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From Urology Times
Spanish researchers have found a means of distinguishing between high-grade prostatic intraepithelial neoplasia (HGPIN) lesions destined to become cancerous and those that will remain benign, which may spare patients the discomfort and inconvenience of unnecessary needle biopsies, according to a study in Clinical Cancer Research (2008; 14:2617-22).
This is teh first studay that I am familiar with that has a genetic marker for patients with diagnosis of high grade PIN. High grade PIN was once thought to be higly associated with prostate cancer (about 50%) and warranted a repeat biopsy. This was when urologists performed 6 biopsies routinely.
Now that we are performing at least 10, the finding is not as ominous as before. About 20% of pateints wil develop cancer.
Medscape article summarizing PSA recommendations:
The most aggressive screening protocol is from the NCCN.
NCCN guidelines start from the premise that the patient has made a decision to seek early prostate cancer detection. They recommend beginning screening at age 40. The baseline PSA level, race, and family history are then used to determine the subsequent screening intervals. They recommend considering a biopsy for men with a total PSA level > 2.5 ng/mL, after further consideration of the PSA velocity, PSA density, and percent free PSA. They explain how these parameters can be used to lessen the possibility of confounding from benign prostatic hyperplasia. Furthermore, they describe how repeating PSA determinations with or without a trial of antibiotic therapy, as well as consideration of variability between different PSA assays, can reduce the likelihood of confounding from prostatitis or differences in PSA assay standardization. Moreover, they provide advice about whether or not repeat biopsies are needed and how to deal with the findings of high-grade prostatic intraepithelial neoplasia or atypical glands suspicious for carcinoma on an initial biopsy.
The controversy over screening for prostate cancer will continue. Information is not adequate to recommend screening men for prostate cancer with digital rectal examination or measurement of prostate-specific antigen (PSA), according to a position statement by the American College of Preventive Medicine (ACPM) published in the February issue of the American Journal of Preventive Medicine. The American Urological Association recommends that men who are 50 years and older and who have an estimated life expectancy of more than 10 years should be offered PSA screening. The American Cancer Society recommends that men who are 50 years and older and who have a life expectancy of more than 10 years should be offered both DRE and PSA screening. The United States Preventive Services Task Force and American Academy of Family Physicians do not find sufficient evidence to recommend for or against PSA or DRE screening. The Canadian Task Force on Preventive Health Care recommends against routine screening with PSA. |
Genetic test in three years to detect prostate cancer | Science | The Guardian: "A genetic test that identifies men most at risk of prostate cancer could be available within three years, scientists said yesterday. British doctors will use the test in screening programmes to spot the disease in its earliest stages, before it has become dangerously advanced or has spread throughout the body."
I had a patient in my office last week who was young, was done having children, and had a strong family history of prostate cancer. He was wondering if it would be reasonable to remove his prostate prophyllactically. I told him that I wasn't ready to do that today, but in the near future I thought it would be reasonable. Breakthroughs like this will help diagnose prostate cancer earlier and more accurately than with prostate biopsies.
There was a good question asked on a prior entry:
Robotic Surgery Blog: Is Prostate Cancer Transmissible?: "Would you please comment on whether there is a connection between sexual activity and elevated PSA. Also, why would test results given to a patient not break down PSA into free and that with protein. Thank you."
PSA can be done in many ways. Most often urologists including myself only order the total PSA, not the free and total test. If the free is ordered I usually do not give it to patients unless they ask. In general a low number (under 10%) gives you a higher chance of having cancer and a high number (over 25%) gives you a lower chance. Most patients would not understand the nuances involved in reading this test.
As for sexual intercourse, I do not think it causes a major jump in PSA. Patients who have intercourse the day before the test may have a slightly higher PSA value. When the studies were done to evaluate PSA values and risk of cancer patients were not asked to abstain from intercourse. Therefore I do not ask patients to modify their behavior.
UroToday - Prostate Cancer Screening Decreases the Absolute Risk of Being Diagnosed with Advanced Prostate Cancer—Results from a Prospective, Population-Based Randomized Controlled Trial
Between the years1995 and 2004, 1,252 cases of CaP were diagnosed; 810 in the screening arm and 442 in the control arm. Men randomized to active screening had a 1.83-fold increased risk of being diagnosed with CaP compared to men in the control group. Most screened men had localized disease. The number of participants with metastatic CaP at the time of diagnosis (or with a PSA >100ng/ml) was 24 in the screening group compared to 47 in the control group (p=0.0084). This represents a 49% reduction in the risk of being diagnosed with metastatic CaP by screening over a 10-year period.
The study minimized selection bias as men were randomized without any prior information. A study limitation is that men had only sextant biopsy, although the biopsies were directly laterally.
