These two guys can teach you something...

Sad times in Thailand

An honour to be living in Thailand at this historical time, witnessing the genuine heartfelt grief of the people who worshipped this great man.

Food for thought on the PSA

This article gives food for thought on the PSA test, a test that had my doctor ignored the results of, I would now certainly have been dead. So for me, PSA remains king, but never forget this:

If your result is between 0 and 4 the medical profession say you are within limits, and thus safe. No, no, no, no and NO! All my tests were within this limit, but my doctor spotted that there had been a doubling in about 18 months, which is a warning sign that all is not well. It doesn't mean you have cancer, but it OFTEN does!

If you are a man over 50 and you do not know your actual PSA test number (not just..." the doctor said it was ok") and have not written it down so you can compare it to the previous year, then you are dicing with death!

Read on...

We are still waiting for a test that can—with complete accuracy—distinguish between men who have prostate cancer and those who are cancer-free. If prostate cancer is diagnosed, the test should also determine whether it’s an aggressive form that requires prompt treatment or a slow-growing tumor that may only need close monitoring.

A number of companies have introduced tests that could take us closer to that goal, but there’s still much to be learned about them and their proper role in the management of prostate cancer. Unfortunately, published studies are limited, and so far none of the tests has a long-term track record in the real world, where doctors screen, counsel, and treat patients.

Once a particular test has been approved by the Food and Drug Administration and is available, it can be marketed without proof of benefit. Furthermore, unsubstantiated claims abound for many tests. For now, all of these tests are intended to augment—not replace—a doctor’s clinical judgment along with the existing proven tests currently used to screen for and monitor prostate cancer.

Time will tell if any of these new tests add information that will significantly affect treatment decisions. Here’s an overview of the latest prostate cancer tests—and the questions we hope they can answer. All of the tests are available in the U.S. unless otherwise indicated.

Tests to indicate the need for a prostate biopsy

An elevated prostate-specific antigen (PSA) level can indicate that a man has prostate cancer; however, findings may also be elevated in men with less serious conditions, such as benign prostatic hyperplasia (BPH), also known as benign prostatic enlargement (BPE). Yet most men with elevated PSA levels end up having an anxiety-provoking biopsy to rule out cancer. Two new tests show great promise in identifying appropriate biopsy candidates with greater accuracy:

• The Prostate Health Index. Commonly known as the phi test, measures blood levels of PSA, free PSA, and a precursor (or early form) of PSA, known as pro-PSA or p2PSA. Research suggests that pro-PSA levels are a better indicator of prostate cancer than total or free PSA levels and that men with elevated pro-PSA levels are at high risk for having an aggressive form of prostate cancer. Using a mathematical equation, the phi test combines all three variants to better determine whether prostate cancer is present.

The test is indicated for use in men age 50 and older whose digital rectal exam showed no signs of cancer and who have a total PSA value between 4 ng/mL and 10 ng/mL—a gray zone that could indicate prostate cancer or a less serious condition such as BPH. Like the other tests described herein, the phi test doesn’t deliver a definitive answer about what action to take—in this case, whether or not to have a biopsy.

Promo block

Instead, the phi test’s results, which are scored from 0 to 55 and above, reflect the probability that a biopsy will detect cancer. For example, a phi test score below 27 is associated with a 9.8 percent probability that prostate cancer is present, while a score of 55 or more suggests a likelihood of greater than 50 percent. As with all of the tests, phi test results must be considered in light of a man’s other risk factors.

• 4Kscore. This blood test (currently available in Europe and Mexico) measures levels of three PSA variants (total PSA, free PSA, and intact PSA), plus an enzyme called human kallikrein 2 (hK2), which is elevated in men with prostate cancer. Some scientists believe hK2 may promote the growth and spread of prostate cancer. The 4Kscore also uses a mathematical algorithm to calculate the risk of prostate cancer in a man with an elevated PSA level.

Tests to rule out a repeat biopsy

Some prostate biopsies produce inconclusive results. Others may be negative even in men with elevated PSA or other high-risk features. Typically, this means the procedure must be repeated even though only 10 to 36 percent of second biopsies detect cancer. The following tests can be used to help determine the need for a repeat biopsy.

• Progensa. This urine test detects the presence of a gene called prostate cancer antigen 3 (PCA3). This gene is overexpressed (or overactive) in 95 percent of men with prostate cancer, but not in men who have healthy prostates or BPH. Results are ranked from less than 5 to greater than 100, with a score of less than 25 indicating a decreased likelihood of a positive biopsy. Progensa is approved for use in men age 50 and older who have had one or more negative biopsies, but who a doctor nonetheless suspects may have prostate cancer.

• ConfirmMDx. Whether a particular gene is turned “off” or “on” can be determined by the presence or absence of specific chemical tags or methyl groups—methylation—of DNA, the building blocks of genes. When this process of DNA methylation turns off the activity of tumor suppressor genes, cancer may develop. Based on technology developed at Johns Hopkins and other institutions, ConfirmMDx analyzes the DNA methylation status of a man’s biopsied prostate tissue. Test results indicate that the biopsy specimen is positive or negative for methylation. A positive finding, which is mapped on a diagram of the prostate, suggests the need for a repeat biopsy.

• Prostate Core Mitomic Test. This test analyzes a man’s biopsied prostate tissue, looking for damage to mitochrondrial DNA (mtDNA) caused by cellular changes associated with prostate cancer development. A negative result suggests that the man is at low risk of undiagnosed prostate cancer and that a repeat biopsy can be deferred.

