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Dr. Felix Feng: Why I Became A Doctor

Dr. Felix Feng is a physician-scientist at University of California, San Francisco (UCSF) keenly interested in improving outcomes for patients with prostate cancer. His research centers on discovering prognostic/predictive biomarkers in prostate cancer and developing rational approaches to targeted treatment for therapy-resistant prostate cancer. He also sees patients through his prostate cancer clinic at UCSF.

Prostatepedia spoke with him about why he became a doctor who cares for men with prostate cancer.

Why did you become a doctor?

Dr. Felix Feng: I became a doctor because my family has a strong history of cancer. Unfortunately, I learned the repercussions of cancer at an early age. All four of my grandparents passed away from some form of cancer. My father has successfully overcome three different cancers. Just last year, my sister, unfortunately, passed away in her 40s from cancer.

Before ever becoming a doctor, I was part of many patients’ families. I saw it strongly from the patient side and decided that if I was going to commit my life to studying something, it was going to be cancer.

So then your journey is really personal.

Dr. Feng: Very personal.

Join us to read Dr. Feng’s thoughts on genomics + prostate cancer.

 


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Join A Prostate Cancer Imaging Clinical Trial

Dr. Peter Choyke, Director of the Molecular Imaging Program at the National Institutes of Health’s National Cancer Institute, is keenly interested in translating molecular imaging methods like MRI and PET into practice.

Prostatepedia spoke with him about his clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer.

Why did you become a doctor?

Dr. Peter Choyke: I was always interested in science. I came from a family of scientists. It just seemed that medical problems were the kind of problems that I needed to do work on. A lot of the problems in physics and chemistry had been solved, but in biology and medicine we really needed a lot more effort. I wanted to devote my life to that.

Can you explain the thinking behind your clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer?

Dr. Choyke: Prostate cancer imaging has been very limited. We’ve only had access to CT and bone scans, both of which had limited sensitivity for picking up prostate cancer. In the beginning of the 2000s, a number of new PET agents—or Positronemission tomography labeled agents—emerged. We started looking at them as they became available. They showed better and better sensitivity and specificity.

About three or four years ago, we accessed a first generation PSMA-targeted PET agent named F-18 DCFBC in collaboration with the person who invented this whole field, Dr. Martin Pomper at Johns Hopkins University.

We formed a collaboration and scanned 135 patients in an earlier protocol. We showed that even though this was a first generation PSMA agent, it was really promising and had much better sensitivity and specificity for prostate cancer than any other agent we had ever looked at.

Then Dr. Pomper, who is partly an imaging specialist and partly a chemist, further developed the compound into F-18 DCFPYL. This is the agent we’re now using in this trial.

F-18 DCFPYL has probably 10 times better sensitivity than the first-generation agent because of the higher affinity of the agent for PSMA and because of lower background. We started using that in the end of the summer of 2017 in a trial looking at high-risk primary cancer and recurrent disease.

If a man enrolls in this trial, what can he expect to happen from beginning to end?

Dr. Choyke: First of all, it’s important to talk about who qualifies for the trial. We have two arms.

In one arm, we’ll have men with high risk cancers, meaning they’re at high risk for metastatic disease or spread outside the prostate. Such men would come to our center and get the scan. They’d also get an MRI of their prostate, because we always correlate the findings of the DCFPyL scan with MRI to anatomically locate where the uptake is occurring. The anatomy is very complex in the low pelvis.

With the MRI in hand, the patient would get an injection of a small amount of radioactivity in the form of this F-18 DCFPyL. About an hour later, they go onto the scanner and simply lie flat for about 20 to 30 minutes until the entire body is scanned from head to toe. Then we’ll report the findings back to his physician.

Part of the reason why this is a research study is that we try very hard to correlate the findings that we see with biopsy specimens. This is still a research agent. We don’t know for sure that the areas of uptake are actually cancer. We can only confirm that with biopsy. We insist that patients undergo biopsy of PSMA-positive lesions as seen on the scan.

We say insist, though of course it may not be medically safe for some people to undergo a biopsy. It may not be feasible. There are exceptions. It’s not an absolute rule. We certainly want to get as much histologic correlation as possible. Otherwise, we could end up in a situation where we think we’re seeing disease, but we are in fact not. That would be very misleading and could possibly cause more harm than good. It’s very important at this stage of development to get as much information as possible.

