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Chemotherapy For Metastatic Prostate Cancer

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Staging Of Prostate Cancer

About Advanced (Metastatic) Prostate Cancer

Doctors will use the results of your prostate examination, biopsy and scans to identify the stage of your prostate cancer .

The stage of the cancer will determine which types of treatments will be necessary.

If prostate cancer is diagnosed at an early stage, the chances of survival are generally good.

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Can Chemotherapy Prolong Life

Chemotherapy appears to have more significant survival benefits for men who are newly diagnosed with metastatic prostate cancer and have not yet done hormone therapy .

Research also suggests that when chemotherapy is given at the same time as hormonal therapy, it can help make the hormonal therapy more effective. Chemotherapy appears to help delay the development of resistance to the hormone treatment, explains Dr. Pomerantz. This prolongs response time and delays the progression of the cancer.

A landmark multi-center study published in the August 2014 issue of the New England Journal of Medicine found that men with newly diagnosed metastatic, hormone-sensitive prostate cancer lived nearly 14 months longer when they received a chemotherapy drug along with hormone therapy compared with those who received hormone therapy alone.

A variety of chemotherapy known as platinum-based chemotherapy is currently being studied for use in metastatic prostate cancer patients. These drugs include:

While studies done with these drugs so far have been of limited size, platinum appears to be helpful for a subtype of prostate cancer patients with BRCA1 and 2 mutations, explains Pomerantz.

Patients with advanced disease who are not responding to standard chemotherapy can talk to their doctors about whether they might be candidates for platinum chemotherapy.

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Side Effects Of Chemotherapy

All chemotherapy drugs work in slightly different ways, making it challenging to predict side effects for individual patients. Dosages, drug combinations and drug responses will vary from patient to patient.

The American Cancer Society lists the following as the most common side effects of chemotherapy:

  • Increased risk of infections

  • Easy bruising or bleeding

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Where You Have Chemotherapy

You usually have treatment into your bloodstream at the cancer day clinic. You might sit in a chair for a few hours so its a good idea to take things in to do. For example, newspapers, books or electronic devices can all help to pass the time. You can usually bring a friend or family member with you.

You have some types of chemotherapy over several days. You might be able to have some drugs through a small portable pump that you take home.

For some types of chemotherapy you have to stay in a hospital ward. This could be overnight or for a couple of days.

Some hospitals may give certain chemotherapy treatments to you at home. Your doctor or nurse can tell you more about this.

Clare Disney : Hello, my name is Clare and this is a cancer day unit.

So when you arrive and youve reported into with the receptionist, one of the nurses will call you through when your treatment is ready, sit you down and go through all the treatment with you.

Morning, Iris. My name is Clare. I am the nurse who is going to be looking after you today. Were going to start by putting a cannula in the back of your hand and giving you some anti sickness medication. And then I am going to come back to you and talk through the chemotherapy with you and the possible side effects you may experience throughout your treatment. Is that okay?

Each chemotherapy is made up for each individual patient, depending on the type of cancer they have and where it is and depending their height, weight and blood results.

Physical Emotional And Social Effects Of Cancer

Current and Emerging Therapies for Bone Metastatic Castration

Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy, surgery, or radiation therapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the treatment plan. You should also talk about the possible side effects of the specific treatment plan and palliative care options.

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In Five Years A Major Treatment Shift

In men diagnosed with metastatic hormone-sensitive prostate cancer, the cancer is typically driven to grow and spread by androgens that are produced largely in the testes. For many years, treatments that block androgen production have been a mainstay for men initially diagnosed with metastatic prostate cancer.

Starting in 2014, that began to change after a large clinical trial showed that adding the chemotherapy drug docetaxel to ADT improved how long men with hormone-responsive disease lived. Shortly after, another clinical trial showed that adding abiraterone to ADT also improved survival in these men, although primarily in men with many metastatic tumors, known as high-volume disease.

However, docetaxel, which works by directly killing cancer cells, can have substantial side effects, and some patients arent healthy enough to tolerate it. And abirateronewhich blocks androgen production throughout the bodycan also cause side effects, including those that affect the liver. It also has to be given in combination with the steroid prednisone, which carries its own toxicity.

Doing so, Dr. Chi said during a presentation of the TITAN data at the ASCO meeting, might help stave off the typically inevitable development of hormone-resistant cancer, which is more difficult to treat and a key driver of prostate cancer deaths.

First Approved Parp Inhibitor To Demonstrate Clinically Meaningful Benefits Incombination With A New Hormonal Agentlynparza In Combination With Abiraterone Extended Median Radiographic Progression

AstraZeneca and MSDs Lynparza in combination with abiraterone and prednisone or prednisolone has been approved in the European Union for the treatment of metastatic castration-resistant prostate cancer in adult men for whom chemotherapy is not clinically indicated.

