PSA Test

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What is a PSA test?

A PSA test measures the level of Prostate Specific Antigen (PSA) in the blood. It is a blood test that can help diagnose prostate disease. Prostate Specific Antigen is a protein made mainly in the prostate gland and low levels of PSA are normally present in the blood stream. As a man ages, the prostate grows and the level of PSA also increases. A high PSA in the blood almost always means that something is wrong with the prostate, but not necessarily prostate cancer. The causes of a high PSA include the benign (non-cancerous) growth that accompanies ageing (benign prostatic hyperplasia, BPH), inflammation or infection of the prostate (prostatitis), and, least commonly, prostate cancer.

Is a PSA test worthwhile if there are no symptoms of prostate cancer?

Although there are still many questions about the value of using PSA to test for prostate cancer because there are too many false positive and negative results, it is the best test that is available. A false positive result occurs when PSA levels are high but there is no prostate cancer.

A false negative result occurs when PSA levels are low or within the normal range, but prostate cancer is present. In the early stages, prostate cancers usually do not show any symptoms. Cancer can grow in the prostate and not affect urine flow until it is late stage prostate cancer. A PSA test will give an indication of problems in the prostate before symptoms have developed.

AGE (Years) Serum PSA (ng/ml) – average Serum PSA (ng/ml) – upper limit of normal
40-49 0.65 2.0
50-59 0.85 3.0
60-69 1.39 4.0
70-79 1.64 5.5

 

AGE (Years) Men who will have a PSA over 4.0 Of these, men who could have cancer
50s 5 out of 100 1-2 men
60s 15 out of 100 3-5 men
70s 27 out of 100 9 men

 

How well does the PSA test work for finding prostate cancer?

About one in three men with a PSA between 4 and 10 ng/ml could have prostate cancer, although this proportion varies with the population tested. Recent studies have shown that there is still a small risk of prostate cancer, even if blood PSA levels are normal for age. Therefore even a normal blood PSA level does not mean that there is definitely no prostate cancer present. The only definite way to confirm whether prostate cancer is present or not is by prostate biopsies (taking small samples of tissue). Transrectal ultrasound (TRUS) biopsies are almost always performed using an ultrasound probe which is placed in the back passage (rectum) to visualize the prostate. A small needle is then inserted into the prostate gland through the rectal wall to remove samples from different parts of the prostate gland. Biopsies are not a minor medical procedure and can be accompanied by short term side-effects such as blood in the urine, faeces and/or ejaculate. After biopsies, patients may have temporary difficulty passing urine. Importantly, there is a low (less than 1%) risk of serious infection as a result of this procedure but it is rarely life-threatening.

How do I make a decision about whether or not to have a PSA test?

Having a PSA test may require further decisions after the test results are back, especially if the blood PSA level is raised. There are several things to consider before having a PSA test for prostate cancer:

  • Your level of concern about having prostate cancer
  • Your risk of having prostate cancer e.g. is there a family history of the disease
  • The risk and benefits of early detection. The benefit being that a PSA test may detect prostate cancer when it is small and curable. The risks being those associated with unnecessary and possibly harmful treatment from surgery or radiotherapy (with or without male hormone suppression) with complications such as erectile problems (difficulty having erections, impotence) and urinary incontinence (inability to hold urine, urine leakage, having to wear urine pads).

Unlike many other cancers, the majority of prostate cancers tend to progress slowly with most men dying from other diseases such as a cardiovascular episode (heart attack, stroke) rather than prostate cancer. Therefore a man’s age and his personal choices must be considered before deciding to have a blood PSA test and/or deciding what to do if raised PSA levels are found. For example, an increased PSA level due to a prostate cancer in an older man aged 75-80 may not be a major health threat when other factors are considered such as life expectancy and general health. On the other hand, in an otherwise healthy younger man aged 50-55, an increased PSA level is more likely to affect his life (due to the effect of prostate cancer or the complications of treatment) and further investigation should be considered. The risk of death from prostate cancer depends on the man’s life expectancy and the aggressiveness of the cancer. As a rule, men with high blood PSA levels with a life expectancy of 10 years or more (or a family history of prostate cancer) should consider further testing to make the diagnosis of prostate cancer. With more aggressive cancers, local treatments do not always cure cancers as microscopic spread may have happened that cannot be detected with scans and X-ray imaging. These patients need to be followed so that other treatments can be undertaken as indicated.

Will a PSA test tell me if I have prostate cancer?

