Events In Prostate Cancer Metastatic Process
The classic model of metastasis of solid tumors, including prostate cancer, is guided by the âseed and soilâ hypothesis first proposed by Stephen Paget in 1889.24 In Pagetâs model, the âseedsâ metastasize only to âsoilâ well suited for the tumorâs growth. Although this concept remains an excellent guiding principle, it does not entirely explain the molecular bases for organ-specific metastases. Metastasis of prostate cancer, like that of other solid tumors, involves multiple steps, including angiogenesis, local migration, invasion, intravasation, circulation, and extravasation of tumor cells and then angiogenesis and colonization in the new site. We will describe only the hallmarks of these events, which have been reviewed in extensive detail elsewhere.25–28 We will then discuss our emerging understanding of properties of metastatic prostate tumor cells that facilitate their growth in the bone.
Should I Make Any Lifestyle Changes Including In My Diet Or Physical Activity
Achieving and maintaining a healthy weight by eating a balanced diet with plenty of fruits, vegetables, and whole grains, and staying physically active, can help your overall health. These lifestyle changes can also have a positive effect for men with bone metastases, Tagawa says. Both diet and exercise, he says, are things that are under a mans direct control.
A healthy lifestyle can help you better manage side effects from treatment as well. Try setting small but realistic goals for yourself when it comes to eating a healthy diet and getting plenty of exercise.
While no single food is likely to have a benefit for prostate cancer, smart food choices may help you feel better day to day. Start by cutting out foods high in sugar, saturated fat, and added flavorings and preservatives.
If youre not sure which healthy foods to choose, ask your doctor for a referral to a dietitian. This specialist can help you develop a meal plan that includes foods that offer the best chance of slowing the cancers growth and keeping you as healthy as possible.
As an oncologist, Tagawa says he concentrates on treating the cancer itself, but hes aware that many of the men he sees with advanced prostate cancer are older and more likely than younger men to have health problems that can benefit from diet and exercise.
And if youre on hormone therapy, talk to your doctor about investing in some weights or elastic resistance bands to support your bone strength too.
Pharmacologic Agents In Prostate Cancer
Gonadotropin-releasing hormone analogues suppress ovarian and testicular steroidogenesis by decreasing luteinizing hormone and follicle stimulating hormone levels, whereas GnRH antagonists lower serum testosterone levels by suppressing LH and FSH.
Bisphosphonates are analogues of pyrophosphate that act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. These agents prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability.
Antiandrogens are used as combination agents to treat prostate cancer. Antifungal agents produce a response similar to that of antiandrogens. These drugs inhibit various cytochrome P-450 enzymes, including 11-beta-hydroxylase and 17-alpha-hydroxylase, which in turn inhibit steroid synthesis. The antiandrogen abiraterone is a 17 alpha-hydroxylase/C17, 20-lyase inhibitor that was approved by the US Food and Drug Administration in 2011 for use in combination with prednisone for treatment of metastatic castration-resistant prostate cancer in patients who received prior chemotherapy containing docetaxel.
An ultramicronized abiraterone tablet was approved in May 2018 for CRPC in combination with methylprednisolone. The ultramicronized formulation may be administered with or without food, whereas, the original tablet formulation must be administered 1 hour before or 2 hours after meals.
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What Is Metastatic Prostate Cancer
If your prostate cancer spreads to other parts of your body, your doctor may tell you that it’s “metastatic” or that your cancer has “metastasized.”
Most often, prostate cancer spreads to the bones or lymph nodes. It’s also common for it to spread to the liver or lungs. It’s rare for it to move to other organs, such as the brain, but that can happen.
It’s still prostate cancer, even when it spreads. For example, metastatic prostate cancer in a bone in your hip is not bone cancer. It has the same prostate cancer cells the original tumor had.
Metastatic prostate cancer is an advanced form of cancer. There’s no cure, but you take steps to treat and control it. Most men with advanced prostate cancer live a normal life for many years.
The goals of treatment are to:
- Manage symptoms
- Slow the rate your cancer grows
- Shrink the tumor
Some cancers are called “locally advanced.” That means the cancer has spread from the prostate to nearby tissue. It’s not the same as metastatic cancer since it hasn’t spread to other parts of your body. Many locally advanced prostate cancers can be cured.
Survival Rates And Outlook
There is currently no cure for advanced prostate cancer, but advances in treatments are extending life expectancy and improving quality of life.
The ACS states that the 5-year relative survival rate for individuals with prostate cancer that has spread to distant lymph nodes, organs, or the bones is 31% . Therefore, people with this stage of prostate cancer are about 31% as likely as those without the condition to live for at least 5 years after diagnosis.
However, survival rates are only estimates, and everyone is different. The following factors are among those that can affect a personâs outlook:
- how cancer responds to treatment
- how far cancer has spread
Ongoing cancer research is also facilitating the development of more effective treatments and leading to improved survival rates.
Here are some answers to questions people often ask about prostate cancer moving to the bones.
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A Genetic Biomarker Test For Newly Diagnosed Prostate Cancer
Results from a study of a different genetic biomarker test suggest that it could one day help inform treatment decisions for men newly diagnosed with localized prostate cancer.
