Conversations With Prostate Cancer Experts

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Active Surveillance V Partial-Gland Ablation

Dr. Behfar Ehdaie is a urologist at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia spoke with him recently about active surveillance versus partial-gland ablation. Join us to read the entire conversation.

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Could low-risk patients just as easily choose active surveillance? Is it just patient choice: active surveillance or partial-gland ablation?

Dr. Ehdaie: I think active surveillance, partial-gland ablation, or focal therapy, and whole-gland treatments, which include radical retropubic prostatectomy or radiation therapy, exist on a spectrum for disease management in prostate cancer.

I do believe that there are patients who we would all agree are very good candidates for active surveillance. Men who’ve been diagnosed with Gleason 3+3 prostate cancer fall into this category. I think our discussion about men who may be eligible for focal therapy or partial-gland ablation would include men with intermediate risk prostate or Gleason 3+4 or 4+3 prostate cancer.

Of course, some of the men with low-volume Gleason 3+4 prostate cancer in foci within the prostate gland would also be considered very good candidates for active surveillance. It’s important that all patients are offered all treatments and that those treatments are explained in detail at every consultation.

Join Prostatepedia to read the entire issue on focal therapy for prostate cancer.

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Focal Therapy Versus Partial-gland Ablation

Ehdaie_130821_14Dr. Behfar Ehdaie is a urologist at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia spoke with him recently about focal therapy and laser ablation.

Subscribe to read the entire conversation.

Why did you become a doctor?

Dr. Behfar Ehdaie: I initially was exposed to medicine in dealing with some of the medical challenges that my mother faced related to cancer. It made a very large impression on me to see how my mother interacted with her physicians and how she was comforted by so many of them. To be able to give back and to provide comfort to other people with regard to different diseases was very important in my decision to be a doctor.

On top of that, being an effective and good physician were challenges that I found to be stimulating.

What is partial-gland ablation versus focal therapy?

Dr. Ehdaie: I think we’ve come to a point in prostate cancer management and treatment in which these distinctions and terminology are becoming more important. As you know, over the past three decades, we have developed proven effective whole-gland treatments for the prostate that include radical surgery and radiation therapy. A less invasive form of prostate cancer treatment must involve less than total treatment of the whole gland. Therefore, the term partial gland has evolved. We use the word ablation to suggest that an area of the prostate will be treated, whether that’s through heating or freezing or other mechanisms to cause cell death and necrosis.

The term focal therapy adds a second dimension to partial-gland ablation. This is a general term to refer to any treatment that offers less than whole-gland treatment for prostate cancer. Focal therapy specifically focuses on an image-guided treatment approach, meaning an area that is visualized is specifically targeted and treated. In partial-gland ablation, we use our current abilities to map the prostate to determine which region is most likely to be involved with cancer; we not only seek to treat that area but also to achieve a margin that may not be visualized on imaging. Focal therapy adds the dimension of image guidance to the armament of prostate cancer treatment, which is more relevant now given that our approach to diagnosing prostate cancer has also evolved over the past decade. We have moved from systematic biopsies to adding biopsies in which we target areas that are first visualized using advanced imaging like multiparametric MRI.

Are you primarily doing focal therapy or partial-gland ablation now?

Dr. Ehdaie: In our different studies and trials, we have different forms of treatment. Specifically, in studies in which we define the area of treatment by MRI, we term those treatments focal therapy. We currently have a clinical trial looking at MR-guided high-intensity focused ultrasound (HIFU) that we perform in the MRI suite. We also have two other clinical trials in which we direct our treatment to a region predominantly defined by the biopsy criteria, in which the imaging is an addition to the tools we have used to define where we want to treat. We currently are performing both focal therapy and partial-gland ablation on patients based on the modalities that they would be eligible for.

How do we know which patients are appropriate for either focal therapy or partial-gland ablation?

Dr. Ehdaie: I think ultimately we can make the distinction between patients who need radical surgery or radiation treatment and those patients who need less invasive forms of treatment that we would term partial-gland ablation specifically, without making the distinction with focal therapy to answer this question.

