ED After Radiation For Prostate Cancer

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.

Prostatepdia recently spoke with him about erectile dysfunction after radiation therapy.

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How common is erectile dysfunction after radiation for prostate cancer?

Dr. Micael Zelefsky: Firstly it’s important to point out that erectile dysfunction represents only one of the many aspects of sexual function that needs to be considered after treatment. Certainly, an important component is the ability to have a sufficient enough erection for penetration. There are other aspects of sexual function that are important to consider. These include the sensation of orgasm, associated pleasure, and the experience of the sexual intercourse, the libido, and as well as other aspects.

When we have a conversation with patients regarding sexual function after radiation, we in general speak not only about the likelihood of maintaining an erection but also about whether there is any associated ejaculatory dysfunction, orgasmic dysfunction, and, while not affected necessarily from radiation, changes in libido. Changes in libido could be related to hormonal therapy, which is often given together with radiation, especially for higher risk patients.

Specifically, erectile dysfunction after radiation therapy is seen in about 25 to 50% of patients. Because erectile dysfunction is a multi-factorial problem, there are many aspects associated with the likelihood of erectile dysfunction. When I say multi-factorial, I mean that there are many characteristics and variables associated with erectile dysfunction in general, such as the age of the patient, the baseline sexual function of the patient, the medications they take which all need to be considered when talking with anybody about erectile function.

Meaning you need to discuss these considerations before a man has radiation?

Dr. Zelefsky: Correct. People who have significant issues or have functional erections in a borderline fashion prior to radiation are more likely to lose erections after radiation. People who have a better baseline status are clearly much better off after treatment and have a greater likelihood of preserving their erectile function. The age of the patient, as has been shown by the Massachusetts Aging Study and other studies, plays a very important role as well. Older patients generally may have a greater likelihood of losing erectile function compared to younger patients.

This, of course, depends on a host of other factors like comorbidities, cardiac disease, peripheral vascular disease, and other medical comorbidities where such patients have clearly higher risks of ED compared to other patients. A smoking history is important; those people who are actively smoking clearly have a lower incidence of preserving their function compared to those who are not smoking. In a patient population getting radiation, often those with some associated comorbidities, generally an older patient population, the incidence of ED may be higher than a surgical patient population, not because of what radiation can do in terms of erectile dysfunction, but because we’re dealing with a very different patient population based on the presence of medical comorbidities, age and sometimes the baseline erectile function status of the patient.

And, as you pointed out, many times men are receiving hormonal therapy at the same time. 

Dr. Zelefsky: Yes. And with hormonal therapy itself, the addition of hormonal therapy could increase the risks of ED in this patient population. I think it’s interesting to mention the ProtecT trial, which was a randomized trial from the UK published in The New England Journal of Medicine that compared active surveillance to brachytherapy compared to external beam radiation therapy. The ten-year data that was published looking at toxicity outcomes specifically noted that among the radiation patients, and in particular among the brachytherapy patients, there was less sexual dysfunction compared to the other groups. We noticed that as well in our own prospective Quality of Life Study where we obtained information from patients sequentially after their radiation treatments. We noted that there was potentially less impact on sexual function among the patients who got radiation, and in particular brachytherapy, within all of the treatment groups.

The take-home message here is that ED does happen after radiation, probably in a range of 25 to 50%. That range is large because it depends heavily on baseline function, age, comorbidities, smoking history, and the concurrent medications that patients may be taking.

A direct comparison of ED after surgery versus after radiation is generally uncommon. It has been made, as I just mentioned, based on the ProtecT trial. In that trial where they made such comparisons, they reported less dysfunction among the non-surgical patients compared to surgery.

Is ED after radiation treated differently than ED after surgery?

 Dr. Zelefsky: Generally the approach is the same. Many years ago, we published a study where we tried to look at the cause of erectile dysfunction after radiation. It seemed that it was somewhat different than surgery where the cause of erectile dysfunction after radiation may be more of a blood vessel dysfunction rather than dysfunction of the nerves controlling the erections. We found that among patients who had radiation, more often, the cause of ED was related to what we called arterogeneic dysfunction, which basically means the small blood vessels are affected by the radiation. Blood flow is obviously critical to the maintenance of an erection. That could be the cause of the issue after radiation, rather than dysfunction after surgery, which is more likely caused by damage to the nerve bundles intimately involved with erections.

The cause of erectile dysfunction after radiation could be related to other things as well, but if it is a blood vessel phenomenon, it makes a good deal of sense why people have responded well to medications like sildenafil, which has about a 70% response rate in such patients. We generally treat our patients with such medications, but there have been a couple of studies that have been explored. It’s certainly been done in the surgical population. We’ve done it as a randomized trial in the radiation population where we randomized patients to getting sildenafil or a placebo as prophylactic therapy before, during, and after radiation. We published some very interesting findings: patients who did end up receiving the sildenafil as a prophylaxis to promote blood flow in the penile complex more often had better preservation of their erections longer term. Overall, those patients felt their erectile function was much better than the group who ended up getting the placebo. This is an approach or a strategy used in surgery patients, which is known as penile rehabilitation.

We routinely utilize that approach in our patients, especially in those who have good baseline function by recommending to them to take medications like sildenafil daily at a low dose before, during, and after their treatment.

How long before radiation do you start the medication?

Dr. Zelefsky: About a week or so before and obviously during the treatment and then ideally for six to twelve months after the course of their treatment. That really covers the effectiveness of treatments. There are other, obviously, approaches besides medication. These include penile injections, vacuum pump, or surgery to promote erections as well by having an artificial device that’s inserted to achieve an erection.

Can you talk a bit about ED among men who have had salvage radiation?  

Dr. Zelefsky: These are patients who have radiation after having had surgery. Even if they still have erections, more frequently than not, their erections are not exactly the way they used to be, although they could still be functional. Additional radiation may increase further their chances or risk of losing erections. About 40 to 50% of patients have ED after salvage radiation. Nowadays, more often than not, salvage radiation after surgery incorporates a six-month course of hormonal therapy. Sildenafil or similar medications may be somewhat less effective among people who had surgery and radiation following this, especially after a patient has had a significant surgery like a prostatectomy with radiation and hormonal therapy to follow. This means a lot of treatments have been placed on the general nerve bundle and vasculature and the risks of ED could certainly be higher in that population.

What is my final advice for patients who are going into radiation for prostate cancer and are worried about ED? In general, if patients have good baseline function before the radiation, I think they have good odds of keeping that function afterwards. They should consider the use of daily sildenafil before, during, and after their treatments and try to continue it at a low dose after their treatments for perhaps six to twelve months. They may use higher doses of the medication when they want to be sexually active.

Those who are entering into a course of radiation need to know, as we discussed before, that there are other aspects of sexual dysfunction patients need to be aware about. These other aspects include a lack of ejaculation in 80 to 90% of patients, although interestingly in most patients, the sensation of orgasm is generally preserved. Patients should also understand the impact of hormonal therapy and the decrease on the libido. It can take a good six or twelve months after cessation of hormonal therapy for testosterone to normalize again. Awareness and appropriate expectations are important.

Finally, for those people who have had radiation and are struggling with ED, there are very good approaches out there. I encourage patients to see a urologist with special expertise in sexual function to work out the various possibilities, such as penile injections and other approaches, which I think could be valuable and potentially effective.

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Penile Prosthesis For ED

Dr. Jean-Francois Eid, of New York City’s Advanced Urological Care, is a urologist who specializes in treating advanced erectile dysfunction.

Prostatepedia spoke with him recently about penile prostheses after prostate cancer.

How did you became involved in treating men with erectile dysfunction (ED)?

Dr. Jean-Francois Eid: When I was a third-year medical student, I did a general surgery rotation in urology, and I went to a lecture about penile implants. I was fascinated that such a device could be made. Because I have an engineering background (I’m a material science engineer), I felt then it would be a dream to work with the industry that produces these magnificent devices, to continue to improve them, and invent surgical equipment to facilitate implantation. My dream came true.

I work with Boston Scientific and Coloplast, companies that make penile implant devices for men who suffer from ED. I’m on their advisory committee, and we collaborate in order to improve these devices. I have a few patents to my name as well. It’s been a great ride for the last thirty years.

I, of course, learned from a lot of many great implant surgeons and have benefited from their experience. I also felt that it was time for me to give back and I was very honored when I was asked to write a chapter on penile implants in the Campbell- Walsh urology textbook, required reading for all Urology Residents.

How common is ED after prostate cancer?

Dr. Eid: It varies depending on the treatment that the patient received and the level of erectile function the patient had before treatment. For example, if a patient had normal erections before radical prostatectomy, studies show that about 7 to 10% of these patients will have normal unassisted erections after the prostate operation. About 30% of these gentlemen will respond to oral therapy such as sildenafil or tadalafil. The remaining 60% will need a more advanced ED treatment option, such as a penile self-injection or a penile implant.

Patients who undergo radiation therapy fair a little bit better. They develop ED about a year to a year and a half after the radiation, and about 50% of these patients will respond to oral medications. The remaining will also need more advanced treatment options such as penile self-injection or penile implant.

What is the progression? You try medication first, and if that doesn’t work, then you go to injections, and finally something like a prosthesis?

Dr. Eid: Exactly. Patients who undergo radical or robotic prostatectomy tend to be younger and healthier, and we recommend a period of penile rehabilitation with either oral therapy, vacuum device or penile self-injections. The data supporting penile rehabilitation is not very robust, nevertheless if a patient had normal unassisted erections prior to the cancer treatment, I would recommend a 12 to 18 month waiting period before proceeding with a penile implant. He is unlikely to recover spontaneous erections beyond the 2-year period, however. Conversely, if a patient relied on oral medications or penile self-injection for satisfactory sexual intercourse prior to the prostatectomy, it is then very unlikely for erectile function to return. In that case, one may proceed with a penile implant before the 12 month waiting period. Oral medications and a trial of penile self-injection is always recommended before proceeding with a penile implant.

