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Metastatic Prostate Cancer To Bone

Should I Make Any Lifestyle Changes Including In My Diet Or Physical Activity

Bone Metastasis: Treatments, Scans & Side Effects | Ask a Prostate Expert, Mark Scholz, MD

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.

Treatment Of Metastatic Stage Iv Or D2 Prostate Cancer

Prostate cancer that has spread to distant organs and bones is treatable, but not curable with current standard therapies. Hormone therapy has been the standard treatment of metastatic prostate cancer for many years. Metastatic prostate cancer can be controlled with hormone therapy for many years and new treatment options continue to become available.

What Happens After Treatment

If you’ve been treated, especially if a surgeon removed your prostate, your PSA levels should start to go down. Doctors usually wait several weeks after surgery before checking PSA levels.

A rise in PSA after treatment may suggest the cancer is back or spreading. In that case, your doctor may order the same tests used to diagnose the original cancer, including a CT scan, MRI, or bone scan. The radiotracer Axumin could be used along with a PET scan to help detect and localize any recurrent cancer.

Though very rare, it’s possible to have metastatic prostate cancer without a higher-than-normal PSA level.

Go to all of your follow-up doctor appointments. At these checkups, let your doctor know about any symptoms youâre having, especially ones like bone pain or blood in your pee. You could keep track of your symptoms by writing them down in a journal or diary.

At home, follow some healthy habits to feel your best:

Eat a balanced diet. It can boost your energy and your immune system. Fill your plate with fruits and vegetables and high-fiber foods. Cut back on fattening foods, sugar, and processed foods and meats.

Let your doctor know if youâre having trouble staying at a healthy weight or if youâre losing your appetite.

Get exercise if your doctor OKs it. It can be good for your body and mind. It can also help you stay at a healthy weight, keep up your strength, and help manage medication side effects.

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Bone Metastasis In Advanced Prostate Cancer

CA Cancer J. Clin.Clin. Geriatr. Med.

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bone homeostasisJ. Musculoskelet. Neuronal Interact.Clin. Cancer Res.

Clin. Cancer Res.J. Bone Oncol.Int. J. Mol. Sci.Bonekey Rep.Crit. Rev. Eukaryot. Gene Expr.

Cancer Cell.Cancer Lett.Front. Immunol.

Cells.J. Extracell Vesicles.Front. Oncol.Int. J. Biol. Sci.

osteomimicryContrast Media Mol. Imaging.Contrast Media Mol. Imaging.

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bone microenvironmentosteotropism

Articlehuman Prostate Cancer Bone Metastases Have An Actionable Immunosuppressive Microenvironment

Xgeva (Denosumab) for the Prevention of Metastatic Bone Cancer

An immune-suppressive microenvironment characterizes bone metastatic prostate cancer

Infiltrating T cells are exhausted and dysfunctional

Inflammatory monocytes and M2 polarized macrophages are enriched and overexpress CCL20

Disruption of the CCL20/CCR6 axes relieves T cell exhaustion and extends survival

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Bone Loss From Prostate Cancer Treatment

Testosterone, the male sex hormone, fuels the growth of prostate cancer but it also is crucial to bone health. Treatment of prostate cancer with hormone therapy, also called androgen deprivation therapy , blocks the production of testosterone which stops or slows the growth of the cancer. Without testosterone, bones can become weak and break more easily. When a man is on ADT, recovery from a bone fracture takes longer than for other men. It is especially important for men taking ADT to speak with their doctor about how to plan for and manage the bone loss before a problem arises. Bone strength can also be decreased as a result of radiation and chemotherapy used to treat prostate cancer.

Fortunately there are ways to strengthen and repair your bones including medicines and lifestyle changes.

  • Bisphosphonates can prevent the thinning of the bone and help make them stronger
  • Oral bisphosphonates include Fosamax and Actonel
  • The intravenous bisphosphonate is Zometa
  • Strive for a healthy diet and make sure to get enough calcium and vitamin D
  • When exercising, include weight bearing and muscle strengthening exercises
  • Avoid tobacco and excessive alcohol


The Role Of Inflammation

Acute inflammation is a biological response triggered by harmful stimuli such as infection, trauma, and tissue injury to eliminate the source of damage . The tumor microenvironment is unequivocally linked with inflammation, whether the infiltration of immune cells engages with tumor cells causing inflammation or chronic inflammation promotes the malignant transformation of cells and carcinogenesis .

