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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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Patients Speak: Facing Mortality

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Mr. Spencer Le Gate spoke to Prostatepedia about his prostate cancer journey and his role in his local support group.

How did you find out that you had prostate cancer?

Mr. Spencer Le Gate: My family doctor put me on a small dose of a statin drug for cholesterol back in 2000. He had the good sense to give me a blood test every three or four months to check all my vital organs for any problems. At the end of 2007, he noticed that my PSA had started to rise. He asked if I knew anything about prostate cancer. Just a month prior, a childhood best friend had died from prostate cancer, so that was my introduction.

We watched my PSA for about a year, and then, in early 2009, I had a biopsy. We determined that mine was not the most aggressive form, so given all of the options, brachytherapy seemed like a good choice. I had the procedure in May of 2009. After that, there was a small spike in my PSA, which we all hoped would diminish as often happens after treatment. Almost two years later, my PSA had gone from around 1 up to almost 11, and that meant I had a recurrence of prostate cancer. Around early 2013, I had a biopsy that confirmed that I was recurrent nonmetastatic. I went on Lupron (leuprolide), which brought my PSA count down very nicely, so I asked if I could do it intermittently.

You asked for that rather than the doctor suggesting it to you?

Mr. Le Gate: Yes. I wanted the vacation because, of course, I experienced side effects.

What kinds of side effects did you experience on Lupron (leuprolide)? How did you manage them?

Mr. Le Gate: The side effects for me were, of course, the most common: hot flashes. At one point, I did have a Depo-Provera (medroxyprogesterone) shot, which diminished the hot flashes pretty well. The others were loss of libido and muscle weakness. I have lost muscle mass throughout my body, but particularly, in my legs. My muscles atrophied.

Were any of these side effects severe?

Mr. Le Gate: I would say, for the first round of my treatment, not so much. But since I went back on Lupron (leuprolide) in 2013, they are more pronounced. When I took the vacation, my PSA went up alarmingly. In other words, it was worse than that scary doubling threshold in three months.

Did they put you back on the Lupron (leuprolide) as soon as that started to happen?

Mr. Le Gate: I’ve been on the Lupron (leuprolide) for almost two years. Now, when I get up in the morning, my legs are painful and I’m a little rickety. Despite the fact that I’ll be 75 in a few months, my legs have been good to me, and I’ve led a very active lifestyle. The pain I feel now in the legs is not just the inevitably of age, but the Lupron (leuprolide).

Does exercise help with the side effects?

Mr. Le Gate: Exercise does. I have backslid some, but until about a year ago, I had a trainer. I went several times a week. I took a 12-week course of training sponsored by a local cancer organization during the intermittent period and it was very beneficial. Should I get the motivation to get back to exercise, it would help me a lot. I am still active and hands-on in my profession. I’m a general contractor. It’s a pretty active job, and I’m up and down all the time. But I learned very quickly once I started aerobic exercise, that it’s more effective than getting up every morning and putting on my tool belt.

Is there anything else that you do to manage the side effects?

Mr. Le Gate: Of course, the change in your mental state. When I’m not working, I’m a person who spends a lot of time reading, and before I decided to become a contractor, I had a pretty good education. I have some sense of my cognition, and I think that your overall mental state has an effect on how well you feel.

Did that go away when you went on the intermittent period?

Mr. Le Gate: It did. Most everything went away. I only had a year. During the intermittent period, I took that phenomenal 12-week course. We met twice a week for two hours of rigorous training, weightlifting—everything.

It was really eye opening for me.

Are you saying the exercise and training impacted the cognitive side effects you were feeling as well?

Mr. Le Gate: Oh, yeah. I think it did. I had some sense of that even before I had cancer. If you’re physically active, there is a positive mental effect to that. Again, some of these things are just so blurred. How much of it is due to aging, and how much is just the burden of a disease that— at this point—cannot be cured?

Stress, you mean?

