What Makes Prostate Cancer Become Aggressive Study Investigates
They suggest that the finding could help predict disease aggressiveness, improve personalized treatments, and open the door to precision medicine for advanced prostate cancer.
In a study paper now published in the journal Cell, they describe how they investigated a genomic variant known to be linked to aggressive prostate cancer.
Using state-of-the-art tools, they confirmed the link in a large group of people with prostate cancer.
They also identified how the variant influences a genetic circuit involving three genes that could potentially drive the disease to an incurable stage.
The genomic variant is a difference in a DNA building block located in chromosome 19q13 that is known as the single nucleotide polymorphism rs11672691.
Previous studies had already linked this particular variant to aggressive prostate cancer. But they did not explain how the link worked.
Comparing the order in which millions of DNA building blocks occur in the human genomes of any two individuals would reveal hardly any differences. But where they do occur, these differences or variants can give rise to disease.
How human genomic variants, says senior study author Gong-Hong Wei, a professor in the Faculty of Biochemistry and Molecular Medicine at the University of Oulu in Finland, cause disease and its progression is in general one of the most compelling puzzles and questions in medicine.
Prostate Cancer Survival Rates
Answering the question of how curable is prostate cancer? first requires understanding what doctors mean when they refer to curability. Regardless of the type of cancer, doctors consider cancer cured when a patient remains cancer-free for a specified period after treatment. The higher the number of patients who stay cancer-free for five years or longer, the higher the curability of that particular disease.
Prostate cancer, therefore, has one of the highest curability rates of all types of cancer, thanks in large part to early detection standards and advances in treatment, such as the stereotactic body radiation therapy offered by Pasadena CyberKnife. When the cancer is detected in the early local or regional stages that is, before the cancer has spread or when it has only spread to limited areas in the pelvic regions the five-year survival rate is nearly 100 percent.
Survival rates decline significantly when cancer is detected at later stages however, the good news is that only about five percent of men are diagnosed after the cancer has become widespread throughout the body. In short, more than 90 percent of men who are diagnosed with prostate cancer live for five years or longer after treatment, making it one of the most curable forms of cancer.
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Diagnosing Rare Prostate Cancers
Rarer prostate cancers can be harder to diagnose. For example, some dont cause your prostate specific antigen level to rise. This means theyre not always picked up by a PSA test. Because of this, some rare cancers may not be diagnosed until they have already spread outside the prostate. Read more about the PSA test and other tests used to diagnose prostate cancer.
Some rare prostate cancers may only be picked up after having a biopsy to check for prostate cancer, or surgery called transurethral resection of the prostate to treat an enlarged prostate. The tissue removed during the biopsy or TURP is looked under a microscope to see if you have common prostate cancer or a rare type of prostate cancer. Rare cancers arent always given a Gleason score after a biopsy. This is because they can behave differently to common prostate cancer and cant be measured in the same way.
Because rare cancer can be aggressive and spread outside the prostate, you will probably have more tests to see if they have spread. These include:
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What Are The Treatment Options For Aggressive Prostate Cancer
The majority of people with prostate cancer nearly 80% are diagnosed early and cured by their treatment, most often radiation or surgery.
But one in five of those diagnosed with prostate cancer has a more aggressive form of the disease. Even before the individual has received any treatment or experienced a recurrence, doctors can identify whether the cancer is likely to be more dangerous and aggressive.
Prostate cancer is determined to be high risk if it is distinguished by any of the following characteristics:
Physicians perform biopsies or take X-rays to determine a cancers grade and stage. The stage is based on the size of the primary tumor or the extent it has spread in the body. The grade describes the appearance of the cancer cells and tissue under a microscope: the more abnormal they are, the higher the grade.
What are the main treatment options for people with aggressive or high-risk prostate cancer and can the sequencing, or order in which different treatments are given, make a difference in overall effectiveness of these therapies?
Why Roswell Park for Prostate Cancer?
Find out what makes Roswell Park unique in treating prostate cancer.
Ne Differentiation And Somatostatin Receptors
An immunohistochemical study investigating the expression of the five subtypes of somatostatin receptors in PCa has shown that the greatest proportion of cells with strong stainings is seen in SSTR2, mainly in the group of CRPCa with NE differentiation . The cloning of the SSTRs has led to the development of subtype-selective analogues. Among those, the SSTR2-specific somatostatin analogues octreotide and lanreotide have attracted significant attention. Typing the somatostatin receptor expression in NE tumors is considered to be of great relevance for somatostatin analogue-based diagnostic and therapeutic approaches. The presence of somatostatin receptors on the cancer cell surface may provide a readily available, noninvasive means to identify PCa with NE differentiation with imaging techniques as well as for peptide receptor radionuclide therapy .
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Surgical procedures to remove the diseased prostate are usually necessary. Surgical procedures are not always necessary. If the disease is caused by bacterial infections, a doctor can treat the symptoms using alpha-blockers or surgery. Physical therapy, relaxation exercises, and warm baths are all recommended. A physician may also prescribe antibiotics to cure the infection. A bacterial infection can also cause a recurrence of the condition.