Currently, I believe eligible patients are those who have an intermediate risk prostate cancer defined as Gleason grade 3+4, or in some cases very low-volume Gleason 4+3 prostate cancer defined by prostate needle biopsy and confirmed with a secondary imaging test to rule out other areas of intermediate-risk prostate cancer. Those patients may have other areas of low-grade, low-risk prostate cancer, specifically Gleason 3+3, which would go untreated and be monitored as they currently are in many active surveillance cohorts. I do not believe focal therapy or partial-gland ablation in its current form should be evaluated or used in patients with high-risk prostate cancer; that includes men with Gleason 4+4 or higher, high-volume Gleason 4+3, with imaging characteristics suggesting bilateral intermediate or high-risk disease, or disease that has escaped the prostate, including locally advanced prostate cancer or prostate cancer that has metastasized to the lymph nodes or the bone.

Join Prostatepedia to read our November issue on focal therapy.

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Focal Therapy + Imaging

Dr. Mark Emberton is a Professor of Interventional Oncology at University College London.

Prostatepedia spoke with him about focal therapy for prostate cancer.

What is focal therapy for prostate cancer?

IMG_0571Dr. Emberton: Focal therapy is an attempt to improve the therapeutic ratio. It addresses the harms and benefits of treatment. In prostate cancer treatment, the harms are too great for the benefit to accrue.

We can’t improve the benefit very much, but we can certainly reduce the harms that we inflict on our patients. Nearly every patient who has been treated for prostate cancer will experience a reduction in quality of life because of the impact on his sexual function, continence, or rectal function.

Focal therapy attempts to address that by preserving tissue. We’ve managed to preserve tissue in all other cancer management: breast through lumpectomy, kidney through partial nephrectomy, liver through partial hepatectomy, and penile cancer through partial penectomy. Prostate is the last bastion. Until recently, all men had the prostatic equivalent of bilateral mastectomy. In other words, their whole prostate tissue was removed irrespective of tumor volume, location, or number. Everyone was treated the same. With focal therapy, we attempt to preserve tissue, which preserves function.

How do doctors determine if focal therapy is appropriate for a man?

Dr. Emberton: It’s not for everybody. At the moment, we do surveillance so that men with very low-risk disease have no treatment. We offer surgery to men with high-risk disease who’ve got extensive, high-burden tumors in the same way we manage, say, breast cancer. We might choose to watch an elderly woman with a small breast lump. We might choose to do a mastectomy on a young woman with very aggressive breast cancer. But the majority of women—currently 80%—can get away with a lumpectomy. This is enabled by the ability to identify tumors and determine location and volume.

That’s a very recent development in prostate cancer. Until very recently, we were treating all men blindly. Since Hugh Hampton Young did his first prostatectomy at Johns Hopkins about 100 years ago, we’ve been treating prostate cancer without knowledge of tumor location.

What is the role of imaging?

Dr. Emberton: The new trick in town is that we can see the prostate cancer with MRI. If we can see it, we can direct needles at it. If we can direct needles at it, we can direct energy at it. We can zap the tumor rather than having to remove the whole prostate. We can have a much more nuanced approach now. Instead of treating all men the same, we can now stratify men by risk with great precision by biopsying them differently depending on where the tumor is and then allocating treatment depending on the risk stratification that has been assessed. If a man has one millimeter of Gleason 4+3, most of us would not treat. I certainly wouldn’t. If he has extensive bilateral disease, I would offer whole-gland treatment in the form of surgery or radiation therapy. If he has got a 0.5 cc tumor in the right peripheral zone of the prostate, I see no reason why we shouldn’t offer a selective destruction of that tumor that preserves erections, ejaculation, and continence. We’re doing that today. We’re having conversations with men today that we couldn’t have had three to four years ago because we didn’t have the tools.

What about other advances in imaging?

Dr. Emberton: PSMA is very useful in staging men. It’s concordant with MRI and the prostate, but it doesn’t give us the spatial resolution that we would require to decide which part of the prostate to treat. The PSMA PET/CT will be positive on the left or the right side of the prostate, but will not give us any more information. It’s really useful in the high-risk man with whom you’re trying to rule out metastatic disease.

