Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center.

Prostatepedia spoke with him about advanced imaging + recurrent prostate cancer.

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Do you have any advice for men considering advanced imaging for prostate cancer?

Dr. Koo: We’ve been talking about better imaging tools for prostate cancer for years. When it comes to other cancers, we moved forward a great deal when FDG PET/CT became available. With prostate cancer, we’ve been stuck with CT and bone scans since the 1970s. They’re great tools. I don’t want to devalue what they’ve done for our patients since then, but we knew we could do better. Urologists and oncologists knew patients had metastatic disease, but our imaging tools limited detection.

We have new tools available to us in 2018. There is no question that costs are going to be higher, but that shouldn’t stop us from exploring and pushing the envelope. The whole purpose is to improve overall survival and treatment for our patients. An ounce of diagnosis could be a pound of cure. If we could identify disease sooner, identify the right patient for these exams, and use them at the right time, then we could probably create treatment plans more appropriate for patients with better outcomes. It’s something that I firmly believe. There is so much potential here.

When radiology is practiced in a vacuum, it’s not as powerful as when it’s integrated into patient histories and treatment plans. Radiology is a very powerful tool. But we often think of it as a commodity, something that does not have any distinguishing value. That is a huge under-estimation of radiology.

When performed correctly in a multidisciplinary setting, with access to the medical record and physicians who are taking care of the patient, radiology unlocks information that can really impact care for patients with prostate cancer. And we are currently only scratching the surface. This will change as analytic tools continue to analyze bigger data sets that include imaging and clinical data. If a urologist determines that their patient needs imaging, they’re going to write a request for imaging that describes what type of test they want and why they need it.

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Patients often go to the closest facility. Convenience is important, but when it comes to certain tests or exams, I urge patients to seek out subspecialized radiology experts and facilities with the experience and expertise in the performance and


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Robotic Prostate Cancer Surgery After Focal Therapy

Dr. Paul Cathcart is a consultant urological surgeon at Guy’s Hospital and St. Thomas’ Hospital in London.

Prostatepedia spoke with him about a clinical trial he’s running that looks at robotic surgery in men whose prostate cancers have come back after focal therapy.

Why did you become a doctor?

Dr. Paul Cathcart: I always liked science; that was my favorite subject. I was thinking about whether to become a vet or a doctor and did lots of school visits. During one of those visits, I met an inspirational character, a surgeon. I spent some time with him, following him around hospital wards and clinics. I thought that he was the sort of person I would like to be: he does the job I’d like to do. I think that’s often the case in life: you meet some inspirational figure who pushes you along one line.

Later on, another inspirational figure who came into my life was a urologist. I was originally going to be a colorectal surgeon. Everything was set for that. Then I met this urologist who showed me the different mix there is in urology, which I found interesting. Then I met Dr. Mark Emberton; I was his research fellow for many years. He’s quite an inspirational person as well. I’ve been working with him for 17 years now on various things.

What is the thinking behind your trial on robotic surgery after focal ablation?

Dr. Cathcart: Focal therapy is a new concept, which Dr. Emberton and one or two other people have pioneered to reduce the side effects and morbidity of prostate cancer treatment. Unfortunately, a proportion of these patients will experience recurrent disease after focal therapy. No cancer treatment is 100% effective. A couple of these focal therapy patients were recurring three or four years after starting the focal therapy program.

No urologist wanted to operate on these patients because they felt that it would be an extremely difficult surgery. In fact, urologists were only offering exenterations to remove the patients’ prostate, bladder, etc.

I got to know quite a few of these patients. (I do a lot of post-radiotherapy surgery, as well.) I decided that this procedure called salvage surgery interested me. We thought that we could do this salvage surgery and maintain good outcomes for our patients because only part of their prostate had been treated during focal therapy. We thought that the side effects of the surgery after focal therapy would actually be a lot less than after radiation, but we needed evidence to prove it. That is why we set up the trial.

We’re also interested in learning why some patients may fail focal therapy. What is it about their disease that leads it to recur? If we can understand why some patients may fail focal therapy, this can help us select up front which patients should have focal therapy and which should not.

What can patients expect to happen during the trial?

Dr. Cathcart: We are halfway through the study at the moment.

Of course, patients undergo a salvage prostatectomy. We take the tissue to be analyzed and look for various genetic markers to see why their cancer may have returned.

This is also a toxicity and side effect study. We have patient-reported outcome measures at baseline and sequentially thereafter. There are a number of blood tests looking at hormone profiles before and after the surgery.

We follow patients for about 12 months after those sequential patient-reported outcome measures; we’re looking to chart that toxicity.

I’ve taken out more prostates after focal therapy than most because of my link with Dr. Emberton. We’re now demonstrating the feasibility and toxicity of salvage focal surgery and trying to understand why these tumors have recurred.

Are you still recruiting patients?

Dr. Cathcart: About 20 patients have undergone the surgery. We’re recruiting 20 more. We haven’t had any adverse events. We were worried about things like rectal injuries, because the rectum can stick to the prostate after focal therapy. We haven’t had any of those.

We’ve actually had a fantastic continence outcome. The prostate cancer community said everyone would be incontinent and impotent, but all our patients so far have been continent.