Mr. Le Gate: Yes, stress. Also, I always have been a bit anxious. Now I think I have to be more careful about managing my anxieties. I mean, I think there’s so much of this disease that can be managed. You can manage it. I don’t have a metastasis. So I’m not in a worse position. I attend a monthly prostate cancer support group here in Sacramento, California. It’s one of the best things I’ve done. I’ve gotten involved in it, and I’ve actually had the good fortune to be asked to lead groups, come up with ideas, and answer folk’s questions. I’ve had a very healthy life and getting a major disease like this has been instructive. I started reading and writing more because of it, even just letters to the paper, letters to friends.

About your disease?

Mr. Le Gate: Not necessarily, no. I’m a political person on the progressive side. I have very strong opinions that I don’t mind sharing. Of course, I’m obliged to do more reading and be more thoughtful about my politics. I think having prostate cancer at this stage of my life has pushed me into this, and I take a great deal of satisfaction out of doing it now.

What advice would you have for a man diagnosed with this disease?

Mr. Le Gate: Find out all you can. Get involved in a group. Neither my oncologist nor urologist ever mentioned support groups. I discovered this just by chance when I was well into the recurrent part of my disease. Had I known that there was such a group when I was first diagnosed, I would’ve been better prepared to make decisions. Your doctor is a human being who can make good and bad choices. You need to be proactive.

I was fairly proactive, but when I first was diagnosed with the disease, had I known there was a support group, I would’ve learned about a number of other options. For example, there’s a group in San Francisco called The Second Opinion. Once you get a diagnosis— for no charge at all—you can meet with a group of doctors and discuss your options. I never knew there was such a thing before. Everybody who’s ever discussed the options thoroughly and looked at all sides of the coin can set their mind at ease before they make any decisions.

Are there other ways that the prostate cancer diagnosis might have had a positive impact on you?

Mr. Le Gate: After a lifetime without serious health problems, it’s not a bad thing to realize that you’re mortal. I think it’s made me more responsible about whatever time is left of me. I want to use my time the best way I can and to learn something, even if it’s just to learn something about the disease. There’s so much to learn about healthcare and the science of treating with medicine, but most people, if they’re healthy, simply ignore this. To be more informed in this way, and to have the disease yourself— if you’re smart and if you have a sense of humanity—you’re going to think about other people who have the disease and be more sympathetic to others.

The diagnosis has made you more—

Mr. Le Gate: Empathetic. I want to reach out to the people I see at my support groups because I know something about the disease, especially for those who have just recently been diagnosed. Because I know a bit more, because I’m old hat, if I’m able to do the slightest thing to relieve their anxieties and fears, that’s a good thing. I’m hopeful that I can put together some sessions at my prostate cancer support group where participants can discuss their mental state. At the last meeting, when I was asked to be the facilitator, I came up with the idea to put together a questionnaire, which would be voluntary and anonymous. I want to see what people have done to mitigate, find some distractions, and to discuss anxieties.

I’ve noticed in our group that we’ve discussed the mechanics more than the emotional. You have to be careful that you don’t make this into a weepy, touchy-feely thing. I’m trying to navigate it so that we can discuss our emotional things in a sensible way that’s helpful, that doesn’t make people more fearful.

You want it to be a positive experience?

Mr. Le Gate: Exactly. I was pleasantly surprised when I raised the point, which was so different than the things we usually talk about. We usually talk about where someone is in their treatment. The response was relatively positive from people.

It’s an Us TOO through the University of California Davis Medical Center and Dignity Health. We alternate between those two venues. I’ve been with this group about three years. I’m not a person who joins things, but it’s become an important part of my life. I have the support of my peer navigator, Bill Doss, and our Director, Beverly Nicholson. They are just fabulous people. I’ve really gotten a lot out of it, and I think others have too. It helps to be almost 75 years old and still have your wits about you.

To realize your experiences in life could be useful for a lot of other people. That’s what’s working for me.

