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Conversations With Prostate Cancer Experts


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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.

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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.


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Prostate Cancer Diagnosis + Risk Stratification

Dr. Leonard Gomella spoke at the 18th Future Directions in Urology Symposium in Colorado Springs in August 2017. In this video interview, he offers a short summary of the talks he gave at that conference.

He focuses on two factors for prostate cancer diagnosis and risk stratification that he is researching and interested in improving. The first factor is the role of genetic testing for prostate cancer risk. He reviewed our preliminary consensus data from a big meeting in Philadelphia back in March to talk about what are the indications to sending a patient on to genetic counseling for further potential screening for inherited prostate cancer risk. He talked about things that will be coming out in his paper at the end of the year.

The second topic he addressed is what he calls Beyond MRI. He spoke about the new evolving next generation imaging involving PET scanning. He talked about the fact that there are 20-30 different PET scan technologies out there, but in reality only about 5-6 are getting attention right now. He believes that these new PET imaging will allow us to move beyond standard MRI and standard CAT scans and get much more information about disease status in individual patients.

 


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Gay Men + Prostate Cancer

william_goeren_mediumWilliam Goeren is the Director ofClinical Programs for CancerCare, a New York-based organization that offers counseling, support groups, education, and financial assistance to cancer patients and caregivers. Prostatepedia spoke with him about common issues gay men with prostate cancer face.

Why did you become a social worker?

Mr. William Goeren: I became a social worker in the mid-1980s in response to the AIDS crisis. This was not the direction I was headed, but the AIDS crisis had so shifted my outlook on life and altered my priorities that I needed to figure out a new direction, a new version of myself.

Like many young men in their early twenties, I had come to New York with dreams of a fulfilling acting career. In the midst of that, I had a shift in priorities. It was a rather dramatic shift. I was just trying to come to grips with grief, loss, death, and dying. And that’s when I attended a five-day workshop called “Life, Death, and Transition” presented by Elisabeth Kübler-Ross in upstate New York. Every day we had workshops, presentations, and individual work in her intervention model designed to help people understand death. It was very powerful to be in her presence. I knew who she was prior to going and was rather in awe of her.

After that workshop and others with a number of other high-profile people of that era, a hospice nurse strongly stated I would make a wonderful social worker. I applied to school, and my path very much changed at that point. I felt very passionate about my new direction.

How did you start at CancerCare and what do you do there?

Mr. Goeren: Earlier in my career, a gay male client in his early 30s who had a rare salivary gland cancer came in to where I was working and said that he was scarred after surgery and radiation. He said: “As a gay man with cancer, there are no services for me at all. If I had HIV, I would have services from A to Z.”

That comment stuck with me, so when I got to CancerCare in 2008, I started working on an LGBT cancer program here. In 2011, I collaborated with a New York organization called Services & Advocacy for GLBT Elders (SAGE), which provides psychosocial and concrete services for gay and lesbian elders. We launched a face-to-face support group for older gay men with cancer. That was the first actual service that we were able to launch. Though there’s a wide range of cancers in the group, the majority of the men have prostate cancer.

We’ve made attempts to launch other services; some are more successful than others. We started a group for gay women with cancer here in New York, but it was difficult to populate and maintain. We launched some online support group services, which are very robust and are for our national LGBT clients. There are currently two online groups for the LGBT community, one for LGBT cancer caregivers and the other for LGBT persons with cancer. Eventually, I would like to launch an online support group for the LGBT community who are bereaved because of cancer. We have a few publications, and I’ve done some talks at some of the national oncology social work conferences. In general, CancerCare now has 42 online support groups, which are social worker-facilitated, password-protected posting boards. These are not live groups but very much function like a face-to-face group.

What are the particular concerns or challenges facing gay men with prostate cancer?

Mr. Goeren: There is some research going on that is limited and minimal.

For example, David Latini, Daniela Wittmann, and Thomas Blank are doing research focusing on issues in the LGBT community and cancer and, in certain studies, research specifically related to gay men who have prostate cancer. They are interested in how gay men, differing from their heterosexual counterparts, react to being diagnosed; the impact of the diagnosis and treatment on their sense of self, emotional wellbeing, and quality of life; as well as how the medical community could be more sensitive and better trained in LGBT and cancer issues.

Research has shown that many gay men feel great shame, stigma, and embarrassment triggered by their emotional reactions and the physical changes related to prostate cancer and its treatment. This shame and stigma touches upon, for many, established internalized homophobia, previous experiences of discrimination and harassment, history of coping with, and in some cases, living with HIV disease, and negative experiences coming out.

Many men experience urinary and bowel incontinence, altered sexual function, and penile shortening (an underreported and under-discussed side effect). All of these impact a sense of masculine identity for men in general. For many gay men, prostate cancer can have a compelling and compromising impact on one’s sense of self within an already disenfranchised and diverse community, his self-esteem, and his ability to relate intimately to other gay men. Gay men report losses associated with prostate cancer for both the man with cancer and his partner. These losses include spontaneity, intimacy, and normalcy in sexually relating, which can lead to fears of rejection, emotional withdrawal, depression, and anxiety.