According to findings published February 24 in JCO Precision Oncology, a biomarker test called the Oncotype DX Genomic Prostate Score accurately predicted the long-term risk of metastasis and death from prostate cancer in men with localized disease. The test needs to be validated in larger forward-looking studies before it can be used to guide treatment, the study researchers noted.
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Nuclear Bone Scan Procedure
The first step in the procedure is the injection of the tracer material. A technician will do this through a vein in your arm or hand. You might feel a sting from the IV.
Then, you wait for the tracer to travel through your body and bind to your bones. That can take 2 to 4 hours.
Your doctor might order a scan before your body absorbs the tracer for comparison, especially if you could have a bone infection. If youâre having two scans, the first will happen right after the injection.
While your body is absorbing the nuclear material, youâll need to drink 4 to 6 glasses of water to flush extra tracer from your body. Youâll use the restroom before the test so any concentration in your urine doesnât cause a misleading picture.
For the scan itself, youâll lie on a table while a camera takes pictures. Youâll have to remain very still for certain portions of the scan, and you may have to change positions several times. The scanning may take up to an hour. Itâs not painful, but lying on the table may become uncomfortable.
Your doctor may also order a type of test called single-photon emission-computed tomography . The camera rotates around your body to make more detailed images.
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Are Achy Bones A Sign Prostate Cancer Has Metastasized
Pain can often be a symptom of advanced prostate cancer, particularly pain felt deep in the bones.
Since more than 60 percent of men with advanced prostate cancer will go on to develop bone metastases, or cancer cells that have spread to the bones, achy bones may be a sign that prostate cancer has metastasized.
While achiness due to weakened bones can be quite painful, there are various ways to manage the pain.
Heres what to be on the lookout for if youre concerned about metastatic prostate cancer, what bone pain really feels like, and how pain and discomfort can be treated.
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The Role Of The Rank/rankl/opg System
The receptor activator of nuclear factor-kappa B /RANKL/OPG system is a key molecular system discovered to regulate the bone modeling and remodeling process. Osteoprotegerin is a decoy receptor produced by osteoblasts that blocks the association between RANKL and RANK, thus inhibiting osteoclastogenesis and increasing bone mass. Apart from controlling the normal bone metabolism, this system also plays an essential role in pathological bone metabolism, such as metastatic disease in bone.
Taken together, these previous findings reiterate that: OPG may be beneficial in preventing osteolytic lesions but overexpression of OPG leads to osteoblastic lesions, and a high level of RANKL expression causes osteolytic lesions, thus RANKL blockade will potentially limit the formation and progression of osteolytic lesions. Hence, maintenance of a balanced profile between OPG and RANKL may represent a potential therapeutic strategy for interfering with prostate tumor metastases and progression to bone.
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How Does Prostate Cancer Spread
Cancer cells sometimes break away from the original tumor and go to a blood or lymph vessel. Once there, they move through your body. The cells stop in capillaries — tiny blood vessels — at some distant location.
The cells then break through the wall of the blood vessel and attach to whatever tissue they find. They multiply and grow new blood vessels to bring nutrients to the new tumor. Prostate cancer prefers to grow in specific areas, such as lymph nodes or in the ribs, pelvic bones, and spine.
Most breakaway cancer cells form new tumors. Many others don’t survive in the bloodstream. Some die at the site of the new tissue. Others may lie inactive for years or never become active.
Cancer Treatmentinduced Bone Loss
The role of sex steroids on bone homeostasis has been extensively studied and, in recent years, the development of mouse models with global and cell-specific deletions in Oestrogen and Androgen Receptors has evolved our understanding of this role . Androgen receptor signalling in osteoblasts is responsible for the protective effects of androgens on trabecular bone mass, leading to a decrease in osteoclast numbers and bone resorption. Oestrogens, produced via aromatization of androgens in males, protect against endocortical resorption, at least in part, via ER signalling in mesenchymal/stromal cells . Oestrogens play an important role in regulating the RANKL/RANK/OPG pathway, which influences osteoclast activity and has important therapeutic implications . Collective evidence from several interventional and observational human studies supports the theory that oestrogen plays a much more significant role in regulating bone metabolism in men than testosterone .
Mechanistic role of androgen deprivation therapy
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Symptoms Of Metastatic Prostate Cancer
Metastatic prostate cancer means that a cancer that began in the prostate gland has spread to another part of the body. It is also called advanced prostate cancer.
If your prostate cancer has spread you might:
- feel generally unwell
- have weight loss for no known reason
You might have specific symptoms depending on where the cancer has spread to. These symptoms can also be caused by other medical conditions so might not be a sign that the cancer has spread.
A Models Of Pca Ob Bone Metastases
Preclinical models that faithfully reproduce PCa bone lesions are essential to gaining a functional understanding of bone-PCa interactions. Existing xenograft models of PCa bone metastases have been developed through a variety of injection approaches to study the processes of bone targeting and PCa growth/bone reaction . The model systems that study bone targeting have been less successful than the intraosseous model that recapitulates the final phase of PCa disease progression. For example, PC3 cells have a 20% to 89% take rate in bone after intracardiac injection, and 19% after intravenous injection compared with 60% to 100% after intraosseous injection . The intraosseous technique has proven to be a reproducible approach for studying tumor-bone interactions and factors governing the bone reaction. summarizes the distinguishing features of human PCa xenograft models using intraosseous injection of bone metastases .
