Can you discuss the signs and symptoms of prostate cancer?

Prostate cancercan present in many different ways. Infact, I would say the most common waythat a man with prostate cancerpresents with this condition is with nosymptoms. For most men actuallyit's detected by their primary caredoctoror a urologist by doing a digital rectalexam and doinga PSA test.

There are some patients whopresentto their physicians with signs orsymptoms ofmore advanced urological process, suchas difficulty with urinationor perhaps even pain in the pelvis. Andthen a minority of the totalwilldemonstrate symptoms frommetastatic disease at the time ofdiagnosis. It might be bone pain

weight loss, etc., but that fortunately isa relatively rare phenomenon.

What are some of the risk factors for the disease?

The most common risk factor for prostate cancer is a family history of prostate cancer. Although not all patients who have prostate cancer do have a family history, it is part of a genetic familial risk related to the BRCA genes. But that's again the minority of the patients with prostate cancer.

For the most part, patients have unknown risk factors. It’s a common disease in aging men – somewhere between one and six and one in eight men will get this disease over the course of their lifetime. There have been a number of dietary, lifestyle and other risk factors that are associated with it, such as a high fat diet, a western diet, obesity is slightly associated with a risk of prostate cancer. But for the most part, we don't point to simply one risk factor when we think about this disease, like we might, for some other cancers.

Can you discuss the recommended age and testing guidelines?

That’s a fluid topic and something that does change from time to time. For the most part, men who are at the age of 50 should be having a conversation with their doctor about whether they should be screened for prostate cancer. That is the general time when screening has started. In some guidelines it's as low as 45.

For gentlemen who have a family history of prostate cancer in their father or a brother, they should think about getting screened for this disease at an age that is about 10 years prior to the age of onset for their family member. So, if dad was diagnosed at age 52 maybe you should start at age 42, for example.

As with many cancers, prostate cancer is a disease that can stay localized to the prostate and could actually exist as a low-grade entity for many, many years before becoming something. That is a little bit more challenging or perhaps life-threatening. Many men who present with this disease actually have a form of prostate cancer that doesn't need treatment right away and they can be followed through active surveillance. But there are some patients who are followed on active surveillance who do go on to develop clinically significant disease. Discovering that and intervening when appropriate and following them expectantly and appropriately is key in order to prevent a conversion of a low-grade prostate cancer, for example, to potentially a higher grade and even a metastatic prostate cancer.

Can you discuss the different grades and the different stages of prostate cancer?

With regards to grade, when I refer to grade, we're referring to what is seen by a pathologist under the microscope when a cancer is diagnosed. If there's no cancer, there's no grade. So, all prostate cancer is assigned what's called a Gleason grade. The Gleason grade has two components – a major component and a minor component. That grade range goes from 3 to 5. So five is the most aggressive and three is the lowest. There really isn't a 2 or a 1 anymore because those have been sort of done away with because they were considered to be not really cancer. So, the lowest grade prostate cancer that one would be diagnosed with in the current era would be a 3 plus a 3, or a grade 6. The highest grade then would be a grade 10, or a 5 plus 5. So, we see everything in the middle from a 3 plus 4, which equals 7, to a 4 plus 3. And as those numbers go up as the grade increases. That roughly corresponds to the likelihood of aggressiveness of the disease, meaning the likelihood of a recurrence after treatment with surgery or radiation or perhaps even the likelihood of the development of metastatic disease ultimately showing up in the bone or the lymph node or some other organ.

How can patients find a specialist and the right health care team so that they get the right treatment?

Prostate prostate cancer is a fairly good example of a multispecialty or a multidisciplinary disease. There are three modalities of treatment for prostate cancer: surgery, radiation therapy and systemic therapy. Systemic therapy has a whole host of different options ranging from hormonal therapy to chemotherapy to immunotherapy to targeted therapies. In general, many men may be diagnosed and may never leave the care of a urologist because they have, for example, low-grade disease that doesn't require treatment and is put on active surveillance.

