Metastatic Prostate Cancer Treatment Options

What Are The Side Effects Of Hormone Therapy For Prostate Cancer

Because androgens affect many other organs besides the prostate, ADT can have a wide range of side effects , including:

• loss of interest in sex

Followup By Primary Care Physicians

The American Cancer Society has released evidence- and expert-based guidelines for the management of prostate cancer survivors by primary care physicians , a response to the fact that as the number of men surviving prostate cancer has increased, reliance on PCPs for their care has grown as well. The guidelines address promotion of healthy lifestyles, surveillance for disease recurrence, screening for second primary cancers, and evaluation and management of adverse physical and psychosocial effects caused by the disease and its treatment. Recommendations include the following :

Treatment Options For Metastatic Prostate Cancer

Matthew Fowler: I want to transition and focus in on metastatic castration-resistant prostate cancer . Can you talk a little about some of the available systemic treatment options for this disease?

Oliver Sartor, MD: We have a lot, so Im going to run through some of the frontline studies and then move in sequence. The granddaddy was docetaxel chemotherapy back in 2004. Then we transitioned into having sipuleucel-T and cabazitaxel, which was indicated for patients with progressive castration-resistant disease after docetaxel administration. Very importantly, we then had abiraterone, initially starting in the postdocetaxel space and then coming predocetaxel. Enzalutamide was postdocetaxel initially, then predocetaxel. Then we had radium, which was important because it was bifurcated into postdocetaxel or predocetaxel, and the FDA approval came in for both. Im sticking with metastatic castration-resistant disease. If I went to nonmetastatic, Id bring in a couple more. But Im still concentrating on metastatic castration-resistant disease.

For each of these, theres a curative sequence in particular ways. Cabazitaxel can come after docetaxel, but not before docetaxel. Theres a little complexity, but you get the idea. Ive gone through it a bit historically, and then brought in the precursors to where we stand today.

Transcript edited for clarity.

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Endocrine Therapy And Prostate Cancer

Male hormones, specifically testosterone, fuel the growth of prostate cancer. By reducing the amount and activity of testosterone, the growth of advanced prostate cancer is slowed. Hormone therapy, known as androgen ablation or androgen suppression therapy, is the main treatment for advanced prostate cancer. It is the first line of treatment for metastatic prostate cancer.

In many patients, endocrine therapy provides temporary relief of symptoms of advanced prostate cancer. Endocrine therapy may reduce tumor size and levels of prostate specific antigen in most men. PSA is a substance produced by the prostate gland that, when present in excess amounts, signals the presence of prostate cancer.

However, hormone therapy is not without side effects. Some of the more serious side effects include loss of sex drive, impotence, weakened bones , and possibly heart problems.

Eventually, most patients with advanced prostate cancer stop responding to hormone therapy. Doctors call this castrate-resistant prostate cancer.

Future Directions In Care

Coupled with advances in imaging and genomic testing, the emergence of new therapeutic options for mCRPC suggests the potential for optimizing outcomes and survival. However, increasing patient access to these therapies remains a challenge, Gomella observed. Cost is one potential barrier, as he noted, Men are living longer, and many of these newer regimens can run $8000 to $10,000 or more a month, a financial burden for most. We are going to have to deal with these practical challenges. Also, it can be difficult to provide patients with appropriate treatment when also navigating challenges associated with insurance coverage and prior authorization. Insurance coverage is one of those unforeseen problems with these advances made over the last 10 years, Gomella said. The costs of developing novel agents are very significant, as well.

