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What Are Advanced Prostate Cancer Treatment Options?

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What Are Advanced Prostate Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

What is advanced prostate cancer and how is it treated? Expert Dr. Tanya Dorff explains advanced prostate cancer and discusses available treatment approaches, including clinical trial considerations.

Dr. Tanya Dorff is Associate Professor in the Department of Medical Oncology & Therapeutics Research at City of Hope. Learn more about Dr. Dorff.

 

Related Resources:

What Is Advanced Prostate Cancer?

What Questions Should Prostate Cancer Patients Ask About Clinical Trials

Transcript:

Katherine:

First, what does it mean to have advanced disease? 

Dr. Dorff:

Advanced prostate cancer signals cancer that’s come back after curative intention or has presented de novo in a way that means we don’t currently have a tool to cure it. That’s at least how I view advanced prostate cancer. You could take a broader definition and consider some high-risk localized patients who need multimodal therapy, but to me, it’s really signaling a shift from something we’re aiming to cure versus something we’re aiming to manage, so that can manifest just as a PSA that’s rising, what we call biochemical recurrence, or it can manifest as visible metastatic disease. 

Katherine:

What does “locally advanced mean? 

Dr. Dorff:

So, “locally advanced” means that it hasn’t metastasized, but it might be involving the local structures, like the seminal vesicles or the bladder or some of the regional lymph nodes, the pelvic lymph nodes. 

Katherine:

How is advanced prostate cancer treated? 

Dr. Dorff:

The cornerstone of treatment for advanced prostate cancer has really been hormone therapy. I think there’s a lot of negative stuff out there on the internet about hormone therapy that I think does a disservice to patients because hormone therapy is truly very, very effective and, for many men, can be quite livable. 

I have patients who live more than a decade on hormone therapy, and they’re running their businesses and they’re raising their grandkids, they’re traveling, they’re running 10Ks, they’re doing all the things that they might want to be doing. That’s not to say there aren’t side effects, but hormone therapy is an effective cornerstone, and I really hope people won’t dismiss it offhand because of the negative things they’ve heard or read about it. 

Katherine:

What about other treatment classes?  

Dr. Dorff:

Most of our other treatments are really layered on top of hormone therapy. We may get to a point – 10 years from now, I don’t know, sometime in the future – when we don’t start with the hormone therapy, so a lot of patients come in asking about the new radiopharmaceutical, the Lutetium-177-PSMA that got approved last year, or about whether chemotherapy can be used. They can be, but they’re really layered on top of hormone therapy, so the hormone therapy is the first treatment, it’s the most effective right now, and then it’s continued as we swap out – we add a novel hormonal agent like abiraterone (Zytiga), or enzalutamide (Xtandi), or one of the others. 

When that is no longer effective, we swap that out, we might use chemotherapy or the radiopharmaceutical. There’s also an immunotherapy that’s been around for more than a decade called sipuleucel-T, and now there’s the targeted therapies – the PARP inhibitors – as well for select patients. 

Katherine:

Where do clinical trials fit into treatment?  

Dr. Dorff:

That’s a great question. I’m so glad you asked. Clinical trials some people mistakenly believe are your last choice, like you’ve gone through every single treatment we have, and then you go to a clinical trial. That’s not the case. Some of the biggest advances in prostate cancer have been when we’ve taken drugs that work in a more advanced resistance setting, like a second- or third-line, and when we move them right up front, first-line, we dramatically amplify their benefit. We dramatically improve survival. 

So, if we don’t think about a clinical trial in the first line, we’re going to miss the opportunity to not only develop those new treatment paradigms, but actually participate in them ahead of when they become the new standard of care down the road. 

Another misconception that people have often about clinical trials is that they are always randomized, there’s always a flipping of the coin in assignment of different treatments, and that they may include a placebo. So, most of our clinical trials at this point do not include placebo. Because we have so many effective treatment options, we’re more and more frequently comparing either two drugs against one, so everyone’s getting at least one effective drug, or we’re not comparing at all, but everyone’s getting some new treatment or some combination of treatments when we’re working out dosing in that scenario, like a Phase II. 

So, clinical trials are really an option at any stage of prostate cancer, even at diagnosis for localized disease all the way through, and truly, I hope people would consider looking at those as options because that’s where some of the most innovative treatment options are going to become available to them. 

Key Questions for Prostate Cancer Patients to Ask Before Joining a Clinical Trial

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Key Questions for Prostate Cancer Patients to Ask Before Joining a Clinical Trial from Patient Empowerment Network on Vimeo.

Dr. Andrew Armstrong, director of prostate cancer research at the Duke Cancer Institute, provides expert advice on what questions prostate cancer patients should ask when considering participation in a clinical trial. 