Many men may be diagnosed by a urologist but may be treated by a radiation oncologist or a combination of a radiation oncologist and an oncologist for patients who develop systemic disease who recur after surgery or radiation. For the most part, those patients are treated by oncologists. That's what I do. I’m a medical oncologist. The typical patient that I would receive into my care would be somebody who may have already undergone local treatment but it's an experience of relapse or his cancer has already left the prostate at the time of the diagnosis.

What are the types of treatment options that men have for prostate cancer?

I’ll put these into two different categories. For men with localized disease, which is the disease that is confined to the prostate gland, that person could be potentially cured either through surgery or through radiation therapy with or without concurrent hormonal therapy. Then when we get into the systemic therapies, what I mean by that is treatments that really go all over the body not just to a local spot in the prostate gland, we would be talking about hormonal therapy, which is really guided towards blocking the effect of testosterone on the cancer. Chemotherapy, which is typically a drug injected by vein that has activity against rapidly growing cells in the body. We have new therapies such as androgen receptor targeted therapies, which are really hormonal therapies but are kind of in the next generation. We have a new class of therapies that have just been approved by the FDA here in the United States, and those are the PARP inhibitors and those block the mechanism by which cancer repairs defects in DNA. There’s many others coming in here as well: Radioisotopes, for example, are injected by vein. It’s essentially a radiation delivered by intravenous injection. We have an immunotherapy that is a cellular therapy that's a product called Sipuleucel-T, or Provenge. You can see there's a lot of different modalities of treatment and there are more coming. We’re likely to see, for example, targeted radio isotopes developed and will become available in the coming years, as well as other modalities of treatment.

Why is it key for men to be their own best advocate when it comes to treatment options?

As I’ve stated, there are a lot of different treatment options. There are a lot of different types of doctors who treat this disease and there's a whole range of treatment necessities ranging from observation or surveillance to chemotherapy. So, it's always advisable for a patient to ask appropriate questions and to think about whether or not they are the full spectrum of physicians who might be able to treat them.

I would break this conversation down into two aspects. Number one is the person who has focal or localized prostate cancer, where the question is: How can I get this cancer cured with the most effective and efficient means possible, whether that be surgery or radiation? And if I’ve already talked to a urologist, should I also talk to a radiation oncologist to get a different perspective on my case? Then, for the patient who has recurrent disease or a systemic disease, the question is: The doctor who is treating me, are they a specialist in systemic cancer? Medical oncologists, that's what we're trained on. That's what our fellowships are in is the systemic therapy of cancer. Many medical oncologists will treat a whole host of cancers, ranging from lymphoma and leukemia perhaps even to prostate cancer. Some urologists, in addition to doing surgery will administer some systemic therapies.

So, I think it's important for the patient to know what tools their doctor has in his or her tool kit in terms of the available treatments that they have in their office.

What would you say is your biggest piece of advice for someone who's newly diagnosed with prostate cancer?

I would say my advice for newly diagnosed patients would be to understand the extent of the disease that they have, the grade of the disease they have and the risks of their disease that they have. One of the interesting things about prostate cancer is there's almost hardly ever a time when there's only one way to do something. I would urge patients to ask the question of what would be the alternative to what's being recommended to me? So many men are perfect candidates for surgery but some of them choose to have radiation instead and vice versa. Asking the question of what if I did it this way, what's the downside? What's the upside> That is a good question.

Just a couple of practical pieces of advice: If somebody's diagnosed with a prostate cancer and they're going to get information and they're going to see perhaps many people and have a couple of different conversations, buy a pad of paper and get a folder. Label that folder and take that pad of paper with you everywhere you go. Take notes and you'd be surprised. That's really, really important. In addition, maybe even more important than taking notes yourself, would be to bring a loved one along with you to help you to take notes. If you're not getting the answers that you need from your doctor, then ask the questions yourself. And if you're still not getting the answers you need or the time you need to make decisions, get a second opinion.

The Basics of Prostate Cancer

In reality, when we, in a clinical situation, are talking about genetics we're talking about genes associated with a cancer. Genes that we inherit from our mother and our father are germline genes or there can be genes in the tumor itself. While many of the genes that are in your normal non-cancer body are in the cancer itself, the cancer itself may have its own set of mutations and other genes.

