Prostate cancer is the development of cancer in the prostate, the gland in the male reproductive system. Most prostate cancers grow slowly; However, some grow relatively quickly. Cancer cells can spread from the prostate to other areas of the body, especially bones and lymph nodes. Initially it may not cause symptoms. At a later stage, it can cause difficulty urinating, blood in the urine or pain in the pelvis, back, or during urination. A disease known as benign prostatic hyperplasia can produce the same symptoms. Other late symptoms may include feeling tired due to low levels of red blood cells.
Factors that increase the risk of prostate cancer include older age, family history of the disease, and race. Approximately 99% of cases occur in men over the age of 50 years. Having first-degree relatives with disease increases the risk two to three times. In the United States, it is more common in African American populations than in the white American population. Other factors that may be involved include diets high in processed meats, red meat or dairy products or low in certain vegetables. Relationships with gonorrhea have been found, but the reasons for this relationship have not been identified. Increased risk is associated with BRCA mutations. Prostate cancer is diagnosed with a biopsy. Medical imaging can then be done to determine whether the cancer has spread to other parts of the body.
Screening for prostate cancer is controversial. Testing prostate-specific antigen (PSA) increases cancer detection, but is controversial as to whether it improves yield. Informed decision making is recommended when it comes to screening among those aged 55 to 69 years. Testing, if done, makes more sense to those who have a longer life expectancy. While 5 -reductase inhibitors appear to reduce the risk of low-grade cancers, they do not affect the risk of high-grade cancers and thus are not recommended for prevention. Supplementation with vitamins or minerals does not seem to affect the risks.
Many cases are managed with active supervision or wait with caution. Other treatments may include a combination of surgery, radiation therapy, hormone therapy or chemotherapy. When it only happens inside the prostate, it can be cured. In those whose illness has spread to the bone, pain medications, bisphosphonates and targeted therapy may, among others, be useful. Results depend on one's age and other health problems as well as how aggressive and extensive the cancer is. Most people with prostate cancer do not end up with death from illness. The 5-year survival rate in the United States is 99%. Globally, this is the second most common type of cancer and the fifth leading cause of cancer-related death in men. In 2012, it happened to 1.1 million men and caused 307,000 deaths. It is the most common cancer in men in 84 countries, more common in developed countries. Prices have risen in developing countries. Detection increased significantly in the 1980s and 1990s in many areas due to increased PSA testing. Studies in men who died of unrelated causes have found prostate cancer in 30% to 70% of those over the age of 60.
Video Prostate cancer
Signs and symptoms
Early prostate cancer usually has no obvious symptoms. Sometimes prostate cancer causes symptoms, often similar to diseases such as benign prostatic hyperplasia. These include frequent urination, nocturia (increased urination at night), difficulty starting and maintaining urine flow, hematuria (urine blood), and dysuria (painful urination). A study based on the 1998 Patient Evaluation in the US found that about one-third of patients diagnosed with prostate cancer had one or more of these symptoms, while two-thirds had no symptoms.
Prostate cancer is associated with urinary dysfunction because the prostate gland surrounds the prostatic urethra. Changes in the gland, therefore, directly affect the function of urine. Because the vas deferens delivers seminal fluid to the prostate urethra, and secretions from the prostate gland itself are included in the cement content, prostate cancer can also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.
Metastatic prostate cancer that has spread to other parts of the body may cause additional symptoms. The most common symptoms are bone pain, often in the spine (spine bone), pelvis, or ribs. The spread of cancer to other bones such as the femur is usually to the proximal or near the bone. Prostate cancer in the spine can also suppress the spinal cord, causing tingling, leg weakness and urinary and fecal incontinence.
Maps Prostate cancer
Risk factors
Complete understanding of the causes of prostate cancer is still elusive. The main risk factors are obesity, age, and family history. Prostate cancer is very rare in men younger than 45 years, but becomes more common with old age. The median age at the time of diagnosis was 70. Many men never knew they had prostate cancer. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandans who died of other causes have found prostate cancer in 30% of men in their fifties, and in 80% of men in their seventies. Men who have first-degree family members with prostate cancer appear to have twice the risk of disease compared with men without prostate cancer in the family. The risk appears to be greater for men with affected brothers compared with men with affected fathers. In the United States in 2005, there were about 230,000 new cases of prostate cancer and 30,000 deaths from prostate cancer. Men with high blood pressure are more likely to develop prostate cancer. There is little increased risk of prostate cancer associated with lack of exercise. A 2010 study found that basal cell prostate is the most common site for prostate cancer.
Genetic
Genetic backgrounds may contribute to the risk of prostate cancer, as suggested by associations with race, family, and certain gene variants. Men with first-degree relatives (fathers or brothers) with prostate cancer have twice the risk of prostate cancer, and those with two first-degree relatives are at risk five times greater than men without history family. In the United States, prostate cancer more often attacks black men than white or Hispanic men, and is also more deadly in black men. In contrast, the incidence and death rates for Hispanic men were one-third lower than for non-Hispanic whites. Twin studies in Scandinavia show that 40% risk of prostate cancer can be explained by inherited factors.
No single gene is responsible for prostate cancer; many different genes have been involved. Mutations on BRCA1 and BRCA2 , important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer. Other related genes include the prostate cancer genes Hereditary 1 (HPC1), androgen receptors, and vitamin D receptors. The fusion of the TMPRSS2-ETS gene family, particularly TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes the growth of cancer cells.