An enlarged prostate can be uncomfortable for both men and women. Some of the symptoms of an enlarged male reproductive organ include a weakened urine stream, urgent need to urinate, and urinary tract infections. BPH can also cause damage to the kidneys. A sudden inability to urinate can be life-threatening, as it can lead to bladder and kidney damage. Unfortunately, most men with enlarged prostrates put up with the symptoms for years before they seek treatment. However, many of the men with symptoms finally decide to go to a doctor for proper gynecological evaluation and to begin enlarged prostatic therapy.
Emergence Of The Neuroendocrine Subtype
Potent hormone therapies like abiraterone and enzalutamide can be effective treatments for men with castrate-resistant prostate cancer. However, almost all men eventually develop drug resistance to these agents.
In some cases, the drug-resistant cancer may look and behave differently than the original cancer, so much so that it is considered a different subtype of the disease. For example, some men who were originally diagnosed with adenocarcinoma prostate cancer develop t-SCNC after treatment with abiraterone or enzalutamide.
Under the microscope, t-SCNC looks quite different from adenocarcinoma: the cells are smaller and more crowded together. And compared to adenocarcinoma prostate tumors, tumors of the t-SCNC subtype are thought to have less hormone signaling and lower prostate-specific antigen.
In addition, t-SCNC shares some features with a small-cell neuroendocrine subtype of prostate cancer that appears in less than 1% of men with newly diagnosed prostate cancer.
To understand how frequently t-SCNC develops after hormone treatment, Dr. Aggarwal and his colleagues analyzed metastatic tumor samples from 202 men with castrate-resistant prostate cancer who had received treatment at multiple institutions. The samples were obtained from metastatic tumors in the bone, lymph nodes, liver, or other soft tissues.
The anatomical site where the metastatic tumor sample had been taken did not appear to affect the frequency of the neuroendocrine subtype, the researchers found.
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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.
Findings Could Lead To A Diagnostic Test And New Treatments
NEW YORK, NY Two genes work together to drive the most lethal forms of prostate cancer, according to new research from the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center . These findings could lead to a diagnostic test for identifying those tumors likely to become aggressive and to the development of novel combination therapy for the disease.
The two genesFOXM1 and CENPFhad been previously implicated in cancer, but none of the prior studies suggested that they might work synergistically to cause the most aggressive form of prostate cancer. The study was published today in the online issue of Cancer Cell.
Individually, neither gene is significant in terms of its contribution to prostate cancer, said co-senior author Andrea Califano, Dr, the Clyde and Helen Wu Professor of Chemical Biology , chair of the Department of Systems Biology, and director of the JP Sulzberger Columbia Genome Center, at Columbias College of Physicians and Surgeons. But when both genes are turned on, they work together synergistically to activate pathways associated with the most aggressive form of the disease.
In many cancer studies, researchers rely on mouse models to identify genes that are expressed in disease. However, inherent differences between species often make it difficult to extrapolate findings in mice to humans, said Dr. Abate-Shen.
The study was supported by grants from the National Institutes of Health .
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Disclosure Of Potential Conflicts Of Interest
H. Beltran reports receiving commercial research grants from Astellas and Millennium Pharmaceuticals. S. Tomlins reports receiving speakers bureau honoraria from VentanaMedical Systems/Roche has ownership interest in Gen-Probe, Inc/Hologic and Ventana Medical Systems/Roche and is a consultant/advisory board member for Ventana Medical Systems/Roche. C. Logothetis is a consultant/advisory board member for, and reports receiving other commercial research support and speakers bureau honoraria from Astellas, Bristol-Myers Squibb, Excelixis, Johnson & Johnson, and Novartis. No potential conflicts of interest were disclosed by the other authors.
When Does Prostate Cancer Become Life Threatening
May 18, 2014
Prostate cancer becomes life threatening when it has metastasized or spread into the body, such as the bones, brain, liver, or lungs. Prostate cancer is generally a slow growing disease however once it has spread to other areas of the body it is considered aggressive and difficult to treat. Usually when any type of cancer spreads throughout the body, it is life-threatening.
When it comes to prostate cancer, the treatment recommendations are based on your PSA score, the grade of cancer, the amount of cancer present, and your medical state/history. If the cancer is present in a very small portion of the biopsy tissue, it is low grade, and poses a low risk of spreading you may be put on active surveillance. With active surveillance your PSA is checked more frequently with the possibility of repeat prostate biopsies if PSA rises. If it is suspected that the cancer is growing, more aggressive management should be implemented. Treatment recommendations will be at the discretion of your doctor, and you should always make sure you follow up regularly for surveillance even if a small amount of cancer is present.
Georgetown, Round Rock, and Austin-area residents seeking prostate cancer treatment should contact Dr. Koushik Shaw and his staff at the Austin Urology Institute.