Promo block

Tests to determine the need for prostate cancer treatment

Many men with positive biopsies have low-risk tumors that won’t spread to other organs and become deadly. For some of these men, active surveillance may be a reasonable alternative to immediate treatment, but standard diagnostic tools are imperfect at distinguishing between indolent and aggressive tumors. Results from the following tests, when combined with a Gleason score and other clinical information, are intended to help provide reassurance about the decision to forgo or institute immediate treatment.

• Prolaris. This test uses a sample of tumor tissue removed during a biopsy and measures how rapidly cells are dividing as a way to gauge whether the tumor is more or less likely to be deadly. Prolaris scores range from -1.3 to +4.7 and are stratified by risk, with higher scores indicating a greater risk of dying from prostate cancer.

•ProstaVysion. For this test, biopsied tissue is analyzed for the presence of two genetic biomarkers for prostate cancer. One biomarker, known as TMPRSS2:ERG, is a fusion of two genes and is associated with the presence of prostate cancer. The other biomarker, PTEN, is a “suppressor” gene that normally helps keep certain forms of cancer in check and is missing in 60 percent of men with metastatic prostate cancer. By examining those two markers, the test provides a molecular analysis of prostate cancer aggressiveness and the patient’s long-term prognosis.

• Oncotype DX. This test examines the interactions between 17 genes in a biopsy sample to predict whether a tumor is likely to be aggressive. The result, the Genomic Prostate Score, ranges from 0 to 100; a low score suggests that the tumor is less likely to grow and spread and aggressive treatment may not be necessary. Conversely, a higher score suggests a poorer prognosis and a greater need for immediate treatment.

Tests to determine the need for treatment after prostate surgery

Some men who have had a radical prostatectomy are at risk for recurrence and would benefit from additional therapies, such as radiation or hormone therapy, but identifying them is a challenge. At least one of the tests discussed above, Prolaris, as well as the tests below, may be able to help with that challenge.

Promo block

•NADiA ProsVue. This blood test measures the rate of tiny changes in PSA levels over time, which can suggest that a man is at risk for recurrence. Patients are categorized as at reduced risk, which indicates that a man is at a lower risk for clinical (not biochemical) cancer recurrence for several years following his prostatectomy, or not at reduced risk.

•Decipher. This test, which is not yet available in the U.S., analyzes tissue from the prostate tumor to look for 22 genes linked to prostate cancer metastasis. The results, which are presented as a percentage score, indicate whether a man is at high or low risk for metastases and, therefore, whether further treatment should be considered.

• Published: October 17, 2016
• Medically reviewed by: Alan W. Partin, M.D., Ph.D.

Interleukin-4 Stimulates the Spread and Growth of Prostate Cancer Cells, Researchers Find

A bone marrow protein that normally works to reduce inflammation after infection was found to also send signals to prostate cancer cells to promote their spread and growth outside of the prostate, a new study shows. The findings could provide the missing link as to why prostate cancer cells migrate to bones and may lead to new therapies that stop the process.

The study, “The immunosuppressive cytokine interleukin-4 increases the clonogenic potential of prostate stem-like cells by activation of STAT6 signaling,” was published in the journal Oncogenesis.

Inflammation is linked to poor prognosis in cancer. Cytokines, which are proteins secreted by cells as part of the normal immune response, are associated with the inflammatory process. For example, the pro-inflammatory cytokine interleukin-6 (IL-6) influences the growth and survival of prostate cancer cells.

Patients with progressive prostate cancer have elevated levels of the anti-inflammatory cytokine interleukin-4 (IL-4), and previous studies have shown that IL-4 can promote the growth and proliferation of certain cancer cells in vitro. This prompted the researchers to investigate the effect of IL-4 on prostate cancer cells isolated from patients.

After six days of growth in the presence of IL-4, the team found that the ability of malignant prostate cancer cells to form colonies, which is a measure of cell survival and proliferation, was enhanced in a concentration-dependent manner. But the cytokine did not influence the migration or invasive potential of prostate cancer cells.

The researchers then set out to identify the mechanism mediating IL-4’s effect on prostate cancer cells. They found that the signaling pathway is mediated by the STAT6 protein, which is known to be involved in metastasis.

The findings suggest that prostate cancer cells that have spread from the prostate into circulation, dock in the bones through the IL-4/STAT6 signaling and multiply to form a new tumor.

Norman Maitland, a professor at the University of York’s Department of Biology in the U.K., and one of the study’s authors, compares the process to that of a space rocket.

“We have always known that the two places where prostate cancer spreads are the bones and lymph nodes, but we have not fully understood why these two locations are preferred,” he explained in a press release. “If we imagine the prostate cancer cell as a floating ‘space rocket’ and the only way for it to perform its mission is to ‘dock’ with another ‘space vehicle’, we start to get a picture of what happens when a cancer cell moves around the body in search of a new home.

“Without this docking station, the ‘ship’, or cell, will just float around, not causing any further harm. The receptors on the ‘docking station’, or the protein in bone, act like a magnet for the receptors on the stem cells of the cancer and once it is ‘docked’, getting rid of the cancer becomes much harder,” he added.

The identification of this pathway offers a potential therapeutic opportunity by blocking STAT6 signaling. By using a STAT6 inhibitor that already has been tested in asthma, the team was able to disrupt the metastatic process.

“Clinical trials are some way off, but this is a positive and exciting step forward in tackling this disease and reducing the number of deaths,” Maitland said.