Family genetics, or germline genetics, are an important part in prostate cancer. Some of it is known and some of it is not known. Some of it is clinically relevant and some of it is not clinically relevant in terms of decision making. The most important observations in recent years, because they hit both of those criteria, would be the observations around DNA repair genes and their risk for prostate cancer. The most known about is the BRCA1 or BRCA2 gene. They’re different genes but they're very similar in terms of what they do. These genes were first discovered in breast cancer, that's why they have the name that they do but they are associated with a number of endocrine cancers, such as breast cancer, ovarian cancer, endometrial cancer, uterine cancer and prostate cancer, even pancreas cancer. A person who has a familial mutation in one of those genes is at higher risk of prostate cancer as they age. If a person who is not a cancer patient who has a strong family history or knows that they carry one of these genes, they should be talking to their doctor about getting screened for the cancers that apply to it. So, that's really genetics. There are other familial genes that are associated with prostate cancer but they're much less common and we're still kind of sorting out the link between family genes and prostate cancer risk. There is another gene called S-POP. But BRCA is really the one that receives the most coverage and is probably the most common.

With regards to genomics, that's a different story. So, genomics refers to the genes in the cancer and how they may correspond to the biology of that particular cancer. For example, a patient has metastatic prostate cancer and I’m wondering what his prognosis is. I’m wondering what types of treatment options might I have available for him. So, if I do a genomic test, I take his prostate biopsy or or the whole prostate if it's been removed from him and I send it to a lab where they look at a panel of mutations. They might look at somewhere between 50 and 500 genes to see if they are mutated. They look at commonly mutated genes in in cancer patients. Then I’ll get a report that will say this patient has two or three or four mutations or maybe no mutations. Not all of those are going to be helpful to me. Some of them are going to be something I don't know what it does and maybe nobody does. Some of them are going to tell me about the patient's prognosis and saying this is a gene that is mutated in a higher risk cancer situation. And some of them are going to tell me not only about prognosis but they might tell me something about a treatment that I might find available. So, for example, I just mentioned BRCA2. If I find a BRCA2 mutation in a cancer specimen, it means a fairly high likelihood that that patient may benefit from that class of drugs that target it, which are called PARP inhibitors.

Why is it important for men who have a history of prostate cancer to make sure that they're getting genetic testing done?

It used to be that genetic testing was really only necessary for family counseling but now it's going to help a patient and a doctor make treatment decisions individually. So, that's what's important about it. And there are certain cases where the genetic mutation in the cancer can drive a very significant difference in outcome when these drugs are used. It doesn't occur in everybody, but it can make a critical difference. The setting in which we think about the cancer genetics, we think about doing the genomic testing in anybody who has metastatic prostate cancer. Certainly, in a patient who develops metastatic cancer, at the first sign of the disease – in other words you have someone who gets surgery and then it recurs as metastatic disease – and in others whose first sign of the disease is metastatic disease. Those are situations in which most guideline panels recommend that genetic testing be done. Subsequently, patients who develop resistance to the standard hormonal therapies, what we call castration resistant prostate cancer, or CRPC, is going to need more therapy. In that setting,

How does genomic testing affect treatment?

Genomics can change over time. So, we have seen cases where patients have had prostatectomy, their prostates removed, and four years later their cancer recurs. Three years after that, they're developing resistance to the therapy that we give them. When we do a genomic test on a tumor specimen from the more advanced form of a cancer and we compare it to the prostatectomy specimen, we see different mutations. So, those are acquired mutations. The term that we use for tumor-associated mutations is somatic. What

somatic means is it's in the body of the tumor. That’s different from the germline mutations. For example, if we find a patient who has a germline BRCA2 mutation that means he probably inherited it from his parents and his siblings. But if we find a patient who has a somatic acquired or a somatic BRCA2 mutation, that's not in his germline. He's not going to pass that to his children, and he didn't get that from his parents. The mutation occurred spontaneously in his cancer and that is something that is a typical phenomenon that occurs with cancer. It is this kind of genetic instability and the development of new mutations.

