The Role Of The Pharmacist
An important aspect of the ordering process of denosumab for patients with bone metastases is the distinction between brand names that are used for different indications. Denosumab is sold under two brand names, Prolia and Xgeva. Xgeva is FDA approved for the treatment of hypercalcemia of malignancy as well as bone metastases.16,22 In addition, zoledronic acid is available under two brand names, Reclast and Zometa, which carry different indications.9,23 For the treatment of metastatic bone disease, Zometa carries the FDA approval and should be the only formulation ordered for this indication.9 Zoledronic acid dosing adjustments must be distinguished between oncologic indications. For bone metastases, there are strict adjustments for renal function due to the concern for accumulation with repeated dosing.9 In contrast, dose adjustments are not required for hypercalcemia of malignancy that can be observed in patients with metastatic PCa as well.9 Close attention should be paid to the differences in dosing and indication for these products to ensure that the indication is clarified and in accordance with the selected product for a given patient. In addition, the cost of denosumab is substantiallyhigher than that of zoledronic acid.
Prostate Cancer In The Bone Microenvironment
Stephen Paget proposed in 1889 that metastasis depends on the cross-talk between metastasizing cancer cells and the organ microenvironment . The bone microenvironment encompasses both osteoclasts and osteo-blasts, whose interaction of resorbing and reforming bone maintains skeletal integrity. In normal bone homeostasis, osteoclasts differentiate from hematopoetic stem cell precursors and adhere to bone, where subsequent resorption releases chemotactic cytokines that attract osteoblasts. Osteoblasts, derived from stromal stem cells, produce osteoid matrix and express both receptor activator of nuclear factor-kB ligand and osteoprotegerin. RANKL binds to the RANK transmembrane receptor on osteoclasts leading to osteoclast differentiation while osteoprotegerin functions as a decoy receptor, sequestering RANKL, helping to modulate the balance between destruction and production. Downstream of RANK in osteoclasts, activation of NF-kB leads to activation of osteoclast genes that lead to maturation, adherence to bone, and secretion of proteins involved in bone catabolism. These proteins include cathepsin K, a protease that catabolizes bone collagen and promotes further osteoclast adhesion, and Src, a tyrosine kinase that is activated in osteoclasts after integrin binding to the bone matrix and which appears to promote osteoclast survival and formation of the âruffled bordersâ and cell polarization needed for bone resorption .
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.
Zometa® 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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Stage 2 Prostate Cancer
In stage 2, the tumor is still confined to your prostate and hasnt spread to lymph nodes or other parts of your body. A doctor may or may not be able to feel the tumor during a prostate exam, and it may appear on ultrasound imaging. The survival rate is still .
The PSA score for stage 2 is less than 20 ng/mL.
Stage 2 cancer is further divided into three phases depending on the grade group and Gleason scores:
- Gleason score: 6 or less
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What Happens If You Stop Hormone Therapy For Prostate Cancer
If you stop your hormone therapy, your testosterone levels will gradually rise again and some side effects will reduce. Your side effects won’t stop as soon as you finish hormone therapy it may take several months. Surgery to remove the testicles can’t be reversed, so the side effects are permanent.
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Myths About Prostate Cancer
Here are some things that will not cause prostate cancer: Too much sex, a vasectomy, and masturbation. If you have an enlarged prostate , that does not mean you are at greater risk of developing prostate cancer. Researchers are still studying whether alcohol use, STDs, or prostatitis play a role in the development of prostate cancer.
Certain Factors Affect Prognosis And Treatment Options
The prognosis and treatment options depend on the following:
- The stage of the cancer .
- The patients age.
- Whether the cancer has just been diagnosed or has recurred .
Treatment options also may depend on the following:
- Whether the patient has other health problems.
- The expected side effects of treatment.
- Past treatment for prostate cancer.
- The wishes of the patient.
Most men diagnosed with prostate cancer do not die of it.
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Choosing To Stop Treatment Or Choosing No Treatment At All
For some people, when treatments have been tried and are no longer controlling the cancer, it could be time to weigh the benefits and risks of continuing to try new treatments. Whether or not you continue treatment, there are still things you can do to help maintain or improve your quality of life.
Some people, especially if the cancer is advanced, might not want to be treated at all. There are many reasons you might decide not to get cancer treatment, but its important to talk to your doctors and you make that decision. Remember that even if you choose not to treat the cancer, you can still get supportive care to help with pain or other symptoms.
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.
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The Role Of Bone Morphogenetic Protein
Bone morphogenetic protein belongs to the TGF- superfamily, which functionally stimulates the replication and differentiation of normal cells in the osteoblast lineage. It also plays a crucial role during the process of mesoderm induction, neural tissue differentiation, and morphogenesis of various tissues . Interestingly, BMPs are not only synthesized by osteoblasts but also secreted by prostate cancers. The unusual expression of BMPs in prostate cancer has been implicated in the progression of the disease.
Taken together, BMP expressions are detectable in either normal prostate tissue or prostate cancer cells. The pattern of BMP expression has a close relationship with the progression of prostate cancer and contributes to the onset of bone lesions. It is clear that BMPs play a role in the vicious cycle of metastatic bone formation from prostate cancer. BMPs produced by prostate cancer will induce osteoblastic activities and promote osteoblastic lesions. On the other hand, BMPs synthesized by osteoblasts subsequently enhance the growth of prostate cancer cells allowing further production of BMPs from prostate cancer.
Prostate Cancer Survival Rates
The good news about prostate cancer is that it usually grows slowly, and 9 out of 10 cases are found in the early stages. Overall, the 5-year relative survival rate is 100% for men with disease confined to the prostate or nearby tissues. Many men live much longer. When the disease has spread to distant areas, that figure drops to 31%. But these numbers are based on men diagnosed at least 5 years ago. The outlook may be better for men diagnosed and treated today.