Two large genome association studies that linked single nucleotide polymorphisms (SNPs) to prostate cancer were published in 2008. This study identifies several SNPs that substantially affect the risk of prostate cancer. For example, individuals with TT allele couples in SNP rs10993994 reportedly were at 1.6 times higher risk of prostate cancer compared to CC allele couples. This SNP explains part of an increased risk of African American male prostate cancer compared to European men of European descent, since C allele is much more prominent in the latter; This SNP is located in the promoter region of the MSMB genes, thus affecting the amount of MSMB protein synthesized and secreted by prostate epithelial cells.
Finally, obesity and elevated testosterone levels in the blood may increase the risk of prostate cancer.
Diet
Eating fruits and vegetables is less useful in preventing prostate cancer. Evidence supports little role for fruit and vegetable diets in the event of prostate cancer. Red meat and processed meats also seem to have little effect in human studies. Higher meat consumption has been associated with a higher risk in some studies.
Lower levels of vitamin D in the blood may increase the risk of prostate cancer.
Folic acid supplements have no effect on the risk of developing prostate cancer.
Drug exposure
There are also some links between prostate cancer and drugs, medical procedures, and medical conditions. The use of cholesterol-lowering drugs known as statins may also reduce the risk of prostate cancer.
Infection
Infection or inflammation of the prostate (prostatitis) may increase the likelihood of prostate cancer while other studies show the infection may help prevent prostate cancer by increasing blood flow to the area. In particular, infection with sexually transmitted infections of chlamydia, gonorrhea, or syphilis appears to increase the risk. Papilloma virus has been proposed in some studies to have a potential role in prostate cancer, but by 2015 the evidence can not be inferred.
Environment
The study, released in May 2007 found that American war veterans affected by Agent Orange had a 48% increased risk of recurrence of prostate cancer after surgery.
Sexual
Although there is some evidence from a prospective cohort study that frequent ejaculation can reduce the risk of prostate cancer, no results from randomized controlled trials concluded that this benefit exists. There is a relationship between vasectomy and prostate cancer, but more research is needed to determine whether this is a causal relationship.
Pathophysiology
The prostate is part of the male reproductive system that helps make and store seminal fluids. In adult men, the prostate is typically about 3 centimeters long and weighs about 20 grams. It lies in the pelvis, under the bladder and in front of the rectum. The prostate surrounds the urethra, a tube that carries urine from the bladder during urination and semen during ejaculation. Because of its location, prostate disease often affects urination, ejaculation, and rarely defecate. The prostate contains many small glands that make up about 20% of the fluid that makes up semen. In prostate cancer, these prostate gland cells mutate into cancer cells. The prostate gland requires a male hormone, known as androgen, to function properly. Androgens include testosterone, which is made in the testes; dehydroepiandrosterone, made in the adrenal gland; and dihydrotestosterone, which is altered from testosterone in the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass.
Most prostate cancers are classified as adenocarcinoma, or gland cancer, which begins when the secreting cells of the prostate gland secrete normally into cancer cells. The area of ​​the prostate gland where adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain confined to other normal prostate glands, a condition known as in situ carcinoma or prostate intraepithelial neoplasia (PIN). Although there is no evidence that PIN is a precursor to cancer, PIN is closely related to cancer. Over time, these cancer cells begin to multiply and spread to the surrounding prostate tissue (stroma) forming a tumor. Eventually, the tumor may grow large enough to attack nearby organs such as seminal vesicles or rectum, or tumor cells can develop the ability to travel in the bloodstream and lymphatic system. Prostate cancer is considered a malignant tumor because it is a mass of cells that can invade other areas of the body. This invasion of other organs is called metastasis. Prostate cancer most often metastasizes to bone, lymph nodes, and can invade the rectum, bladder and lower ureter after local development. The metastatic route to the bone is considered a vein as a prostate vein plexus that drains the prostate connected to the vertebral vein.
The prostate is an organ that produces citrate-zinc accumulation. The ZIP1 protein is responsible for the active transport of zinc into the prostate cells. One of the important roles of zinc is changing cell metabolism to produce citrate, an important component of semen. The process of zinc accumulation, changes in metabolism, and citrate production are not energy efficient, and prostate cells sacrifice enormous amounts of energy (ATP) to complete this task. Prostate cancer cells generally do not have zinc. This enables prostate cancer cells to save energy not make citrate, and utilize new energy abundance to grow and spread. The absence of zinc is thought to occur through the silencing of genes that produce ZIP1 transport proteins. ZIP1 is now called the tumor suppressor gene product for the SLC39A1 gene. The cause of epigenetic silencing is unknown. The strategy of transporting zinc into the modified prostate cells effectively removes these cells in animals. Zinc inhibits the NF-B pathway, is anti-proliferative and induces apoptosis in abnormal cells. Unfortunately, oral zinc consumption is ineffective because high concentrations of zinc into prostate cells are not possible without the active transporter, ZIP1.