The root of your question is when is the best time to do this test? The most frequent time that we test it or the most frequent specimen we use is the prostate biopsy; however, it is not unreasonable for us to be doing biopsies of the bone or of a lymph node in a patient who has developed metastatic disease because it's more up-to-date. With genetic information, the problem is it's really hard to get those tissues sometimes and we can't be biopsying every patient you know every three months. It's just too much to put a person through that.

Potentially, an answer to that question would be if we can look at mutations through the blood and there are tests that are called cell-free DNA tests or circulating tumor DNA tests. Both of those tests apply and basically what that is is that you put a tube of blood in the arm of the patient and then you capture some of the DNA that's circulating in the blood. We all have DNA circulating in our blood because there's just so much DNA in all of our cells that some of it just is escaping into the blood. But if a person has cancer, some of that circulating DNA is from the tumor and some of those mutations that are in the tumor can show up in the circulation. So that is a potential solution to this problem, which is that we can look at cell-free DnA testing.

It is not uncommon for us to detect mutations that come from the cancer that we detect in the blood.

If this testing hasn't been done, why is it important to make sure that patients are asking their doctors about genomic testing?

It’s important for two reasons. Those of us who treat cancer patients, we can tell a lot just by looking at the types of mutations that we see in these tumors. There are tumors that we know are corresponding to a higher risk, a higher likelihood of death from this disease. So, for me, whenever I get a genomic test back, I’m answering two questions: What does this tell me about the biology of this patient's disease and what does it tell me about his prognosis? And what does it tell me about these select PARP inhibitors or these targeted therapies that we might be able to use?

There are some other genetic panels that are out there. There's one called Decipher, for example, which is done on a prostate tissue and it's about 50 genes that they look at. They look at a combination of genes and they can they can tell basically through mathematical models using the combination of these genes where the patient is on a spectrum of risk. So, it's not just looking at one gene, it's looking at a whole family of genes and how they interrelate with one another. I neglected to mention that before, but that's a panel that's done on the prostate. Then there are genetic germline genetics that are done on the germline tissue that we inherit

mom and dad and pass on to our children, perhaps. And then there are somatic mutation panels that we can do on tumor specimens that can be metastatic tumor specimens. Then, there's the cell-free DNA that we can do from the blood. So, there's all kinds of different ways we can get at the genetics of this tumor.

What would you say is the number one thing that patients should know about genetics and genomics?

The first question a patient should ask is how can genetics and genomics help me to make a decision for my case? If you have localized disease and you're thinking about having a radical prostatectomy or thinking about having radiation therapy, you might want to think about one of the studies like the Decipher panel or others that are done that can give a sense of the patient's place on the spectrum of risk. This tells us a little bit more information than the Gleason score, for example, because we do occasionally see patients who have a low Gleason score suggesting low risk but they have a high Decipher score suggesting higher risk. That might tell them maybe we should have radiation and hormonal therapy as opposed to surgery or maybe we just need to be watching this carefully more carefully or maybe I shouldn't be doing active surveillance. Maybe I should move ahead with surgery. And that's a complicated decision-making process that involves the patient and the physician talking through this. For the patient who has recurrent disease or metastatic disease, then they should be asking the question: Should I be checking my germline genes so that I can counsel my family? The big issue there is should I be checking my somatic or my tumor genes to help see if it can help my doctor with assessing my prognosis and with potentially assessing for for future treatments?

Understanding Genetics and Genomics in Prostate Cancer

There's been a high survival rate in prostate cancer over time, but with distant prostate cancer, those rates can significantly drop. Can you discuss how metastatic prostate cancer is different?

Metastatic, when applied to a cancer, implies that the cancer cells started in the organ of origin, which in this case is the prostate. The most common site of cancer prostate cancer spreading or metastasizing is to the bone or to the lymph nodes. Less commonly, it can go to the liver or the lung.