What Do My Test Results Mean
Your doctor will look at your test results to find out if the cancer has spread and how quickly it might be growing.
How far has my cancer spread?
The stage of your cancer tells you whether it has spread outside the prostate and how far it has spread. You might need scans, such as an MRI, CT or bone scan, to find out the stage of your cancer.
Depending on the results, your cancer may be treated as:
- localised prostate cancer its contained inside the prostate
- locally advanced prostate cancer its started to break out of the prostate or has spread to the area just outside it
- advanced prostate cancer its spread from the prostate to other parts of the body.
Is my cancer likely to spread?
Your doctor may talk to you about the risk of your cancer spreading outside the prostate or coming back after treatment.
Your prostate biopsy results will show how aggressive the cancer is in other words, how likely it is to spread outside the prostate. You might hear this called your Gleason grade, Gleason score, or grade group.
Your cancer may be low risk if:
- your PSA level is less than 10 ng/ml, and
- your Gleason score is 6 or less , and
- the stage of your cancer is T1 to T2a.
Your cancer may be medium risk if:
- your PSA level is between 10 and 20 ng/ml, or
- your Gleason score is 7 , or
- the stage of your cancer is T2b.
What happens next?
Prostate Cancer Bone Metastases
Bone is the most common site of metastasis from prostate cancer as shown in an autopsy study of 1589 patients with prostate cancer in which 90% were found to have bone involvement . Bone metastases are associated with an increased morbidity and a negative impact on quality of life mainly through SREs . Treatment strategies are therefore directed at delaying the onset of SREs and hence preserving the quality of life and functional status in this patient group .
The exact mechanisms for development of bone metastases in prostate cancer patients remain unclear and studies are ongoing in this field. The bone microenvironment, however, is recognized as a significant mediator of prostate cancer bone tropism and this is mediated by the CXCL16/CXCR6 axis. Circulating tumour cells migrate towards the bone based on a gradient of chemokines and ligands released by the bone marrow. These tumour cells then parasitize the bone microenvironment for haematopoietic stem cells and become dormant in the bone marrow. It is therefore suggested that a specific component of the bone marrow microenvironment can serve as a potential therapeutic target in prostate cancer patients with bone metastases .
Further studies looking at the specific molecular mechanisms controlling the formation and progression of bone metastases in prostate cancer patients are important as they can set new targets for the development of novel therapies in this patient group.
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What Are My Treatment Options With Advanced Prostate Cancer
The treatments your doctor recommends will depend on factors specific to you, from your overall health to how advanced your cancer was when it was first diagnosed.
Many men receive ADT, a type of hormone therapy, which deprives the body of the male hormones that the cancer needs to keep growing.
For most men, however, hormone therapy stops working at some point. Alternatives to hormone therapy were approved by the Food and Drug Administration in 2018, and Tagawa often starts men on these therapies as soon as theyre diagnosed with bone metastases. Other treatment options may be available through clinical trials.
In addition, chemotherapy, surgery, and immunotherapy as well as radiation treatments, like external beam radiation, which directly target bone problems may be considered. Major cancer centers, such as Memorial Sloan Kettering Cancer Center in New York City and MD Anderson Cancer Center in Houston, have teams of prostate cancer specialists, as well as sophisticated radiation and other treatment equipment consolidated in one place, which can help with the coordination of care.
Advanced Prostate Cancer: Caring For Your Bones
If you have advanced prostate cancer, it means the cancer has moved to a part of your body outside your prostate gland. The bones are a common place for it to spread.
The cancer may show up in your spine, pelvis, ribs, or the upper part of your thigh bone, called the femur.
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Metastatic Prostate Cancer Treatment
Treatments for metastatic prostate cancer may depend on where in the body the disease has spread. Options include:
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Treatment Of Bone Complications
Patients with advanced prostate cancer can have cancer cells that have spread to their bones, called bone metastases. Bone metastases commonly cause pain, increase the risk of fractures, and can lead to a life-threatening condition characterized by an increased amount of calcium in the blood called hypercalcemia. Treatments for bone complications may include drug therapy or radiation therapy.
ZometaÂ® is a bisphosphonate drug that can effectively prevent loss of bone that occurs from cancer that has spread to the bones thereby reducing the risk of fractures, and decreasing pain. Bisphosphonate drugs work by inhibiting bone resorption, or breakdown. Zoledronic acid may be used to reduce the risk of complications from bone metastases or to treat cancer-related hypercalcemia,
Xgeva targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts . Studies have suggested that Denosumab may be more effective than Zoledronic acid at delaying bone complications in prostate cancer patients with bone metastases. Denosumab is associated with side effects including hypocalcemia and osteonecrosis of the jaw .
Radiation therapy: Pain from bone metastases may also be relieved with radiation therapy directed to the affected bones.
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