There are a variety of forms of focal therapy, correct?

Dr. Emberton: I think conceptually, it’s very clear. We offer men focal therapy when we can treat the tumor plus a margin and we think we can do so faithfully. But there are lots of ways to do it. Just like surgery, you can have an open, transperineal, laparoscopic, or robotic prostatectomy. In brachytherapy, high-dose rate (HDR), low-dose rate (LDR), CyberKnife, TrueBeam, protons, external beam, the principle is the same.

Yes, we have a few options with focal therapy, though not as many as surgeons and radiation therapists. We’re often accused of having a cornucopia of ways of treating. Actually, we don’t. We have heat (hot or cold) and we have electricity in the form of radio frequency or electroporation.

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Is There A Consensus On Focal Therapy?

David Crawford, the distinguished Professor of Surgery, Urology, and Radiation Oncology, and Head of the Section of Urologic Oncology, at the University of Colorado Anschutz Medical Campus frames Prostatepedia’s November discussions on focal therapy for prostate cancer.

There is a lot of interest in focal therapy right now. Years ago, when I used to recommend radical prostatectomy and radiation to patients, they would ask why I couldn’t just take out a part of their prostate and not the whole thing. I would chuckle and say, “You can’t do that.” I’d say that prostate cancers tend to be multifocal. We can’t just operate on part of your prostate. We have to treat the whole thing.

That resonated with many urologists for years. Then Drs. Gary Onik and Winston Barzell started using cryotherapy to ablate prostate tumors and mapping biopsies to localize the cancer. Like a lot of things in medicine, there was a backlash of people who felt focal therapy was inappropriate because prostate cancer is multifocal.

Dr. Onik persisted. When somebody came in with a low-grade or even intermediate-grade prostate cancer on the left side of the prostate gland, he would biopsy the right side of the prostate extensively. If there wasn’t any cancer, he would do an ablation and treat the whole left side. That was the beginning of focal therapy.

I became interested in what I call targeted focal therapy about 15 years ago. Of course, focal therapy hinges on our ability to effectively biopsy patients so that you know you’re not missing other, more aggressive tumors. Focal therapy means focally treating a lesion, but I like the term targeted focal therapy because we’re targeting exactly where the tumor is with our mapping biopsies.

There are many ways to do focal therapy. We can use lasers, cryotherapy, or high-intensity focused ultrasound (HIFU). We’re working on using immunotherapy to target lesions. We can even put alcohol into the lesion and get rid of the cancer that way. Ablating the tumor isn’t the hard part. The hard part is knowing where the lesion is and targeting it.

Fifteen years ago, we had several hundred radical prostatectomy specimens; a researcher from Japan named Dasako Hirano, who had been with us for two years, outlined the tumors on acetate paper and then we put them into a 3D system so that we could simulate where these tumors were using different biopsying techniques. We showed that if you use the transperineal approach to place a needle into the prostate every five millimeters, you could sample the whole prostate without missing many significant cancers. I felt that it was safe to go forward with targeted focal therapy.

We knew we would not do any harm with 3D mapping biopsies.

We also talk about MRI in relation to focal therapy. MRI has been around for a long time. We’ve gone from 1 Tesla to 3 Tesla and now 5 Tesla MRI units. We’re getting better at reading the MRI results. There has been a lot of discussion about how accurate MRI is and what it misses. MRIs still can miss aggressive cancers. Depending on which expert you believe, MRI misses anywhere from 7-10% up to 30% of aggressive cancers. MRI is a lot simpler than our painstaking 3D mapping biopsy, though, so it’s caught on.

Dr. Mark Emberton was the first to champion MRI in the United Kingdom. Dr. Emberton and his team now have a lot of experience in using MRI in focal therapy, primarily cryotherapy.

But to me, the gold standard remains the mapping biopsies. MRI is good, but not perfect. Perhaps we can use molecular markers along with MRI to rule out more aggressive cancers.

Focal therapy is a response to overtreatment and it does have a place, but with prostate cancer, we’ve got to follow people a long time before we come to a consensus.

Subscribe to read about focal therapy on November 1.