Dr. Andrew J. Armstrong is a medical oncologist and director of clinical research at the Duke Cancer Institute’s Center for Prostate and Urologic Cancers. For more information on Dr. Armstrong here.

See More From Prostate Clinical Trials 201

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Should Prostate Cancer Patients Consider a Treatment in Clinical Trials?

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Why Should Prostate Cancer Patients Be Empowered?

 How Can Prostate Cancer Patients Access Clinical Trials

How Can Prostate Cancer Patients Access Clinical Trials?

Transcript:

Katherine Banwell:

What are some key questions that patients should ask their healthcare team before even participating in a clinical trial?  

Dr. Armstrong:

I think number one is what are the alternatives that I would have if I did not participate in the clinical trial? What are the standard of care therapies? And prostate cancer now has a vast menu. There is two different types of chemotherapy. There are two different types of target radiotherapy, that’s Pluvicto and radium. There’s immunotherapy, with Sipuleucel-T and other immune therapies. There are multiple hormonal drugs. There are precision medicines, like I mentioned, for men with certain hereditary types of prostate cancer. So, it’s important to hear what the standard of care is, and many patients don’t necessarily even hear that. 

And then based on what patients have already seen and what’s the expectation? Risks and benefits around those. 

And then on top of that, research can complement that or either replace or come after those standard of care approaches. Certainly if a patient has exhausted the standard of care approaches, a trial can offer real benefits. 

It’s important to ask about risks. What have other patients experienced going into that study? What kind of toxicities, good or bad? What other – what’s the evidence that it has helped people before? If it’s never been studied in people, the evidence might just come from the laboratory. But hearing about why is this so promising, why have you chosen to invest so much time and energy in this trial, is a good question. 

And then if you’re hearing about a trial and you’re making a decision to travel, sometimes asking questions about whether the trial will cover your lodging or transportation, gas money, airport travel. Some trials do do that. 

You can also look on clinicaltrial.gov for sites that are near you. So, many centers open the same trial in a different state, so you can look on that website to see if there’s a trial near you for what you’re looking for.  

Navigating Treatments and Prognosis for Stage 3 Breast Cancer

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Editor’s Note: This resource, Navigating Treatments and Prognosis for Stage 3 Breast Cancer, was originally published by MyHealthTeam.

During a breast cancer diagnosis, your doctor will determine the stage of your cancer. Stages range from 0 to 4, based on the size of the breast tumor and whether the cancer has spread to other organs. If your doctor determines you have stage 3 breast cancer, that indicates you have advanced breast cancer that has begun to impact the tissue surrounding the breast.

Knowing the stage can help your doctor choose the best treatment and predict your prognosis (estimated outlook).

How Is Breast Cancer Stage Determined?

Breast cancer is staged using the TNM staging system, where TNM stands for tumor, node, metastasis. The system looks at the following:

  • Tumor — How large is the primary tumor?
  • Node — Are there cancer cells in nearby or distant lymph nodes?
  • Metastasis — Has the cancer metastasized (spread) to other parts of the body?

A higher degree of cancer spread corresponds to more advanced-stage disease. Understanding the nature of the disease and determining the best treatment options also requires additional information, such as:

  • Hormone receptor status — Does the cancer contain estrogen receptors (ERs) or progesterone receptors (PRs), which are types of proteins?
  • Tumor grade — How do the abnormal cancer cells look compared to the normal cells?
  • Human epidermal growth factor receptor 2 (HER2) status — How high are your levels of the protein HER2?

What Is Stage 3 Breast Cancer?

Also called locally advanced breast cancer, stage 3 breast cancer is a more advanced form of invasive breast cancer. Cancer cells have spread from the milk ducts into the nearby lymph nodes, the skin of the breast, or the chest wall.

Stage 3 breast cancer may further be classified into substages — stage 3A, 3B, or 3C — depending on the size of the breast tumor and the extent of the cancer spread. Notably, breast cancer stages are sometimes referred to using Roman numerals, such as stage III instead of stage 3.

Stage 3A Breast Cancer

Stage 3A breast cancer refers to one of the following situations:

  • The doctor doesn’t find a tumor in the breast, or if there is a tumor, it may be of any size. Additionally, cancer is found in four to nine axillary lymph nodes (those that are in the armpit region) or in the lymph nodes closest to the breastbone
  • The tumor is larger than 5 centimeters, and there are small groups of breast cancer cells between 0.2 millimeters and 2 millimeters in size in the lymph nodes.
  • The tumor is larger than 5 centimeters, and the cancer has spread to one to three axillary lymph nodes or to the lymph nodes near the breastbone.

Stage 3B Breast Cancer

In stage 3B breast cancer, the cancer has spread to the lymph nodes and the chest wall, referring to the protective structures around the lungs. The cancer is also in the skin of the breast, resulting in ulcers or swelling.