So, what are the different stages of advanced prostate cancer? Well, I think prostate cancer can be divided into a number of different ways. Stage is something that typically refers to where the cancer has gone in relation to the organ of origin. So, stage 1 prostate cancer, for example, would be a tumor that's confined to the prostate. A stage 2 prostate cancer would be cancer that has gone to the edge of the prostate or has gone through the capsule of the prostate, perhaps. Stage 3 is more locally advanced through the capsule even to the regional lymph nodes. Stage 4 would be prostate cancer that's spread to a distant organ, such as the bone. But in my daily practice, I don't talk about these stages that much because what really matters is two things with regards to the outcome of a patient with advanced or metastatic prostate cancer: Factor number one is has it spread outside of the prostate that we can see on a scan like a bone scan or the CAT scan. Factor number two is it resistant or sensitive to the hormonal therapy that we typically use?

When we talk about a life-threatening form of prostate cancer and you hear somebody who dies of prostate cancer, those patients are typically patients who have both of those phenomena. The cancer spreads typically to the bone and standard hormonal therapy stops being effective. And the cancer begins to grow, despite the lowering of testosterone. That’s not to say that there aren't treatments for that entity. There are a lot of treatments for that entity.

Can you discuss the current standards of care for advanced prostate cancer?

There are many different types of treatments for prostate cancer. In fact, the number of treatments for prostate cancer has really exploded in the last four or five years and it's actually going to get even bigger in the next few years. So, that's good news but when we think about the standards of care, I would say we can divide it into three or four categories.

Hormonal therapy, the standard of care would be some form of ablation of the level of testosterone in the body. We typically do this with injections that lower the level of testosterone by about 90%. The most commonly used drugs would be leuprolide, (Zoladex [goserelin]), (Trelstar [triptorelin]), (Vantas [histrelin]) and (Firmagon [degarelix).

On top of that, we have second-line hormonal therapies that also block the effect of testosterone but they're effective in doing it even when the first-line of therapies have failed. That’s where we have drugs like (Xtandi [enzalutamide], (Zytiga [abiraterone]), (Erleada [apalutamide]) and (Nubeqa [darolutamide]). Those are targeted hormonal therapies compared to some other cancers.

We use relatively little chemotherapy but we do have some very effective chemotherapies. There’s one called docetaxel, which can be used in advanced hormone-resistant disease or can be used in upfront metastatic disease. We have a drug called cabazitaxel, which has a similar set of indications.

The new class of drugs that we're using now are the PARP inhibitors, which are those that are targeting the mechanism of DNA repair in prostate cancer.

We have a cellular therapy called sipuleucel-T, which is used in castration resistant metastatic disease. We have a radioisotope called radium-223, which is used in bone metastatic disease typically in patients with bone pain.

Why is treatment adherence so vital when it comes to these regimens?

Treatment adherence has to do with whether the prescribed medication actually gets into the patient. We can lose adherence for a number of reasons. One is a patient could take a bottle of pills home, put in his medicine cabinet and never take it. There's not much we can do about that as the doctors. But it could be, for example, that a patient starts to take a pill medication for his cancer and because he doesn't feel so good, he stops taking it. That’s a different story we would want to hear about. We want to know why he doesn't feel well and whether we could reduce the dose or give a treatment break. That’s what we do as oncologists. That's our job.

Adherence for an injected drug is, of course, high if a patient shows up and has the drug injected into them. It’s a situation where adherence is almost 100%, but the reality is all the research in the world that leads to the development of a new therapy isn't effective if we don't get it into the patient. It is a dialogue between the doctor and the patient about what can or cannot be administered and why it may not be one factor.

Unfortunately, a problem in this country is that patients sometimes bear a lot of the cost of their medication. It could be that they're getting an oral medication and they have a significant copay, for example.So, not being able to pay the copay would be one risk for a patient not adhering to the treatment regimen. That is something that I, as a doctor, would want to hear about. I wouldn't want a patient to keep that from me because again we can think about ways for patient assistance programs if they exist in your area. Or we can think about ways we can reduce the dose and do other things that might to allow us to as effectively deliver the drug, perhaps on a slightly different schedule or a slightly more cost-effective one.