A single PSA test is not a reliable indication of prostate cancer, unless it is extremely high. Men with a blood PSA level over 10 ng/ml have a 50 per cent risk of having prostate cancer. An increased PSA level may cause concern and anxiety in some men. It is important to remember that not everyone with increased levels of PSA has prostate cancer. Other prostatic conditions, such as BPH or prostatitis can also cause increased PSA levels. Results of a PSA test need to be interpreted with caution. Prostatic biopsies are needed to confirm prostate cancer is present and to give an idea of how aggressive the prostate cancer is. New research suggests that the rate or how quickly PSA levels rise over time is important (this is called PSA velocity). Regular tests, every one to two years, are necessary to check if the level of PSA changes with time. If the PSA level doubles in 12 months, this is of concern as it may be due to the presence of a fast growing cancer or infection in the prostate (prostatitis). So, if PSA level is increasing, further action should be taken and a specialist Urologist consulted for more detailed monitoring. What are the benefits and risks of testing for prostate cancer? An important benefit of testing for prostate cancer is that early detection of prostate cancer when it is smaller and curable gives better chance for more effective treatment and cure. Risks of testing for prostate cancer include:

  • If the PSA level is raised, it does not always indicate prostate cancer. Biopsies will be needed to determine if cancer is present.
  • Prostate biopsies and treatments for prostate cancer have side-effects that may affect the quality of life.
  • If prostate cancer is slow-growing, a decision may be made not to undergo any active treatment (watchful waiting/ active surveillance with further biopsies at a later date) but to have careful monitoring. In some men this approach can cause considerable anxiety.

What if I choose to get tested?

If a man makes an informed decision to be tested for prostate cancer, it is important that a digital rectal examination (DRE) is also performed. A combination of a PSA test and DRE is better than either one alone. If a PSA test is performed, it is important to return to your GP for follow-up testing every 12 months. And if a PSA level is high for your age, the test should be repeated. For men with PSA values less than 1ng/ml with no risk factors, further testing may not be needed for several years.

What other tests can check for prostate cancer?

There are currently no tests better than PSA for testing for prostate cancer. Throughout the world, investigators are trying to develop more accurate and reliable tests for prostate cancer. There are some refinements of the PSA test that some doctors believe may add more value to the test. For example, the free to total PSA ratio is another blood test that can help determine whether or not an elevated PSA level may be a result of prostate cancer. A proportion of the PSA circulating in the blood is free. Non-free PSA is bound to proteins. Men with prostate cancer will usually have lower levels of free PSA as a proportion of their total PSA measurement, than men with prostate enlargement (BPH). This ratio (or percentage) is most useful for PSA values between 4 and 10 ng/ml. This information can help the patient and doctor make a decision regarding the options for further investigation and management. The decision to be tested for prostate cancer is entirely a personal one in consultation with your doctor to help you make the best informed choice for your situation. This information is provided to help men and their families understand the PSA test, and to make discussion with a doctor easier. Andrology Australia recommends readers speak to a local doctor about PSA testing and any other health concerns.

Andrology Australia wishes to acknowledge and thank all those who contributed to and reviewed this information.

1-4 Oesterling JE et al. 1995; Fang et al. 2001;
Gann et al. 1995; Carter et al. 1992

 

Prostate Cancer Patients Show Improved Response From Repeat Radionuclide Therapy

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For prostate cancer patients with bone metastases, repeated administrations of radionuclide therapy with 188Re-HEDP are shown to improve overall survival rates and reduce pain, according to new research published in the November issue of The Journal of Nuclear Medicine.

Approximately 50 percent of prostate cancer patients develop bone metastases that are predominately osteoblastic, that is, have the tendency to fracture resulting in serious morbidity. This type of bone metastasis often leads to chronic pain syndrome in prostate cancer patients; as many as 50 percent of prostate cancer patients with chronic pain syndrome are reported to receive inadequate pain treatment, which makes them candidates for radionuclide therapy.

The retrospective study, “Palliation and Survival After Repeated 188Re-HEDP Therapy of Hormone-Refractory Bone Metastases of Prostate Cancer: A Retrospective Analysis,” reviewed cases of 60 patients with hormone-refractory prostate cancer. The patients, all of whom had more than five lesions documented by a bone scan, were divided into three groups – those who received one therapy, two therapies or three or more therapies.

“Radionuclide therapy of bone metastases has been used for several decades for those with prostate cancer,” noted lead author of the study Hans-Juergen Biersack, MD. “For this study, we developed 188Re-HEDP as a novel radiopharmaceutical which – due to it is short half life of 19 hours – makes sequential therapy possible.”