References

1. Lowrance WT, Breau RH, Chou R, et al. Advanced prostate cancer: AUA/ASTRO/SUO guideline part I. J Urol. 2021 205:14- 21. doi:10.1097/JU.0000000000001375

2. Cancer stat facts: prostate cancer. National Cancer Institute/ Surveillance, Epidemiology, and End Results Program. Accessed June 22, 2021. https://seer.cancer.gov/statfacts/html/prost.html

3. Rice MA, Malhotra SV, Stoyanova T. Second-generation antiandrogens: from discovery to standard of care in castration resistant prostate cancer. Front Oncol. 2019 9:801. doi:10.3389/ fonc.2019.00801

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Emerging Treatment Options For The Management Of Metastatic Castration

Prostate cancer is the most common solid organ malignancy diagnosed in men in the United States, accounting for 13% of new cancer cases annually.1,2 Although localized disease is associated with high survival rates, advanced or metastatic disease has proven more challenging to treat, with 5-year survival rates found to be approximately 30%.2

Metastatic castration-resistant prostate cancer is responsible for the majority of prostate cancerrelated deaths. In recent years, newer imaging technologies have yielded additional insights about mortality risks, including the number and location of metastatic sites, whereas novel therapeutic agents have provided more options for patients.1,3

Newer imaging technologies may impact some men with nonmetastatic CRPC based on standard imaging, according to Gomella. A big unknown right now is in the setting of stage M0 CRPC disease and the impact of the PSMA scan, Gomella observed. Will the PSMA scans widespread use suddenly reduce the number of men considered to be M0 and reclassify them as stage M1? That remains to be seen and is something well be watching.

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Are There Any Lifestyle Changes I Should Consider While In Treatment For Metastatic Prostate Cancer

The most important thing you can do is to stay physically active and strong. This includes following a heart-healthy diet and exercising.

Cardiovascular exercise is the most important. The degree, or intensity and duration, of cardio exercise depends on the individual person.

Several studies have pointed to a link between obesity and aggressive prostate cancer, although the mechanism is still being worked out.

Weight loss is generally encouraged if youre overweight, but excessive or unintentional weight loss can be a sign of disease progression and should be discussed with your doctor.

Finally, if youre a smoker, stop! If youre finding it hard to quit, ask your doctor about products and medications that might help you.

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Your Cancer Care Team

People with cancer should be cared for by a multidisciplinary team . This is a team of specialists who work together to provide the best care and treatment.

The team often consists of specialist cancer surgeons, oncologists , radiologists, pathologists, radiographers and specialist nurses.

Other members may include physiotherapists, dietitians and occupational therapists. You may also have access to clinical psychology support.

When deciding what treatment is best for you, your doctors will consider:

• the type and size of the cancer
• what grade it is
• whether the cancer has spread to other parts of your body

Surgically Removing The Prostate Gland

A radical prostatectomy is the surgical removal of your prostate gland. This treatment is an option for curing prostate cancer that has not spread beyond the prostate or has not spread very far.

Like any operation, this surgery carries some risks, such as urinary incontinence and erectile dysfunction.

In extremely rare cases, problems arising after surgery can be fatal.

It’s possible that prostate cancer can come back again after treatment. Your doctor should be able to explain the risk of your cancer coming back after treatment, based on things like your PSA level and the stage of your cancer.

Studies have shown that radiotherapy after prostate removal surgery may increase the chances of a cure, although research is still being carried out into when it should be used after surgery.

You may want to ask your doctors about storing a sperm sample before the operation so it can be used later for in vitro fertilisation .

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Justification For A New Guideline

Clinicians treating men with advanced prostate cancer are challenged with the rapidly evolving prostate cancer landscape given the approval of new classes of agents for use in various prostate cancer disease states. The increasing complexity of advanced prostate cancer management underscores the need for the current clinical practice guideline, developed to provide a rational basis for treatment of patients with advanced disease, based on currently available published data. To assist in clinical decision-making, guideline recommendations are furnished according to disease state across the entire continuum of advanced prostate cancer.

Family History And Genetics

Until recently, doctors assumed that the key risk factors for prostate cancer were age, a family history of prostate cancer and being of African-American ancestry. Today, however, researchers like Dr. Heather Cheng are looking at family history more broadly.