The loss of cancer-suppressing genes, early in prostate carcinogenesis, has been localized on chromosomes 8p , 10q , 13q , and 16q . The p53 mutation in primary prostate cancer is relatively low and more often seen in metastatic settings, so p53 mutations are a late event in the pathology of prostate cancer. Other tumor suppressor genes that are thought to play a role in prostate cancer include PTEN (gen) and KAI1. "Up to 70 percent of men with prostate cancer have lost a copy of the PTEN gene at the time of diagnosis." Relative frequencies of E-cadherin and CD44 loss have also been observed.
RUNX2 is a transcription factor that prevents cancer cells from undergoing apoptosis thus contributing to prostate cancer progression.
The PI3k/Akt signaling standard works with beta/SMAD signaling cascade growth factors to ensure prostate cancer cell survival and protection against apoptosis. X-linked inhibitor of apoptosis (XIAP) is hypothesized to improve survival and prostate cancer cell growth and is a research target because if this inhibitor can be killed then apoptotic cascade may perform its function in preventing the proliferation of cancer cells. Macrophage inhibitory cytokine-1 (MIC-1) stimulates the focal pathway of adhesion kinase (FAK) that leads to the growth and survival of prostate cancer cells.
Androgen receptors help prostate cancer cells to survive and are a target for many studies of anti-cancer research; so far, inhibiting androgen receptors have only been shown to be effective in rat studies. Prostate-specific membrane antigens (PSMA) stimulate prostate cancer development by increasing folate levels so that cancer cells can be used to survive and grow; PSMA increases the folate that is available for use by hydrolyzing glutamated folate.
Diagnosis
The American Cancer Society's position on early detection with PSA testing is "Research has not proved that the potential benefits of testing outweigh the dangers of testing and treatment.America Cancer Society believes that men should not be tested without learning about what we know and do not know about risks and possible benefits of testing and care Starting from the age of 50, (45 if African American or sibling or father suffers from condition before age 65), talk to your doctor about the pros and cons of testing so you can decide if testing is the right choice for you. "
There are also several other tests that can be used to gather more information about the prostate and the urinary tract. Anal rectal examination (DRE) allows doctors to detect prostate disorders. Cystoscopy shows the urinary tract from within the bladder, using a thin and flexible camera tube inserted into the urethra. Transrectal ultrasonography creates a prostate image using sound waves from the probe in the rectum. But the only test that can fully confirm the diagnosis of prostate cancer is a biopsy, the removal of small pieces of prostate for microscopic examination.
Prostate imaging
Ultrasound (US) and magnetic resonance imaging (MRI) are the two main imaging methods used to detect prostate cancer. Urologists use transrectal ultrasound during prostate biopsy and can sometimes see hypoechoic areas (tissues or structures reflecting relatively less than ultrasound waves directed at them). Because ultrasound has poor network resolution, it is generally not clinically used.
MRI prostate has better soft tissue resolution than ultrasound.
MRI in those at low risk can help people choose active surveillance, in those at high risk can help determine the stage of the disease, while those at high risk may help find bone disease.
Currently (2011), MRI is used to identify targets for prostate biopsy using MRI fusion with ultrasound (AS) or MRI guidelines only. In men who are candidates for active surveillance, MR/AS fusion guided prostate biopsy detected 33% of cancers compared with 7% with standard ultrasound guided biopsies.
The MRI prostate is also used for surgical planning for men undergoing robotic prostatectomy. It also proves to help the surgeon decide whether to resect or stock a neurovascular bundle, reset it to the urinary continent, and help assess surgical difficulties.
For MRI Prostat there is PI-RADS Reporting System. PI-RADS is an acronym for Prostate Imaging-Reporting and Data Systems, defining high-quality clinical standards for Multi-parametric Magnetic Resonance imaging (mpMRI), including image creation and reporting.
Biopsy
If cancer is suspected, the biopsy is offered appropriately. During biopsy, a urologist or radiologist obtains tissue samples from the prostate through the rectum. The biopsy gun inserts and removes a special hollow-core needle (usually 3-6 on each side of the prostate) in less than a second. Prostate biopsy is routinely performed in outpatients and rarely requires hospitalization. Antibiotics should be used to prevent complications such as fever, urinary tract infection, and sepsis although the most appropriate way or antibiotic is still undefined. Fifty-five percent of men report discomfort during prostate biopsy.
Gleason Score
The tissue samples were then examined under a microscope to determine whether cancer cells were present, and to evaluate microscopic features (or Gleason scores) of the cancers found. The specific prostate membrane antigen is a transmembrane carboxypeptidase and shows the activity of folate hydrolase. This protein is expressed in prostate cancer tissue and is associated with a higher Gleason score.
tumor marker
The tissue samples can be stained for the presence of PSA and other tumor markers to determine the origin of malignant cells that have metastasized.
Small cell carcinoma is a very rare type of prostate cancer (1%) that can not be diagnosed by using PSA. In 2009 researchers are investigating ways to screen for this type of prostate cancer, as it quickly spreads to other parts of the body.
Oncoprotein BCL-2 is associated with the development of androgen-independent prostate cancer, due to its high expression rates in androgen-independent tumors in advanced stages of pathology. Increased regulation of BCL-2 after androgen ablation in the prostate cancer cell line and in the male-castrated male model further formed a relationship between BCL-2 expression and prostate cancer progression.
Ki-67 expression by immunohistochemistry can be a significant predictor of patient outcomes for men with prostate cancer.