If a man struggled with ED before going into prostate cancer treatment, will that impact if he has ED after treatment?

Dr. Eid: Yes, the ED is more likely to be advanced and be more difficult to treat. Penile atrophy, deformity and permanent shrinkage are more likely to occur. Early placement of a penile implant may in that circumstance be a better option as it will prevent further penile deformity and shrinkage while restoring erectile function.

What is penile implant prosthesis, and what are the different types?

Dr. Eid: There are basically two types of penile implants: malleable and inflatable implants. Malleable implants are always firm and positional so that they can be concealed by manually bending it down when not in use. These are the simplest of the penile implant devices. However, the feel of the penis is not as natural as for the inflatable devices. Because the shaft of the penis is always firm, pressure atrophy of the flesh of the penis will occur over the long run.

The inflatable devices can be further divided into two groups: devices with a self-contained reservoir, also referred to as a two-piece implant and the multi-component implant with cylinders, pump, and a separate reservoir referred to as the three piece implant. The reservoir is needed in order to store the saline when an erection is not desired. The two-piece devices are comprised of a pair of penile cylinders with a small saline reservoir built into the back of each cylinder and a scrotal pump. To obtain an erection the scrotal pump is squeezed, transferring the saline from the reservoir into the cylinders. The volume of saline is limited, which means there’s a compromise between penile rigidity when inflated, and the flaccidity of the penis when the cylinders are deflated.

The three-piece inflatable implants are the more physiological devices with a better erection when inflated and better flaccidity when deflated. The separate reservoir is easily concealed and because it contains a much larger volume of saline it enables the bearer to have a much firmer erection.

There are approximately 25,000 implants performed in the United States every year of which 90% are the multi-component inflatable devices. These devices were invented in 1973, and they’ve been refined since. There are only two companies that make them: American Medical Systems, (Boston Scientific), and Coloplast. Both are excellent companies and current implants have an average life expectancy of 8 to 12 years. When they fail, they are easily replaceable. The procedure to remove and replace it is a lot less cumbersome for the patient because the space inside the penis is already fashioned. There’s less pain and swelling than for the original implant placement.

Is there a difference in performance between the two types of devices?

Dr. Eid: The multi-component inflatable devices give the most natural feel of the erection and are a lot more comfortable when the patient no longer wants to have an erection. The malleable implants have a very firm and abnormal feel to them. Over time, the flesh of the penis will become looser over the rigid cylinders. This renders the malleable implant to be less firm than the inflatable device. On the other hand, when the inflatable devices are deflated the cylinders no longer apply pressure on surrounding penile flesh, preventing long-term penile atrophy

When is a penile implant prosthesis a possible solution for men with ED? When is it not a viable solution?

Dr. Eid: Any man that can have an erection on his own or respond well to oral medications may forgo the need for a penile implant

We don’t expect patients who rely on penile self-injections to stay on them for the rest of their lives, and even if the response to injections is very good, it is not unreasonable to proceed to a penile implant. There are very few circumstances that contraindicate placement of a penile implant; these are the presence of an infection or in situations where the patient is medically unstable.

What is the procedure once he decides this is what he wants to do?

Dr. Eid: It is most important to seek the most experienced surgeon that one can find. That surgeon may not be necessarily the one closest to one’s home or in one’s insurance plan. A penile implant specialist is preferable to a general urologist. A penile implant specialist has a much greater success with fewer complications. Each specialist will have their individual pre-operative protocol.

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How A Urologist Approaches ED

Dr. R. James Yu is a urologic oncologist with MarinHealth Urology | A UCSF Health Clinic in Marin County, California.

He spoke with Prostatepedia about he approaches erectile dysfunction after prostate cancer treatment.

Why did you become a doctor?

Dr. James Yu: My parents always engrained in me the importance of helping others. When I was younger, my mom was also diagnosed with a rare thymus cancer that metastasized to her lung. I got to see first-hand the impact cancer had on someone’s life and on the people around them. I saw her going through chemotherapy and the recovery from surgery. It created an instinctive affinity and empathy in me towards cancer patients. As a result, going into medicine was an easy decision for me, specifically in the field of urologic oncology. I was specifically drawn to urology because of the relationships that I could develop with the patients, which I don’t feel is a common thing in surgical subspecialties.

Have you had any patients over the years who have stood out in your mind as either changing how you think about your own role or how you view the art of medicine?

Dr. Yu: Definitely, but I think my mom had the biggest impact. That’s because I got to see cancer from the other side of the exam room, from the patient’s perspective. I learned from her the importance of having a team when fighting cancer. Everyone has a role to play: the patient, spouse, kids, church, friends, surgeon, medical oncologist, and radiation oncologist. It’s because of her team that helped her beat that cancer.

I see my role in a few different phases when treating prostate cancer. The first phase is when you initially get diagnosed. Of course, my job is to educate about the disease, the treatment options, and all the pros and cons of each modality; but my other job is to help alleviate the anxiety when hearing the C word in their body. Most patients have already done their preliminary research when they come to see me. Their minds have already naturally jumped to conclusions. That is what I saw my mom go through. Dealing with that emotional side of things is important. Until you’ve done that, patients won’t hear what you’re saying. That is why we spend so much time with patients at that initial consultation.

The second phase is actually doing the technical part of the surgery, which is critically important. It requires a lot of experience and expertise to deliver great results. The last phase is the survivorship. This part of the patient’s journey is often overlooked. Patients are having to continue surveillance for their cancer, and are sometimes dealing with some of the side effects of treatments. They always tell me they are super anxious to see their PSA results. But as time passes, they gain more confidence in their cancer control, and also see their side effects improve or resolve. You start to see the tension melt away in their faces. It really brings me a lot of joy to see my patients go through that growth and evolution.

How do you approach the subject of erectile dysfunction after surgery with your patients? Do you introduce the subject in that initial consult?

Dr. Yu: Sexual health, in general, is a delicate and sensitive topic for many patients and their partners. That’s especially true when discussing the sexual impacts that prostate cancer treatments can have on patients. In some cases, the embarrassment in talking about sexual health can negatively impact the patient’s overall recovery. That’s why communication before and after treatment is so important for erectile function. That communication needs to exist between the patient and his doctor AND the patient and his partner. My advice to patients is to not assume the other party knows what you are thinking, or that you know what they are thinking. Only talking about these issues can make things better.

Of course, urologists also know that there’s a natural barrier to talking about these topics. As a result, we give patients a questionnaire that prompts us to start the conversation. These questions usually ask about your sexual activity, confidence level, libido, need for medication, and if other medical problems exist that might impact erectile function. This helps to establish a baseline, which impacts treatment results. I also am very proactive in discussing the potential effects of erectile and ejaculatory dysfunction after prostate cancer treatments in our initial discussions. However, despite these tools, and the doctor asking specific questions, it still requires the patient to engage and answer openly and honestly.

You’re saying that some people are reluctant to talk about it no matter how much you press?

Dr. Yu: Sometimes. But everyone processes things differently and on different timelines. Sometimes, we just need to circle back at a later time to address this issue.

What kinds of questions do you suggest men ask their urologists about ED before they have surgery?

Dr. Yu: First, I believe it is up to the surgeon to bring up the specific risks to erectile function related to any prostate cancer treatment. That’s part of informed consent. From the patient’s standpoint, the main questions I would be asking include, “What is your plan for me before, during, and after surgery to optimize my erectile function recovery?” Related to that is, “Do you recommend a specific regimen for penile rehabilitation protocol? Also ask about specific erectile function recovery rates after surgery specifically for that surgeon. But having a specific plan for what’s going to happen after surgery helps alleviate some of the anxiety related to that potential side effect.

I also think the patient should ask themselves and their partner, some questions: “What is the level of intimacy that we have right now? What do we want it to be in the future?” A change in the way couples are intimate can definitely affect a relationship. I recommend that patients bring their partners into the appointment to not only serve as another set of ears, but also to participate in discussions about issues like this.

Some recommend that men seek out a sexual medicine expert before surgery. Do you think that’s warranted? Or would you only recommend that once a man is already having problems?

Dr. Yu: That is always an option. I don’t usually send patients to sexual medicine experts because I’m comfortable having that open discussion with them.

Is there anything men can do before surgery to prevent potential erectile dysfunction after treatment?

Dr. Yu: There aren’t really any studies that show specifically treating men before surgery with a drug regimen actually improves erectile function after surgery. However, there are many strategies to optimize their overall health which will improve their chances—like eating a healthier diet, losing weight if you’re overweight, and improving your exercise tolerance. Quitting smoking is important because that also impacts vascular disease. Lower your stress levels. Drink less alcohol. Manage the things we know directly impact erectile function like diabetes, cardiovascular disease, and hypertension.

Doing these things are not only good for erectile function, but also good for overall longevity. I tell patients that a cancer diagnosis is oftentimes a wakeup call, and they should take this opportunity to adopt healthier lifestyles.

Are there any ED treatments that are more effective than others after surgery?  

Dr. Yu: I don’t think one ED treatment is more effective than another after surgery. However, doing something is better than doing nothing. Also, the sooner you do it, the better, in order to reduce the risk of poor oxygenation, fibrosis and scarring in the penile tissue. It’s very much a “use it or lose it” mentality. I recommend whichever treatment best enables the patient to resume sexual activity quickly after treatment.