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Patients Speak: Getting The Gallium-68 PSMA Scan

Mr. Michael Dietrich had the gallium-68 PSMA scan as part of a clinical trial when his PSA starting rising three years after the completion of radiation therapy. He spoke to Prostatepedia about the scan and how the results altered his treatment path.

How did you find out you had prostate cancer?

Mr. Michael Dietrich: I had a bad case of prostatitis in 2006. A PSA test done at that time read a value of 6 ng/ml. My urologist was concerned and I had a six-core biopsy performed. All six cores came back negative. I was treated with antibiotics for the prostatitis, which alleviated my symptoms. The urologist thought my elevated PSA was related to the infection and did not stress close monitoring of my PSA. I didn’t know any better and I put it out of my mind. I had another bout of prostatitis in 2011. A PSA test then revealed a high value of 65 ng/ml. A 12-core biopsy (a newly established standard) was performed and revealed 80% involvement, 4+3=7 Gleason score, and seminal vesicle involvement. I don’t know if there is a relationship between my prostatitis and my cancer, but the synchronicity is odd. Either way, the prostatitis led me to my urologist and, weirdly enough, I have to say I’m grateful for it. Gratitude for prostatitis. Weird, huh? I also was diagnosed with osteoporosis at that time. I was 50 years old.

Young.

Mr. Dietrich: Yes, pretty young. Though undetected, I probably had prostate cancer at 45 years old when I had that original PSA test and biopsy done. If I had had a 12-core at the time rather than a six-core biopsy, they very well may have found it then. Needless to say, I’m a fan of 12-core biopsies.

What treatments were suggested to you and which did you choose?

Mr. Dietrich: After the tumor board at Hollings Cancer Center here in Charleston, South Carolina, discussed my case and I was presented all my options, I opted for aggressive radiation and hormone therapy. As I had seminal vesicle involvement, I believed I would need radiation anyway, as I understood typical surgical outcomes involving seminal vesicles were often not so great.

What type of radiation did you get?

Mr. Dietrich: I had both intensity modulated radiation therapy (IMRT) and brachytherapy. For about six months before treatment, I had androgen deprivation therapy (ADT). I chose to have it a little longer than normal in hopes that it would further shrink the tumors to narrow the target for radiation and further sensitize the cancer to radiation toxicity. I don’t know if the wait really helped, but in my mind it made sense. After radiation treatment was finished, I received 18 months of ADT3: Lupron (leuprolide), Casodex (bicalutamide), and Avodart (dutasteride). I’ve really been very happy with all the treatments I’ve received.

What kinds of side effects did you have from the radiation and ADT?

Mr. Dietrich: During radiation treatment, I got tired and a little achy. It also constipated me, which surprised me because a more common symptom is diarrhea. I asked for a peristaltic drug as I felt GI motility was an issue, so I was on Reglan (metoclopramide) at the end of treatment and it did help. Currently, I have the extended side effect of having to urinate a couple times a night, but it’s tolerable. I have moderate, not severe, erectile dysfunction (ED). I use Viagra (sildenafil) if necessary.

My very fine radiologist is an advocate for the use of rectal balloons during radiation treatment to help protect the colon from unwanted exposure. They were used during every treatment. Having a rectal balloon inserted in your colon (20 plus times) in conjunction with maintaining a full bladder during treatment to minimize organ movement is not a comfortable combination, but yes, it’s absolutely worth the beads of sweat you may develop on your brow it if helps with outcome and your future health.

The hormone therapy had its challenges for sure (like hot flashes, mood swings, and tender nipples), but like any other experience that a life can be presented with, be it negative or positive, I found it a learning experience.

As I was going through hormone therapy, my wife was going through menopause at the same time. We would trade the ceiling fan remote back and forth all night long dealing with our hot flashes. It was a bonding experience and it was interesting to be a guy understanding menopause.

I tried an experiment: from the day I started my hormone injections, I never shaved. I wondered how a lack of testosterone would impact beard growth and, interestingly enough, I had a 5-inch beard after my two year castrate period. Much of my body hair receded, though.