Staging
An important part of evaluating prostate cancer is determining the stage, or how far the cancer has spread. Knowing the stage helps determine prognosis and is useful when choosing therapy. The most common system is the four stage TNM system (abbreviated from Tumor/Nodes/Metastasis). Components include tumor size, number of involved lymph nodes, and presence of other metastases.
The most important difference made by the staging system is whether the cancer is still limited to the prostate. In the TNM system, T1 and T2 clinical cancers are found only in the prostate, while T3 and T4 cancers have spread elsewhere. Some tests can be used to look for evidence of dissemination. Professional organizations of medical specialists recommend not to use PET scans, CT scans, or bone scans when a doctor performs an early stage of prostate cancer with a low risk for metastasis. Such tests would be appropriate in cases such as when the CT scan evaluates the spread within the pelvis, bone scan seeks spread to bone, and magnetic resonance imaging of the endorectal coil to closely evaluate the prostate capsule and seminal vesicles. Bone scanning should reveal the appearance of osteoblastic owing to increased bone density in the bone metastases area - in contrast to that found in many other metastatic cancers.
After a prostate biopsy, a pathologist looks at the sample under a microscope. If cancer is present, the pathologist reports tumor levels. Values ​​show how many tumor tissues differ from normal prostate tissue and show how quickly the tumor will grow. The Gleason system is used to assess prostate tumors from 2 to 10, where Gleason 10 scores show the most abnormalities. The pathologist assigns numbers from 1 to 5 for the most common patterns observed under a microscope, then do the same for the second most common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method that is sometimes used.
Prevention
Diet and lifestyle
Data on the relationship between diet and bad prostate cancer. Given this level of prostate cancer is associated with the consumption of Western diet. There is little evidence to support the link between trans fats, saturated fats, and carbohydrate intake and prostate cancer risk. Evidence on the role of omega-3 fatty acids in preventing prostate cancer does not suggest that they reduce the risk of prostate cancer, although additional research is needed. Vitamin supplements seem to have no effect and some may increase the risk. High calcium intake has been associated with advanced prostate cancer. Eating fish can reduce the death of prostate cancer but does not seem to affect the incidence. Some evidence supports lower rates of prostate cancer with a vegetarian diet. There is some tentative evidence for foods containing lycopene and selenium. Diet rich in vegetables, soybeans, nuts and other legumes can be linked to lower risk of prostate cancer, especially advanced cancers.
Men who exercise regularly may have slightly lower risk, especially strong activity and advanced prostate cancer risk.
Drugs
In those who are regularly screened, 5-alpha-reductase inhibitors (finasteride and dutasteride) reduce overall risk of being diagnosed with prostate cancer, but there is insufficient data to determine if they have an effect on the risk of death and they may increase the likelihood of more serious cases.
Screening
Screening for prostate cancer is an attempt to find unexpected cancer in those without symptoms. Options include digital rectal exam (DRE) and a special prostate antigen blood test (PSA). Such screening is controversial and, for many, can lead to unnecessary harassment and potentially dangerous consequences. Population-based filtration damage, mainly due to excessive diagnosis (detection of latent cancers that should be asymptomatic and not found) may outweigh the benefits. Others recommend joint decision making; an approach in which individuals have the option of undergoing an examination after thorough consultation with their physician on both positive and negative matters.
The United States Agency's Prevention Task Force (USPSTF) recommends whether or not a decision to perform a PSA examination is based on decision-making between patients and doctors for men aged 55 to 69 years. USPSTF recommends against PSA screening for men aged 70 and older. The Centers for Disease Control and Prevention shares conclusions before the USPSTF. The American Society of Clinical Oncology and the American College of Physicians minimize screening for those who are expected to live less than ten to fifteen years, while in those with greater life expectancy, decisions must be made by the person concerned based on the potential risks and benefits. In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are of adverse value associated with subsequent unnecessary screening and treatment." The American Urological Association (AUA 2013) guidelines call for weighing the benefits of preventing death of prostate cancer in 1 man for every 1,000 men screened over a ten year period against known damage associated with diagnostic and treatment tests. The AUA recommends to offer screening to 55 to 69 based on joint decision making, and that if screening is done, it should occur no more often than every two years. In the UK by 2015 there are no programs for prostate cancer screening.
Management
The first decision made in managing prostate cancer is whether treatment is necessary. Prostate cancer, especially low-grade forms found in elderly men, often grows so slowly that no treatment is required. Treatment may also be inappropriate if a person has other serious health problems or is not expected to live long enough for symptoms to appear. An alternative approach that delayed active treatment and instead involves the supervision of diagnosed prostate cancer called management expectations. Expectation management is divided into two approaches: Watchful Waiting, which has palliative intentions, and Active Supervision, which has curative intentions.
Which choice is best depends on the stage of the disease, Gleason score, and PSA level. Other important factors are age, general health, and one's view of potential care and possible side effects. Because most treatments can have significant side effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing therapeutic goals with lifestyle change risks. Combination treatment options are often recommended for managing prostate cancer.
Treatment guidelines for specific clinical situations require good estimates of one's long-term life expectancy. People can also use the 18-item questionnaire to find out if they have a good knowledge and understanding of their treatment options before they choose. Most of those newly diagnosed and made care options can not answer more than half the questions.