Most men start with medications, because that is the easiest to administer. Published studies don’t show a difference between taking it daily versus on demand, although both regimens are most effective when used consistently in the first year. Some men also use a vacuum erection device (VED) to help them have penetrative intercourse sooner after surgery. VEDs have also been shown to reduce penile length loss after surgery, So again, doing something is better than doing nothing. I tend to recommend a daily regimen post-operatively in combination with vacuum device therapy. Every patient has a different mentality about how aggressive they want to be with their rehab. Some couples are not active at all, so they only do on-demand therapy. Others stick with medications, VED, and some of the other treatments out there in combination. These include intra-urethral alprostadil, or intracavernosal injection therapy with either Caverject or Bimix or Trimix.

Then, of course, if all those fail, you can always consider a penile implant. We usually wait for one to two years before talking about the penile implant, just because the expectation is that we will see patients continue to improve for the first one to two years. Nerves don’t regenerate that quickly. Doing something as permanent as a penile implant that quickly after the surgery is usually discouraged.

Are these treatments covered by insurance?

Dr. Yu: It depends on the insurance. The costs of medications was definitely more prohibitive three to five years ago, but many of these medications are now offered as a generic. This makes it more affordable for patients to pursue even if their insurance does not cover it. The VED and injections usually are not covered as well, so patients pay out of pocket for those regimens. A surgical approach like the penile implant is usually covered by insurance.

There has been a lot of recent publicity for low intensity penile shock wave therapy in patients with de novo erectile dysfunction. This treatment has not been studied in patients with ED after prostate cancer surgery so we don’t know its applicability, safety or effectiveness.

Is that painful?

Dr. Yu: Usually not. A numbing medicine is applied to the penis before the shockwave treatments are given.

Do you have any advice for men who are either worried about ED before surgery yet or who are already struggling with ED after treatment?

Dr. Yu: One thing to keep in mind is to look at the big picture and maintain perspective. We need to really consider the prostate cancer first. The reality is that sometimes we need to be aggressive with our treatments for prostate cancer in order to preserve your life. That may come at the risk to certain functions. In other cases, we can offer active surveillance of prostate cancer because we don’t want to risk impacting erectile function while treating an insignificant cancer. Treatment needs to be individualized to the patient.

For patients who have some baseline erectile dysfunction, there is definitely the risk of persistent or worsened erectile function after surgery or radiation. The good news about erectile function is that even if there is poor recovery, there are still many ways for patients get their sexual function back. It may require some inconvenience, but that’s something that the urologist on your team can help you with. Having a proper expectation going into treatment and recovery helps: understand that recovery takes 12 to 24 months in some cases. And that recovery process can be frustrating because things do not feel natural at first. That’s why it is important to keep the lines of communication open. This is not something that is easily tackled alone. Seek help, even though it is such an intimate topic.

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Chemotherapy: An Infusion Nurse’s Experience

Catherine Guider is an infusion nurse with Kaiser Permanente in Sacramento, CA.

She offers Prostatepedia her perspective on chemotherapy for prostate cancer.

Why did you become an oncology nurse?

Ms. Catherine Guider: I was interested in oncology even back in nursing school. I had a grandfather who had cancer and was given a very short timeline of survival, and he was one of those that beat the odds and made it to 93. I got to see a side to cancer that some people don’t get to see.

In nursing school, I did some time on an oncology inpatient floor and found it challenging and rewarding when it came to the personal relationships that I got to build with patients and their families.

When I came to Kaiser, I didn’t start in that department, but after a couple of years, I took an opportunity to move to the floor that does inpatient chemotherapy. A short time later, I was certified with chemotherapy and biotherapy, and I stayed there for many years. Now, I’m in the outpatient infusion oncology clinic.

Have you had any patients over the years who changed how you see your own role or how you see nursing in general?

Ms. Guider: Because I was in the inpatient side where sometimes people stayed for longer than a day or two, I saw the impact that we can have on their lives. I would spend my lunchbreak with some of our oncology patients, sharing lunches and time together, and I noticed that sitting with them would help them eat more and make them feel lighter. It’s gone both ways; they have enriched my life also.

There are definitely some who have impacted me. Being on the infusion oncology team, I’m part of a patient’s cheer group and their support group. When they cry, sometimes I cry, and sometimes that’s difficult. It’s definitely made nursing more personal for me.

What’s the process like for getting chemo for men with prostate cancer?

Ms. Guider: We have a good process here when it comes to onboarding new chemotherapy patients. Our doctors work with our nurse navigators, who then work with our triage on our medical assistance to get the patient scheduled for their chemo class and their first chemo treatment. All these people make sure that labs, pre-med home medications, and post-treatment meds are ordered with support. Overall, there are a lot of people involved to make sure that the patient and their family are well-informed. When they come in, they already have an idea of what that day and treatments are going to be like.

When they arrive, we make sure that a patient is up to chemotherapy. We make sure that they are physically and mentally well, and then we notify our pharmacy to make the medication. We have our own pharmacy within our department. If there is anything questionable, we get in contact with the patient’s oncologist, and they’re directly across the hall from us, so it’s very easy to do. All of that is addressed right then and there.

What is the infusion like? Is it painful?

Ms. Guider: No. You have to start an IV or access a port, which could be painful. But the majority of people don’t feel the chemotherapy. There’s always a potential reaction to certain medications, but we are good about how we handle those. We already have medications ordered that we can administer if someone has a side effect on the premises, and we can get that side effect reversed.

How long does the actual infusion last?

Ms. Guider: It all depends on the regimen. With prostate cancer, that’s normally Taxotere (docetaxel), and that is an hour infusion.

I have only given Jevtana (cabazitaxel) once or twice before, but I believe that’s an hour also. Taxotere (docetaxel) is still the first choice IV treatment.

What kinds of side effects have you seen patients deal with after chemo?

Ms. Guider: The normal: nausea. We send patients home with a list of medications to use for the nausea, and we recommend smaller meals throughout the day to stay ahead of it. There’s the hair loss, nailbed changes. You can have peripheral neuropathy with the chemotherapy. There’s fatigue, of course, and the impact on white blood cells, red blood cells, and platelets that we’re watching for as well.

Do you have any tips or advice for men to make the whole process of getting chemo easier?

Ms. Guider: Somebody’s mindset has a lot to do with how they come into it and how they handle it.

Somebody who’s active, eating a well-balanced meal, and good on their hydration normally does better than someone who isn’t. Some people don’t like to take additional medication, and so there is not that adherence there.

We give patients a list of antiemetics to use if they become nauseated. Sometimes, they take them that first or second day, just as a safety measure to keep the nausea away. Some people don’t like to do that. But it’s always better to stay ahead of the nausea than let the nausea set in because it’s hard to play catch-up and get it to go away once it’s there. Nausea doesn’t only make patients feel unwell, but they’re not going to drink the amount of fluids that they need or eat the meals that they need if they’re nauseated. Coming in with all of that already in place, makes somebody tend to do better.

What role do you see the caregivers playing in the whole chemo process?

Ms. Guider: We invite caregivers to the chemo class. It’s always up to the patient if they want their caregiver to come to join them. Sometimes people and their family members come for the first appointment, and then after a while, the patients come by themselves. We have other people whose family members come every time. It all depends on the role that they already have in the relationship.

Sometimes caregivers are more of the voice for the patient. Sometimes they speak up and say that the patient is having a difficult time getting their food in, or they’re having this nausea afterwards, but the patient is not telling us.

Other times, caregivers are the cheerleaders who will bring a sandwich, and when the patient eats half, they’re the cheerleader saying “why don’t you take just one more bite? Don’t quit yet.” They all have different roles.

We also have caregivers who take an unproductive role, and that’s probably been in the relationship. Encouraging people to do better or take that next bite is very different than a person saying: “you need to eat that.”

Presentation can be huge, and if that avenue isn’t already developed between them, then sometimes we’ll see people bicker over how much they drank the day before.

I guess any conflicts that are already in the relationship will be highlighted by a situation like this, right?

Ms. Guider: Yes, along with the stressors of all of it.

Any other tips you have for men who are about to get chemo or maybe have already had chemo and are struggling with side effects?

Ms. Guider: When it comes to the side effects, you don’t have to struggle through them. Your team is there for you if you speak up. We can change pre-medications around. We can change medications at home. We can try completely different meds. We also have a social worker. We have nutrition. We have mental health. We have various support groups. Be open to reaching out.

Be open to asking questions, getting things clarified, and gathering more information, especially if it’s researched-based. There’s a lot of misinformation on Google that can backfire. You need to make sure that your information is based on research.

We all come in with a different knowledge base, so when it comes to what’s on the internet, sometimes it’s written for a certain group only, and at times there’s not even anything factual.

It’s great to talk to other people who have gone through cancer and treatment, but always keep in mind that every body is different. You could have the same people going through the same exact treatment, and for whatever reason, their side effects will be different, and how they handle them will be different. It’s not a cookie cutter.

Just like everybody comes in with a different level of fitness and a different mindset, right?

Ms. Guider: Yes, and it’s the history of how they took care of their bodies. The other comorbidities that they might have will factor in how they’re going to physically handle the chemotherapy. There’s the whole emotional side of handling the cancer itself. Just the word brings so much with it.

Chemotherapy, Xtandi, and Zytiga

Dr. Julie Graff is a medical oncologist at Oregon Health & Sciences University.

Prostatepedia spoke with her recently about chemotherapy, Xtandi (enzalutamide), and Zytiga (abiraterone) for prostate cancer.

Why did you become a doctor?