Continue reading "European study shows that prostate cancer screening leads to less advanced prostate cancer" »
UroToday - EAU 2007 - Session on Prostate Biopsy 1
The 7,074 biopsies were performed in 5,153 men. Minor complications included hematuria >1 day (13.8%), hematospermia (35.8%), and rectal bleeding (2.1%). Major complications were prostatitis, epididymitis, fever >38C, rectal bleeding >2 days, and urinary retention, all <1.0%. This study validates the safety of TRUS biopsy of the prostate.
This is a lower number than I would have guessed for blood in the semen (hematospermia), but a nice study to advise patients of possible side effects from a prostate biopsy.
This is what we need to consider when I asked the question of doing biopsies on everyone.
There were 2 articles summarized from the EAU 2007 conference on Urotoday.
They seemed to be conflicting, with one saying that delaying therapy did not seem to hurt many people and the other concluding that screening helped.
UroToday - EAU 2007 - Session on Prostate Cancer Screening:
 Dr. Pelzer, Innsbruck presented data that the pathologic characteristics of PC detected in screened patients is favorable compared to PC detected in non-screened men. Of 997 RPs performed 1999-2006, 806 men were treated for screen detected PC and 191 were referred for surgery and not screen detected. Patient age and PSA levels were similar between the groups. The screen detected patients had statistically lower pathologic stages at surgery and lower Gleason scores. The rate of positive surgical margins was 11.7% in the screened group and 24.4% in the non-screened group. The worse pathologic variables suggest that the non-screened group is at higher risk for disease relapse compared to the screened patients. Dr. Pelzer, Innsbruck presented data that the pathologic characteristics of PC detected in screened patients is favorable compared to PC detected in non-screened men. Of 997 RPs performed 1999-2006, 806 men were treated for screen detected PC and 191 were referred for surgery and not screen detected. Patient age and PSA levels were similar between the groups. The screen detected patients had statistically lower pathologic stages at surgery and lower Gleason scores. The rate of positive surgical margins was 11.7% in the screened group and 24.4% in the non-screened group. The worse pathologic variables suggest that the non-screened group is at higher risk for disease relapse compared to the screened patients.
In the screening studies in Europe the screening only gets done every 4 years. They are still very useful and I look forward to seeing their results.
As the study I quoted points out, even though patients by be "curable" as defined by having disease confined to the prostate, there is still a higher volume of cancer and there is probably more people that will not be cured by surgery as evidenced by the higher positive margin rate.
2 recent studies recommend lowering the psa velocity.
UroToday - Age Adjusted Prostate Specific Antigen and Prostate Specific Antigen Velocity Cut Points in Prostate Cancer Screening
Traditional recommendations for prostate biopsy have included a total serum PSA of 4.0 ng/ml or greater and a PSA velocity of 0.75 ng/ml per year or greater. While recent trends have moved towards a PSA threshold of 2.5 ng/ml or greater in men younger than 65 years, specific recommendations for PSA velocity thresholds in younger men have not been agreed upon.
In the February issue of the Journal of Urology, Moul, Albala, and colleagues from Duke University report the results of a cohort of 33,643 men who formed part of a prostate cancer early detection study. Of these men, 11,861 patients were identified with 2 or more serum PSA values over a 2 year period. Total PSA and PSA velocity threshold values with the highest sensitivity and specificity for prostate cancer detection were identified for men 50 to 59 years old.
In men age 50 to 59 years, a serum PSA threshold for biopsy of 2.0 ng/ml or greater achieved the highest sensitivity (84%) when compared to thresholds of 2.5 ng/ml, 3.0 ng/ml, and 3.5 ng/ml with sensitivities of 82%, 79%, and 77%, respectively. The specificity of a PSA threshold of 2.0 ng/ml in these men was acceptable at 74.4%, which was not significantly different from the specificity of using a threshold of 2.5 ng/ml (80%).
Using a PSAv of 0.4 ng/ml/year in men age 50 to 59 years achieved a specificity of 84% and sensitivity of 72%, compared with a PSA threshold of 0.75 ng/ml with sensitivity and specificity of 70% and 84%, respectively.
UroToday - Prostate Specific Antigen Velocity Threshold for Predicting Prostate Cancer in Young Men:
Using a PSA velocity of 0.4 ng/ml/year or greater may enhance prostate cancer early detection especially in men with a total PSA lower than 2.5 ng/ml. A PSA velocity threshold of 0.4 ng/ml per year or greater was independently predictive of cancer irrespective of age, total PSA, family history of prostate cancer, or race. What was most dramatic was that this criterion had the strongest association to cancer in multivariate analysis, even in patients with a total PSA less than 2.5 ng/ml. Using a PSA velocity threshold of 0.4 ng/ml/year was found to have a sensitivity of 67%, specificity of 81%, positive predictive value of 16%, and negative predictive value of 98%.