The researchers found that post-treatment survival increased with the number of radionuclide therapies administered. Patients with progressive hormone-refractory prostate cancer receiving one therapy added 4.5 months, those receiving two therapies added 10 months, and those receiving three or more therapies improved their survival by 15.7 months. In addition, while the Gleason scores – a grading system used to evaluate the prognosis of men with prostate cancer – for each group were similar, the number of life-lost years for patients receiving three or more therapies was significantly lower.

In regards to pain reduction, no significant difference was found among those receiving 188Re-HEDP therapies. Pain reduction was achieved in 89.5 percent of those receiving one therapy, in 94.7 percent of those receiving two therapies and in 90.9 percent of those receiving three or more therapies.

“For patients failing chemotherapy or hormone treatments, 188Re-HEDP is a promising therapy that can both extend the number of survival years and help relieve pain from bone metastases,” noted Biersack. “The findings support and expand the role of molecular therapy with radioisotopes in oncology.”

Starving Prostate Cancer

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Prostate cancers are hungry, growing cells. Now we know how to cut off their food supply thanks to research to be published later this month in Cancer Research work funded by Movember and the Prostate Cancer Foundation of Australia.

Researchers at the Centenary Institute in Sydney have discovered a potential future treatment for prostate cancer – through starving the tumour cells of an essential nutrient they need to grow rapidly.

Their work, with human cells grown in the lab, reveals targets for drugs that could slow the progress of early and late stage prostate cancer.

Each year about 3300 Australian men die of prostate cancer. It’s Australia’s second worst cancer killer for men, matching the impact of breast cancer on women.

Current therapies for prostate cancer include surgical removal of the prostate, radiation, freezing the tumour or cutting off the supply of the hormone testosterone – but there are often side-effects including incontinence and impotence.

Growing cells need an essential nutrient, the amino acid called leucine, which is pumped into the cell by specialised proteins. And this could be prostate cancer’s weak link.

Dr Jeff Holst and his team at the Centenary Institute found in a study to be published in November’s Cancer Research that prostate cancer cells have more pumps than normal. This allows the cancer cells to take in more leucine and outgrow normal cells.

“This information allows us to target the pumps – and we’ve tried two routes. We found that we could disrupt the uptake of leucine firstly by reducing the amount of the protein pumps, and secondly by introducing a drug that competes with leucine. Both approaches slowed cancer growth, in essence ‘starving’ the cancer cells,” Jeff says.

First author Dr Qian Wang says by targeting different sets of pumps, the researchers were able to slow tumour growth in both the early and late stages of prostate cancer. “In some of the experiments, we were able to slow tumour growth by as much as 50 per cent. Our hope is that we could develop a treatment that slows the growth of the cancer so that it would not require surgical removal. If animal trials are successful over the next few years then clinical trials could start in as little as five years,” he says.

Jeff says one of the other spin-offs of the discovery is a better understanding of the links between prostate cancer and eating foods high in leucine. “Diets high in red meat and dairy are correlated with prostate cancer but still no one really understands why. We have already begun examining whether these pumps can explain the links between diet and prostate cancer.”

“Given one in nine men in Australia may develop prostate cancer in their lifetime, this discovery could touch thousands of lives.”

The publication of the study comes just in time for Movember, a month-long charity drive in which thousands of people around the globe grow moustaches to raise money for men’s health issues including prostate cancer.

“This fundamental research tells us more about how prostate and other cancers grow, and will open the way for new treatments in the long term,” says Movember chairman Paul Villanti.

“Movember is now one of the largest non-government global funders of prostate cancer research. We strongly support innovative targeted research that leads to significantly improved clinical tests and treatments to reduce the burden of prostate cancer. It’s great to see the progress that Dr Holst and his team have made with the support of a Movember Young Investigator grant.

PCFA and Movember have been working together since 2004 to reduce the impact of prostate cancer on Australian men and their loved ones.

PCFA CEO Dr Anthony Lowe says research that has the potential to reduce the impact of prostate cancer on those who are diagnosed is a huge priority for the PCFA’s grants program. “We commend the team at the Centenary Institute on the remarkable progress they are making in this regard,” he says.

“This is part of a body of work that is investigating the very nature of cancer and opening up new avenues for cancer treatment,” says Centenary Institute executive director Professor Mathew Vadas.