Dr. Graff: Even as a child, I wanted to become a doctor, so my whole life I thought about it. Then I went to college, I fell in love with science, and I thought I would get a job somewhere working in a lab.

During college, I volunteered for a hospice, and I realized how much I love patients, how special people are, and how people with cancer are among the strongest people. I was drawn to work with them, and also, my scientific side could still be engaged in research.

Have you had any patients over the years who stand out in your mind as having either changed how you see your own role as a doctor or how you view the art of medicine in general?

Dr. Graff: I’ve had multiple patients who’ve meant a lot to me over the years. Someone I met in hospice stands out. The first time I met him, he said, “I know that I’m 80. You look at me, and what you don’t realize is that I want to live just as much as you do.” He had emphysema and was dying, but the drive to live can stay so strong, even at 80. Your body’s not even working that well anymore, and you’re suffering. Still, just this drive to stay alive is important. I’ve kept that in mind since then.

On the other hand, I’ve had some patients who say that years don’t matter—it’s quality of life. I can appreciate both sides. When I talk to patients, even those who say they want to live forever, I tell them that what we want to do is help them live as long as possible while maintaining a quality of life that they can enjoy.

I guess each person falls somewhere along that spectrum.

Dr. Graff: Exactly. As a doctor, you really just have to educate people, and tell them, “I know you want to live and that you think it’s a good idea to get surgery, even though there’s a 50% chance you could die during surgery or whatnot. But what are your real goals, and how can we help you reach them?” We want to move the focus of the conversation a little bit.

Can you give us a brief overview of how and when chemo is used for prostate cancer. I know it’s different from how and when chemo is used in other cancers.

Dr. Graff: In prostate cancer, there are a couple of settings where chemotherapy is used. We’ve been using the drug Taxotere (docetaxel) for 15 years now. It used to be something we gave at the very end of the disease course, when the hormone shots stopped working, but as of 2015, we use it early in the disease also.

Chemo has a bad rap in some ways. It’s thought to be something you should avoid at all costs, but what people don’t realize is that, when symptoms of the cancer (such as bone pain) get bad, chemo can help. The type of chemo we use in prostate cancer is not as toxic as we do for other cancers. We just use one drug. It doesn’t cause a lot of nausea and vomiting, which is a lot of patients’ worst nightmare. We use it in early and late settings, and I don’t think anything’s going to replace it. Even though we have other drugs now, we run out of hormonal options, and chemo’s a decent option.

When and how are Zytiga (abiraterone) and Xtandi (enzalutamide) used in prostate cancer?

Dr. Graff: Zytiga (abiraterone) and Xtandi (enzalutamide) are similar to chemo in that, initially, they were used at the very end of the disease. Now they can be used up front when people are diagnosed with metastatic prostate cancer, so it depends.

Most people get some mileage out of one or the other, but there is a large degree of cross-resistance between the two. It’s not likely that people would get good cancer response out of both of them. It’s going to be interesting to see what happens to Xtandi (enzalutamide) now that there are other drugs that target the same pathway.

What is androgen-receptor splice variant 7 messenger RNA (AR-V7), and what is its role in resistance to Zytiga (abiraterone) and/or Xtandi (enzalutamide)?

Dr. Graff: The androgen receptor has several domains, and one of them is the ligand-binding domain, which is very important. As this androgen receptor floats around in the cell, the androgens (male hormones) bind to that ligand-binding domain, and so does Xtandi (enzalutamide) for that matter. Cancer cells can lose that part of the androgen receptor, then lose their dependence on the androgens that are circulating and lose the target for Xtandi (enzalutamide). The AR-V7 splice variant can predict resistance to both Zytiga (abiraterone) and Xtandi (enzalutamide), and it might be a reason why there’s cross-resistance between them.

What role does chemotherapy play in this resistance to Zytiga (abiraterone) and/ or Xtandi (enzalutamide) that we see?

Dr. Graff: Fortunately, chemotherapy is still active in people whose cancers are resistant to Zytiga (abiraterone) and Xtandi (enzalutamide), so it still plays an important role. It can be very useful when people have prostate cancer-related symptoms.

We use chemo early on in metastatic disease, right after diagnosis. There are three studies presented in the past year in which they use chemo followed by Xtandi (enzalutamide) or a drug like it. It might be more effective in combination with those other drugs. We’re trying to learn still.

Can chemo reverse resistance to Zytiga (abiraterone) and/or Xtandi (enzalutamide), or does it play any role in that scenario?

Dr. Graff: I don’t know if it can reverse it. I have seen data showing that, if you’re on Xtandi (enzalutamide) and the cancer cells become resistant to that, then if you put a patient on chemo, some of those cells that aren’t resistant to Xtandi (enzalutamide) might come back, and it might be reasonable to re-treat it then. That’s not carved in stone.

Is it being explored in any clinical trials that you know?

Dr. Graff: I hope so. I don’t know which trials those would be.

What about the side effects of these various agents?

Dr. Graff: It’s complicated. Chemotherapy can cause some low blood counts and a risk of neutropenic fever, but then it has other side effects, like neuropathy in the hands and feet, that don’t just reverse automatically. There is also some tear-duct scarring and watery eyes. These might get a little better off the chemo, but they could be permanent side effects for the patients.

This type of chemo doesn’t hurt the kidneys, you need good liver function to get it, and it doesn’t seem to cause hypertension. In those ways, chemo is a good option for elderly men with prostate cancer.

Zytiga (abiraterone) can cause mineralocorticoid excess, which means the adrenal glands aren’t functioning normally. You could get too many of one type of hormone that causes high sodium and low potassium. Zytiga (abiraterone) can also irritate the liver, so we’re careful to watch for the liver function. It can also exacerbate the hormonal side effects of castration.

Xtandi (enzalutamide) is known to cause profound fatigue, which was its dose-limiting toxicity. Of course, it’s linked to seizures, but in people without a history of seizures, that’s pretty unusual. And just like Zytiga (abiraterone), it can cause hypertension. Management of blood pressure and cognitive decline is critical. People have reported that they feel a bit foggier on Xtandi (enzalutamide), and they have also reported increased falls, especially in the elderly. Once you’re off Xtandi (enzalutamide), some of those things will reverse, but it’s possible that being on Zytiga (abiraterone) and Xtandi (enzalutamide) could result in muscle mass loss or other things that won’t recover off those treatments.

What would you suggest to manage those side effects?

Dr. Graff: Exercise is critical for any prostate cancer patient. The drugs we use—even just the initial hormone therapy of turning off the testicles —lead to so many side effects like thin bones, muscle loss, weight gain, and all those things can be mitigated with some exercise. They won’t be taken away, but they could at least be improved. That exercise should continue on the other drugs.

It’s really hard to exercise when you’re on these drugs because you’ve got more fatigue. A lot of patients with prostate cancer have arthritis or some barrier to exercise that makes it difficult for them, but as much exercise as possible is important.

I guess any exercise is better than none, right?

Dr. Graff: Exactly.

Do you have any further thoughts about chemo, Zytiga (abiraterone), or Xtandi (enzalutamide) that you think patients should know about or might not be aware of?

Dr. Graff: They’ve been out for a while now. Any prostate cancer patient starts with a blank slate and has to learn all this stuff with the help of the provider. Think about your goals in life and if these drugs are going to interfere with those. If your goal is to continue working as an architect or something that requires a lot of thought and careful planning, maybe Xtandi (enzalutamide) is not the best choice, and maybe Zytiga (abiraterone) is a better choice.

Some of these drugs are contraindicated in certain patients. A patient with bad heart function, like congestive heart failure or something, should not be on Zytiga (abiraterone), and a patient with a history of seizures should not be on Xtandi (enzalutamide). A lot of thought should go into picking these. The first drug you use is likely to be the most effective, and then as you go down the line, they become less effective.

As a prostate cancer patient, you have several options now; it’s not just chemo or nothing once the prostate cancer becomes resistant to the androgen blockade. Consider lifestyle when making a choice.

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Dr. Michael Morris’s Clinical Trial: Combining Taxotere + Xofigo

Dr. Michael J. Morris is a medical oncologist who specializes in prostate cancer at Memorial Sloan Kettering Cancer Center in New York City where he serves as the Prostate Cancer Section Head.

He spoke with Prostatepedia about a clinical he’s running that looks at combining Taxotere (docetazel) and Xofigo (radium-223).

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What attracted you to medicine in the first place? Why did you become a doctor?

Dr. Michael Morris: I came to medicine from a somewhat different background than many physicians. I grew up in a family that’s heavily focused on the humanities—history, culture, and literature. I inherited those genes from my family, but I also had a real scientific interest that I found to be equally compelling.

In college, I divided my time between literature and science. What attracted me to medicine was that it perfectly merged humanism and science – both patient care and research require an understanding of the history of a patient, his disease, and his treatments. The challenge of medicine is to creatively conceive how biology can be brought to bear to alter these for an individual and the field.

Have you ever had any patients over the years whose stories have changed how you view either the art of medicine or your own role?

Dr. Morris: Many people feel absolutely devastated when they get prostate cancer, which for many people can be a chronic disease. The anxiety provoked by a cancer diagnosis, and even by a detectable or rising PSA can be existential. One of my patients was a Vietnam War veteran. He had been through his share of battles before, and saw more than a few of his closest friends not live past early adulthood. For him, prostate cancer was a reminder to him of what he had survived already. He felt that he was lucky to have lived long enough to face prostate cancer as the primary threat to his life. He took his prostate cancer journey as the next opportunity to lead, to teach, and to be in charge of and help so many people through their disease. Even in our waiting room, he was guiding people and keeping everybody’s anxiety in line. That made a huge impression. People who have faced risks before can be incredibly helpful to those who are not experienced with the helplessness and fear that a cancer diagnosis provokes. We have a lot of first responders in our practice, and their experience managing risk and anxiety can be very helpful to those without those skills. They can help the care providers as much as the patients, too.

