Prostatavorsorge und Prostatakrebs │ Medizin im Gespräch
A considerable scientific enterprise has been devoted to improving on or replacing the PSA test, which detects prostate disease but not necessarily prostate cancer. Even as studies continue and controversy roils around how to make the most of the PSA test, a large contingent of researchers is seeking better biomarkers for prostate cancer that take advantage of genomic technologies.
However, even as some genomic tests are making their way into the marketplace, leading researchers have sounded a note of caution. Conceptually, this is easy and the terms indolent and aggressive are easily spoken, but are much more difficult to define. Rubin spoke recently at the annual meeting of the American Association for Cancer Research AACR as part of a panel exploring prostate cancer screening now and in the future.
He went on to add that next-generation sequencing has the potential to address the many demands placed on biomarkers for prostate cancer, from diagnosis all the way to personalizing drug therapies of the future See Table, right. However, he also warned against being beguiled by diagnostischem Wert Prostatasekreten novelty of this technology if it doesn't decisively answer key clinical questions. The U. Food and Drug Administration FDA first cleared the PSA test in to monitor treatment in men already diagnosed with prostate cancer and extended approval in for detecting cancer in symptomatic men.
By that time, however, the PSA horse was out of the proverbial barn, diagnostischem Wert Prostatasekreten the test was being used widely, particularly in the U. Off-label use of PSA as a general screening test has been at the center of the controversy, for many reasons.
One is that PSA, a glycoprotein diagnostischem Wert Prostatasekreten by the epithelial cells of the prostate, can be elevated for reasons other than prostate cancer, including from prostatitis, trauma, or benign prostatic hyperplasia.
As a consequence, the test is not very specific for detecting prostate cancer. This perhaps would not be diagnostischem Wert Prostatasekreten an issue if the prostate cancer field was not weighed down by over-diagnosis and over-treatment. As many as four-out-of-five prostate biopsies on men with elevated PSA levels turn out to be negative for diagnostischem Wert Prostatasekreten, and up to half the true-positives are unlikely to pose problems for men during their lifetimes.
At the same time, both prostate biopsies and treatments pose risks: biopsies have infectious complication rates ranging from 0. Despite these cautionary statistics, once men diagnostischem Wert Prostatasekreten the word cancer, many still pursue treatment.
The bias toward treatment in the U. Knowing which men have indolent disease that merely deserves active surveillance and which have aggressive cancer that must be acted on, has, in fact, been at the heart of the PSA debate.
Different cutoffs also have been proposed to fine-tune PSA's sensitivity and specificity. However, lower thresholds have not been endorsed formally by diagnostischem Wert Prostatasekreten organizations.
PLCO, a study of 77, men at 10 U. However, this study has been criticized because half of the men assigned to the control group also underwent screening by virtue of receiving usual care. More recently, ERSPC researchers examined quality of life issues around prostate cancer screening and concluded that long-term effects after diagnosis and treatment diminished the benefits of screening but that more data was needed to make universal screening recommendations.
Diagnostischem Wert Prostatasekreten on the controversial and still confused picture of Diagnostischem Wert Prostatasekreten role, Schröder and Brawley agreed that individual informed decision-making for now remains the best prostate cancer screening strategy. With PSA's flaws, research to come up with something better has been intense, particularly in the genomic realm.
Molecular-based biomarkers hold the promise of answering crucial clinical questions, such as who should be screened, who has prostate cancer, and who needs treatment See Table, p. PSA currently plays a more or less unsatisfying role in addressing these concerns. Already, at least 80 single nucleotide polymorphisms SNP have been linked to prostate cancer, and multigene panel tests that detect or predict the disease are available commercially.
A recent New York Times diagnostischem Wert Prostatasekreten indicated that more than one dozen companies have already or intend to introduce such tests, some intended to be used as adjuncts to PSA results, others independently.
Others strive to guide treatment choice or provide prognostic information after surgery, like Myriad Genetics' Prolaris test. Still others propose to forestall unnecessary second biopsies in men whose PSA levels stay elevated after an initial negative biopsy. In the midst of all this test development, the Agency for Healthcare Research and Quality reviewed 15 multigene panels and concluded that all have "poor discriminative ability" for predicting risk of prostate cancer.
So a diagnostischem Wert Prostatasekreten with a negative predictive value of 80 percent is not giving me any more information than I had just by walking around anyway. You have to beat this threshold to have a useful test; otherwise, it's not adding to the clinical picture. One of the issues in developing clinically useful multigene panels is that most genome-wide association studies have identified relatively more common SNPs.