How have oral options helped to improve quality of life for men?

It is nice to have oral therapies available. I would say that, for the most part, the oral therapies that we use in prostate cancer are reasonably well tolerated with some exceptions. And they require maintenance monitoring by the doctor. There’s no drug with zero side effects at all. So, it's something that patients need to be honest with and they need to share with us about what's going on so that we can make adjustments and help them with regards to quality of life.

I'll say, the major driver of quality of life in advanced prostate cancer is the efficacy of the therapy and this has been shown, for example, with chemotherapy. Many men might think chemotherapy is going to be associated with a very poor quality of life but in a study that was done many years ago, in which newly diagnosed patients with metastatic disease were treated with standard hormonal therapy with chemotherapy. The patients who were on the chemotherapy had a slightly lower quality of life after about three months of treatment, but after 12 months of starting treatment the patients who had received the chemotherapy had a better quality of life. That was because 12 months after starting the treatment, the patients had already been done with the treatment for six months and they were less likely to have their cancer worsening. Better cancer control leads to better quality of life.

It’s not a uniform outcome that chemotherapy is associated with a worse quality of life. It’s not always the case that oral therapy has no side effects or that they are associated with better quality of life.

Can you discuss some trials going on in the space right now?

There are many trials that are going on. I would put clinical trials into one of two categories. Category one would be optimization studies using therapies that we know that exist but maybe we're testing them in an earlier disease population, maybe we're looking for a better outcome by giving it to patients with a lower volume of disease. So, for example, there are studies where we use enzalutamide and abiraterone, these are two very commonly used drugs that when they first started to be administered, they were given to patients who had received all prior therapies and chemotherapy, but then we showed that we could give them to patients with CRPC who did not have chemotherapy and then we showed that we could give it to newly diagnosed patients. The outcomes were better than giving standard hormonal therapy alone. Now, the studies that are going on are looking at patients who do not have metastatic disease but they might have a PSA that's detectable and rising after surgery or they might even be patients who are at high risk but getting radiation therapy and do not have any sign of metastatic disease either. That has been a general principle in oncology for decades and the best example of that is probably breast cancer, where we have seen 30 or 40 now years of clinical research which has taken medicines that work in very advanced forms of the disease and have given it now to women even before they have their breast removed or their tumor removed from their breast. It leads to improvements in outcome. We’re optimizing prostate cancer therapy use. We're moving them earlier in the disease spectrum. We're maybe changing doses, etc.

The next type of clinical trial would be new therapies and new approaches. It’s always really fun to be a clinical scientist and to be thinking about new approaches to the treatment of cancer. And prostate cancer is a really good example.

If you ask me what would probably be the most up-and-coming novel therapies for prostate cancer, I would think of three of them that come to mind right away. The first would be the PARP inhibitors, which have only been approved for about two months. Those are relatively new and I think there are a lot of clinicians out there who still don't have any experience with these therapies. The two that are approved currently, one is called (Lynparza [olaparib]) and the other one is called (Rubraca [rucaparib]).

The second category that's really exciting is PSMA-targeted therapies. We have one that's looking really interesting. It's been in a number of clinical trials, many of them have been done outside of the United States, notably in Australia where they've done a lot of this amazing work where they've shown that a molecule that targets PSMA, which is not the same as PSA. It’s a different thing on prostate cancer cells. This molecule is really interesting. On one end it binds to PSMA and then on the other end it has this molecular basket and in this basket you can put a molecule. In this case, it's lutetium 177, which is a radio isotope. It's one atom of radioactivity

and you put it on the targeted treatment. It hand delivers the radiation therapy to the prostate cancer cell. That looks really interesting and there's a major trial called the VISION trial and others that are going to be reading out in the United States in the next few months to the next year that might lead to the FDA approval of this agent that's available in other countries.