I lived in a beach town while I was on hormone therapy. If you fully want to understand how testosterone rules an adult male’s perception, remove sex hormones from your body, go to the beach, and monitor your perception and interest. An attractive, half-naked body can be as interesting as a sea gull or a dead horseshoe crab. Interesting, yes. Desirable, not so much.

I was surprised to find, at times, a certain beauty in neutrality and in being in a state of unsexually biased perception. Like the lifting of an obscuring fog to some degree. I was happy when my hormone therapy was over and I got my energy and sexual interest back, but the window of perception was interesting.

I found myself often viewing the world more like when I was a 10-year-old boy. I often experienced lightheartedness and unbiased acceptance of everybody. It was a perception benefit that I’ll never forget for the rest of my life. To this day, because of that insight, I am very aware of how hormones currently skew my perception. Aggression, arousal, competitiveness. It’s all there, but now subject to more acknowledged objectivity than before I attended eunuch university.

I’ve not heard that before.

Mr. Dietrich: Really? I am 50. I went to a liberal arts college in the 1970s where there was quite a bit of experimentation with mind-altering substances, myself included. Controversial, I know, but maybe that early use of hallucinatory drugs in my formative years did set a template for accepting/embracing shifts in perception. Maybe, maybe not. Regardless, I would encourage anybody entering hormone therapy to not be overly wary of it and realize that as your testosterone levels fall, so falls your caring about the fact that your testosterone is going away. Testosterone tends to be very possessive of itself. Be flexible with its passing. Speaking of mind-altering drugs, I was on a low dose of the antidepressant Effexor (venlafaxine) for hot flashes. It cut back hot flashes by 50% and did impact mood as well. It no doubt helped my attitude.

Getting off the Effexor (venlafaxine) definitely requires gradual weaning. I missed a dose or two by accident and felt quite nuts. It requires quite a structured commitment, a commitment not to be deviated from.

What did all this do for the cancer control? Did the radiation and ADT keep your prostate cancer in check?

Mr. Dietrich: My hormone therapy ended in 2013. My testosterone came back to my normal (between

700 and 900) and my PSA stabilized between 0.2 and 0.4. Normal readings for a patient who had received radiation, that is. After three years of stability, my PSA started rising mid-2016.

My mother passed away in January of 2016. Right afterward, my PSA started rising. My father passed on as well in December. My parents lived next door to us and we grew incredibly close. Perhaps it was coincidental, but I can’t help but wonder if the extreme grief and stress I experienced exacerbated my recurrence and contributed to my short three-month doubling time.

Progressively, my PSA rose beyond 2 plus my nadir of 0.15, signaling likely recurrence in a radiated patient. I had a skeletal CAT scan and an MRI. The bone scan was negative. The MRI was largely negative, but it revealed one—and I can quote—area of enhancement involving the right apex and the right posterolateral midgland to base, which could possibly represent residual recurrent disease, and no lymphadenectomy or other metastatic disease to the pelvis. My oncologist here in Hollings, South Carolina, mentioned the gallium-68 PSMA scan. We found a clinical trial at the University of California, San Francisco (UCSF), which I went ahead and joined.

You traveled so far to get the scan?

Mr. Dietrich: Yes. I had options somewhere on the East Coast and in Texas, but I chose UCSF because I have friends and family out there.

What was it like to get the scan?

Mr. Dietrich: I had to wait for about a month for a space to become available on the clinical trial. The scan generally costs $4,000, but my insurance covered it.

It wasn’t much different than an MRI. Very benign. I was worried about side effects, but I can’t say it was any more than with the MRI I had done with a tracer involved. I guess the only thing that really comes to mind is that there was a fairly ominous stainless steel-encased device that shielded the syringe from radiation leakage. I didn’t have any side effects from the solution or the scan. Within days, I communicated with the team performing the scan and they sent me an image and reading. There was one active 3mm node on my right side and a vague, nondescript one on the left, indeterminate but suspicious. No uptake shown on the prostate gland or anywhere else.