In the second arm of this trial, we are scanning patients who have already undergone radical prostatectomy or radiation therapy and who now have a rising PSA, which indicates recurrent disease. We would do the scan in the same way as in the first arm with correlation of the MRI. Again, we’re trying to get as much histologic confirmation as possible.

Join us to read the rest of Dr. Choyke’s comments about his clinical trial.

 

 


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ZERO’s Jamie Bearse On Cancer Recurrence

Mr. Jamie Bearse is the CEO of ZERO — The End of Prostate Cancer (www.zerocancer.org). ZERO is a United States-based nonprofit with a mission to end prostate cancer.

He talks to Prostatepedia about dealing with recurrence.

Finishing your prostate cancer treatment is cause for celebration and relief. Life is best lived in the moment as we all only have today. However, stress about side effects and thoughts of recurrence creep in. It’s critical not to live in an anxious world of what if, but it’s important to know that up to 40 percent of men will experience a recurrence after completing treatment. For those who do experience recurrence— whether it is biochemical or metastatic disease—we’d like to share some tips for coping with the journey ahead. Talk to your doctor about every aspect of your new diagnosis, including your treatment options.

It’s important to understand whether you are experiencing biochemical recurrence or if your cancer has become metastatic and what your treatment options are. At your appointment, take detailed notes, or bring someone with you to do so. Afterward, do your own research about what you discussed with your doctor, and if you still feel unsure, seek a second opinion. Much like when you were first diagnosed, it’s important to understand all options available to you based on your specific disease and circumstances.

Consider joining a support group.

Support groups offer the chance to share feelings and fears with others who understand, as well as to exchange practical information and helpful suggestions. Connecting with other men whose cancer journey is similar to yours can allow you to explore options and seek advice from someone who has been there before.

Try to lean on your loved ones.

Your loved ones want to help you through this newest obstacle – try not to be afraid to open up and talk about how you’re feeling. If you don’t feel comfortable talking to someone, write down your thoughts in a journal. Talking and thinking about your concerns as you work through your options can help you feel less afraid or anxious and more in control.

Utilize all resources available to you.

If you don’t feel comfortable talking to a loved one or a support group, or if you feel you need additional support, consider calling ZERO360 at 1-844-244-1309 Toll-Free, a free one on- one patient support service that can help you find qualified counselors and emotional support resources. The fear of recurrence is normal and reasonable for all cancer survivors. Although you cannot control whether your cancer recurs, you can control how you move into this next phase of your prostate cancer journey. ZERO also offers a new, peer-to-peer MENtor program, which can match you with a patient or survivor who has experienced a similar diagnosis or treatment pathway for one-on one support. In addition, if you’re experiencing recurrence and are looking for additional resources to help, visit http://www.zerocancer.org/ get-support/zero360.

Subscribe to read the rest of this month’s conversations about prostate cancer recurrence.


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3 or Fewer Prostate Cancer Mets

Dr. Piet Ost is a radiation oncologist at Ghent University in Belgium. His work focuses on post-surgery radiation therapy and metastasis-directed therapy for oligometastatic prostate cancer, or a cancer recurrence with three or fewer metastases.

Prostatepedia spoke with him about treating men with so few metastases after treatment.

Can you define oligometastatic prostate cancer?

Dr. Ost: First of all, if your doctor talks about oligometastatic disease, I think it’s very important to ask them what they mean by that? When we look through literature, there are several definitions used.

Some people use oligometastatic while others use oligorecurrence, synchronous metastases, or low volume metastases. Many of these probably mean the same, but there is no uniform definition.

In 1995, Hellman and Weichselbaum first defined oligometastases as metastases limited in number and location. These tumors have not developed the full capacity for metastatic growth. It could be an issue with the metastases—or the seed—or it could be an issue with the soil—the environment in which the metastases started to grow. That’s the biological definition.

This is not very useful as a clinician. What is limited? Is that a certain number? If you look through literature, many clinicians define it as up to three metastatic lesions with no more than two different organs involved. That is probably the most used definition, but there are alternatives. Some say that it’s only one metastasis while others say it’s as many as five or even 10 in case of brain metastases. Some say there has to be a certain amount of time between primary diagnosis and the occurrence of metastasis.