From a clinical trial standpoint, I’m struck by the selflessness of so many of our patients. They understand that their treatments are the result of the efforts of patients on studies who have preceded them, and they’re willing to volunteer so that we can learn how to best treat those patients who will follow them. They’re saying, “I’m going to give my body to a clinical trial so that the next generation of prostate cancer patients can learn from my experience.” That’s inspiring.

Talk to us about your Phase III trial combining Xofigo (radium-223) and Taxotere (docetaxel). Why this particular trial? Why now?

Dr. Morris: In general, my research focus is where nuclear medicine and medical oncology intersect. That is, looking at drugs that you can deliver systemically, that are targeted to either the prostate cancer cell itself or to the host organ of most metastatic disease which is bone. And that also means looking at combining those drugs with other drugs that can help patients either feel better or survive longer.

This trial comes out of a long history of work, trying to combine radioligand therapy, which are essentially liquid systemic radioactive drugs, with other systemic treatments, to target both the cancer cell itself and bone, which is the host organ to most metastatic disease.

Xofigo (radium-223) is a known, life-prolonging radioactive agent that targets metastatic disease to bone. Since most metastatic disease in prostate cancer is in the bones, you can really encompass most of the disease by targeting that one bony compartment. Within the bone is the cancer itself, and the chemotherapy is used to target the prostate cancer cell. It’s a concept of dual targeting, both the environment that the cancer is hosted in and the cancer itself. That’s why we’re using these two agents, one of which targets bone and the other cancer, and both of which prolong survival independently, to see if those effects can be amplified by giving them together.

What will you be doing step by step?

Dr. Morris: The first thing is, a man has got to qualify for the trial, which means that he has to have predominantly bone metastases because that is the target for the Xofigo (radium-223).

The second thing is that he can’t have a significant amount of soft tissue disease in either the lungs or the liver. He has to have progressed through standard testosterone-lowering agents, such as Zytiga (abiraterone) or Xtandi (enzalutamide). If that patient is otherwise a chemotherapy candidate, then the treatment involves giving chemotherapy once every three weeks and then the Xofigo (radium- 223) once every other chemotherapy dose, so every six weeks. They’re both IV agents. That’s the essence of the treatment of the study.

Xofigo (radium-223) is a unique radioactive drug. It emits an alpha particle, which releases a lot of energy in a very tiny distance, only a few cell-lengths deep. It has virtually no side effects, so it’s a well-tolerated, life-prolonging treatment.

Chemotherapy is standard first-line chemotherapy in the form of Taxotere (docetaxel). It’s given every three weeks. It’s life-prolonging as well, and is a member of a class of taxane-based chemotherapy.

What are the side effects like for that?

Dr. Morris: Primarily fatigue, but some patients can have tingling in their fingers and toes as well, and sometimes changes in taste. A very small number of patients can have their white blood cell counts suppressed.

How long are you going to be following these men while they’re on these two agents?

Dr. Morris: Patients receive a total of six doses of Xofigo (radium-223) and no more than ten doses of chemotherapy. After that, they’ve completed the treatment portion of the protocol, and they could go on, if they needed, to any other treatments. But we follow them for the rest of their lives.

Are there any fees associated with the trial? I’m assuming the Xofigo (radium-223) and the Taxotere (docetaxel) are provided.

Dr. Morris: The Xofigo (radium-223) is provided by the study, and the patient is responsible for the docetaxel, which is standard chemotherapy.

What else do you hope to learn from this study?

Dr. Morris: There are a whole host of innovative biomarkers and science that is built into this trial, so we learn as much as we can about each patient as they’re treated.

We’re looking at circulating tumor cells and cell-free DNA. We’re looking at the impact of the treatment using novel imaging techniques. We’re looking at quality of life. There’s a whole component of the study that will allow us to learn as much about the prostate cancer and the efficacy of the drugs as well.

Those will be covered under the trial as well, right?

Dr. Morris: Absolutely. Those are all covered by the study.

Is that information shared with the patient?

Dr. Morris: Any information we gather in real-time can be shared with the patient. Some of the scientific aspects of the trial will only be performed after the trial is done, so results from those will be delayed until after the study. But as we learn new information, we pass it on to our patients.

Join us to read the rest of this month’s conversations.

Dr. Alicia Morgans: Putting Chemo Into Perspective

Dr. Alicia Morgans is a medical oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago. She specializes in treating advanced prostate cancer and is particularly interested in addressing treatment side effects.

Prostatepedia spoke with her about chemotherapy for prostate cancer.

Why did you become a doctor?

Dr. Alicia Morgans: I’ve known since junior high school that I wanted to not only become a doctor but an oncologist. I knew I wanted to do something in science that engaged people on a personal level, and I had always admired the way physicians could do that. When visiting my grandmother during summers, I often went to her doctor appointments. I loved trying to understand things on a biologic level, and seeing the way the physicians she had listened and tried to help her. Even when they didn’t have a fix to a problem, they could at least serve as a witness to validate her experience and lend support in any way they were able. Oncology specifically has always been a really challenging puzzle to understand, and the best opportunity to form long-term relationships with patients.

Medicine is an amazing way for individuals to engage at a very deep level, not only with intricate and exciting science but also with really rewarding human interaction. I’m glad I made the decision.

Have you had any patients over the years who have changed how you view the art of medicine or how you view your own personal role?

Dr. Alicia Morgans: There are always patients who change how we move forward with the practice, art, and science of medicine. As it comes to chemotherapy, in particular, there are a number of men that come to mind who, when offered chemotherapy, said there was no way they could do it.

These statements come probably from their prior experience with family members or loved ones who have had bad experiences with chemotherapy. These are real experiences that certainly need to be acknowledged, but I haven’t met a person who we can’t get through at least one cycle of chemotherapy to see if they truly can’t manage it.

Most everyone can get through chemotherapy for prostate cancer because it’s different than chemotherapy for things like breast cancer or leukemia, where we use many drugs in combination that can be intense. This is typically one chemotherapy drug at a time, unless we’re specifically studying more intense combinations in clinical trials.

Most men do pretty well. There are several men who have been so sick from their cancer that, when I’ve given them chemotherapy, they actually feel a lot better, and that is really rewarding. It’s an experience that I use to guide conversations with patients who are frightened of chemotherapy. Sometimes the people who feel the worst at the start feel much better with chemotherapy.

Because the chemo’s killing their cancer?

Dr. Morgans: Exactly.

That’s a really important point you’re making. Just because, say, your neighbor had chemo for breast cancer and had a terrible time, that doesn’t necessarily mean that you will have a terrible time with chemo for prostate cancer.

Dr. Morgans: Absolutely, and there are a number of men who I’ve taken care of through chemotherapy for prostate cancer, men in their 60s and 70s, who have continued to work. Sometimes, men who are in that phase of their career have a little more flexibility with their job, and they can do half days or relax in the afternoon for a half hour and go back to work. Sometimes these are men with relatively physical jobs, and they’re still able to work, other than the day when they’re actually getting treatment, when they’re not able to be physically at work because they’re getting chemotherapy.

It is different than the treatments that we give to young women with breast cancer or people who are getting treatment in the hospital. This is an outpatient treatment. It typically takes about an hour to an hour-and-a-half to infuse. It’s something that we are sure to monitor very closely because we want to be safe, and we want to support people as they develop symptoms. For the most part, people do much better with this type of chemotherapy than they would expect.

At which points are men likely to encounter chemotherapy for prostate cancer?

Dr. Morgans: There are various points at which men can encounter chemotherapy in their prostate cancer journey. This has changed over the last few years. When men have metastatic disease today, whether that’s hormone sensitive or castrate-resistant, we recommend chemotherapy. As of yet, we do not routinely recommend chemotherapy for men who are having radiation for localized disease or for men with biochemical recurrent disease (though both of those populations have been studied in clinical trials, and there appears to be, at least in some of these patients, potential benefits related to that).

There have also been studies looking at neoadjuvant chemotherapy, which is chemo before prostatectomy. There appears to be a potential benefit to that, particularly in high-risk patient populations. But again, that’s not routinely recommended.

For the most part, men with metastatic disease are more routinely being offered chemotherapy, either in hormone-sensitive metastatic disease in the frontline setting or as one of the treatment options in metastatic castrate-resistant disease.

How is it usually sequenced? Or is there a usual sequence?

Dr. Morgans: There’s not a usual sequence, and every individual who is being treated for advanced prostate cancer is probably aware that we don’t have exact data to say which drug should be first, second, or third. These are conversations between men, their doctors, and their families to choose the treatment option that’s best for them.

For men with brand new prostate cancer that is metastatic from the get-go, or for men who have had prostate cancer treatment in the past and now have recurrent disease that’s metastatic but hasn’t yet been treated, we often recommend chemotherapy, particularly for men who have a high volume or high burden of metastatic disease. In that setting, we use six cycles of chemotherapy, and we can help men live longer and feel better. We have data on both the efficacy for improving survival and on the quality of life that show benefits in that population.

It’s important that we use it in that earliest stage of metastatic disease so that we only have to use six cycles of chemotherapy to get a pretty dramatic benefit whereas, if we use it in the later settings, we may use up to ten cycles of chemotherapy for lesser benefit. That’s a consideration when I’m talking to men with high-volume, hormone-sensitive disease.