What was the plan after imaging?

Mr. Dietrich: That was a process to navigate. Treating oligometastatic disease is controversial with many people feeling that there is no long-term survival benefit in local treatment of local lesions and the correct treatment path is to go on systemic therapy. I was presented with chemotherapy (docetaxel) in conjunction with ADT3. I wasn’t ready for that and my gut instinct (or an extreme sense of denial) kept me looking for an alternative.

Having already had radiation to my pelvis, I was wary of further exposure so I looked into lymph node surgery.

I discovered Dr. Jeffrey Karnes at the Mayo Clinic, who regularly performs lymph node dissections on oligometastatic patients.

He performed a biopsy of my prostate and seminal vesicles, which luckily turned out negative on all cores.

On July 12, 2017, I had the lymph node dissection. Twenty-seven lymph nodes were removed. The pathology revealed two active nodes, the very same two nodes that the gallium-68 PSMA scan revealed. I’m in recovery right now from that surgery.

If you compare the gallium-68 PSMA scan to my MRI, the MRI suggested possible local disease in the prostate and nothing in my lymph nodes. The gallium-68 PSMA scan didn’t show anything in the prostate but did show active lymph glands, which was accurate. It was clear. Very clear.

Had I not had that gallium-68 PSMA scan done, it wouldn’t have been clear to me what to do. The clarity of the scan and the biopsy made me comfortable with the option of lymph node dissection, which in my situation may offer an up to a 20% chance of durable remission/cure or, if nothing else, may extend my time till I have to consider systemic treatment. A gamble perhaps, but one worth taking I feel, especially as I currently have no gross negative side effects.

How is the recovery going?

Mr. Dietrich: So far, I just have regular incision tenderness and soreness. No infection or anything else. The gastrointestinal recovery is a slow process. They have to really move your guts around quite a bit and anesthetize your intestines in order to work. Motility and digestive activity take a while to return even if you’re not feeling pain. I should probably have waited a couple more days for the flight back home, as it was just a week after surgery.

Do you have any advice for men who are considering getting this scan?

Mr. Dietrich: I wouldn’t hesitate. When I compare the results of what my MRI read compared to the clarity of the gallium-68 PSMA scan, it’s a no-brainer.

Do you have any thoughts about participating in a clinical trial?

Mr. Dietrich: Well, the gallium trial was just an investigational scan, not a comparative trial involving placebos or a control group. It just felt like any other scan.

As far as my thoughts of seeking treatment options, it can be a frustrating process as you can be presented contradictory beliefs on what’s your best path. Keeping focused on current data and talking to several educated oncologists is essential.

Collect data from everywhere, remain objective, and don’t stop. Web health message boards can be extremely good sources of both knowledge and support. There are other patients present on boards who are fighting for their lives as well and are very aggressive hounds on collecting and sharing current clinical trial, evidence-based data.

I own a company that services pathology instruments here in the Southeast. I’m always telling my technicians to practice distant objectivity and try to revoke preconceived notions when diagnosing a complicated, failed instrument. Preconceived beliefs can block our subconscious mind from connecting abstract dots into a correct forward path of figuring out a complicated problem.

Beginner’s mind?

Mr. Dietrich: Yes, beginner’s mind. That’s a good way to put it. Be confident. As a patient, you are in a position where you might be more open-minded, motivated, and educated on current data than even some physicians. You are fighting for your life and if you remain open-minded and if you don’t have a preconceived belief or a professional position to defend, you can think your way clearly.

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How Has Imaging Impacted Treatment?

Shore_001Dr. Neal Shore comments on this month’s discussion of the ways imaging has impacted prostate cancer treatment.