If radiation therapy is done first, and fails, radical prostatectomy becomes a very technically challenging and possibly unfeasible operation. On the other hand, radiation therapy performed after surgical failure may have many complications. This is associated with a small increase in bladder and colon cancer.
In localized disease, it is not known whether radical prostatectomy is better or worse than waiting with caution.
A meta-analysis on the effect of urinary position on urine in men with prostate enlargement suggests that sitting is superior to standing. Bladder emptying is significantly increased, while there is a tendency toward higher urinary flow and shorter urinary time.
Supervision
Many men diagnosed with low-risk prostate cancer are eligible for active supervision . This term implies careful observation of the tumor from time to time, with the intention of treatment for healing if there are signs of cancer progression. Active surveillance is not synonymous with cautious waiting, old terms implying no maintenance or special monitoring program, assuming that palliative , not curative, treatment will be used if continued, Symptomatic disease develops.
Active monitoring involves monitoring the tumor for signs of growth or appearance of symptoms. The monitoring process may involve serial PSA, prostate physical examination, and/or repeated biopsy. The purpose of surveillance is to avoid over-treatment and sometimes serious permanent side effects from treatment for a slow-growing or self-limited tumor that will never cause a problem for the person. This approach is not used for aggressive cancers, but it can cause anxiety for people who mistakenly believe that all cancers are deadly or they themselves have life-threatening cancers. For 50% to 75% of people with prostate cancer, it will not cause harm before someone dies due to other causes.
Aggressive Cancer
Treatment of metastatic prostate cancer can be difficult. Treatment of aggressive prostate cancer may involve surgery (ie radical prostatectomy), radiation therapy including brachytherapy (prostate brachytherapy), external radiation therapy, high intensity focused ultrasound (HIFU), chemotherapy, oral chemotherapy drugs (temozolomide/TMZ), cryosurgery, hormonal therapy , or some combination.
Although the widespread use of prostate-specific antigen (PSA) screening in the US has resulted in a diagnosis at an early age and the stage of cancer, the majority of cases are still diagnosed in men older than 65 years, and about 25% of cases are diagnosed. in men older than 75 years. Although the US National Comprehensive Cancer Network guidelines recommend the use of life expectancy greater than or less than 10 years to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as radical prostatectomy or radiation therapy and are even treated with therapy hormonal. or wait with caution. This pattern can be attributed to factors such as medical co-morbidity and patient preference related to quality of life in addition to specific risk factors for prostate cancer such as PSA pretreatment, Gleason score and clinical stage. Because the average life expectancy increases due to advances in the treatment of cardiovascular disease, lung and other chronic diseases, it is likely that more elderly patients will live long enough to suffer the consequences of their prostate cancer. Therefore, there is currently much interest in the role of aggressive prostate cancer treatment modalities such as surgery or radiation in elderly populations that have localized disease.
If the cancer has spread beyond the prostate, treatment options change significantly, so most doctors who treat prostate cancer use various nomograms to predict the possibility of spreading. Active monitoring/alert supervision, external beam radiation therapy, brachytherapy, cryosurgery, HIFU, and surgery are, in general, offered to men whose cancer remains in the prostate. Hormonal therapy and chemotherapy are often reserved for diseases that have spread beyond the prostate. There are exceptions: radiation therapy can be used for some advanced stage tumors, and hormonal therapy is used for some early stage tumors. Cryotherapy (tumor-freezing process), hormonal therapy, and chemotherapy can also be offered if initial treatment fails and the cancer develops.
Sipuleucel-T, a cancer vaccine has been found to produce benefits (increased survival for four months) for men with metastatic prostate cancer.
Hold-drilling
Most hormone-dependent cancers become resistant to treatment after one to three years and continue growth despite hormone therapy. Previously thought to be "hormone-refractory prostate cancer" or "androgen independent prostate cancer," the term immune has replaced "refractory hormones" because while they are no longer responsive to castration treatment (reduction of available androgen/testosterone/DHT by chemical or surgical means) , this cancer still shows dependence on hormones for androgen receptor activation.
Docetaxel chemotherapic cancer has been used as a treatment for CRPC with an average survival benefit of 2 to 3 months. Second-line chemotherapy treatment is cabazitaxel. The combination of bevacizumab, docetaxel, thalidomide and prednisone appears to be effective in the treatment of CRPC.
Immunotherapy treatment with sipuleucel-T in CRPC improves survival for 4 months. The second line of hormonal therapy abiraterone improved survival by 4.6 months when compared with placebo. Enzalutamide is another second-line hormonal agent with a 5-month survival advantage over placebo. Both abiraterone and enzalutamide are currently being tested in clinical trials on those with CRPC who have not previously received chemotherapy.
Only a small percentage of people who respond to drugs block androgen signals and certain cells with stem cell-like characteristics remain unaffected. Therefore, the desire to improve outcomes from people with CRPC has resulted in claims of further dose enhancement or combination therapy with synergistic androgen signaling agents. But even this combination will not affect cells like mains that do not exhibit androgen signaling. It is possible that for further advancement, the combination of androgen-inhibiting agents with cell-directed cell differentiation therapy drugs would prove ideal.