This study suggests that using a PSA velocity biopsy threshold of 0.75 ng/ml/year for men younger than 60 years may be inappropriate. Using a PSA velocity of 0.4 ng/ml/year or greater may enhance prostate cancer early detection especially in men with a total PSA lower than 2.5 ng/ml.
Urologists at Georgetown, Northwestern, Washington University, and Duke have been advocating lowering the PSA velocity which should trigger the recommendation for a biopsy. I admit that I often perform a prostate biopsy on young healthy men with a PSA of 2.5 or a lower PSA velocity of 0.4. I am performing more biopsies and finding more cancers. You certainly can make the argument that waiting for a higher PSA may not diminish the cure rate and may find cancers that are more clinically significant.
I understand that some urologists do not believe in PSA as a screen for prostate cancer at all.
I am sure that one day we will have better screening tests that are more specific and probably more sensitive.
I wonder what people think of a prostate biopsy done as a baseline study. I would compare this to a screening colonoscopy which likely has a similar rate of complication (low), can be done under local anesthesia, and will find some prostate cancers that we are not finding now.
The major obvious downside would be putting most men through a biopsy which will not reveal cancer and finding cancer that may not need to be treated for months to years.
IngentaConnect The incidence of high-grade prostatic intraepithelial neoplasia a...:
CONCLUSION:
Identifying multifocal HGPIN on first saturation biopsy is associated with an overall cancer detection rate of 80% on repeat 10-12-core biopsy. Although there were few patients, the detection of multifocal HGPIN warrants additional searches for concurrent invasive carcinoma by repeated biopsy.
The diagnosis of high grade PIN is an area that once required a repeat prostate biopsy. Recently, with an increase the number of biopsies that are done initially, there has been feelings that patients who only have high grade PIN do not need another biopsy. This article suggests that these patients should have a repeat biopsy. I believe follow-up with a PSA is a recent option in older patients with high grade PIN.
UroToday - "False-Positive" Prostate Cancer Screenings Assessed
"Men can discuss the pros and cons of getting a PSA test with their
doctors. However, once a man decides to go ahead and get a PSA test, if
its results are abnormal, he typically should have ongoing follow-up and
surveillance for prostate cancer," Katz said.
Katz said that a strength of the UI study was that it did not rely on
volunteers. "Volunteers who sign up for a prostate cancer screening
study represent a different type of population than that comprised by
the individuals in our study, who were patients seen in the usual course
of care," he said.
However, Katz noted, a limitation of the study is that the researchers
were not able to obtain baseline data on how the men originally felt
about their health prior to screening. In addition, the study focused
primarily on Caucasian men.
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This is an interesting study, but I think it needs further investigation prior to making any definitive conclusions.
I think that a man who has a low PSA may have a better sexual outlook than a man who is offered screening and refuses. You would have to also follow the consequence of bringing up PSA screening with patients and look if just the discussion of prostate cancer is a detriment since it is usually picked up prior to there being any symptoms.
UroToday - European Urology - Prostate Cancer Screening Decreases the
Absolute Risk of Being Diagnosed with Advanced Prostate Cancer—Results from a
Prospective, Population-Based Randomized Controlled Trial
| Conclusions: Even
though the reduction in metastasis at the time of diagnosis seen in the
present study is a prerequisite for a successful prostate cancer-screening
program, the ultimate outcome in the screening studies is a difference in
prostate cancer mortality. As the very large combined screening efforts (ERSPC
and PLCO trials) are to be analyzed regarding survival in 2008, we
strongly suggest that decisions regarding large-scale screening efforts
are deferred pending these reports. |
This was already a well accepted position. I agree that the important thing will be to see if it can be proven to lower mortality.
Age Adjustment of
PSA Measures Might Improve Prostate Cancer Screening: Source (Medscape)
The team concludes that standard PSA and PSA
velocity cutoff points could be decreased to 2.0 ng/ml and 0.40 ng/ml per
year in order to improve cancer detection in these younger men.
The author of an editorial comment, Dr. H. Ballentine Carter of Johns
Hopkins School of Medicine, Baltimore told Reuters Health that in studies
he and his colleagues conducted 'men with PSA levels below 4.0 ng/mL who
have a PSA velocity exceeding 0.3 to 0.4 ng/mL per year' have about a
fivefold greater risk 'of being diagnosed with life-threatening prostate
cancer over the next 2 decades' when compared to those with a lower PSA
velocity. 'Thus, these men require more careful monitoring.'