Imaging is important for newly diagnosed prostate cancer patients who may or may not have localized disease, and it’s especially important for advanced prostate cancer patients, whether they continue to be androgen sensitive or have developed some level of androgen resistance. For earlier stages of disease, there has been a lot of interest regarding multiparametric MRI. Nonetheless, the efficacy of multiparametric MRI is limited by the expertise of the interpreting radiologist. The fusion technology software championed by several of the academic centers has been rolled out without consistency within the community. For some practices, it was adopted due to marketplace competition and the device developers’ promotions. Companies that develop multiparametric fusion technology have not made a significant contribution to the advancement of urologic and radiologic educational needs. That said, some groups incorporated dedicated specialists within their practice to train for high-quality multiparametric fusion-based biopsies. Purchasing the newest promising technology without ensuring a framework to optimize clinical results will lead to poor implementation. In the United States, MRI is still mostly recommended for patients who have had a negative prostate biopsy, but due to age, PSA kinetics, or rectal examination, there is still a concern of possible malignant disease that was missed on the first biopsy. MRI is most uniformly accepted for additional information when evaluating patients for the need for a second biopsy. MRI will no doubt have an ongoing role in the active surveillance population. MRI will no doubt have an eventual role in decision making for possible first biopsies.

 

There has been a lot of very good, evidence-based literature coming from European countries that suggests that whole-body MRI, with the right software protocol, is exceptionally helpful in evaluating metastatic disease. Unfortunately, in the United States, this protocol takes 45 to 60 minutes to accomplish, and unfortunately, translates to a challenging economic utility model for the MRI efficiency from an administrator perspective. There are many interesting and promising blood-, tissue, and urine-based markers, genomic assays, and additional imaging techniques, which require ongoing trials to determine how best to use them for the most efficient value-based care model. No single test—MRI or any other blood-, tissue-, or urine-based marker—is perfect. Eventually, we will hopefully develop a cost-effective algorithm that combines a panel of all the different biomarkers. MRI is part of that discussion, but we don’t have that sorted out currently. There have been multiple PET scan technologies developed in the last several years that have been assessed for improved potential sensitivity and specificity, and ultimately, to improve the accuracy of the data that shows cancer spread and its location. MRI and Axumin PET scanshave been approved for advanced prostate cancer patients. There have been other PET scans such as FDG, C-11 Acetate, C-11 Choline, sodium fluoride, which have not received widespread reimbursement approvals nor widespread accessibility. There is also no consensus recommendation for these technologies.


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Advances In Imaging

In October, we’re discussing advances in imaging that could dramatically improve how we treat prostate cancer. (Issue to be released to subscribers on Wednesday October 4.) In our Guest Commentary, Dr. Neal Shore does an excellent job summarizing these advances from a urological perspective, expanding on the interviews by Drs. Matthew Cooperberg and Raoul Concepcion. Dr. Michael Zelefsky discusses the impact these new imaging approaches, especially MRI, have in prostate cancer treatment planning.

Several common themes emerge. One is that the American healthcare system renders the best imaging technologies so expensive that rapid implementation at the community level is limited. The situation in Europe is markedly different; costs are 70-80% lower. As a result, Europe is leading both the development of better imaging technologies and the delivery of these technologies at a community level.

Another common theme is that advanced training and experience are required to use these imaging technologies well. Dr. Cooperberg does an excellent job of outlining this problem in prostate multiparameter MRI. The message for you is just because a nearby medical facility has purchased state-of-the-art imaging equipment does not mean they know how to use that equipment well. For now, travel to centers with a documented track record in using a new imaging technology.

Perhaps the most important point is that before a new imaging technology becomes standard treatment, extensive clinical trials need to validate the technique. How do you know when an imaging technique has passed such scrutiny? One landmark is whether or not the imaging technology has been FDA approved. For example, the C-11 Choline and Axumin imaging scans are FDA approved and covered by Medicare to detect metastatic prostate cancer. The Gallium-68 PSMA PET/CT scan is very promising, but not yet FDA approved.

In several of this month’s conversations, we mention the role of imaging in the management of oligometastatic disease. In oligometastatic disease treatment, we use radiation or surgery to eliminate metastases, potentially delaying cancer’s progression for a clinically useful time. By now, it is clear that there are patients who benefit from this treatment.