In an experiment performed by Morrissey et al., it was found that IL-6 was highly expressed in prostate cancer bone metastases. PC-3 cells inhibited osteoblast activity and induced osteoblast to produce IL-6 that promoted osteoclastogenesis . In addition, a recent study by Roca et al. observed that macrophage-driven efferocytosis induced the expression of pro-inflammatory cytokines, such as C-X-C motif chemokine ligand 5 by activating the signal transducer and activator of transcription 3 and the nuclear factor kappa-light-chain-enhancer of activated B cells signaling. CXCL5-deficient mice had reduced tumor progression. These findings suggested that the myeloid phagocytic clearance of apoptotic cancer cells accelerated CXCL5-mediated inflammation and tumor growth in bone . In summary, findings from available evidence suggest the alleviation of chronic inflammation as a potential therapeutic approach for prostate cancer bone metastases.

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B The Role Of The Rank/rankl/osteoprotegerin Signaling Pathway In Pca Bone Metastases

Many of the factors that control bone homeostasis are at play in pathologic PCa bone metastases. In normal bone remodeling, osteoblasts mediate osteoclast differentiation and function by secreting RANKL, which induces osteoclast differentiation when bound to the RANK receptor on osteoclasts and OPG, a decoy receptor that binds to RANKL and inhibits its activity. Previous reports demonstrate that PCa cells in bone express RANK, RANKL, and OPG and communicate directly with bone cells via this same signaling pathway . High RANKL in the bone microenvironment favors osteolysis and promotes PCa growth in bone. Osteolysis releases PCa growth-promoting factors from the bone matrix including TGF-, IGF-1, matrix metalloproteinases , fibroblast growth factors , bone morphogenic proteins , and platelet-derived growth factors . The RANK/RANKL/OPG pathway is also involved in OB bone metastases. High levels of OPG are associated with end-stage OB bone metastases, and serum OPG levels are the most reliable indicator of such lesions . Recently, it has been shown that maturing osteoclasts secrete vesicular RANK that binds to OB RANKL and promotes bone formation by triggering RANKL reverse signaling and activating Runt-related transcription factor 2 . It is plausible that vesicular RANK derived from PCa cells in bone has a similar effect on pathologic bone formation in OB PCa metastases.

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Epidemiology Of Advanced Prostate Cancer

Metastatic Bone Cancer: Bone Pain When Breast & Prostate Cancer Spreads

Approximately 12.5% of men will develop prostate cancer in their lifetime, with the likelihood increasing with age prostate cancer is most often diagnosed in men age 65 to 74 years, and the median age at diagnosis is 67 years. Since the advent of prostate-specific antigen screening, prostate cancer is being detected and treated earlier.

Overall, incidence rates of prostate cancer began declining in 2000. Acceleration in the decline began in 2008, when organizations began recommending against routine PSA screening From 2011 to 2015, the rate decreased by about 7% per year.

A review of almost 800,000 cases of prostate cancer diagnosed from 20042013 found that although the incidence of low-risk prostate cancer decreased from 2007-2013 to 37% less than that of 2004, the annual incidence of metastatic prostate cancer during those years increased to 72% more than that of 2004. The increase in metastatic prostate cancer was greatest in men aged 5569 years.

At diagnosis, 77% of prostate cancer cases are localized in 13%, the cancer has spread to regional lymph nodes, and 6% have distant metastasis. The 5-year relative survival rate for localized and regional prostate cancer is 100%, compared with 30.5% for metastatic cases.

The mortality rate associated with prostate cancer continues to increase in Europe and in countries such as Australia, Japan, and Russia.

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The Underlying Molecular Mechanisms In Prostate Cancer Bone Metastases

Various types of prostate cancer cell lines, including LuCaP 23.1, LNCaP, C4-2, and IGR-CaP1, were utilized as prostate cancer models. The LuCaP 23.1 and LNCaP cells are highly sensitive to androgen . The C4-2 cell lines showed features of reduced androgen sensitivity and increased metastatic capability . In the androgen-sensitive prostate cancer cell lines, the downregulation in androgen receptor expression reduced AR-mediated transcription and cell growth. Meanwhile, the knockdown of AR expression had a marked effect on AR-mediated transcription and cell growth in the androgen-insensitive prostate cancer cell lines . The expression of AR is an important regulator of prostate cancer cell growth and development at the early stage. However, prostate cancer progresses to castration-resistant prostate cancer at the later stage. Thus, possible correlation between AR expression and the signaling molecules involved in prostate cancer bone metastasis could be considered. On the other hand, the IGR-CaP1 cell line represents a unique model recapitulating widespread bone metastasis with mixed osteoblastic and osteolytic bone lesions that resemble the conditions observed in patients .

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.

Surgery And Advanced Prostate Cancer

Metastatic Prostate Cancer to Bone

An indication for immediate bilateral orchiectomy is spinal cord compression. Surgical intervention is mandatory for pathologic fractures involving weight-bearing bones.

In patients with clinical stage T3 prostate cancer at initial presentation, radical prostatectomy has not historically been considered beneficial, because of the increased probability of incomplete resection of the cancer, likelihood of micrometastatic disease, and increased morbidity.