There's another, less known genetic genetic-based study of a drug ipatasertib. That is a drug that targets a molecule called AKT. AKT is an activated circuit or pathway in the prostate cancer. When the cancer has a certain mutation, a mutation of a gene called p10. That’s a very common mutation of prostate cancer. If that mutation is activated and stimulating the cancer, the drug blocks AKT. So, that’s a phase 3 trial that is in the process of completing and we might hear data on that in the coming year. That could be something that could become available for prostate cancer patients, most likely in the advanced castration resistant metastatic setting.

 What do patients with advanced prostate cancer have to look forward to most?

It’s an exciting time for those of us who are treating this disease because we begin to see multiple different options for synchronizing our treatment with where the patient is in the disease. Some of the drugs that we saved until very late in the disease spectrum we're now giving early. That’s a good thing because we're able to knock out more of the cancer when it's less aggressive and it's in a lower volume. We started, maybe 20 years ago now, thinking about this idea of personalized medicine and targeted therapies. We're kind of there. We’re not quite there totally, and what I mean by that is the idea that a patient could go to his doctor. His doctor can take his tumor and take him in terms of who he is and what his other medical problems and his age and his other needs are. They can analyze his tumor and can prescribe a medication that would be appropriate for that. We are certainly able to do that in some cases now and it's very gratifying because it's nice to be able to say I did a test on your tumor and it tells me not only about your prognosis but it tells me this about a therapy that I want to use. So, we're getting there. I think it's still a bit off that we'll get to the point where every patient has some unique profile that comes up with some special cocktail of treatment. I think that's still a little bit far off but we are seeing the beginning of this process.

Learning About Advanced Prostate Cancer

What is the difference in the risk for prostate cancer when it comes to African American men compared with Caucasian or Hispanic men?

It’s a very interesting time to think about this question because we're finding out more and more about the relationship of race to prostate cancer outcome. We’ve known for a long time that African American men are more likely to develop prostate cancer compared to Caucasian men. We’ve also known that African American men appear to have a worse prognosis once diagnosed with the disease. That has been something that has permeated a lot of our concern over clinical trials and development over the years. Men from a Hispanic background have an intermediate risk between them and men of an Asian background have a lower risk than Caucasian men. So, while while men in Asia are not free from the risk of prostate cancer it does occur at a lower frequency in the population.

Is this risk consistent between newly diagnosed disease and advanced disease?

The conversation about this risk is complicated because it factors in a number of biological and societal factors. The issue around African American race and prostate cancer has long been held that African American men were more likely to initially be diagnosed with advanced prostate cancer, meaning that when they are diagnosed they're more likely to have an aggressive form of it. Now, is this because they were less likely to be screened? Were they not getting the right screening tests? Were the standards of how we looked at normal versus abnormal and needing adjustment, that's been one of the questions. So, that has been an observation now for many decades that African American men are more likely to have advanced disease when they're diagnosed.

What’s changing is that we think there might be some differences in the biology of this disease based on race,and not altogether unfavorable for African Americans. So, for example, there have been some nice analyses that have shown that certain drugs like (Zytiga [abiraterone]), a drug we use quite commonly, is actually quite effective and perhaps even more effective in African American men than in Caucasian men. There’s an immunotherapy called sipuleucel-T, or Provenge, where there have been a couple of analyses that have looked at the outcome of African American men and have shown that it is superior to Aaucasian men when they receive this therapy. Why that is we don't quite know but these are consistent observations that have occurred.

While we talk about the risk of presenting with prostate cancer, is having a disparity where African Americans appear to be at slightly greater risk when it comes to the treatment of advanced disease. That difference might be going away and the other thing that's really interesting and sobering actually is that there have been a number of analyses that have looked at the outcome of African American versus Caucasian men with prostate cancer. They looked at the systems in which the patients are treated. If you look at overall epidemiological data of the country, overall African American men appear to have higher risk, shorter survival, etc. If you look in the VA system, the Veterans Administration system, where basically a veteran walking into the VA hospital in San Diego is probably going to get the same protocol and the same system of care that he would in Boston. These differences lessened so that once you erase differences and treatment patterns, the differences in racial outcomes by race go away. And then if you look at African American men enrolled on clinical trials where we follow very strict protocols in terms of how we treat them and compared to Caucasian men treated on the clinical trials, it actually also shows no real difference in the outcome. That was really a fascinating series of papers to read on that topic because it really said to us that yes while there might be a biological difference, we also need to be mindful of our systems of care and how our systems may fail patients more than the biology might fail them.