About Prostate cancer

Prostate cancer is the most common cancer in Australian men and is the second most common cause of cancer deaths in men (after lung cancer). Generally at the early and potentially curable stage, prostate cancer does not have obvious symptoms. This makes it different from other benign prostate disorders, which may result in urinary symptoms. Men aged 50 and over should talk to their doctor about prostate cancer and if they decide to be tested, to do so annually. If there is a family history of prostate cancer; men should talk to their doctor from the age of 40.

Abstract

L-type amino acid transporters such as LAT1 and LAT3 mediate uptake of essential amino acids such as leucine. Here we report that prostate cancer cells coordinate the expression of LAT1 and LAT3, thereby maintaining sufficient levels of leucine for mTORC1 signalling and cell growth.

We show that inhibition of LAT function leads to decreased cell growth and mTORC1 signalling in prostate cancer cells. These cells maintain amino acid influx via androgen receptor regulation of LAT3 expression, and ATF4 regulation of LAT1 expression after amino acid deprivation.

These responses are intact in primary prostate cancer, as indicated by high levels of LAT3 in primary disease, and an increase in LAT1 following hormone ablation and in metastatic lesions.

These data show that prostate cancer cells respond to the demand for increased amino acids through an integrated pathway, leading to increased amino acid transporter expression and cell growth.

Prostate Cancer Study Shows Radiation Plus Hormone Therapy Greatly Improves Survival For Men With High-Risk Disease

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Men with locally advanced or high-risk prostate cancer who receive combined radiation and hormone therapy live longer and are less likely to die from their disease, shows clinical research led by radiation oncologists at the Princess Margaret Hospital (PMH) Cancer Program, University Health Network.

The findings are published online today in The Lancet (doi: 10.1016/S0140-6736(11)61095-7). Principal investigator Padraig Warde, deputy head, PMH radiation medicine program, says: “The study shows combining radiation and hormone therapy improves overall survival by 23 percent and disease-specific survival by 43 percent, compared with treating with hormone therapy alone.

“Based on these results, we believe adding radiation to the treatment plan should become part of the standard therapy.” Dr. Warde is also a Professor in the Department of Radiation Oncology, University of Toronto.

Prostate cancer is the most common malignancy in men and between 15% and 25% percent of cases are high risk, says Dr. Warde. The Canadian Cancer Society estimates 25,500 new cases will be diagnosed this year and that 4,100 men will die from the disease.

In the randomized study of 1,205 men to investigate appropriate treatment for high-risk prostate cancer, half the participants received androgen deprivation therapy (“hormone therapy”) alone and half received hormone therapy plus radiation.

After seven years, 66 percent of men who had hormone therapy only were still alive, compared with 74 percent who received the combined therapy. Among those in the hormone-only group, 26 percent died from their prostate cancer versus 10 percent who received hormone therapy plus radiation.

“This study will challenge the prevailing dogma of only using hormone therapy alone for locally advanced prostate cancer,” says Dr. Warde. “As well, we found the radiation therapy was tolerated well with no significant toxicity.”

He believes the benefits of combined therapy could actually be even greater now given the use of more targeted radiation techniques that have been developed since the study began in 1995.

“Our study shows the way to combine existing, effective treatment options that are readily available to improve outcomes for many men with high-risk prostate cancer.”

The study, conducted by the NCIC Clinical Trials Group (NCIC CTG) at Queen’s University in Kingston, Ontario in collaboration with the Medical Research Council UK involved clinical researchers and staff from participating sites throughout Canada and internationally. Patients were enrolled onto the study between 1995 and 2005.

The research was funded by the Canadian Cancer Society Research Institute, the US National Cancer Institute and the Medical Research Council UK. Dr. Warde’s research is also supported by The Princess Margaret Hospital Foundation.

Prostate Cancer Survival Improves With Radiotherapy And Androgen Deprivation Therapy

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An article published Online First in The Lancet reveals that men with locally advanced prostate cancer, which has not spread, who receive radiotherapy (RT) in combination with their androgen deprivation therapy (ADT) are more likely to have a greater overall chance of survival compared with those on ADT alone. According to the authors, Dr Padraig Warde of the Radiation Medicine Program at the Princess Margaret Hospital in Toronto, ON, Canada, Matthew R Sydes at the MRC Clinical Trials Unit in London, UK, and Dr Malcolm Mason at the Cardiff University School of Medicine in the UK and their teams, the advantages of combined treatment should be discussed with all men who suffer from locally advanced prostate cancer that has not spread.