Palliative care
Palliative care is a medical treatment that focuses on the treatment of symptoms of serious illness, such as cancer, and improves quality of life. One of the goals of treatment in palliative care is the control of symptoms rather than the underlying cancer cure. Pain is common in metastatic prostate cancer, and cancer pain associated with bone metastasis can be treated with bisphosphonates, drugs such as opioids, and palliative radiation therapy to known metastases. Spinal cord compression can occur with metastasis to the spine and can be treated with steroids, surgery, or radiation therapy. Other symptoms that can be addressed through palliative care include fatigue, delirium, lymphedema in the scrotum or penis, nausea, vomiting, and weight loss.
Prognosis
Prostate cancer rates are higher in developed countries than in other parts of the world. Many risk factors for prostate cancer are more common, including longer life expectancy and a diet high in red meat. Also, where there is more access to screening programs, there is a higher level of detection.
In the United States, local or regional prostate cancer at the time of diagnosis has a 5-year survival rate of almost 100%, while those with distant metastases have a 5% survival rate of 29%. In Japan, deaths from prostate cancer were a fifth to a half level in the United States and Europe in the 1990s. In India in the 1990s, half of those with prostate cancer were confined to the prostate died within 19 years. African-American men have 50-60 times more prostate cancer and deaths from prostate cancer than men in Shanghai, China. In Nigeria, 2% of men have prostate cancer, and 64% of them die after 2 years. Most Nigerian men come with metastatic disease with typical survival for 40 months.
In patients undergoing treatment, the most important clinical prognostic indicators of disease outcomes are stage, pretreath PSA level, and Gleason score. In general, the higher the level and the stage, the worse the prognosis. Nomograms can be used to calculate the individual risk estimates. Prediction is based on the experience of a large group of cancer patients at various stages.
In 1941, Charles Huggins reported that androgen ablation therapy led to regression of primary prostate cancer and androgen-dependent metastasis. He was awarded the 1966 Nobel Prize for Physiology or Medicine for this discovery. Androgen ablation therapy causes remission in 80-90% of patients undergoing therapy, resulting in an average development-free survival of 12 to 33 months. After remission, an androgen-independent phenotype usually occurs, where the overall average survival is 23-37 months from the time of initiation of androgen ablation therapy. It is unclear how prostate cancer becomes androgen-independent or how it rebuilds its development, although some possibilities (about how) have been proposed. And how cancer changes, to overcome androgen deficiency, may vary between patients.
System classification
Many prostate cancers are not destined to be lethal, and most men ultimately will not die as a result of the disease. Decisions about the type and timing of treatment can, therefore, be informed by an estimate of the risk that the tumor will eventually recur after treatment and/or develop into metastasis and mortality. Several tools are available to help predict outcomes, such as pathological stages and recurrence after surgery or radiation therapy. Most incorporate stages, levels, and PSA levels, and some also add the number or percentage of the core of a positive biopsy, age, and/or other information.
- The D'Amico Classification rates men with low, medium, or high risk based on stage, grade, and PSA. It is used extensively in clinical practice and research settings. The main disadvantage of a 3-level system is that it does not take into account some adverse parameters (eg, high Gleason score and high PSA) in stratified patients.
- The Partin table predicts pathological results (margin status, extraprostatic extension, and invasion of seminal vesicles) based on the same three variables and published as search tables.
- The Kotan nomogram predicts relapse after surgery and/or radiation therapy, based on data available either at the time of diagnosis or after surgery. Nomograms can be calculated using paper charts or software available on websites or for handheld computers. Kotan scores indicate the possibility of being free of disease at certain intervals after treatment.
- The UCSF Cancer Assessment Prostate Risk (CAPRA) score predicts pathological status and recurrence after surgery. It offers a comparable accuracy as Kotan's preoperative nomogram and can be calculated without a paper or calculator table. Points are assigned based on PSA, Level, stage, age, and percentage of positive core; the number generates a score of 0-10, with each 2 points representing approximately double the risk of recurrence. CAPRA scores are derived from community-based data in the CaPSURE database. It has been validated among more than 10,000 prostatectomy patients, including patients from CaPSURE; the SEARCH registry, representing data from several Veterans Administration and active military medical centers; multinational groups in Germany; and a prostatectomy cohort at Johns Hopkins University. More recently, it has been shown to predict metastasis and mortality after prostatectomy, radiation therapy, alert waiting, or androgen deprivation therapy.
Life expectancy
Projected life expectancy is average for the entire male population, and many medical and lifestyle factors modify these numbers. For example, studies show that a 40-year-old man will lose 3.1 years of life if he is overweight (BMI 25-29) and 5.8 years of life if he is obese (BMI 30 or more), compared with normal weight men. If he is overweight and smoker, he will lose 6.7 years, and if obese and smokers, he will lose 13.7 years.
At the moment, there is no evidence that neither surgery nor light radiation has an advantage over the others in this regard, the reported lower reported mortality rate by surgery appears to be due to surgery more likely to be offered to younger men with less serious forms. cancer. Insufficient information is available to determine whether the radiation of seeds prolongs life more easily than other treatments, but the data so far does not indicate that it is happening.
People with low-grade disease (Gleason 2-4) may not die from prostate cancer within 15 years after diagnosis. Older men (aged 70-75) with low-grade disease had overall survival of about 20% at 15 years due to death from a competing cause. Men with high-grade disease (Gleason 8-10) have high prostate cancer deaths within 15 years of diagnosis, regardless of their age at diagnosis, underscoring the very aggressive nature of poorly differentiated prostate cancer.