In the later stages of disease, if we’ve used androgen receptor or hormonal therapies first, then often we switch to chemotherapy after that hormonal approach because it’s a novel mechanism of action and is expected to be more effective. Rather than continuing to hit on the same androgen receptor pathway, we’re using a different way to approach the cancer and overcome resistance.

What are the side effects of chemo like on its own? What about when you’re sequencing it either before or after hormonal therapy? Is there some sort of synergistic or cumulative effect to the side effects?

Dr. Morgans: Usually, we’re using chemotherapy alone with a gonadotropin-releasing hormone (GnRH) agonist or antagonist therapy. That would include therapies like Lupron (leuprolide), Zoladex (goserelin),

and Firmagon (degarelix), medicines that act to stop the testes from making testosterone. Then we add on Taxotere (docetaxel) chemotherapy when we choose the first chemotherapy for men with prostate cancer. The side effects are generally similar whether you use it earlier or later if you’re using it just in combination with that medicine.

With these injections, the most common side effect is fatigue. The next most common thing is neuropathy, which men would experience as a numbness or tingling in their fingertips or toes that, with repeated exposure, can go up into their hands or feet. It can become a more long-lasting issue, or eventually can lead to permanent numbness, especially as you get higher numbers of cycles. For example, if you use ten cycles in the metastatic castrate-resistant setting versus six cycles in the metastatic hormone-sensitive setting, you’re going to have a higher risk of things like neuropathy.

At any point when we’re using chemotherapy, we expect to cause blood counts to go down. Some men need a blood transfusion of either red cells for anemia or platelets for a low platelet count, though that’s relatively uncommon. What’s more common and possible is that the white count, the infection fighting cells, can go down with each dose of chemotherapy, and that count stays down until the bone marrow starts making more cells. We don’t have a transfusion we can give people to make that improve more quickly. That puts men at risk of what’s potentially a life-threatening infection when their blood counts are down, and the more cycles that they have of chemotherapy the longer it takes for their blood counts to recover. That’s another reason to think about using it when you only have to do six cycles as compared to ten.

As men get older, sometimes the side effect burden can become a little more noticeable to them. If we have the opportunity to use chemotherapy in men in their 50s or 60s as opposed to their 70s, we may see that there are fewer side effects. If they’re having a lot of side effects like loss of appetite and weight-loss, fatigue, and pain related directly to their cancer, the side effects of chemotherapy can actually be reduced fatigue, reduced pain, and improved quality of life between cycles.

Because as we said, it’s killing the cancer?

Dr. Morgans: Yes. There was a clinical trial that reported recently indicating that combined Xtandi (enzalutamide) and Taxotere (docetaxel) in addition to the GnRH agonist or antagonist therapy produced more side effects related to chemotherapy when we piled on an additional androgen receptor-directed therapy with the chemotherapy. Although the trial is done, and we see that people ultimately tolerated that more or less, because there was more toxicity and not a benefit to that triple-therapy approach, we’re not recommending that we do anything more at this point than chemotherapy with a GnRH agonist or antagonist. We’re not using a third androgen receptor-directed type medication in that cocktail, and that’s just to say that the more treatments that you add together, the more toxicity related to chemotherapy.

Is there anything men can do before getting chemo to prevent some of these side effects?

Dr. Morgans: One side effect I didn’t mention is that men can have some hair thinning. Usually, they don’t go completely bald, but they can have some hair thinning and some hair loss. Men can use a cold cap during each cycle of chemotherapy, which can reduce hair loss during chemotherapy.

I’ve had a number of patients whose job requires that they put forth a healthy image. We all want a healthy image, but for some men who work in financial spheres, trying to get people to invest in their companies, or if they work in investing, they have expressed to me that they can’t look sick, they can’t have hair loss.

They’ve used these cold caps and have not lost their hair. It’s impressive and surprising to me how effective the caps were for them.

That is something that they can do to try to reduce hair loss. Cold caps are approved for women with breast cancer who are receiving chemotherapy, and they also seem to work in men. They’re not always covered by insurance, but they can be really effective.

Cold caps were FDA-approved in 2017. You can read the FDA press release here: https:// http://www.fda.gov/news-events/ press-announcements/fda-clears-expanded-use-cooling-cap-reduce-hair-loss-during-chemotherapy.]

Other than that, it’s important that men do their best to stay active. The more active they are before chemotherapy, the better able they’ll be to stay active while they’re getting chemotherapy and to make sure that their bowels are moving as regularly as possible. Some of the medicines that we use for even mild nausea associated with chemotherapy can cause constipation.

Download the issue to read the rest of Dr. Morgans’ comments.

Dr. Tanya Dorff On Chemotherapy For Prostate Cancer

Dr. Tanya Dorff is a medical oncologist who serves as associate clinical professor in the Department of Medical Oncology & Therapeutics Research and the Head of the Genitourinary Cancers Program at City of Hope, a research and treatment center for cancer based in Duarte, California.

Dr. Dorff’s research interests in prostate cancer range from clinical trials in PSA-recurrent prostate cancer to the role of fasting in chemotherapy tolerability to CAR T cells that are primed to target prostate cancer tissue.

She leads one of the largest clinical trial portfolios in genitourinary cancers.

Dr. Dorff spoke with Prostatepedia about chemotherapy for prostate cancer.

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Why did you become a doctor?

Dr. Tanya Dorff: When I was around three years old, I decided that what I wanted to do with my life was help people. And being a concrete thinker as a three-year-old, I felt like being a doctor was the only way to do that.

Have you had any patients over the years who have changed how you view the art of medicine or how you view your own role?

Dr. Dorff: There are so many who have influenced me. My mom had a rare form of leukemia when I was in college. It was uniformly fatal. But they had recently developed a new treatment with the discovery of a specific translocation of the retinoic acid receptor for acute promyelocytic leukemia (APL). All-trans retinoic acid was developed, and she received it as experimental (at the time) through compassionate access. She was cured, and she’s still alive today. That influences how I feel about clinical trials and translational science. If we hadn’t understood that biology, we couldn’t have designed the overwhelmingly effective treatment.

How is chemotherapy used today for men with prostate cancer?

Dr. Dorff: When I started treating prostate cancer, chemo was pretty much our only tool besides standard hormone therapy. It worked, but it was sort of end-of-the-line. People didn’t tolerate it very well, in part, because we used it in really advanced cases. Then, the drugs like Zytiga (abiraterone) and Xtandi (enzalutamide) came out, dramatically improved the situation for prostate cancer patients, and chemotherapy got pushed later and later.

The CHAARTED study was presented five years ago. That study showed that using chemotherapy early with the initiation of hormone therapy dramatically improved survival, above and beyond using it later. About 75% of the patients on the control arm got the chemo when they became resistant, so it was a pretty good experiment of now versus later, and not now versus never. To see that just using it early added an extra year or more of life for these men was really profound. That reinforced the strong role chemotherapy has in this disease.

With which other kinds of agents is chemotherapy frequently combined?

Dr. Dorff: Combinations with Taxotere (docetaxel) have never yet been successful in prostate cancer. There was Taxotere (docetaxel) with a high-dose Vitamin D, which was not only negative in that it failed to improve outcomes, but patients who received the combination actually fared worse. There was Taxotere (docetaxel) with Revlimid (lenalidomide), Taxotere (docetaxel) with atrasentan, Taxotere (docetaxel) with GVAX… All of these combinations have failed.

One of the ASCO presentations that prostate cancer physicians might remember most vividly is a slide presented by David Quinn in his presentation of the negative results of the SWOG S0421, the study of Taxotere (docetaxel) alone or with atrasentan. He showed a slide of a graveyard, implying that any drug tried in combination with Taxotere (docetaxel) is doomed to fail.

Why do you think that is? Is it just that the combination is too toxic?

Dr. Dorff: I don’t know. I don’t think it’s too toxic. All of these combinations go through safety before they go into Phase III, and you can combine them safely. I do not understand why combinations fail. Maybe it goes back to biology. Why would the combination succeed? You want something that makes the chemo work better, or you want the chemo to make the drug work better. That’s where we should probably start when planning combination studies. Even then, things that look good in early testing can fail in Phase III, so in some cases it may be that we need to sub-classify patients in order to design more successful trials.

Maybe a more interesting question when we’re talking about combinations is: how do we get the best use of the chemo and do the least damage to the patients?

At University of Southern California, we started a study looking at a fasting-mimic diet to make the Taxotere (docetaxel) better. We found preliminary evidence that fasting prior to chemotherapy reduced toxicity, and I envision that could have two specific benefits in men with prostate cancer who might get Taxotere (docetaxel).

One might be that if we could mitigate toxicity, more men would actually receive it. There was a lot of therapeutic nihilism out in the community about how chemotherapy doesn’t work so well for prostate cancer, or that these older patients can’t handle it. If we could ratchet down the toxicity, maybe more prostate cancer patients would actually get chemo.

The second benefit might be that if we could reduce toxicity to normal host cells, we would be more likely to get in full doses on time, which might make it work better against the cancer versus what happens now, which is that we frequently dose-reduce and dose-delay because of toxicities. The fasting-mimic diet study is still ongoing but these are the outcomes I was hoping for when designing it.

How long are they fasting before they start the chemo? What does that look like?

Dr. Dorff: They fast for 48 hours on a fasting mimic diet, which means they get vegetable broth and an energy drink. So, it’s a liquid, low calorie diet. It’s hard, so that’s part of why the study is still ongoing.

In our earlier trial, in which we did fasting with platinum chemo for up to 72 hours (48 before and 24 after the chemo dose), people really swore by it. They really felt like they had so much less toxicity compared to chemo cycles in which they didn’t fast.