Stage 3C Breast Cancer

In stage 3C breast cancer, there may be no sign of cancer in the breast. If there is a tumor, it may be any size and may have spread to the chest wall and/or the skin of the breast. Additionally, the cancer must have spread to one or more of the following places:

  • Ten or more axillary lymph nodes
  • Lymph nodes above or below the collarbone
  • The axillary lymph nodes or lymph nodes near the breastbone

Inflammatory Breast Cancer

Stage 3 breast cancer is classified as inflammatory breast cancer (IBC) when the cancer cells block vessels in the skin of the breast, causing the skin to feel warm and change in appearance.

Treatments for Stage 3 Breast Cancer

Stage 3 breast cancer treatment often starts with chemotherapy, followed by surgery. For cancers with certain genetic mutations, targeted drugs are also used in treatment.

Chemotherapy

Chemotherapy is often the first approach for treating stage 3 breast cancer. Chemotherapy is usually administered as neoadjuvant therapy, meaning it is given prior to surgery. This approach is beneficial in that it can:

  • Shrink the tumor to make it easier to remove
  • Test that a particular chemotherapy is effective
  • In some cases, allow for a less extensive surgical procedure

Mastectomy or Lumpectomy

A mastectomy, which is the removal of the breast tissue, is often required to treat stage 3 breast cancer. Alternatively, a lumpectomy — also referred to as breast-conserving surgery or partial mastectomy — involves the removal of only the breast tumor and some of the surrounding normal tissue.

Many people with stage 3 breast cancer are not eligible for a lumpectomy and likely need a mastectomy to get rid of the tumor completely. However, if neoadjuvant chemotherapy can shrink the tumor enough, a lumpectomy might become a viable option.

Following surgery, some people may choose to have reconstructive surgery to restore the appearance of their breasts.

Radiation

Radiation therapy is often administered following an operation to kill off any remaining breast cancer cells that may have been missed by treatment.

Lymph Node Dissection

Lymph nodes containing cancer cells must also be removed. An axillary lymph node dissection is done to remove the lymph nodes in the armpit. The procedure is usually performed at the same time as a mastectomy.

Hormonal Therapy

Some breast cancers contain proteins called hormone receptors on the surface of breast cancer cells. The hormone receptors that play a role in breast cancer progression are the estrogen receptors and progesterone receptors.

Hormone receptor-positive stage 3 breast cancers can be treated with hormonal therapy drugs such as tamoxifen or exemestane (sold as Aromasin), which specifically target the hormone receptors.

Targeted Therapy

Targeted therapy drugs work by stopping the function of a particular protein or group of proteins. HER2 is a protein that is present at high levels in some breast cancers and affects how the cancer grows. HER2-positive stage 3 cancers may be treated with drugs that specifically target the HER2 protein.

Immunotherapy

If breast cancer cells are negative for ER, PR, and HER2, the cancer is called triple-negative breast cancer. Triple-negative breast cancer is difficult to treat effectively with standard treatments, so newer forms of treatment like immunotherapy may be used to improve outcomes.

Immunotherapy drugs work by interacting with a person’s immune system so that it can recognize and fight the cancer cells. Pembrolizumab (sold as Keytruda) is an immunotherapy drug that can be used along with chemotherapy to treat triple-negative stage 3 breast cancer that has returned or spread after surgery.

Prognosis for Stage 3 Breast Cancer

Stage 3 breast cancer is an advanced stage disease, so prompt treatment is crucial for improving the prognosis.

Overall, stage 3 breast cancer has a somewhat favorable prognosis with a five-year survival rate as high as 86 percent. This means 86 percent of people with the condition live at least five years after being diagnosed. This rate can vary depending on the exact substage of cancer. For instance, IBC has a markedly lower survival rate, closer to 41 percent.

Hormonal therapy and other targeted drugs have helped to improve outcomes for cancers with specific genetic features. Some people may be encouraged to participate in clinical trials, which can advance the discovery of new effective treatments for stage 3 breast cancer.

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 58,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Have you or a loved one been diagnosed with stage 3 breast cancer? Share your experiences in the comments below, or start a conversation by posting on MyBCTeam.

Treatment Options for Advanced Prostate Cancer

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Treatment Options for Advanced Prostate Cancer from Patient Empowerment Network on Vimeo.

What are treatment options for advanced prostate cancer? Expert Dr. Maha Hussain provides a breakdown of hormone therapy and explains how targeted therapy is used in prostate cancer care.

Dr. Maha Hussain is the Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about this expert here.

See More From INSIST! Prostate Cancer

Related Resources

Prostate Cancer Treatment and Research News

Understanding Prostate Cancer Staging and Progression

How to Engage in Your Prostate Cancer Treatment Decision

Transcript:

Katherine:

Now that we understand how test results can help inform a patient’s cancer and how it may behave. Let’s discuss how they can affect treatment options for men with advanced disease. First, let’s do a brief review of the treatment types currently available. There’s hormone therapy, right. What else?