In addition, HIV affects many gay men who have cancer, whether they live with HIV, have survived multiple HIV-related losses, or are coping with issues of safer sex and determining their risk of exposure and infection. Another immense challenge for a gay man with prostate cancer is finding an oncologist who is educated in the complexly sensitive and layered issues that confront any gay man with prostate cancer. It is essential that an oncologist provide a comfortable, secure, and safe atmosphere, in which a gay man can disclose and discuss his sexual orientation, lifestyle, and activities.

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Prostate Cancer Mortality Rates?

john_davis.jpg.resize.810.1150.highAt a presentation he gave at the18th Annual Future Directions in Urology Symposium, Dr. John W. Davis of the University of Texas M.D. Anderson Cancer Center, talks about prostate cancer mortality statistics:

One of the common things we rally around is the efficacy of PSA screening and what guidelines panels have shown. The US Task Force panel in 2012 gave PSA screening a poor rating and downstream this impacted biopsy and other effects to treating prostate cancer.

Their study quoted a 1990s study that said 1 in 200 men undergoing prostate surgery died within 30 days…the problem was that it lost data when the patient was discharged…the data set is now better, it is called premier perspective, and now it does capture discharged data so you can get a clear 30 day rate.

There has been a dramatic shift, when we first looked at the database from 2004-10, so the predominant technique was open surgery. Now, looking at the 2008-16 data, and the shift is heavily robotic.

Over the decades, the mortality rate for surgery is significantly improved over what the Task Force quoted in their evidence review, and we need to continue this trend. If you look at how many people screening saves in prostate cancer mortality, if you create a new treatment-related mortality that is non-prostate that has undone your effort. In the future direction of prostate cancer we need to also pay attention to non-prostate mortality.

Dr. John W. Davis talks about mortality statistics after both prostatectomy and radiation.


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What Comes After MRI?

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Dr. Matthew Cooperberg is an Associate Professor of Urology and the Helen Diller Family Chair in Urology at the University of California, San Francisco. He is keenly interested in risk-stratifying prostate cancer to better match treatments to those most likely to benefit.

Prostatepedia spoke with Dr. Cooperberg recently about the role imaging plays in prostate cancer treatment.

Are there any other imaging techniques on the horizon that may replace the MRI?

Dr. Cooperberg: There is a lot of excitement for what will be the next-generation MR spectroscopy based on hyperpolarized Carbon-13 imaging. This is next-generation MR imaging in which we can essentially watch metabolic pathways unfold in real time at the millimeter level. That’s going to be incredible. This technology was developed by John Kurhanewicz at UCSF and is in late phase testing now. A few of these machines exist so far around the world; this may really be a game changer.

Technologies for next-generation ultrasound may also be able to yield a very high-resolution picture. These technologies have to be studied carefully head-to-head. It may bear out that better ultrasound technology will prove more cost-effective and easier on the patient than MRI, which requires separate visits, separate costs, and multiple physicians. Plus, MR is competing—especially when we talk about active surveillance—with blood, urine, and tissue biomarkers. Should a surveillance candidate who is on the edge get an MRI, a Decipher test, or both?

Would you use multiple tools or just one?

Dr. Cooperberg: Potentially multiple, but if everyone uses multiple tools, the cost increases exponentially. We don’t always know what to do with conflicting information. If you have a reassuring MRI and a concerning Decipher score, what do you do? If you have a high biomarker score and the MRI still doesn’t show anything, what do you do? These are challenging questions.

From a research standpoint, this is what makes it fun. But for the man on the ground, there is a lot of confusion. It’s part of the reason that I’m skeptical about how aggressively a number of these tests are marketed in the prostate cancer community.

You mean how tests like Decipher are marketed in the community?

Dr. Cooperberg: And MRI. It’s all in the same category. When I give a talk on MRI, I consider it to be a novel biomarker. It faces all the same challenges and has to play by all the same rules as Polaris or Decipher. You’ve got to prove that it’s going to give you better information than you can get from the basic clinical assessment. You’ve got to prove it’s going to help you make a better decision. And you’ve got to prove that it gets better outcomes, just like the biomarkers. Just as we’re not quite there with the biomarkers, we’re not quite there with MRI.

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Imaging + Prostate Cancer Staging

UrAwMC-22Dr. Matthew Cooperberg is an Associate Professor of Urology and the Helen Diller Family Chair in Urology at the University of California, San Francisco. He is keenly interested in risk-stratifying prostate cancer to better match treatments to those most likely to benefit.

Prostatepedia spoke with Dr. Cooperberg recently about how advances in imaging have impacted how we diagnose and stage prostate cancer.