The trial is the first to be adequately equipped to compare RT in combination with ADT to ADT as a stand-alone treatment. After examining a total of 1,205 patients, researchers found that 1,057 patients had locally advanced (T3 or T4) prostate cancer or organ-confined disease (T2). 119 patients were receiving a prostate-specific antigen (PSA) concentration of more than 40 ng/mL or PSA concentration more than 20 ng/mL and 25 patients had a Gleason score of 8 or higher. The researchers randomly assigned 602 patients in the ADT only group and 603 patients in the ADT and RT group to lifelong treatment with a median follow-up at 6 years.

At the time of analysis, 175 patients in the ADT only group and 145 patients in the ADT and RT group had succumbed to their illness.

The findings revealed overall survival rates of 74% in the ADT and RT group compared with 66% in the ADT only group at 7 years. The researchers noted that serious long-term genitourinary or gastrointestinal toxicity from RT was uncommon and recorded low numbers of serious adverse events in each group.

The researchers conclude:

“This trial provides convincing evidence that local control of disease in the prostate improves survival in patients with locally advanced prostate cancer. Our findings suggest that the benefits of the combination of ADT and RT should be discussed with all patients considering a curative treatment approach.

Dr Matthew R Cooperberg from the Department of Urology at the University of California in San Francisco, CA, USA, says in a linked comment:

“This study has provided the strongest evidence to date that androgen deprivation therapy alone for men with high-risk prostate cancer is not adequate. These patients require an aggressive, multimodal approach incorporating prostate-directed local therapy. However, the crucial question – whether the optimum initial strategy should include radiation combined with androgen deprivation therapy, or surgery followed by selective radiation on the basis of pathological findings and early biochemical outcomes – is still open. The definitive answer will only come through trials of men with high-risk disease randomly assigned to receive surgery or radiation as an initial treatment.”

Written by Petra Rattue
Copyright: Medical News Today

Experimental Drug Shows Great Results On Prostate Cancer

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An experimental drug known as MDV3100 made by Medivation Inc. has improved survival rates for men with metastatic castration-resistant prostate cancer. Those on MDV3100 by Medivation outlived those on a placebo by an average of 4.8 months, in a phase 3 trial. The manufacturer Medivation Inc. shares shot up 150% on the news and they announced that an independent committee monitoring the trial recommended stopping the trial after reviewing interim results. It would be unfair and arbitrary to those on the placebo, to continue just for the sake of gathering relatively unneeded data.

Howard I. Scher, MD, coprincipal investigator of the AFFIRM study and chief of the genitourinary oncology service at the Memorial-Sloan Kettering Cancer Center in New York City said in a press statement :

“MDV3100 was rationally designed to target androgen-receptor signaling, a key driver of prostate cancer growth … If approved, MDV3100 will be a welcome option for men with prostate cancers who have progressed on hormones and after initial chemotherapy.”

The success of MDV3100 is somewhat of a comeback for Medivation Inc and its CEO David Hung as an exciting experimental drug for Alzheimer’s failed in late stage testing during 2010.

Prostate cancer kills about 250,000 men a year globally and is the second most common cause of cancer death in men in the United States, after lung cancer. Having a better understanding of the molecular abnormalities underlying prostate cancer has led to new approaches such as Medivation’s MDV3100. If approved by the FDA MDV3100 will compete with Johnson and Johnson’s product Zytiga which is being touted as having great medical and commercial potential. Experts think that MDV3100 looks better than Zytiga though.

Professor Johann de Bono, M.D., MSc, Ph.D. FRCP, Honorary Consultant in Medical Oncology, Professor of Cancer Medicine at the Institute of Cancer Research and Royal Marsden Hospital, and the co-principal scientist in the AFFIRM study said :

“MDV3100 has a novel mechanism of action, inhibiting androgen receptor signaling at three distinct points in the signaling pathway … I am thus particularly pleased with the results of the AFFIRM interim analysis, as there is a real need for new treatments in advanced prostate cancer that target the cancer in different ways.”

Medivation and its development partner Astellas Pharma Inc. plan to hold a pre-NDA meeting with the Food and Drug Administration (FDA) in early 2012 and will provide an update on regulatory timelines for MDV3100 subsequent to that meeting.

Steven Ryder, M.D., president of Astellas Pharma Global Development said :

“We are very excited about these results and will work closely with our alliance partners at Medivation to pursue regulatory submissions in the United States, Europe and Japan … This is consistent with our corporate commitment to pursue innovative approaches to improving patient care and our strategic intent to be a global catergory leader in oncology.”

Written by Rupert Shepherd

View drug information on Zytiga.