What is not clear is how effective we are at identifying who those patients are. This will only be resolved by well-designed randomized clinical trials. Fortunately, such trials are in progress and additional trials planned.

Charles E. Myers, Jr., MD

 

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Living With Erectile Dysfunction After Prostate Cancer

Steve A. talked with Prostatepedia about his experience with erectile dysfunction (ED) after surgery and radiation for his Gleason 9 prostate cancer.

What was your life like before you had prostate cancer?

Steve A: A hell of a lot better than it is now. I think about and read about prostate cancer daily. I have no symptoms. Never have had any. But I work hard to combat the side effects of treatment and forestall recurrence. Eat right, exercise daily, and try to help others with prostate cancer.

I’m retired. I was a senior executive at a Fortune 10 company. I retired early back in 1998 and moved part-time to a resort community. I played a lot of golf and worked in community projects, including community government, and started a real estate development business.

I moved here full-time in 2001 and noticed that I had a problem with urination frequency. I saw a urologist who determined that I had benign prostatic hyperplasia (BPH) and put me on Avodart (dutasteride).

Then my prescription drug plan dropped Avodart (dutasteride), so I switched to Proscar (finasteride). Later my urologist added Flomax (tamsulosin) to shrink my prostate. I was on Proscar (finasteride) and Flomax (tamsulosin) continuously until 2013. They controlled my BPH pretty well but impacted my sexual performance. My sex life was not as good as it was before that as a result. I had mild ED.

Did you go on any medication for the ED at that point—like Viagra (sildenafil) or Cialis (tadalafil)?

Steve A: I tried them. They worked.

When and how did you find out you had prostate cancer?

Steve A: I had been getting annual PSA tests since age 40 as part of annual company physical exams. The PSA was around 0.4 for years, then increased gradually as I aged. But it was never considered a problem since it was well below the magic 4.0 considered “normal.”

Then, in 2013, my PSA suddenly doubled to 5.4 from 2.7 in 2012. I had it checked again and this time it went up to 6.6 in only a few months. So my GP, who recognized that PSA velocity (doubling time) was an indicator of a potential problem, recommended a biopsy. I found out that finasteride cuts PSA roughly in half, so my PSA was actually 13.2. This shocked me. Should I have had a biopsy years earlier? Could I have cured my cancer if I’d found it earlier?

So you had a biopsy?

Steve A: I got a biopsy from my local urologist. The Proscar (finasteride) had reduced my prostate size quite a bit, so I only needed to have six cores taken. It was painless. Pathology found 40% prostate cancer in one core and 10% in another core. The others were clean. My Gleason score was 4+4=8. I had a second opinion done by prostate cancer doctor Jonathan Epstein at Johns Hopkins; he upgraded my Gleason score to 4+5=9.

My urologist talked about what I should do. Was I a candidate for active surveillance? He didn’t think so. Turns out that was a huge understatement!

He said I was a candidate for either radiation or surgery due to my age (69 then) and otherwise good health.

So I saw a couple of radiation oncologists and a couple of surgeons. In addition to seeking a cure, I was concerned about three things: ED, hormone therapy, and dragging out the treatment process. I’m the kind of person who likes to get stuff done my part. I now question my decision to have surgery since the cancer had already escaped the prostate. Should the urologists or I have known that?

When you met with these different surgeons and radiation oncologists, did any of them speak to you about ED after treatment?

Steve A: I asked both surgeons if they could do nerve-sparing surgery because I was concerned about my sex life after treatment. The local surgeon said, “No, I wouldn’t try it. With Gleason 9, I’ve got to go pretty wide on the margins to ensure I get it all. I can’t promise that at all.” He was totally unconcerned about ED. I didn’t like his bedside manner!

When I spoke to Dr. Epstein he said he would do nerve-sparing surgery and gave me printed handouts which addressed all facets of what I could expect post-op, including incontinence, ED, etc. I liked his can-do attitude and was impressed with his credentials and Johns Hopkins’s reputation in the field of urology.