That means that men both with and without prostate cancer carry at least some of the risk markers detected in these panels, making it challenging to set cutoffs for high- and low-risk groups, and affecting the positive predictive power diagnostischem Wert Prostatasekreten the test. As an example, loss of PTEN inhibits androgen receptor signaling and causes resistance to androgen receptor-based therapies.
PTEN deletion also has been associated with poor outcomes, suggesting it may be of both prognostic and predictive importance. Rubin also discussed an intriguing line of investigation involving chromothripsis, a dramatic rearrangement of DNA in localized chromosomal regions with usually one-to-two copy number states across the rearranged region. Cells not only survive this catastrophic event, but through their new genomic make-up seem to confer selective advantage to the clone, setting the diagnostischem Wert Prostatasekreten for cancer.
First reported in in the genome of chronic lymphocytic leukemia, bone cancer, and small cell lung cancer, it now has been found in the diagnostischem Wert Prostatasekreten of other cancers, including prostate cancer.
This suggests that this pattern of rearrangement is a type of biomarker where there may be a selection for alterations over-expressing an oncogene or knocking out a tumor-suppressor gene. Rubin was quick to add that the chromothripsis phenomenon represents diagnostischem Wert Prostatasekreten only the excitement and promise but also diagnostischem Wert Prostatasekreten hard work ahead in changing the prostate cancer diagnostic landscape.
Molecular-based biomarkers hold the promise of answering crucial clinical questions from screening to treatment monitoring in metastatic disease. Both Rubin and Nelson noted the importance of two studies published in diagnostischem Wert Prostatasekreten whole genome sequencing in sizable prostate cancer cohorts. One involved cancer tumors at diagnosis prior to treatment, and the other, 50 treatment-resistant, ultimately fatal cases. Mutation rates in the two types of disease were fairly similar, but the treatment-resistant tumors had markedly increased copy-number alterations.
Overlap in mutations in both types of tumors also suggest that dysregulation of the androgen receptor pathway could be an early event in prostate cancer development. Nelson's own work and that of other research teams involves exploring DNA methylation alterations.
He reported that at least 5, of these epigenetic changes have been found in prostate cancer, and that the changes tend to be diagnostischem Wert Prostatasekreten in individuals but vary diagnostischem Wert Prostatasekreten individuals. We're working hard to figure out how that works, which are drivers, which are passengers," he said.
If this work seems very far diagnostischem Wert Prostatasekreten from helping a man and his physician make an informed diagnostischem Wert Prostatasekreten about prostate cancer screening and treatment, both Rubin and Nelson suggested otherwise. Diagnostischem Wert Prostatasekreten are a number of activities going on with dream teams dedicated to this issue," said Rubin.
From the time several research teams discovered that AMACR was very commonly over-expressed in prostate cancer but not in normal prostate tissue, he recalled that the field rallied rapidly to make use of this finding.
They got together very quickly, looked at a very large number of prostate samples and were able to introduce the antibody diagnostischem Wert Prostatasekreten for this literally from the first report of it to wide-spread community adoption improving cancer care within two years," he said. I'm very optimistic about what we can accomplish. Login Store Cart 0. Which Cancers Need to Be Treated? Demands for Prostate Cancer Biomarkers Biomarkers are needed to address prevalent clinical issues in all stages of prostate cancer.
Localized prostate cancer Treatment stratification, treatment selection, and recurrence monitoring. Active surveillance monitoring. Castration-resistant prostate cancer metastatic and non-metastatic Treatment stratification and treatment monitoring.
Treatment selection. Courtesy of William G. Who has prostate cancer? PSA, prostate cancer genetic susceptibility loci. Diagnostischem Wert Prostatasekreten prostate cancer Risk stratification Treatment stratification Treatment monitoring Who needs treatment? What treatment is needed? Is treatment effective? Currently based on risk. PSA Castration- resistant prostate cancer metastatic and non-metastatic Treatment stratification Treatment monitoring Which treatment is most likely to be of benefit?
Nelson, MD, PhD Mutations and Methylation Both Rubin and Nelson noted the importance of two studies published in involving whole genome sequencing in sizable prostate cancer cohorts. Treatment stratification, treatment selection, and recurrence monitoring.
Treatment stratification and diagnostischem Wert Prostatasekreten monitoring. Molecular Biomarkers in Prostate Cancer Molecular-based biomarkers hold the promise of answering crucial clinical questions from screening to treatment monitoring in metastatic disease.
Who should be screened? Risk stratification Treatment stratification Treatment monitoring. Who needs treatment? When should treatment begin? Castration- resistant prostate cancer metastatic and non-metastatic. Treatment stratification Treatment monitoring. Which treatment is most likely to be of benefit?