There’s a lot of confusion throughout the literature. If you read an article, you have to look at their definition. When doctors talk to each other, and when patients talk to each other, they all use the word oligometastatic, but it might be that they’re talking about a different disease.

Is there any sort of restriction on where those metastases are located—for example, in only the pelvic area?

Dr. Ost: At this time, I don’t think so. It’s a biological phenotype. We care less where the metastasis occurs. For example, we have had patients with unique lung mets at the time of recurrence where we remove those lung mets, and then these patients remain disease-free for many months or even years.

Normally, when you have a patient with lung mets, those are visceral mets, and their prognosis is supposed to be very poor no matter what. There appears to be a subset of patients with a limited number of metastases, even visceral metastases, who still benefit from removing or irradiating the metastases. We have several of those cases documented already. It’s not about the location. It’s something about the biology, and that is the big problem at this time.

Currently, when we propose a certain oligometastatic or metastasis directed therapy to a patient, we don’t know if the metastases we see and treat are the only ones there, or if three months after we remove or eradiate them, there will be 20 new metastases. We don’t know that at the start. This shows us that imaging is still far from perfect and sometimes we only see the tip of the iceberg.

When we look at the distribution or pattern of metastases in recurrent prostate cancer with Choline PET/CT and PSMA PET/CT imaging, we see that, after receiving prior prostate cancer treatment, the majority of patients relapse first in the lymph nodes.

That is mainly in the pelvic lymph nodes. If we look at all the patients that we screen for now, 70% have nodal recurrences, 25% have bone metastases, and 5% have visceral mets. If we look at all of those recurrences, two thirds of those relapses are what we call oligometastatic, meaning up to three metastatic spots. We don’t believe that there is a true limitation on the organs. How it evolves is actually a fingerprint of the disease.

When you start, you don’t know whether it’s a true oligomet. We cannot predict at this time how the disease will evolve.

How do you normally treat oligomets? With radiation or surgery? How do you decide which is most appropriate?

Dr. Ost: We still counsel our patients on the standard options. For patients with upfront metastatic disease, the landscape has changed dramatically where we now introduce Androgen Deprivation Therapy (ADT) plus Taxotere (docetaxel) or ADT plus Zytiga (abiraterone) as a standard of care.

We still do not know if these options are helpful in treating the primary tumor and its mets with metastatic-directed therapy. In situations with upfront oligometastatic disease, we counsel our patients that the standard of care is systemic drugs while the addition of any metastatic-directed therapy is one big question mark. We do not advise it outside clinical trial.

The situation is a bit different in the recurrent setting. In the recurrent setting, there’s a gray zone. For example, the older data said that starting ADT for a PSA relapse following primary therapies—just starting ADT—is not advised; it’s better to wait and see and do a delayed ADT at the time of symptomatic progression.

Now with the very sensitive imaging, we see mets earlier at PSA relapse. What should we do with these? Do we still say the standard of care is wait and see, ADT, or something else? Because new imaging created this gray zone, all of a sudden we saw a boom in these oligometastatic patients, so we decided to do a clinical trial in this setting.

In our paper published in The Journal of Clinical Oncology (JCO), we randomized our patients to wait and see. One group had surveillance while starting ADT, and the other group had surgery or radiotherapy to the mets followed by surveillance. In that study, we found that surgery or radiotherapy is better at postponing further progression to polymetastatic disease rather than just observing patients.

We have an alternative now in counseling patients: metastaticdirected therapy with either surgery or radiotherapy. We know that it’s very safe, because we did not see any grade 2 or higher toxicity, which is a positive thing to tell men with prostate cancer. We can offer you something without a whole lot of toxicity. We still have to tell you this was a Phase II trial. The endpoint was time to progression.

I’m still not sure that giving metastatic-directed therapy will change your disease in the long run, that it will make you live any longer compared with immediate ADT or surveillance. It’s still too early to tell. We try to counsel our patients with these different options.

Join us to read the rest of Dr. Ost’s comments. (Subscribers can read the conversation in their March issue of Prostatepedia.)


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Dr. Eric Rohren: Why Radiology?