What about the radiation oncologists?

Steve A: I don’t remember them saying anything about ED. But they both agreed that hormonal therapy would be necessary before and after radiation therapy. That turned me off completely. I had read about the side effects of hormonal therapy and wanted no part of it. However, in addition to talking to people, I do a lot of reading. I read that you’re going to have ED with surgery, but that it’ll go away after a year or maybe two. ED with radiation comes later on.

I decided I’d rather have ED up front and get it over with than have it come two or three years later. So I went with surgery.

What happened after the surgery?

Steve A: The day before surgery, the doctor changed his mind and suggested that I have open surgery rather than robotic. He wanted to be able to feel the tumor, margins, and lymph nodes to determine which to resect. I was a bit concerned about recovery from open surgery, but he convinced me it would be no worse than robotic.

He resected about 10 lymph nodes and found nothing there. Pathology ended up very poor: positive margin at the base, seminal vesicle invasion, and extracapsular extension. It was serious because it had already escaped the prostate. I was downgraded from stage pT1c to stage pT3b.

When the surgeon came in to talk to me about my prognosis, he was not happy and said, “You’re going to be fighting this for the rest of your life.” Turns out I was one of the 10% with a high-risk case. I asked him how long I had to live. He said I’d still be alive in 10 years and sent me a nomogram that scored each of my risk factors in terms of life expectancy. I hope he was right!

So obviously, I had ED after surgery. I had incontinence for a while too, but it was mild. I wore one pad a day for 13 weeks, but haven’t had much of a problem since. I had no complications from surgery. My wife and I flew to Baltimore. She stayed in my recovery room. We flew back home three days later. The catheter and stitches were removed by my local urologist 10 days later. I was playing golf three weeks after the surgery. I’ve been unable to have any sex ever since. But subsequent radiation treatments are probably the main cause of my ED now. I’ve been fried.

Were you able to talk to your doctor about it?

Steve A: Yes. He said you have to use it or lose it. Then I had recurrence (rising PSA) so I no longer conferred with my surgeon. Only six months after surgery, my PSA started going back up again. I needed hormone therapy and radiation after all! In mid- 2014, I had 38 fractions of salvage radiation therapy (SRT). I was also on Lupron (leuprolide) for six months. That completely destroys your libido anyway. I didn’t even have any desire for sex.

Were you more worried about the recurrence than any ED?

Steve A: Absolutely. When you have Gleason 9 with my poor post-op pathology, survival—not sex—is all that matters.

I’ve had recurrence twice since SRT: in two pelvic lymph nodes in 2015 and in my right femur in 2017. In 2015, I went down to Florida to have 50 fractions of intensity-modulated radiation therapy (IMRT) to all my pelvic lymph nodes and was on Lupron (leuprolide), Casodex (bicalutamide), and Avodart (dutasteride) for 13 months. Just a month ago, after stopping hormonal therapy, they found a lesion on my upper right femur. I’m now back on hormonal therapy and had stereotactic body radiation therapy (SBRT) in three fractions locally to my femur. I’m also on Xgeva (denosumab) for bone mets.

So far, no cancer has been found in my prostate bed, lymph nodes, or other soft tissue or organs. In that sense, I guess I’m lucky.

I’ve completely forgotten about the whole issue of sex. At night, when you dream, you sometimes think about it and really miss it, but the reality is that my primary goal is to be healthy, happy, and live as long as I can. I don’t need sex for that.

Did you ever seek treatment?

Steve A: I talked to my urologist. After surgery, I used the pump.

Did it work?

Steve A: It was marginally successful. I just wasn’t too keen on it. I thought it was more of a pain than anything else. I didn’t try injections. I tried daily Cialis (tadalafil). That didn’t do anything. The urologist talked to me about having an implant.

I haven’t really given that any thought. Now that I’m back on Lupron (leuprolide), I don’t have the desire for anybody. I’m just totally oriented to quality of life and length of life at this point. Quality of life doesn’t necessarily mean sex anymore.

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