With the fasting mimic diet (created by L-Nutra), because it’s not pure fasting, we extended it to three days before chemo. The first day is a fairly robust number of calories, just plant based and with specific amino acids left out, which is felt to be part of the effect. Then there’s the two days before chemo with lower calories, and one day after. After fasting or the fasting-mimic diet the body needs a bridging diet for the first meal, and the L-Nutra regimen also included supplements to replenish the body.

If someone reading this is interested in participating, can they contact you directly or should they contact someone else?

Dr. Dorff: Sure, they can contact me directly at tdorff@coh.org. But the trial is going on only at USC, so they may wish to contact the clinical trials office at USC or the medical oncology group at USC.

Are you combining diet with chemo instead of another agent?

Dr. Dorff: Yes.

What kinds of side effects can patients expect from chemotherapy? What are you hoping to reduce?

Dr. Dorff: One of the most concerning side effects is the peripheral neuropathy, which can become permanent, but I don’t want to scare any readers.

Can you explain what that is?

Dr. Dorff: It’s damage to the small nerves out in the fingers and toes that can manifest as numbness or pins and needles, burning kinds of discomfort. That can be permanent.

Is there anything patients can do before or during getting chemo to reduce the likelihood of that happening?

Dr. Dorff: Not that we know of.

There’s no way to predict who might suffer from that or not?

Dr. Dorff: It’s not a complete no. We know patients who already have some preexisting neuropathy, whose nerves are already damaged, are more susceptible, for instance patients with diabetic nerve damage. That’s one reason we might try to get them Jevtana (cabazitaxel) instead of Taxotere (docetaxel) because Jevtana (cabazitaxel) doesn’t impact the nerves in the same way. I’m not sure if that’s what patients worry about, but that’s one of my number one concerns because I’ve seen patients a few years after chemo who are still vexed by the neuropathy.

If Jevtana (cabazitaxel) doesn’t result in neuropathy, why wouldn’t you use that agent over Taxotere (docetaxel)?

Dr. Dorff: Because insurance typically won’t cover it. Head-to-head, they were compared in the FIRSTANA trial, and they were equally effective; one wasn’t much better than the other. So, insurance companies can say that Jevtana (cabazitaxel) is not more effective; it’s equally effective. Taxotere (docetaxel) is a fraction of the price because it’s off-patent, and Jevtana (cabazitaxel) is actually approved specifically in post-Taxotere (docetaxel) patients, so it’s off-label to use it first-line. You can make a case when you have a guy with neuropathy, but even if you have a guy without neuropathy, you sure would like to leave him without neuropathy at the end of his treatment.

We start to see the neuropathy around dose five. If you stop, it’s more reversible, but if you keep going, that’s where it can become permanent, and so again, when we’re getting to how we can enhance the efficacy, if we could get more doses in without being limited by neuropathy, maybe we would do better with the drug, or maybe we just avoid the neuropathy, have equal efficacy and patients suffer less. There’s two ways we can win.

Equal efficacy and side effects are a huge issue for men.

Dr. Dorff: Patients really worry about hair loss. I don’t think we’re impacting that with the diet, unfortunately. That is reversible. They also complain about the taste changes and mouth sensitivity because that really impacts eating.

Does that go away once chemotherapy is finished, or does that linger after?

Dr. Dorff: That goes away.

It’s just while they’re getting chemo that they lose sense of taste?

Dr. Dorff: Yes, but it’s a long time to not be able to taste.

And the hair loss only happens while they’re getting chemo, too? It comes back?

Dr. Dorff: Yes, it grows back.

What combinations with Taxotere (docetaxel) do you think will work best?

Dr. Dorff: The ongoing combinations that I think people are still interested in are platinum with taxane and carboplatin with Jevtana (cabazitaxel). That’s an important combination for the more aggressive variants.

Part of how we think Taxotere (docetaxel) chemotherapy works is that it interferes with antigen receptor (AR) translocation in the cell to the nucleus, because the microtubules are needed for that. It still may be more for patients whose cancer is using a lot of AR signaling whereas platinum is more for cancer that might not be as dependent on that mechanism. That combination is pretty important.

There are some other biologics being studied together with Taxotere (docetaxel), but I’m not sure that those will be successful. There’s Taxotere (docetaxel) with immunotherapy, but we have the negative GVAX trial that tried combining vaccines with Taxotere (docetaxel). We are also combining it with Xofigo (radium-223), which is a little interesting, but I don’t know why those agents would necessarily help each other. Again, when you’re looking at a combination, it’d be nice if there were a reason to expect synergy.

What about favorite sequences?

Dr. Dorff: We know that after you’ve had Zytiga (abiraterone) or Xtandi (enzalutamide), you can induce the androgen receptor splice variants such as AR-V7. These are associated with less responsiveness to Zytiga (abiraterone) or Xtandi (enzalutamide). Patients might want to go from Zytiga (abiraterone) straight to Xtandi (enzalutamide), but we know there’s a lower likelihood of success, and we know AR-V7 is a big part of that. If we sequence in chemo, since they’ve shown that AR-V7 positive patients still benefit from chemo, I view the optimal sequence as Zytiga (abiraterone) or Xtandi (enzalutamide), followed by wiping out the AR-V7 population with a chemo drug, and then going to Zytiga (abiraterone) or Xtandi (enzalutamide) next. We don’t know for sure if that’s what happens when we use that type of sandwich approach, but it has theoretical appeal, and that’s how I talk to patients about it. The other way to go is a clinical trial, especially for combination with Zytiga (abiraterone) or Xtandi (enzalutamide).

What about the side effects profile when you do those kinds of sequencing?

Dr. Dorff: Hormone drugs like Zytiga (abiraterone) and Xtandi (enzalutamide) have much better side effect profiles, generally speaking, but the chemo side effects are largely reversible, and we tell patients that it’s not forever. There are good days and bad days, so it’s important to note that most people are not feeling bad every single day that they’re on the chemo. I don’t think the side effects vary based on sequence.

Some of my colleagues feel that when they use chemotherapy up front like in the CHAARTED study, they see more side effects if they start the chemo right away, but they see fewer side effects if they wait a month or two into the hormone therapy to add the chemo.

Is that because the patients become used to the side effects and learn how to manage them before you add something else?

Dr. Dorff: No, because the side effects are totally different between the two treatments. This is speculative, but I think you debulk. I think that part of the reason people get a lot of chemo side effects is that when we’re killing a lot of cancer there’s a big inflammatory reaction. You can feel sick from it, and we see that anecdotally in certain patients. If you can debulk the cancer a little bit with a couple months of hormone therapy, and then give the chemo, it might be better tolerated.

That’s interesting. So as the cancer’s dying, it throws off some kind of signal?

Dr. Dorff: It does. There’s a lot of dead stuff that has to be cleared by the body, and maybe that means it doesn’t have as much attention to do the healing that it needs to do with the chemo. I don’t know; that’s purely speculation.

Is there anything else you think men should know about chemotherapy for prostate cancer?

Dr. Dorff: First and foremost, chemo is effective. People downplay the role but CHAARTED really showed us that this is a good tool. We are working on tools that have fewer side effects. I’m working on whether diet can help mitigate side effects, and other people are looking at things like exercise, but the bottom line is that chemo is a good tool.

But still some patients draw a line in the sand and say they’ll never receive chemo because they’ve seen other patients getting chemo for other cancers. The chemo we use for other cancers is different than what we use for prostate, and every person’s reaction to chemo is different. Of course, you can’t erase that impression that’s made on you when you see someone who you care about struggling through chemo, but it doesn’t mean that’s what your experience is going to be.

Your doctor’s job, and your oncologist’s job, is to make it livable, to allow you to still do the things you want to do and to keep you safe and healthy through your chemo. There are tricks up our sleeves that we use to make that happen.

Sometimes patients are surprised to hear that they can actually feel better on chemo.

Why would that be?

Dr. Dorff: Because sometimes the cancer’s driving their side effects. It’s a catch-22. There are patients who might want to wait until they’re feeling better to get chemo, but if they’re feeling bad from the cancer, it’s really the chemo that’s going to make them feel better.

I have patients who’ve been unable to eat, in too much pain to really get out and do anything, and when they start chemo, they feel better, they eat better, they have more energy, and they can do more. If you take someone with no cancer symptoms, sure, the chemo’s going to make them feel worse. But if you take somebody with cancer symptoms, they may actually feel better.

That’s interesting because there’s this whole cultural perception of chemo as being catastrophic. The idea that chemo would make you feel better seems bizarre, but it makes sense the way you explain it.

Dr. Dorff: Yes, I think a lot of patients are shocked to hear it, and I think that’s a good thing to put out there.

Do you have any suggestions for men as to how to handle side effects before going into it?

Dr. Dorff: Communication with your doctor is the way to be successful in your chemo. A lot of people don’t want to bother the doctor, or they want to tough it out, but the earlier they tell the doctor that there’s a side effect, the easier it is for the doctor to intervene and reverse it. There’s no medal at the end of chemo for not having had to take a treatment for a side effect or not having called the doctor. Just pick up the phone and call. That’s how your doctor can do their best by you, and how you can be most successful with your treatment.

Aside from that, staying active is really important. Getting out and walking, even if you’re not exercising per se, but just moving around and not being sedentary is important for circulating the blood. We don’t want you to get a blood clot during chemotherapy because you’re not moving. It helps you expand your lungs, so maybe it can help keep your respiratory tract and heart healthier. Go into chemo as fit as possible, and try to maintain activity and mobility during treatment.

Read the rest of this month’s conversations about chemotherapy for prostate cancer.