Epidemiology
In 2012, prostate cancer is the second most frequently diagnosed cancer (in 15% of all male cancers) and the sixth leading cause of cancer deaths in men worldwide. In 2010 it resulted in 256,000 deaths rising from 156,000 deaths in 1990. Rates of prostate cancer vary widely around the world. Although the rates vary widely between countries, most common in South and East Asia, and more common in Europe, North America, Australia and New Zealand. Prostate cancer is most common among Asian men and is most common among black men, with rates for white men in between. The annual average incidence rate of prostate cancer between 1988 and 1992 among Chinese men in the United States is 15 times higher than their counterparts living in Shanghai and Tianjin, but this high rate can be affected by increased detection rates. Many suggest that prostate cancer may be under-reported, but the incidence of BPH in China and Japan is similar to levels in Western countries.
More than 80% of men will develop prostate cancer by age 80. In most cases, the cancer will grow slowly and slightly worried not harmful. In such men, diagnosing prostate cancer is an overdiagnosis - the unnecessary identification of technically distorted conditions that will never harm a patient - and the treatment of the man exposes them to all adverse effects, without the possibility of prolonging their life.
United States
It is estimated that by 2018, about 164,690 new cases and 29,430 prostate cancer-related deaths will occur in the United States. Prostate cancer is now the second leading cause of cancer deaths in men, surpassed by lung cancer and colorectal cancer. It accounts for 19% of all male cancers and 9% cancer-related deaths in men. The age-adjusted incidence increased steadily from 1975 to 1992, with a dramatic increase associated with the widespread use of prostate-antigen (PSA) screening in the late 1980s and early 1990s, followed by a decrease in incidence. Decreased incidence rate of early prostate cancer from 2011 to 2012 (19%) in men aged 50 years and older remained until 2013 (6%).
Between 2013 and 2015, the mortality rate appears to have stabilized. It has been suggested that decreasing mortality rates in certain jurisdictions reflect the benefits of PSA screening, [3] but others have noted that these observations can be explained by independent phenomena such as better care. The estimated lifetime risk of a diagnosis of prostate cancer is about 14.0%, and the lifetime risk of death from this disease is 2.6%. Cancer statistics from the American Cancer Society and National Cancer Institute (NCI) show that between 2005 and 2011, the proportion of diseases diagnosed at the locoregional stage was 93% for whites and 92% for African-Americans; the proportion of diseases diagnosed in the late stages is 4% for whites and 5% for African Americans. An autopsy study of white and Asian men also found an increase in prostate cancer occult with age, reaching nearly 60% in men older than 80 years. More than 50% of cancers in Asian men and 25% of cancers in white men have Gleason 7 scores or greater, suggesting that Gleason score may be an inappropriately indicator of clinically insignificant prostate cancer.
Canada
Prostate cancer is the third leading cause of cancer in Canadian men. By 2016, about 4,000 people die and 21,600 men are diagnosed with prostate cancer.
Europe
In Europe in 2012 it is the 3rd undiagnosed cancer after breast and colorectal in 417,000 cases.
In the UK it is also the second most common cause of cancer deaths after lung cancer, in which about 35,000 cases are diagnosed each year and about 10,000 of them die.
History
Although the prostate was first described by the Venetian NiccolÃÆ'² Mass anatomy in 1536, and illustrated by the Flemish anatomist Andreas Vesalius in 1538, prostate cancer was not identified until 1853. Prostate cancer was originally regarded as a rare disease, probably due to shorter life expectancy and detection worse. method in the 19th century. The first treatment of prostate cancer is surgery to relieve urinary obstruction. The removal of the entire gland (radical perineal prostatectomy) was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital. The surgical removal of the testes (orchiectomy) to treat prostate cancer was first performed in the 1890s, but with limited success. Transurethral resection of prostate (TURP) replaces radical prostatectomy to relieve symptoms of obstruction in the mid-20th century because it is better to maintain erectile function of the penis. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh. This surgical approach allows removal of the prostate gland and lymph nodes by maintaining the function of the penis.
In 1941, Charles B. Huggins published a study in which he used estrogen to oppose the production of testosterone in men with metastatic prostate cancer. The discovery of this "chemical castration" won Huggins, the 1966 Nobel Prize in Physiology or Medicine. The role of the gonadotropin-releasing hormone (GnRH) in reproduction is determined by Andrzej W. Schally and Roger Guillemin, both of whom won the 1977 Nobel Prize in Physiology or Medicine for this work. GnRH receptor agonists, such as leuprolide and goserelin, are further developed and used to treat prostate cancer.
Radiation therapy for prostate cancer was first developed in the early 20th century and originally consisted of intraprostatic radium implants. External beam radiotherapy is becoming more popular because of the stronger sources of X-ray radiation became available in the mid-20th century. Brachytherapy with seeds implanted (for prostate cancer) was first described in 1983.
Systemic chemotherapy for prostate cancer was first studied in the 1970s. Early cyclophosphamide and 5-fluorouracil regimens were rapidly followed by several regimens using a number of other systemic chemotherapy drugs.