However, in another editorial, Dr. Donna Pauler Ankerst of the University
of Munich, Germany and Dr. Ian M. Thomson of the University of Texas
Health Science Center at San Antonio, take Dr. Moul and colleagues to task
on a number of issues including verification bias. They also find fault
with a somewhat comparable study by other investigators that had
contrasting results.
'The biostatistics of this discussion seem far removed from the clinical
practice of urology,' the editorialists conclude. 'However, they are not,
because conclusions reached from studies of PSA have an enormous impact on
millions of men annually.' |
The controversy will go on, but I do admit that for healthy young men, I use 2.5 as my cutoff before I discuss a biopsy.
UroToday - Effect of 1 mg/day Finasteride on Concentrations of Serum
Prostate-Specific Antigen in Men with Androgenic Alopecia: A Randomized
Controlled Trial
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At completion of the study, 1mg/day finasteride resulted in a median serum
PSA decrease of 40% (95% CI 34 to 46) in men ages 40-49 years (mean PSA
0.8 ng/ml) and 50% in men ages 50 to 60 years (mean PSA 1.1 ng/ml). These
were statistically significantly different from decreases in PSA in men
taking placebo for both age groups [0% (mean PSA 1.0 ng/ml) and +13% (mean
PSA 1.2 ng/ml) respectively]. |
It was felt that even low doses of finasteride may lower PSA. According to this well done study it appears that the PSA is lowered by 40-50%.
Patients should make sure they tell their physicians if they are taking medicines to prevent hair loss.
There are other studies that show that this medicine in higher doses may lower the risk of developing prostate cancer, but a higher percentage of cancers were high grade. It would be a good idea to discuss your use of this medicine with your PMD or urologist.
There is a new company that is using the PCA3 gene that has obtained approval in Europe. In the US there are 2 companies that have the test, Ameripath and Bostwick laboratories, currently the PCA3-plus test.
We have had a lengthy discussion about this test on another blog entry on my site.
The test works by looking at the ratio of this PCA3 RNA to the total PSA RNA that is expected to be constant.
The idea is that a higher ratio means that you are more likely to have cancer. I have found several cancers using this test as my basis for performing a prostate biopsy.
One interesting development is the change in Bostwick's interpretation of the result. Ameripath always used 35 as the "normal" cutoff, and Bostwick started at 10. Bostwick has increased the normal value of the test to 35 now.
UroToday - ‘Muscle’ Protein Drives Prostate Cancer: "Researchers at the Johns Hopkins Kimmel Cancer Center have for the first time implicated the muscle protein myosin VI in the development of prostate cancer and its spread.
In a series of lab studies with human prostate cancer cells, the Hopkins scientists were surprised to find overproduction of myosin VI in both prostate tumor cells and precancerous lesions. When the scientists genetically altered the cells to silence myosin VI, they discovered the cells were less able to invade in a test tube. Researchers at the Johns Hopkins Kimmel Cancer Center have for the first time implicated the muscle protein myosin VI in the development of prostate cancer and its spread.
In a series of lab studies with human prostate cancer cells, the Hopkins scientists were surprised to find overproduction of myosin VI in both prostate tumor cells and precancerous lesions. When the scientists genetically altered the cells to silence myosin VI, they discovered the cells were less able to invade in a test tube."
Discoveries like this will one day replace PSA as our screening tests for prostate cancer.
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Prostate Cancer: Major Genetic Risk Factor Found: "Harvard Medical School researchers have identified a DNA segment on chromosome 8 that is a major risk factor for prostate cancer, especially in African American men. The paper appears in the August electronic edition of the Proceedings of the National Academy of Sciences (also see PNAS's
news tip below).
'This paper identifies a genetic risk factor that about
doubles the likelihood of prostate cancer in younger African American
men,' says principal investigator David Reich, PhD, Harvard Medical School
assistant professor of genetics with the HMS Department of Genetics and
the Broad Institute. 'This finding may explain why younger African
Americans have an increased risk for prostate cancer than do other
populations--and may also explain why this increased risk in African
Americans attenuates with older age.'"
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Source:
Medical
News Today
Continue reading "Genetics and inherited prostate cancer risk" »
Hopkins Researchers Find Better Blood Test for Prostate Cancer
Source: consumeraffairs.com
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New studies of a blood protein recently identified at
Johns Hopkins, early prostate cancer antigen-2 (EPCA-2), may change the
way men are screened for prostate cancer -- a disease that kills tens of
thousands of men every year.
Results showed that the EPCA-2 test was negative in 97
percent of the patients who did not have prostate cancer. Men with no
evidence of disease (regardless of their PSA levels), as well as the
control group of patients with other cancer types and benign conditions,
all had EPCA-2 levels below the cutoff.
In contrast, in a multi-institutional study p | |
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