Dr. Hussain:

Perhaps, it’s simpler if we focus on advanced disease, specifically metastatic disease.

So, if that’s the deal, then the backbone of treatment is hormone treatment. And it really is. We call it hormone, but technically it’s an anti-hormone. What we’re trying to do is shut down the hormonal pathway that stimulate the testes, which is the factory that makes testosterone. So, we are looking at shutting down testosterone production from the testes in order to starve the cancer.

Now, the male hormone is produced predominantly – somewhere about 95 percent of it is made by the testes, and then there are about 5 percent-ish that comes from other sources. These are, again, male hormones like the adrenal gland and so on. And there was a while ago some research – I want to say from the MD Anderson crowd, but this is two years ago – that suggested also that the tumor may start to make sort of in-house production of male hormone to support itself.

Now, having said that, again, testes continue to be the source of the majority of the male hormone. And so, historically, the first data that showed benefit was actually by surgically removing the testes, which is what we call orchiectomy or bilateral orchiectomy. And then medications began hitting the market and were evaluated in the late ’80s and then 1990s, beginning with Lupron – which by the way, in the ’80s, it was an injection that the patient had to give themselves every day, which is remarkable.

But even then, there is a personal preference by patients to go and take injections as opposed to go through surgery with orchiectomy. But still, I would say for some patients it may be an option until it ought to be discussed as an option. Then what we know is this, is because of the

potential other sources for the male hormone, the concept of what we call combined androgen depravation was being evaluated.

And again, this goes back to the ’80s when the first drug was flutamide and then bicalutamide, and there are other drugs that became. And they kind of added a sprinkle, I call it, to survival. But it wasn’t dramatic, huge differences in survival. And so, generally, while we used it, everybody believed in using it. Moving forward, the drugs like abiraterone, enzalutamide, apalutamide are the three hormonal drugs that have demonstrated conclusively really an advantage in terms of prolonging life when added to the Lupron.

So, what I tell my patients is that, when it comes to hormone treatment there is really no way around it. You can delay it. Some people are exploring for some patients who don’t have a lot of cancer, maybe a couple of areas, maybe just do targeted radiation and then leave the person alone to buy them some treatment-free time.

And, to me, this is where the discussion that has to happen with the patient. What is the objective? Is the objective to kind of be ahead of the game and maximally treat the cancer with the hope of prolonging life? Or is the objective to delay treatment? And I would tell you that, with these types of conversation, nine out of 10 or 9.5 out of 10 men opt for moving aggressively up front with management. So, that’s that.

Now, the one thing I should point out, one of the trials that also was a landmark trial in this disease was the study CHAARTED, which was an intergroup clinical trial at the time it was designed, led by ECOG, and the PI was Dr. Chris Sweeney. I was part of the team that worked on the design also of the study.

And that was a trial that looked at adding docetaxel to hormone therapy, versus hormone therapy alone, to try to see if it adds something. Historically, all the chemotherapies prior to that that were added to hormone treatment for patients with newly diagnosed metastatic disease had not delivered. And docetaxel did.

However, one thing I should point out, based on that trial – and I don’t want to go into too much details for the sake of time – the patients that seemed to be benefiting were the patients that had more aggressive, more disease in their system. And so, liver metastases, lung metastases spread in the bone at different areas, not like few isolated areas in the spine or the pelvis, but much more than that.

And so, for the patients who have what we call high-volume prostate cancer based on scans – and I’m happy to explain what that means if it’s needed – these are the patients that I would offer either the docetaxel plus hormone treatment, which is the injection, or the injection plus the hormonal pills that I mentioned earlier.

Katherine:

What about targeted therapy? How is that used?

Dr. Hussain:

Okay. So, let’s begin with the molecularly targeted therapy. So, as we speak right now, for patients who have newly diagnosed metastatic disease that we call hormone-sensitive, molecularly targeted therapy is not standard of care. So, I would encourage patients who may qualify for clinical trial to be involved in those. The flipside is – we can talk about it – is that molecularly targeted therapies, specifically with PARP inhibitors have pretty much entered in the space of prostate cancer with a couple of drugs that were FDA-approved.

The other way of targeted treatment, which would be what we refer to targeted radiation, this would be a different story. This is not systemic treatment. This is a local treatment. And what is done is basically if patients do not have a lot of cancer in their body based on scans, and only certain areas, and they are starting systemic therapy, they can certainly consult with a radiation oncologist to target radiation to areas that are visible on scan. So, if somebody has a couple of, let’s say, pelvic bone lesions, maybe a lymph node, and they are already starting systemic therapy, they can consult with a radiation oncologist focal radiation. And so, that would be the general scheme.