We’ve got the patient-reported outcome measures to demonstrate it.

The potency rates are taking a little bit longer to return to baseline. The outcomes from potency won’t be as good as the continence outcomes. We haven’t had any side effects at the time of surgery. No complications or anything, so we’re delighted with the way things have gone.

Does the fact that the man has had focal therapy make the potency issues worse?

Dr. Cathcart: It depends on the location of their focal treatment. In those with anterior tumors (tumors away from the neurovascular bundles), we’ve noticed potency returns faster. If they’ve had an ablation on the peripheral zone, near where one of the nerve bundles is located, potency returns more slowly.

We’re also noticing a difference between different treatments. You can give focal therapy with high-intensity focused ultrasound (HIFU), cryotherapy, or something called electroporation. The different energy sources have different effects on the structures surrounding the prostate and a different impact on the chance of potency returning. Electroporation seems to be very precise and leaves the least amount of collateral damage. In those patients, potency returns faster. Cryotherapy creates more periprostatic fibrosis and scarring; potency takes slightly longer for those patients to return. Potency return for HIFU patients falls somewhere in the middle of the modalities.

I’ve also taken out prostates after photodynamic therapy. Photodynamic therapy is better relative to preserving the tissue planes, but it does depend on which part of the prostate has been ablated in the first place.

Is there anything else you think patients should know about your trial?

Dr. Cathcart: We’re going to get a great understanding of why these patients in particular failed focal therapy. The genetic markers and the locations of the tumors will inform which patients are suitable for focal therapy from the beginning. There may be parts of the prostate, or particular types of tumors or genetic markers, which will identify patients best suited to a whole-gland approach such as a radical prostatectomy up front.

It’s not just about the location and grade of the tumor, but also about the tumor’s genetic signature, which may predispose a particular tumor to being better suited for focal therapy.

It’s interesting, in some patients you knock out one tumor say on the right-hand side and that’s it, the tumor never comes back. Other patients’ prostates seem somewhat unstable and have multiple tumors that keep appearing throughout the prostate. I’m sure there is a genetic basis to it.

Because we’re taking out these patients’ prostates, we can analyze all the different tumors. Some people even think that by treating part of the prostate we may be changing the genetics of that tumor—i.e., it gets angrier. I don’t think that’s the case. This study will help prove that point. We’re also going to open up a comparative arm of the study very soon for patients who have had whole-gland radiation or ablation techniques—open to anyone who has had the whole of their prostate treated with brachytherapy, radiotherapy, HIFU, or cryotherapy. We’ve been finding that patients who have had surgery following focal therapy have better outcomes than those who have had whole-gland therapy up front. We’re going to recruit into that second arm to demonstrate that surgery after focal therapy has a better outcome.

Can non-UK residents come to you for surgery?

I’ve got a clinic called the Recurrent Prostate Cancer Clinic. I have a reasonable number of patients who come from the United States. They normally come to Dr. Emberton for focal therapy, then if they develop recurrent disease, I operate on them. A lot of urologists wouldn’t operate on these patients. Certainly, in the United States, hardly anyone operates on post HIFU patients simply because HIFU has not been available until very recently.

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Focal Therapy + Prostate Cancer

Dr. Charles “Snuffy” Myers offers his comments on our November issue on focal therapy for prostate cancer:

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Last month we reviewed the impact of new tools like imaging on treatment choices for newly diagnosed men. We discussed how improved imaging impacts planning of both radiation therapy and surgery, as well as the role imaging plays in active surveillance in terms of patient selection and monitoring. .

This issue is a logical extension of those conversations as we look at focal therapy treatment options based on those imaging tools. The renaissance of focal therapy is due to MRI, which has the ability to visualize cancer within the prostate gland with much greater precision than older techniques.

Focal treatment makes sense when the cancer is of limited extent, usually limited to a single major lesion on one side of the prostate. If the cancer is truly limited to only part of the gland, it may not be necessary to destroy the whole prostate. The hope is that focal therapy will have less impact on sexual function and urination than radical prostatectomy or radiation therapy to the whole gland. A frequently used analogy is a lumpectomy versus mastectomy for breast cancer.

As you read the interviews, there are a number of issues to keep in mind. With radical prostatectomy and radiation therapy, we know in detail the odds of long-term cancer control. This information is lacking for the various forms of focal therapy. One reason that cancer control might be less complete after focal therapy is that focal therapies largely depend on the ability of the MRI to identify patients with cancer limited to one area of the prostate gland. But, as we learned last month, the MRI is not a perfect tool and can miss small, aggressive cancers. Also, first-rate MRI facilities with well-trained radiologists are limited in number.

As a medical oncologist, I have recently had to deal with a particularly difficult situation. With the arrival of new, highly sensitive imaging for metastatic disease, such as the C-11 Acetate, fluciclovine F 18, and PSMA PET/CT scans, I am seeing a growing number of patients who have had radiation therapy and the only detectable recurrent cancer is in the prostate gland. Focal therapy in this setting is difficult because of radiation damage to surrounding normal tissue as well as dense scar formation within the gland. Several interviews touch on treatment options for this situation, but those options are far from ideal. It is unclear what the right path is for these men.

Subscribe! Don’t miss our focal therapy issue when it debuts next Wednesday.