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Emerging Therapies For Prostate Cancer
Researchers are pursuing several new ways to treat advanced prostate cancer. Vaccines that alter the body’s immune system and use genetically modified viruses show the most promise. One vaccine technique works by manipulating blood cells from the patient’s immune system and causing them to attack the prostate cancer.
Blood is drawn from the patient. From the blood sample, cells that are part of the immune system are exposed to cells that make up prostate cancer. Then the blood cells are placed back in the body, with the hope that they will cause other immune system cells to attack the prostate cancer. In a more traditional type of vaccine, the patient is injected with a virus that contains PSA. When the body is exposed to the virus, it becomes sensitized to cells in the body that contain PSA and their immune system attacks them.
Immune or genetic therapy have the potential to deliver more targeted, less invasive treatments for advanced prostate cancer. This would result in fewer side effects and better control of the prostate cancer.
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How Prostate Cancer Spreads
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 â tiny blood vessels â 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 break-away cancer cells form new tumors. Many others donât survive in the bloodstream. Some die at the site of the new tissue. Others may lie inactive for years or never become active.
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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:
Characteristics Of Lymph Node Metastasis
Taken together, the concept of the pre-metastatic niche also holds true in prostate cancer lymph node metastasis. Identifying key pathways of niche communication may have significant implications for prognostic and therapeutic purposes in prostate cancer, such as targeting the VEGR3-VEGF-C axis to halt the progression of lymph node metastasis and improve the patient´s prognosis.
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Questions To Ask Your Doctor Or Nurse
- What type of hormone therapy are you offering me and why?
- Are there other treatments I can have?
- What are the advantages and disadvantages of my treatment?
- What treatments and support are available to help manage side effects?
- Are there any lifestyle changes that might help me manage my cancer, symptoms, or side effects?
- How often will I have check-ups and what will this involve?
- How will we know if my cancer starts to grow again?
- What other treatments are available if that happens?
- Can I join any clinical trials?
- If I have any questions or get any new symptoms, who should I contact?
Good Prostate Cancer Care
Your MDT will be able to recommend what they feel are the best treatment options, but ultimately the decision is yours.
You should be able to talk with a named specialist nurse about treatment options and possible side effects to help you make a decision.
You should also be told about any clinical trials you may be eligible for.
If you have side effects from treatment, you should be referred to specialist services to help stop or ease these side effects.
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Prostate Cancer Bone Metastases Thwart Immunotherapy By Producing Tgf
MD Anderson researchers find abundant cytokine crowds out helper Tcells crucial to treatment
MD Anderson News ReleaseNovember 14, 2019
Prostate cancer that spreads to the bone triggers the destruction of bone tissue that, in turn, thwarts the effectiveness of immune checkpoint inhibitors by blocking the development of T cells that are crucial to successful treatment, researchers from The University of Texas MD Anderson Cancer Center report in Cell.
The discoveries by a team led by Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology at MD Anderson, explain why immunotherapy has been largely unsuccessful against prostate cancer bone metastases and point to a possible combination that could reverse the resistance.
Their findings also highlight the need to look at metastatic cancer in a different light.
We tend to think of stage 4 disease as being uniform, but its not all the same, Sharma says. We need to be more thoughtful about the immune microenvironment in different areas of metastasis to take into account different immune responses in those microenvironments when we develop treatments.
Research points to anti-TGF-, anti-CTLA-4 combination
The team found that the bone destruction caused by tumors leads to massive production of transforming growth factor-beta , a protein that causes helper T cells to polarize into Th17 CD4 cells instead of the Th1 CD4 effector cells required to trigger an anti-tumor immune response.
Research Into Secondary Bone Tumours
Research is going on all the time into improving treatments for secondary bone cancer and helping people to cope with symptoms. Cancer Research UK supports a lot of UK laboratory research into cancer and also supports many UK and international clinical trials.
Current research is looking for biomarkers in blood, urine, tears and saliva for people with breast cancer. They hope by finding a biomarker they see in advance if it may spread to the bones.
Other clinical trials include looking at ways to treat and manage pain with:
- high intensity focused ultrasound and an MRI scan
- a drug called tanezumab
Early research is looking at having pembrolizumab and radium 223 together. This is to treat people with non small cell lung cancer . The doctors want to find out about the side effects this has and how well it works at shrinking the cancer.
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National Institute for Health and Care Excellence , October 2012
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Metastatic Bone Disease: A Guide to Good PracticeBritish Orthopaedic Oncology Society and British Orthopaedic Association, 2015
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National Institute for Health Care Excellence , September 2016
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Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysisS Burdett and others
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What Treatments Are Available
If you have advanced prostate cancer, treatment wont cure your cancer. But it can help keep it under control and manage any symptoms.
If youve just been diagnosed with advanced prostate cancer, you may be offered the following treatments:
- chemotherapy with hormone therapy
- clinical trials.
Research has found that having radiotherapy together with one of the main treatments listed above can help some men with advanced prostate cancer to live longer. But radiotherapy isnt suitable for all men with advanced prostate cancer.
If you live in Scotland, you may also be offered a type of hormone therapy called abiraterone acetate together with standard hormone therapy. In the rest of the UK, abiraterone is currently only given to men with advanced prostate cancer that has stopped responding to other types of hormone therapy. The National Institute for Health and Care Excellence is currently deciding whether to make it available for men who have just been diagnosed with advanced prostate cancer.
Before you start treatment
Before you start any treatment, make sure you have all the information you need. Its important to think about how you would cope with the possible side effects. Speak to your doctor or nurse about this.
It can help to write down any questions you want to ask at your next appointment. It may also help to take someone with you, such as your partner, a family member or friend.
If you have any questions, speak to our Specialist Nurses.