What factors can we contribute to risk and mortality that's associated with the disease and African American men?

If every patient was matched by a stage with the same treatment, same dose, etc., one might find that African Americans don't have much of a different outcome once diagnosed. When you match them by stage, there might even be certain circumstances where some treatments are preferable for African Americans who have a better outcome. It's really getting the patient diagnosed and it's really the systems that lead to the risks and presenting them to the physician in the first place. That might drive this difference and that's what those papers that I just cited tend to suggest that once you normalize for everything else the outcomes aren't as different as one would think really.

Have improved responses to certain treatments contributed to improved survival rates over the years or are there other factors that we can attribute to this increase?

A big factor we can contribute to the increase and improvements in outcome in all patients, including African Americans, would be programs like yours and efforts like yours to get the word out about cancer risk, about treatment, patient involvement and treatment decision making. Yes, the addition of new therapies has had an impact, but I think it's wrapped up in a whole system of improvements that have occurred. We've still got a long way to go. Our system still fails a lot of patients and that's a problem that we need to address in this country.

But we're making headway in terms of understanding our biology of the disease and matching treatments to the biology of the disease. We're making headway in our understanding of who's at risk and who needs treatment. We're also making headway in identifying pockets of the population where we need to go and do screening and identify patients who are at risk whether it be through family history, race disparity of primary care.

Are there any ways that African American men can reduce their risk for prostate cancer?

One way to reduce the risk of prostate cancer is to be evaluated early because some people will have pre-cancerous prostate cancer. That could allow them to change to have modified lifestyle. This is a challenging area because there is a lot of very interesting retrospective data on what types of lifestyle activities that one does and lower risk of prostate cancer. So, for example, there's data out there published on the consumption of broccoli, the consumption of salmon, the consumption of coffee and the number of times one vigorously exercises per week. All of those have negative associations with death from prostate cancer, meaning the more you do it the less likely you are to die from prostate cancer. The problem is we don't know if we took a 55-year-old man and who has never eaten broccoli in his life and we had him eat broccoli and salmon every day for five years whether we can alter that risk or whether there's sort of a lifetime of benefits built into some of these lifestyle risk factors. There are studies underway, for example, looking at resistance exercise and dietary modifications prospectively, but the major doubt I have is by the time you get to be 65 years old and you've been in hormonal therapy for your prostate cancer if you haven't really been exercising up until that point, how much is a change in your lifestyle going to be able to do it and how effective is it going to be to?

What is your advice to help combat some of these racial disparities in prostate cancer?

It forces us to address some challenges in our system in terms of the delivery of care. It unfortunately, or fortunately, has us confronting some of our systemic biases that we have, that all of us in medicine are thinking about a lot and trying to figure out how we confront some of these intrinsic biases. Whether or not we are failing patients in terms of identifying those through early detection. A health care system that addresses equal care, the issues around primary care and also on all segments of the population could help to combat some of these disparities. I actually think having more African Americans be urologists and oncologists and primary care doctors in addressing this issue is a good thing because we have under-representation of certain urologists and primary care doctors and oncologists. The medical field is making changes in that regard but those changes take generations because people need to be educated and trained and it just doesn't happen overnight. It’s a very complicated situation.

We are making progress and I think some of these observations, where now when we do clinical trials we will analyze the outcomes by race, that helps us to identify disparities. It helps us to identify opportunities for improvements and treatment outcome and it puts the issue really out front and center. One of the great challenges, unfortunately, because of some unfortunate historical events that have happened with regards to research, is to get African Americans on clinical trials. Nobody is questioning why those historical disparities have created this opportunity but we really need to work to get over those challenges so that we can begin to address some of the biological, clinical, societal and economic disparities that are challenging for this field.

Discussing Trends in Prostate Cancer

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