However, a retrospective review of approximately 840 men with stage cT3 prostate cancer who underwent RP at the Mayo Clinic reported outcomes similar to those with organ-confined disease during the same period at this institution. Pathologic stage, Gleason grade, positive surgical margin, and nondiploid chromatin were found to be independently associated with increased progression of disease.

In another Mayo Clinic study, in which the long-term survival of patients with high-risk prostate cancer was compared after RP and after external beam radiation therapy , RP alone and EBRT plus ADT provided similar long-term cancer control. However, the risk of all-cause mortality was greater after EBRT plus ADT than after RP.

In the study, RP was used in 1238 men, EBRT plus ADT was used in 344 men, and 265 received EBRT alone. The 10-year cancer-specific survival rates in the study were 92% in patients treated with RP or EBRT plus ADT, and 88% in those receiving EBRT alone, with a median follow-up of 6-10 years.

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General Statement On Bone Metastases

Bone metastasis is a devastating condition that has wide-ranging negative impacts on the lives of patients with advanced cancer . To date, no large-scale etiological studies on the prevalence or incidence of bone metastasis have been conducted worldwide . However, the current 5-year survival rate for prostate cancer is> 95% across numerous countries , and an increase in survival time may increase the incidence of bone metastasis.

Irrespective of the primary malignant location, bone metastases are commonly found in the spine, pelvis, shoulder, and distal femur . These bone lesions can cause serious complications, such as spinal cord and nerve root compression, pathological fracture, and hypercalcemia . Bone metastases most commonly affect the axial skeleton. In adults, the axial skeleton contains red marrow, which suggests that the properties of the circulation, cells and extracellular matrix within this region assist in the formation of bone metastasis . Batson showed that venous blood from the breast and pelvis flowed not only into the vena cava but also into the vertebral venous plexus, which extends from the pelvis to throughout the epidural and peri-vertebral veins . Blood drainage to the skeleton via the vertebral venous plexus may, at least in part, explain the tendency of breast and prostate cancers to produce metastases in the axial skeleton and limb girdles .

Fig. 1

Batsons venous plexus. Cited from Diseases of the Spine and Spinal Cord

Fig. 2

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What Are The Chances Of Getting Metastatic Prostate Cancer

About 50% of men diagnosed with local prostate cancer will get metastatic cancer during their lifetime. Finding cancer early and treating it can lower that rate.

A small percentage of men aren’t diagnosed with prostate cancer until it has become metastatic. Doctors can find out if it’s metastatic cancer when they take a small sample of the tissue and study the cells.

Can I Survive Advanced Prostate Cancer Whats The Prognosis

Bone Scan for Metastatic Prostate Cancer

Prostate cancer is the second leading cause of death from cancer in men, according to the National Cancer Institute. While theres no cure, men can live with it for years if they get the right treatment. Each man with advanced prostate cancer is different, of course. You and your cancer have unique qualities that your doctor takes into consideration when planning the best treatment strategy for you.

According to Harvard Medical School, the prognosis for men with advanced prostate cancer is improving because of newer medications that help them get past a resistance to androgen-deprivation therapy that typically develops after a few years of treatment. With these medications, many men are living longer, and a number of men diagnosed with advanced prostate cancer are dying with the cancer, not from it.

Promptly treating prostate cancer bone metastases with the newest medication can help change a mans prognosis dramatically, Tagawa says. There are men who do well for decades, he says. Some men can even stop treatment, go on to live many years, and actually die of something unrelated.

Tagawa says that cancer specialists who use sophisticated imaging technologies, like positron-emission tomography scans, have gotten very good at finding even tiny bone metastases, which is valuable in diagnosing and removing early stage metastases.

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Advanced Prostate Cancer And Bone Metastases

Most all prostate cancer patients worry about metastases. Metastases used to signal that death was near. Most prostate cancer metastases take place in bones. New treatments such as Xofigo have helped thousands of men delay health while maintaining a pain free high quality of life. Bone metastases are tumors that have spread from the prostate to your bones. Usually bone metastases occur in the pelvis, spine, thighs and ribs. But, they can develop in any bone anywhere in your body. Bone metastases can become extremely painful. Which is why it is reasonable and very human to fear bone metastases. So, if you are feeling anything that you imagine to be bone pain, talk to your doctor right away.

Diagnosing Bone Metastases

Bone metastases symptoms are sometimes confused with arthritis. The symptoms such as pain seem to be the same. So, if you are already diagnosed with prostate cancer, you must talk to your doctor about anything at all that you imagine to be pain in your bones. X-rays can diagnose bone metastases best, but bone scans, CT scans, PET scans, MRIs and blood tests are also used for diagnosis.

Untreated bone metastases in a man with castrate resistant prostate cancer could cause fractures and other skeletal problems none of which are pleasant.

Early detection of bone metastases allows more effective treatment to delay bone pain and other complications.

Preventing and Treating Bone Metastases

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