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How have advances in imaging improved our ability to accurately diagnose and stage prostate cancer?

Dr. Cooperberg: Imaging plays an emerging role. We have to be careful in this field—and specifically in this place in history—not to confuse advances in research with advances in clinical care. There are lots of exciting things going on with imaging research in prostate cancer that are presented to patients as being ready for prime time, but they are not ready yet in most community settings.

Two major imaging stories are evolving right now. One is better local assessment of the prostate itself, mostly based on MRI. The other is better staging with advanced imaging modalities centering on PET/CT, specifically prostate-specific membrane antigen (PSMA) PET/CT imaging. MRI imaging of the prostate has been a little bit of a challenge. Prostate cancers are notoriously not visible on CT scan and are only marginally visible on the historical MRIs that would be done in single phase, primarily to image the lymph nodes. Ultrasound, which is what we use to guide prostate biopsies, can identify a reasonably high proportion of prostate cancers, especially high-risk prostate cancers. However, doing ultrasound well takes a lot of experience and expertise. There are urologists who use ultrasound to identify the different regions of the prostate and don’t spend that much time looking for the cancers. With practice, it is possible to see at least a significant proportion of cancers with ultrasound.

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In the last few years, the goal with MRI is to do a better job with local assessment of prostate cancers. Can we see the cancers? Can we accurately stage them using a multiparametric MRI exam? That means looking at T2-weighted imaging, which is essentially anatomic imaging. We look at diffusion weighting, which is intended to give an indication of cellular density. And we look at dynamic contrast, which gives us a sense of how much angiogenesis is going on. That combination of imaging modalities all within a given MRI exam definitely gives us a lot more information than before.

The goal is to see the tumor within the prostate and to get a measure of its stage. However, this all depends on accuracy, which remains highly variable. The UK has been a major proponent of MRI for a long time. Most reports suggest that there is improved accuracy when you do an MRI biopsy versus an ultrasound-guided biopsy. This means that we miss fewer high-grade cancers. The problem with a traditional biopsy has always been both under-sampling and over-sampling.

You find small Gleason 3+3 prostate cancers that you do not need to find, and there is a chance of missing higher-grade cancers. With MRI, both the over-diagnosis problem and the under-diagnosis problem tend to improve. Most agree that an MRI can identify cancers that would be missed on the ultrasound. Whether MRI can replace the standard mapped-out biopsy is more controversial.

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In places like the UK, they are on the cusp of implementing a policy in which patients with an elevated PSA get an MRI-targeted biopsy if the MRI shows something. If the MRI doesn’t show anything, you don’t get a biopsy. But I don’t think the world is nearly ready for that. Even in the best series, there is quite a substantial risk of under-sampling with MRI-targeted biopsy alone. It is common to find higher-grade cancer with the non-MRI-guided biopsy.

The bigger problem, moreover, which is barely discussed, is with observer variability in reading the multiparametric MRI. A CT scan of the kidneys, for example, is a very consistent, straightforward test. Pretty much any radiology center can push “start” on the CT scan and generate similar-looking pictures. Any half-decent radiologist should be able to read the CT scan of the kidneys.

A multiparametric MRI of the prostate is a completely different story. There’s a lot of subtlety and a lot of expertise required in programming the machine, protocoling the exam, and interpreting the results.

We see patients who had a prostate MRI at an outside radiology center that is completely unreadable: it hasn’t been performed correctly, let alone interpreted correctly. Even if it is done right, there is an observer variability problem. There have been studies in places like the National Cancer Institute (NCI), who are major experts at MRI, but even at the NCI, there is major interobserver variation because there are shades of gray in terms of how we identify these lesions. (Observer variability is the failure to read the test accurately; interobserver variability refers to two or more clinicians interpreting different results.)

Would you say that MRI-guided biopsy plus the traditional biopsy would be a better approach?

Dr. Cooperberg: Because of the interobserver variability problem, I don’t think we should be anywhere close to getting rid of the traditional biopsy—not even in a center of excellence like NCI, and certainly not in a community radiology setting. Also, the sensitivity of MRI for high-grade cancer is still not as high as we’d like it to be.

There are lots of other questions. How do you do an MRI-targeted biopsy? Do you do what is called cognitive fusion, meaning you just review the MRI to guide your ultrasound-guided biopsy? Do you use fusion systems where we overlay the MRI images onto the ultrasound picture at the time of biopsy? Or are we doing an in-bore MRI-guided biopsy where the biopsy is done under direct MRI guidance in real time? These latter options increase complexity and cost. There is minimal evidence that one is particularly better than another.

Plus, the better you are at identifying lesions by ultrasound, the less commonly you are going to miss something on ultrasound that you would have seen on MRI. We do a lot of MRI at UCSF. We’re a big MRI center, and I order MRIs all the time because we have subspecialty radiology expertise available. A community radiologist who looks at one prostate MRI a month is not going interpret as well as a radiologist who reads them frequently.

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