Origin
A series of studies published in Science involves introducing viruses known to cause cancer mutations in prostate cells: AKT, ERG, and AR are isolated samples from basal and luminal cells and transplant tissue that is processed into mice. After 16 weeks, none of the luminal samples had undergone a malignant mutation, while the basal sample mutated into a prostate tubule which later developed a malignancy and formed a cancerous tumor, which looked identical to the human sample under enlargement. This leads to the conclusion that basal cell prostate may be the most likely "home site" of prostate cancer.
Society and culture
People with prostate cancer generally face significant disparities in awareness, funding, media coverage, and research - and therefore, inferior treatment and poorer outcomes - compared to other cancers of the same prevalence. In 2001, The Guardian noted that the UK has 3,000 nurses who specialize in breast cancer, compared with just one for prostate cancer. It also found that the waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer. A 2007 report by the US National Prostate Cancer Coalition states that for every prostate cancer drug on the market, there are seven used to treat breast cancer. The Times also notes the "anti-men bias in cancer funding" with a four-to-one difference in the UK by the government and by cancer charities like Cancer Research UK. Equality lawyers such as author Warren Farrell cite striking spending inequalities such as a clear example of an unfair government supporting women's health above men's health.
Disparities also extend to areas such as detection, with governments failing to fund or mandate prostate cancer screening while fully supporting breast cancer programs. For example, a 2007 report found 49 US states mandated insurance coverage for routine breast cancer screening, compared with 28 for prostate cancer. Prostate cancer also experienced much less media coverage than other cancers, equally prevalent, with studies by the Prostate Coalition showing 2.6 breast cancer stories for each that included prostate cancer.
Prostate Cancer Awareness Month takes place in September in a number of countries. Light blue ribbons are used to promote the cause.
Research
CRPC
MDV3100 is in Phase III trials for CRPC (chemo and post-chemotherapy patients) and obtained FDA approval in 2012 as an enzalutamide for the treatment of prostate cancer resistant to castration.
Alpharadin completed phase 3 trials for CRPC patients with bone metastases. Preliminary provisional analyzes show improved survival and quality of life. The study was discontinued for ethical reasons to provide the same placebo treatment group. Alpharadin uses Radium-223 bone that is targeted to kill cancer cells by alpha radiation. It is approved by the US Food and Drug Administration (FDA) on May 15, 2013 ahead of schedule under the priority review program. Alpharadin is still awaiting approval from the European Medicines Agency (EMA).
In 2016 PARP inhibitor olaparib has shown promise in clinical trials for CRPC. Also in trials for CRPC are: ipilimumab checkpoint inhibitor, CYP17 inhibitor galeterone (TOK-001), and PROSTVAC immunotherapy.
Pre-clinical
Arachidonate 5-lipoxygenase has been identified as playing an important role in the survival of prostate cancer cells. Drugs targeting this enzyme may be an effective therapy for limiting tumor growth and cancer metastases as well as inducing programmed cell death in cancer cells. In particular, the 5-lipoxygenase arachidonate inhibitor results in a large and rapidly programmed cell death in prostate cancer cells.
Cancer model
Scientists have established several pathways of prostate cancer cells to investigate the mechanisms involved in prostate cancer progression. LNCaP, PC-3 (PC3), and DU-145 (DU145) are commonly used prostate cancer cell lines. The cancer cell line of LNCaP is formed from the metastatic lymph nodes of prostate adenocarcinoma human adenocarcinoma. Cell PC-3 and DU-145 are formed from human prostate adenocarcinoma to the bone and brain, respectively. The LNCaP cells express the androgen receptor (AR), but PC-3 and DU-145 cells have very little or no AR. AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Prostate development depends on the androgen signals mediated through AR, and AR is also important during prostate cancer development. LNCaP cell proliferation is androgen dependent but PC-3 and DU-145 cell proliferation are insensitive to androgens. Increased AR expression is often observed in advanced prostate tumors in patients. Several independent androgen LNCaP subcards have been developed from dependent dependent LNCaP and dependent cells after androgen removal for prostate cancer progression studies. This androgen-independent LNCaP cell has increased the expression of AR and expressed the prostate-specific antigen on androgen treatment. The paradox is that androgens inhibit the proliferation of these androgen-independent prostate cancer cells.
Infection
In 2006, a previously unknown retrovirus, Xenotropic MuLV-related virus (XMRV), was associated with human prostate tumors, but subsequent reports on the virus were contradictory, and the original findings of 2006 were due to previously undetectable contamination. The Science and Plosone journals both pulled out the XMRV-related article.
Diagnosis
Currently, an active area of ​​research and investigation that is not applied clinically involves non-invasive methods of prostate tumor detection. A molecular test that detects the presence of cell-associated PCA3 mRNA in fluid obtained from prostate samples and first-void urine has also been investigated. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly overexpressed in prostate cancer cells. The current test results are reported as the ratio of PCA3 mRNA specimens to the PSA mRNA. Although not a substitute for PSA serum levels, the PCA3 test is an additional tool to help decide whether, in men suspected of having prostate cancer (especially if the initial biopsy fails to explain the increase in serum PSA), biopsy/rebyoption is absolutely necessary. The higher the PCA3 expression in the sample, the greater the likelihood of a positive biopsy; that is, the presence of cancer cells in the prostate.
See also
- The Prostate Cancer Foundation
References
External links
- Prostate cancer in Curlie (based on DMOZ)
- Patient-centric information from the European Urological Association
Source of the article : Wikipedia
0 Comments