This approval by the European Commission was based on results from the PROpel Phase III trial and follows the positive recommendation in the EU by the Committee for Medicinal Products for Human Use in November 2022.

In the trial, Lynparza in combination with abiraterone and prednisone or prednisolone, reduced the risk of disease progression or death by 34% versus abiraterone and prednisone or prednisolone . Median radiographic progression-free survival was 24.8 months for Lynparza plus abiraterone versus 16.6 months for abiraterone alone. Furthermore, a planned rPFS analysis by blinded independent central review showed Lynparza plus abiraterone had a median rPFS of 27.6 months compared to 16.4 months with abiraterone alone, extending median rPFS by almost one year.

Updated results from a second planned analysis presented at ESMO 2022 showed a favourable trend towards improved overall survival with Lynparza plus abiraterone versus abiraterone alone , however, the difference did not reach statistical significance at the time of this data cut-off .

Notes

Despite the advances in mCRPC treatment in the past decade with taxane and new hormonal agent treatment, there is high unmet need in this population.12,13,14,15

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How Prostate Cancer Is Treated

In cancer care, different types of doctorsincluding medical oncologists, surgeons, and radiation oncologistsoften work together to create an overall treatment plan that may combine different types of treatments to treat the cancer. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as palliative care experts, physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, physical therapists, and others.

The common types of treatments used for prostate cancer are described below. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patients preferences and overall health.

Cancer treatment can affect older adults in different ways. More information on the specific effects of surgery, chemotherapy, and radiation therapy on older patients can be found another section of this website.

Because most prostate cancers are found in the early stages when they are growing slowly, you usually do not have to rush to make treatment decisions. During this time, it is important to talk with your doctor about the risks and benefits of all your treatment options and when treatment should begin. This discussion should also address the current state of the cancer:

About Dr Dan Sperling

New Approaches to Metastatic Hormone Sensitive Prostate Cancer

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group andSperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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A Note About Sex And Gender

Sex and gender exist on spectrums. This article will use the terms male, female, or both to refer to sex assigned at birth. .

  • neuroendocrine tumors

Experts believe some males can also have a mixed type, which combines a common and a rare type of prostate cancer. Rare forms of prostate cancer are more likely to metastasize.

Prostate cancer overall is the second most common cancer in males after skin cancer. Doctors discover most prostate cancers in the prostate or nearby tissues. However, about 16% of new cases spread into distant locations.

Between 2012 and 2018, about more cases of prostate cancer occurred in the United States.

Research has shown the incidence of prostate cancer for African American males is that of people who are white. Among African Americans, the cancer types tend to be more aggressive, and deaths are double compared with white Americans.

The differences in outcomes for African American males may originate from:

  • Physical: Higher prostate-specific antigen levels in the blood.
  • Genetic: Some African American males carry certain gene mutations or chromosomal abnormalities that can increase prostate cancer risk.
  • Environmental: Social disparities may cause people from historically marginalized groups to live on a lower income and have limited access to healthy food.
  • Social: Disparities in healthcare can limit genetic screening or disease treatment access, leading to underdiagnosis.

Other people should begin screening at the age of 50.

Role Of Perioperative Or Adjuvant Chemotherapy In Localized Prostate Cancer

Chemotherapy has also been evaluated in the neoadjuvant and adjuvant settings for high-risk localized prostate cancer. Numerous neoadjuvant trials evaluating docetaxel or paclitaxel, alone or in combination with hormone therapy prior to radical prostatectomy, have shown a low rate of pathologic complete responses and mixed toxicity profiles.

SWOG S9921 was the largest prospective adjuvant trial designed to evaluate the addition of mitoxantrone to ADT vs ADT alone in 983 high-risk prostate cancer patients after radical prostatectomy. Unfortunately, this trial was terminated early after three cases of acute myelogenous leukemia were reported in the mitoxantrone arm. Based on results released for patients treated on the ADT-only arm, the estimated 5-year biochemical failurefree survival was 92.5% and 5-year overall survival was 95.9% . The final overall survival results comparing the two arms have not been reported. A pilot French study that randomized 47 patients with high-risk prostate cancer to receive adjuvant ADT with or without weekly paclitaxel treatments for 8 weeks reported no impact on quality of life or symptoms post-prostatectomy however, survival data have not been reported.

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Upfront Chemotherapy For Metastatic Prostate Cancer

In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting.