Dr. Eric Rohren is the chair of the department of radiology at Baylor College of Medicine.

Prostatepedia spoke with him about the path that led him to radiology.

Subscribe to read Dr. Rohren’s comments on radium therapy + imaging.

Why did you become a doctor?

Dr. Eric Rohren: I actually tried my best not to become a doctor initially. My father was a doctor. I grew up in the shadow of the Mayo Clinic up in Minnesota. I knew I was interested in science, but for a long time, I thought I wanted to pursue a career as a research scientist and not a physician.

As I made my way through college and looked at what I really enjoyed and what a career would look like, I wanted to focus on patient care and do things that impacted people. I looked for a career that could combine the science that I enjoyed with the ability to directly interact with people, to hopefully make their lives better. I came full circle, landing back in a career in medicine.

How did you end up in radiology and nuclear medicine?

Dr. Rohren: That was also a little bit indirect. Most medical students aren’t introduced to radiology until very late in their medical training.

A lot of people make the decision to do medicine or surgery well ahead of time, but radiology is often a latecomer. Nuclear medicine is even more so. It’s a subspecialty of imaging, its own medical specialty, but it can also be considered a part of radiology. Medical students often make it through their entire medical training without learning about nuclear medicine at all.

I was fortunate to have a mentor in the radiology department at the Mayo Clinic who taught me what he loved about radiology and how impactful it was on patient care. He got me further plugged in to nuclear medicine.

As I went into my residency and pursued it further, I decided that the science that I loved and the ability to do new things were most focused in radiology, and particularly in nuclear medicine. That’s the career I ended up with.

Many people assume radiology is just imaging. Is that the case? Where does it branch off into nuclear medicine? What kinds of therapies would a radiologist administer?

Dr. Rohren: A big part of being a radiologist is reading images. We also oversee the acquiring of the images, so we monitor the acquisition of the scans and the technologist performing the scans. Many of the people reading this article will have had X-rays, CTs, and MRIs. While technologists and nurses take them into the scanner and get them positioned, ultimately, the radiologists are the ones who oversee the program and make sure that the scans are acquired in the right way. They’re responsible for patient safety, the patient’s experience, and things like that.

At the back end, once the scan is complete, radiologists interpret the scans and look for the findings that may be used to guide medical decisions. Whereas many radiologists can go through their day and not see a patient, they do see the patient’s images. However, there are components of radiology that are directly related to therapy and directly patient-facing.

In interventional radiology, we do biopsies and endovascular procedures, catheter-based procedures, embolizations, administering treatment, and things like that. In women’s imaging such as mammography and breast cancer screenings, those radiologists spend a lot of their time talking to patients and counseling them about their diagnosis and procedures.

One area of radiology where we do meet with a patient face-to-face and interview or talk with them is in nuclear medicine. In that role, we act as “real doctors,” where we walk in, interview the patient, review their labs, go over the plan, do a consent process if it’s for a therapy that has some risks associated with it, and then we administer the therapy directly there in the clinic. When I serve in that role, I feel much more like a patient-facing physician than I do a traditional radiologist. It’s one of the most enjoyable things about it for me.

People tend not to be familiar with specialists until they need them. They might not really understand what you do until they’re at the point where they need your services.

Dr. Rohren: Generally, that is the impression, that the radiologist sits in a dark room, reads scans, and that’s the end of it. The national societies for radiology really encourage us to interface with patients and physicians to make our presence known. Radiologists need to do a better job of that. We have a critical role to play in the management of patients and the diseases that they’re dealing with, so the more we can be out there, share our professional knowledge, act as consultants, and act as physicians for the patients, that’s a positive thing.

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PET/CT Imaging + Radiation?

 

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Dr. Michael Zelefsky, a radiation oncologist, is Professor of Radiation Oncology, Chief of the Brachytherapy Service, and Co-Leader of the Genitourinary Disease Management Team at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia recently spoke with him about how advances in imaging have impacted radiation therapy. Subscribe to read the entire conversation.

Do you think molecular imaging will be incorporated soon?

