Organ-confined disease more common in screen-detected prostate cancer

Source: MedWire News

Prostate cancers detected by screening have a higher rate of organ-confined disease and a lower rate of extracapsular extension and positive surgical margins than non-screen-detected cancers, say researchers.
The widespread use of prostate cancer screening had led to stage migration, with more cancers detected at a lower stage, which has led to a reduction in the age-adjusted mortality rate. However, it is not clear whether some men are being treated unnecessarily, says the team.


Another study that shows men that are screened for prostate cancer with PSA bloodwork have cancers that are more likely to be contained to the prostate.

A Step Backward: The ACPM Recommendations on Prostate Cancer Screening

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.

Screening for prostate cancer

The controversy over screening for prostate cancer will continue.

clipped from www.medscape.com

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.

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European study shows that prostate cancer screening leads to less advanced prostate cancer

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.

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Prostate Cancer: Is PSA Screening effective

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:

beige_quote.bmpDr. 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.

Lowering PSA and PSA velocity: Are we doing the best thing

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

beige_quote.bmpTraditional 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:

beige_quote.bmpUsing 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.
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