Chemotherapy

Many patients fear chemotherapy not only because of its side effects but also because of what the need for chemotherapy implies about their prognosis. Fortunately, each physician we spoke with this month addresses both issues.

Taxotere (docetaxel), the chemotherapy drug most commonly used to treat prostate cancer, is usually used to treat patients with an aggressive form of this disease. However, multiple randomized trials have shown that this drug prolongs survival. We see the most dramatic impact in patients who have extensive metastatic disease at the time of diagnosis. The CHAARTED trial showed that initial treatment with Lupron (leuprolide) plus Taxotere (docetaxel) was markedly more effective than Lupron (leuprolide) alone in prolonging survival. There is a definite benefit to receiving the drug, if you need it.

The most common side effect of Taxotere (docetaxel) is fatigue, which is usually mild after the first dose, but worsens with each subsequent dose. Sometimes, this limits the total number of doses administered. Usually, this side effect disappears over time. Exercise lessens its potency, and each physician in this issue recommends exercise. Taxotere (docetaxel) damages the nerves in the hands and feet. This leads to a feeling of numbness and tingling in the fingers and toes called neuropathy. This grows in severity with each dose of the drug, but when stopped in a timely fashion, the side effect is reversible.

In 2003, Gedlicka et al. reported that alpha lipoic acid minimized nerve damage. Since the publication of this paper, we recommended two 300 mg tablets of time-release alpha lipoic acid twice a day during Taxotere (docetaxel) treatment in my practice. It appears to have a marked impact on the severity of this side effect.

Taxotere (docetaxel) damages the production of hair and nails. Hair loss can be prevented by chilling the scalp as the drug is administered. Chilling the hands and feet also seems to lessen the nail damage.

Prolonged Taxotere (docetaxel) treatment can also damage and block the tear ducts, causing tears to flow. Some physicians recommend inserting silicon rubber tubes in the tear ducts when the symptoms first appear. Once the tear ducts have closed, repair is much more difficult.

Many chemotherapy drugs cause a drop in hemoglobin, white cells, and platelets. While these can be a problem with Taxotere (docetaxel), it is milder than in the multidrug combinations used for other common cancers, such as breast cancer. Transfusions can be used if the drop in hemoglobin becomes clinically significant. Low white cell count can be managed with granulocyte stimulating factor (G-CSF). While a low platelet count can be managed by platelet transfusions, these lose their effectiveness over time. This can be a major problem in a few patients.

Patients on Taxotere (docetaxel) often experience inability to taste food. Patients have often reported that bland creamy foods are easier to eat.

Overall, the side effects of Taxotere (docetaxel) develop gradually as the number of cycles on the drug accumulates. If treatment is limited to six cycles, these side effects are usually mild and reversible. Most patients have nearly complete recovery within 6 months. If the cancer is still sensitive to the drug, a second round can be effective and well tolerated.

Read the rest of this month’s conversation about chemotherapy with:

• Tanya Barauskas Dorff, MD: Chemotherapy
• Alicia Morgans, MD: Putting Chemo in Perspective
• Michael Morris, MD: Clinical Trial: Combining Taxotere + Xofigo
• Julie Graff, MD: Chemotherapy, Xtandi, and Zytiga
• Benjamin Gerendash, MSN, RN, NP Chemo: A Nurse’s Perspective
• Catherine E. Guider, RN An Infusion Nurse’s Perspective
• Patients Speak: Getting Chemo: My Story

Clinical Trial: Free Genetic Testing

Dr. Heather Cheng is an Assistant Professor at the University of Washington and Fred Hutchinson Cancer Research Center, and the Director of the Seattle Cancer Care Alliance Prostate Cancer Genetics Clinic.

Prostatepedia spoke with her about a clinical trial she’s running that looks at inherited genetics of men with metastatic prostate cancer.

What attracted you to medicine?

Dr. Heather Cheng: There are a couple of things I love about medicine and especially oncology. One is getting to know patients, finding out what’s most important to them as people, and using that information to help guide discussions and decisions about their treatment in a way that is true to what is most important to them. These days I guess you call this shared decision-making. That’s the most rewarding part about what I do.

Have you had any patients over the years who have changed how you see your own role or how you view the art of the medicine?

Dr. Cheng: I have a lot of patients who fit those criteria. My interest in this area started when I was a first-year Hematology and Oncology fellow. I was in the clinic and it was when we were at the beginning of this wave of new exciting drugs that prolong survival, such as Zytiga (abiraterone) and Xtandi (enzalutamide).

I met this patient who was 43 years old; he had new, aggressive metastatic prostate cancer. His disease blew through every one of the new drugs. It was extremely humbling and disappointing because we were so excited about these drugs, but they didn’t do much to slow his disease. And it was heartbreaking because he was so young. He had a family history of cancer but not prostate cancer. He had a teenaged son. We had a lot of discussions about the effect of his disease on his son. I wondered if there was something genetic, something that was making his cancer so aggressive. And then, what could this mean for his son? His memory has stuck with me.

When I think about the work and research that I do, it’s not just for the individual patient in front of me. I’m also thinking about how we can improve things and advance the field so things can be better for the next generation. How can we make progress as quickly and with as much positive impact as possible?

I met another patient who had a great effect on me. He had just been diagnosed with high-risk prostate cancer, Gleason 9. He was planning to get radiation. As part of a research study, we offered to sequence the DNA of his cancer because he had an unusual appearance of his cancer– ductal histology. He was kind and generous enough to volunteer and participate. It wasn’t going to affect his treatment, but he agreed to help us learn more.

In his cancer, we found a mutation in the BRCA2 gene, the one that many people may have heard of because of its association with breast and ovarian cancer risk. There was suspicion that the mutation could be inherited, so we brought him back for dedicated genetic testing for inherited cancer risk. And, it turns out he did have an inherited version of that mutated BRCA2 gene. He was the first person in his family to be found to carry the mutated version of BRCA2. Neither he nor his family would have known until later if we had not looked in his tumor.

After this, some of his relatives had genetic counseling and were also tested. The sister who had breast cancer had a recurrence and was found to carry the BRCA2 mutation. This information was important for her because it offers additional treatment opportunities for her cancer that might not have otherwise been considered. His daughter was also found to carry the BRCA2 mutation and after learning of this, had a mammogram and was diagnosed with breast cancer. She’s still curable, so she’s going through treatment, but it is possible that she might not have known until much later otherwise.

The importance of test results can extend to relatives in a way that might help more than one person, not just the person that I see in the clinic, but other members of their family. I do want to be clear that these mutations are not found in most people— even those with cancer—but for the people who have these mutations, it can be life saving information for their family members.

What will you be doing, and what can men expect to happen, during your clinical trial?

Dr. Cheng: You can learn about the study from your doctor, support group, or by visiting our website, http://www.GentlemenStudy.org. There is information about the study. You can consent online, confirm that you have metastatic prostate cancer, and check that you’re interested in genetic testing for cancer risk.

There is a questionnaire that many take about 40 minutes to complete, that asks about your knowledge of genetics, basic health, family history of cancer, and demographic information about where you live.

You can upload supporting information about your diagnosis, or you can check a box saying you’d like help from the research team to gather that information on your behalf. Because there are strict privacy laws around medical records, you need to give permission to our team to get medical information for the study on your behalf.

To be eligible, you must have metastatic prostate cancer and must live in the United States. There’s one other exclusion, which is that if you have some blood disorders such as leukemia, we cannot be sure that the test results are valid.

If you meet criteria, you will be mailed a saliva kit, a medical-grade genetic test through Color Genomics, with instructions on how to provide a saliva sample. Follow the instructions carefully and then mail the kit back. Results are typically available within 4 weeks. You will have access to a genetic counselor following your results, and you are invited to follow up in person to our clinic if you live in the area. If you don’t live near us, we can direct you to resources to find a genetic counselor for in-person visit or by telehealth.

The testing for this study is not recreational testing. It is not the same as Ancestry.com or 23andMe. This is clinical, medically appropriate testing if you have metastatic prostate cancer.

Do you share this information with their doctor, or is it up to them to share the information with their doctor?

Dr. Cheng: We strongly encourage participants to share the results and information with their doctors, but our ethical board does not allow us to do this for participants without their specific consent.

Are there any fees for patients?

Dr. Cheng: There is no fee for the patient.

It sounds similar to the process for the Metastatic Prostate Cancer Project, except I don’t think they share their results.

Dr. Cheng: Yes, it is similar to that project. The difference is that the patient or the participant gets results that apply to them individually. The Metastatic Prostate Cancer Project, which is fantastic and an important and innovative study, is de-identified, and the patient doesn’t get individual-level results back.

Their goal is to amass as much data as they can for research.

Dr. Cheng: Correct, yes.

Are you also cataloging the information that you collect?

Dr. Cheng: Yes.

What will you do with the data that you collect?

Dr. Cheng: We’ll be looking at demographics, the proportion of people who have mutations (pathogenic variants), information about family history, and validated measures of knowledge, distress measures and satisfaction with testing.

If patients consent to re-contact, they will be contacted at the conclusion of the study. If there are other follow-up studies, they can opt to learn about those. There will also be an invitation for those who agree to subsequent studies, like treatment studies or PARP-inhibitor studies, for example.

We’re still learning about certain genes, such as ATM mutations and CHEK2 mutations. As we learn more, we may want to update participants on what the field has learned. There are still many important questions that the field needs to answer, and patient engagement and participation will make this happen more quickly. There will be opportunities for those downstream studies.

How many patients are you looking for, overall?

Dr. Cheng: The plan was for 2,000. We have sent kits out to over 350. We still have room for participation!

Join us to read the issue and learn how to participate in Dr. Cheng’s study.