Traditionally, androgen deprivation therapy has been the standard initial treatment for metastatic hormone-sensitive prostate cancer , with chemotherapy utilized in the castration-resistant setting. Data reported from three recent clinical trials shed new light on the role of upfront docetaxel in advanced or mHSPC. Two of these studies-CHAARTED and STAMPEDE-showed significant improvement in overall survival, while the third study, GETUG-AFU 15, showed no statistical difference. The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. These numbers are remarkable when compared with the 2.9-month survival benefit from docetaxel in the metastatic castration-resistant setting, which has been the standard setting for the use of docetaxel in advanced prostate cancer. In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting.

Possible Side Effects Of Chemotherapy

Metastatic Prostate cancer Chemotherapy

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow , the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells can also be affected by chemo, which can lead to side effects.

The side effects of chemo depend on the type and dose of drugs given and how long they are taken. Some common side effects can include:

These side effects usually go away once treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting.

Along with the risks above, some side effects are seen more often with certain chemo drugs. For example:

  • Docetaxel and cabazitaxel sometimes cause severe allergic reactions. Medicines are given before each treatment to help prevent this. These drugs can also damage nerves , which can cause numbness, tingling, or burning sensations in the hands or feet.
  • Mitoxantrone can, very rarely, cause leukemia several years later.
  • Estramustine carries an increased risk of blood clots.

If you notice any side effects while getting chemo report them to your cancer care team so that they can be treated promptly. In some cases, the doses of the chemo drugs may need to be reduced or treatment may need to be delayed or stopped to prevent the effects from getting worse.

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Bone Protection In Patients Receiving Androgen Blockade

Two drugs, the bisphosphonate zoledronic acid and the RANKL inhibitor denosumab, have been approved to treat osteoporosis secondary to androgen deprivation. Zoledronic acid is administered as an intravenous infusion. Denosumab is administered subcutaneously. These drugs are given along with supplemental vitamin D and calcium. Patients should be monitored regularly for hypocalcemia. Both agents are associated with a low incidence of osteonecrosis of the jaw. Both drugs delay the risk of skeletally-related events by relieving bone pain, preventing fractures, decreasing the need for surgery and radiation to the bones, and lowering the risk of spinal cord compression.

A double-blind, placebo-controlled, multicenter study in men with primary or hypogonadism-associated osteoporosis found that over a 14-month period, treatment with zoledronic acid reduced the risk of vertebral fractures by 67%. New morphometric vertebral fracture occurred in 1.6% of men taking zoledronic acid and in 4.9% taking placebo. Patients receiving zoledronic acid had significantly higher bone mineral density and lower bone-turnover markers. However, the rate of myocardial infarction was higher in the treatment group .

Where Is There A Role For Nonchemotherapy Treatment Of Metastatic Prostate Cancer

We will have to weigh the pros and cons of each approach in terms of the duration of therapy, side effects, and cost when deciding which course is best suited for CRPC patients.

New studies provide a useful information on how to personalize management and how to select and sequence existing therapies. Use of newly approved therapies must be balanced against many other factors . We tailor the regimen to give them the most effective therapy that also works with their lifestyle. Using these precepts, it is possible to divide treatments into those that control pain or symptoms, those that delay the development of skeletal-related events, and those that delay death rather than those that achieve reductions in prostate specific antigen levels, tumor shrinkage, favorable bone scans, or reductions in circulating tumor cells .

Fig. 1
Fig. 2

Personalized therapy in advanced-stage prostate cancer: current therapeutic landscape.

The radiopharmaceutical agent radium-223 emits alpha-radiation and selectively targets bone. In a phase III trial, treatment with radium-223 was well tolerated and increased both OS and time to first symptomatic skeletal-related event in patients with symptomatic bone metastases and no known visceral metastases . There are no randomized trials that compare radium-223 with other agents known to prolong OS in patients with mCRPC. Patients should be followed carefully for bone marrow toxicity prior to dosing and over time.

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Early Versus Delayed Treatment

In the years following the introduction by Huggins and Hodges of hormone therapy for prostate cancer, early institution of such treatment was recommended, based on comparison with historical controls. Later, the Veterans Administration Cooperative Urology Research Group studies resulted in the recommendation to defer hormone therapy until symptomatic progression occurred this was thought to avoid the promotion of early androgen resistance in prostate tumors.

Subsequently, the controversy of the appropriate timing of ADT was renewed because of the advent of an LHRH antagonist and LHRH agonists. Laboratory studies demonstrated that early hormone therapy does not confer early resistance. Moreover, clinical trials found that it provided significantly longer survival with fewer complications than did deferred treatment.

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