An associate professor of medical oncology at the University of Washington School of Medicine, Cheng says there are proven genetic links between prostate cancer in men and breast, ovarian and pancreatic cancer in their female relatives.

If there is an inherited cancer risk, that risk may manifest itself in female relatives differently than in male relatives, Cheng says.

The genetic links work both ways. When sharing their family history with their doctors, men should include information about female relatives on both sides of the family who have had cancer. And men who are diagnosed with metastatic prostate cancer should undergo genetic testing, as should their siblings and children if a mutation is discovered.

That doesnt mean a person will definitely get cancer, but it may increase their risk, Cheng says. It also provides information for them to use that risk knowledge to be proactive.

Family history can also help inform a patients decision about whether to have a PSA test. That test is no longer routinely recommended due to the potential for overtreatment, but Cheng says it becomes more important if a man has a known mutation or if theres a family history of early breast and ovarian cancer.

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Standards Of Care In Hormone Therapy

Most doctors agree that hormone therapy is the most effective treatment available for patients with advanced prostate cancer. However, there is disagreement on exactly how and when hormone therapy should be used. Here are a few issues regarding standards of care:

Timing of Cancer Treatment

The disagreement is due to conflicting beliefs. One is that hormone therapy should begin only after symptoms from the metastases, like bone pain, occur. The counter belief is that hormone therapy should start before symptoms occur. Earlier treatment of prostate cancer is associated with a lower incidence of spinal cord compression, obstructive urinary problems, and skeletal fractures. However, survival is not different whether treatment is started early, or deferred.

The only exception to the above, is in lymph node-positive, post-prostatectomy patients, given androgen deprivation as an adjuvant immediately after surgery. In this situation, immediate therapy resulted in a significant improvement in progression free survival, prostate cancer specific survival, and overall survival.

Length of Cancer Treatment

The disagreement in this situation is between continuous androgen deprivation and intermittent androgen deprivation.

Combination vs. Single-Drug Therapy

External Beam Radiation Therapy

This is the most common type of radiation therapy, and it is painless. Before treatment, your radiation team will use computerized tomography scans and magnetic resonance imaging scans to map out the location of the prostate and tumor cells.

During each treatment session, X-ray beams are focused on the targeted cancer areas. Oncologists can change the intensity of doses and radiation beams to better deliver high doses of radiation to tumor cells while delivering lower doses to surrounding healthy tissues.

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Prostate Cancer Treatment Approved In England

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Prostate cancer cell. Credit: LRI EM Unit.

Following its approval in Scotland 2 weeks ago, a new treatment will now be available on the NHS in England for some people with prostate cancer.

Currently, androgen deprivation therapy is a cornerstone of prostate cancer treatment as it reduces the level of testosterone . However, in cases where this treatment doesnt work, there are no alternatives other than to continue.

But the latest decision changes that. The National Institute for Health and Care Excellence approved darolutamide with standard hormone therapies for adults whose prostate cancer hasnt spread outside the prostate, has stopped responding to ADT and are at high risk of developing metastatic disease in the future.

Kruti Shrotri, head of policy development at Cancer Research UK.

Darolutamide works by blocking the activation of testosterone receptors on cancer cells, thereby limiting the growth of the cancer.

Clinical trial data has shown that individuals taking darolutamide alongside ADT have more time before their cancer spreads outside of the prostate compared to those taking ADT on its own. The data also suggest that this combination increases the length of time people live , but the long-term benefits are unclear.

Prostate Cancer Is A Disease In Which Malignant Cells Form In The Tissues Of The Prostate

The prostate is agland in the malereproductive system. It lies just below the bladder and in front of the rectum . It is about the size of a walnut and surrounds part of the urethra . The prostate gland makes fluid that is part of the .

Prostate cancer is most common in older men. In the U.S., about 1 out of 5 men will be diagnosed with prostate cancer.