Dr. Zelefsky: There’s a lot of excitement with PET/CT imaging. PET imaging fused with MRI is also emerging now. This has been used effectively for various disease sites, not only prostate cancer. For prostate cancers specifically, newer PET tracers such as PET C-11 Choline and exciting developments in PSMA tracers will be used. These provide us unique opportunities to see where micrometastatic disease could be lodged. That information is critical for the radiation oncologist to pinpoint the disease. There are also exciting developments using some of these tracers as a form of therapy. Tracers such as PSMA are linked to lutetium-177 and tracers can be integrated with radiation planning as well. We are on the verge of seeing these new developments; these changes will soon be integrated with radiation.

Is there anything else you think patients should know about imaging’s role in radiation therapy?

Dr. Zelefsky: With new advances in imaging and by working in close collaboration with diagnostic radiology, we are getting much more accurate information concerning where microscopic disease is located and the critical zones within the prostate where tumors are lodged. We use imaging to consider re-biopsying patients where there may be a discrepancy between what looks like earlier states of disease, but the MRI shows there is greater volume of disease than what was anticipated. We need to know this information in order to plan the radiation well. We need to consider opportunities to intensify the dose to the DIL in the prostate and whether there is nodal disease and where exactly the nodal disease could be within the pelvis. Imaging plays a huge role in our follow-up with patients, allowing us to detect recurrences earlier than ever before. This is vital information for patients because earlier detection of recurrences allow for salvage therapies much sooner and treating such patients at earlier time points is often associated with more successful outcomes.

In the future, imaging will help us consider focal ablative therapies where the paradigm is shifting in earlier cancer s. Simply put, we could just focus on the DIL and spare the rest of the prostate if we can be sure that there is no significant disease in other parts of the gland. There have been a number of efforts to use focal therapy with advanced imaging to small subunits of the prostate. So new imaging possibilities are opening up new directions and opportunities in the treatment of prostate cancer.

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Imaging + Radiation Therapy

Dr. Michael Zelefsky, a radiation oncologist, is Professor of Radiation Oncology, Chief of the Brachytherapy Service, and Co-Leader of the Genitourinary Disease Management Team at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia recently spoke with him about how advances in imaging have impacted radiation therapy. Subscribe to read the entire conversation.

What role does imaging now play in radiation therapy?

Dr. Zelefsky: Radiation therapy has been linked to imaging for many years. In the late 1970s and early 1980s with the advent of the CAT scan, those images were used in the treatment planning process to provide greater accuracy for targeting the radiation. Over the ensuing 20-30 years, there have been significant advances in imaging, from CAT scanning to MRI, and from multiparametric MRI to molecular imaging. These advances in diagnostic imaging continue to be linked to radiation treatment. We use multiparametric MRI imaging to target radiation to the prostate with exquisite precision. Just as importantly, we use these technologies to understand the geometry and anatomy of the surrounding normal tissues. For the prostate, that could mean the bladder, rectum, bowels, and even specific anatomic regions like the bladder neck and the neurovascular bundles that control erectile function.

Advances in imaging have allowed us to visualize these normal tissue structures, and this information is incorporated into treatment planning, giving us a way to deliver the radiation with a precision we’ve never had before.

What sorts of changes do you think are on the horizon as we develop better imaging techniques?

Dr. Zelefsky: We have successfully moved from CT-based imaging to MR-based imaging. Now, we commonly use MRI and fuse those images with the CAT scan. At Memorial Sloan Kettering, we have moved to the next step, which is pure MRI-based planning. This means we don’t need the intermediary step of a CT scan anymore. We can plan directly off the MRI, and we map everything out from these sets of specific We’ve also moved beyond MRI to what we call multiparametric MRI. We look at different sequences and formats of the MRI, including dynamic contrast enhanced imaging, and diffusion-weighted imaging to give us further information about the location of the disease within the prostate, which is called the dominant intraprostatic lesion (DIL). This dominant intraprostatic lesion is an important area to target because recurrences after radiation stem from regrowth of disease from that initial site of disease in the prostate.

Radiation oncologists are recognizing that there may be opportunities to intensify the focus of the radiation to the DIL to improve the tumor control rates with radiation. We have moved from CT-based to MR-based radiation therapy to pure MRI-based planning, and now we incorporate important information from multiparametric imaging. In the future, we’ll also incorporate molecular imaging, which comes from advanced nuclear medicine studies.

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