Learn more about when to get a prostate exam to see if you are at risk.
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What Is Bone Metastasis
The bone is a common site for metastasis. Bone metastasis or âbone metsâ occurs when cancer cells from the primary tumor relocate to the bone. Prostate, breast, and lung cancers are most likely to spread to the bone. However, other cancers are not excluded. Bone metastases do not begin from the bones but move there from the primary tumor site. On the other hand, primary bone cancers are rare cancers where the primary tumor actually starts in the bone. Therefore, bone cancer and bone metastases are not the same.
As an example, consider a patient with prostate cancer. Prostate cancer cells from the primary tumor can break away and get into the bloodstream. Once in the blood, the cancer cell can travel to the bone and form a new tumor. It is important to remember that this secondary tumor is made up of abnormal prostate cancer cells, not abnormal bone cells. The result of this process is referred to as prostate cancer that has metastasized to the bone or metastatic prostate cancer. This is otherwise known as bone metastasis.
When cancer cells metastasize to the bone, they can cause changes to the bone. The process by which portions of the bone are damaged is called osteolysis. Oftentimes, small holes result from osteolysis. These holes in the bone are referred to as osteolytic lesions or lytic lesions. Lytic lesions can weaken the bones and increase the risk of breakage or other problems. It is also common for bone metastasis patients to experience pain with lesions.
Prognostic Factors That Determine The Need For Further Investigation Following A Negative Biopsy
In developing a recent UK National Institute for Health and Care Excellence clinical guideline for the diagnosis of treatment of prostate cancer, the UK National Collaborating Centre for Cancer undertook a systematic review to identify the prognostic factors that determine the need for further investigation following a prior negative biopsy in men who have been referred with suspected prostate cancer. The review included retrospective and prospective cohort studies that reported on the following potential prognostic factors: age, ethnicity, family history of prostate cancer, DRE, total PSA, free-to-total PSA%, PSA density, PSA velocityii and PCA3 score at the time of initial biopsy, and histopathological features reported on initial biopsy .
The NICE systematic review classified the results of relevant predictive studies into two broad groups: results of univariate analyses and results of multivariate analyses . The multivariate analyses are likely to provide more reliable evidence, because they reduce the risk of bias due to confounding variables. The most frequently addressed potentially confounding variables were age, DRE, PSA, free-to-total PSA%, PSA density, PSA velocity, high-grade PIN, ASAP and prostate volume.
Age
Family history
Digital rectal examination
The updated NICE systematic review found one additional study, which reported an OR of 1.36 for abnormal DRE relative to normal DRE in a multivariate model.
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Can Prostate Cancer Treatment Affect Your Quality Of Life
Your age and overall health will make a difference in how treatment may affect your quality of life. Any health problems you have before youre treated, especially urinary, bowel or sexual function problems, will affect how you recover. Both surgery and radiation can cause urinary incontinence or impotence .
For Many Men Diagnosed With Prostate Cancer The Treatment May Be Worse Than The Disease
To screen or not to screen? For prostate cancerthe second leading cause of cancer deaths in men, after lung cancerthat is the bedeviling question.
The dilemma springs the wide variation in the potential of prostate cancers to spread to the rest of the body. The vast majority of these malignancies, especially those discovered with the extensively used prostate-specific antigen, or PSA, test, are slow-growing tumors that are unlikely to cause a man any harm during his lifetime. Yet in 10 to 15 percent of cases, the cancer is aggressive and advances beyond the prostate, sometimes turning lethal.
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Deregulation Of Other Nuclear Factors
Cyclin D1 functions in a complex with cell cycle-dependent kinases 4/6 to promote cell cycle progression. The role of CCND1 in t-NEPC remains elusive, as contrary results on its expression have been found. Exploration of mRNA and microRNA expression levels in a cell model of NED has revealed upregulation of CCND1, while no significant changes have been detected in other cyclins. This altered expression level has been caused by decreased expression of the microRNA-17 family, which bind to the CCND1 mRNA . In contrast, Tsai et al. reported the loss of CCND1 expression to be indicative of small cell-like PCa in patient tissue, as 88% of samples classified as small cell carcinoma have been observed to be CCND1-negative compared to less than 10% of the adenocarcinomas . Additionally, a recent study in de novo NEPC identified loss of CCND1 expression in patient tissue . Possibly, CCND1 loss is predominantly involved in de novo-emergence of NEPC. Despite its function in cell cycle progression, CCND1 also has kinase-independent functions, as it has been shown to act as a co-repressor of AR signaling in PCa . Together with CDKN2A, CCND1 expression levels have also been suggested as a biomarker for RB1 functional status .
What Are The Symptoms Of Prostate Cancer
Early-stage prostate cancer rarely causes symptoms. These problems may occur as the disease progresses:
- Frequent, sometimes urgent, need to urinate, especially at night.
- Weak urine flow or flow that starts and stops.
- Painful urination .
- Lower back pain, hip pain and chest pain.
- Leg or feet numbness.
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