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How Is Prostate Cancer Diagnosed

Screenings are the most effective way to catch prostate cancer early. If you are at average cancer risk, youll probably have your first prostate screening at age 55. Your healthcare provider may start testing earlier if you have a family history of the disease or are Black. Screening is generally stopped after age 70, but may be continued in certain circumstances.

Screening tests for prostate cancer include:

• Digital rectal exam: Your provider inserts a gloved, lubricated finger into the rectum and feels the prostate gland, which sits in front of the rectum. Bumps or hard areas could indicate cancer.
• Prostate-specific antigen blood test: The prostate gland makes a protein called protein-specific antigen . Elevated PSA levels may indicate cancer. Levels also rise if you have BPH or prostatitis.
• Biopsy: A needle biopsy to sample tissue for cancer cells is the only sure way to diagnose prostate cancer. During an MRI-guided prostate biopsy, magnetic resonance imaging technology provides detailed images of the prostate.

Treatments To Help Manage Symptoms

Advanced prostate cancer can cause symptoms, such as bone pain. Speak to your doctor or nurse if you have symptoms there are treatments available to help manage them. The treatments above may help to delay or relieve some symptoms. There are also specific treatments to help manage symptoms you may hear these called palliative treatments. They include:

This is the team of health professionals involved in your care. It is likely to include:

• a specialist nurse
• a chemotherapy nurse
• a diagnostic radiographer
• a therapeutic radiographer
• other health professionals, such as a dietitian or physiotherapist.

Your MDT will meet to discuss your diagnosis and treatment options. You might not meet all the health professionals straight away.

Your main point of contact might be called your key worker. This is usually your clinical nurse specialist , but might be someone else. The key worker will co-ordinate your care and help you get information and support. You may also have close contact with your GP and the practice nurses at your GP surgery.

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Radiation Therapy Versus Surgery

In 2014, the Agency for Healthcare Research and Quality found insufficient evidence to determine whether any type of radiation therapy results in fewer deaths or cancer recurrences than radical prostatectomy does in patients with clinically localized prostate cancer. The importance of dose escalation in disease control complicates the extraction of meaningful conclusions from current radiation therapy treatments .

Brachytherapy has also been compared with surgery in the management of early-stage disease. Direct comparisons are not readily available, but preliminary data from most centers suggest that permanent prostate implants yield comparable local control and biochemical disease-free rates.

Valid comparisons of surgery and radiation therapy are impossible without data from randomized studies that track long-term survival rather than PSA recurrence. Variation in radiation techniques and dosage administered the variable use of androgen ablation, which improves survival in intermediate- and high-risk disease and the variable impact on the quality of life complicate comparison using uncontrolled studies.

Treatment For Advanced Cancer

Stage IV prostate cancer is cancer that has spread or metastasized. Cancer metastases results from a primary prostate cancer tumor that has spread to other parts of the body such as the bones, brain, lungs, and liver via varying routes including the circulatory system, lymphatic system, or skeletal structure. Prostate cancer frequently spreads to the bones. Bone metastases causes severe pain and is characterized by a dull, constant ache with periodic spikes of pain. Watch our expert medical oncologist, Alicia Morgans, discuss treatment options for advanced prostate cancer.

Hormone therapy is an important treatment for men with advanced prostate cancer. Many treatments for patients with metastatic prostate cancer are relatively new. These include immunotherapy and targeted therapy options. For more information on immunotherapy, visit the immunotherapy section of our website. For more information on targeted therapy, visit the targeted therapy section.

To learn more about all types of treatment, such as hormone therapy and radiation, available for prostate cancer, visit the treatment section of our website.

Watch as ZEROs CEO, Jamie Bearse, discusses new prostate cancer treatment news:

Listen to our archived webinar, Advanced Prostate Cancer Treatments Insights from a Provider and Patient, as Dr. Morgans from Northwestern University and Col. Paul Taylor discuss treatment options, managing side effects, and clinical trials.

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