Controversy is often driven by presumption and perception


A new article in JAMA Internal Medicine this week is likely to keep the fires burning under the PSA screening controversy for quite a while to come.

The research letter by Zavaski et al. documents the differing ways in which the urology community and the primary care community have seemed to react to the US Preventive Services Task Force’s October 2011 statement that PSA testing is not recommended as a means to “screen” men for risk of prostate cancer on a population-wide basis. Context related to this research letter can be found in an editorial commentary by Aaronson and Redberg in the same issue of JAMA Internal Medicine as well as in this article on the Reuters web site.

The authors show that, based on an analysis of data from 1,222 men in the National Ambulatory Medical Care Survey (113 of whom were seeing a urologist and 1,109 of whom were seeing a primary care physician for a preventive care visit):

  • There was a decrease in the percentages of patients undergoing PSA testing for risk of prostate cancer
    • From 38.7 percent in 2010 to 34.5 percent in 2012 among urologists (odds ratio [OR] = 0.34; P = 0.09)
    • But from 36.5 percent in 2010 to 16.5 percent in 2012 among primary care physicians (OR = 0.43; P = 0.009)

The problem, of course, is that — at least in part — what seems like a really good idea to some men (and to some doctors) looks like a much less good idea to other men (and other doctors). There is no “right” and “wrong” here yet because — quite frankly — we still don’t have the relevant data to determine who really benefits from early detection of prostate cancer. We therefore all bring our individual preconceptions and predjudices to the table when we try to discuss the subject.

We think and hope and want to believe that the men who are most likely to benefit from regular PSA testing are the ones at meaningful risk for clinically significant prostate cancer, i.e., those with unfavorable, intermediate-risk and high-risk disease that is found early enough to be cured because it presents significant risk for prostate cancer-specific metastasis and mortality. But let us be very clear that many men treated in what appears to be a timely manner for these types of prostate cancer still progress to have metastatic disease, so we aren’t necessarily curing all of those patients who are diagnosed each year (or anything like).

In this context, it is also worth noting the formal publication by Vickers et al. (in Urology) in the past few days of the current Memorial Sloan-Kettering Cancer Center protocol for use of PSA testing to detect risk for prostate cancer. We have noted this protocol before, but it is worth repeating here.

The MSKCC guidance was designed to address the the well-known limitations of earlier screening guidelines:

  • The lack of a sufficient evidence-base
  • The failure to link screening with treatment, and
  • The lack of any risk stratification (to take account of higher known risk levels in some subsets of patients like African Americans and men with a clear family history of prostate cancer).

The objective of the recommendations is to maximize the potential benefits of PSA testing (with the goal of reducing risk for prostate cancer-specific mortality) and to minimizes the potential harms of PSA testing (with the goal of reducing risk for both over-diagnosis and over-treatment).

MSKCC now recommends the following schema for those men who elect to get tested for their risk of prostate cancer:

  • Starting at age 45, such men should have a PSA without a DRE.
  • If their PSA is ≥ 3 ng/ml, they should consider a prostate biopsy (but see below).
  • If their PSA is ≥ 1 but < 3 ng/ml, they should return for PSA testing every 2 to 4 years.
  • If their PSA is < 1 ng/ml, they return for PSA testing at 6 to 10 years.
  • PSA testing should end
    • At age 60 for men with a PSA ≤ 1 ng/ mL
    • At age 70 unless a man is very healthy and has a higher than average PSA
    • At 75 for all men.

Vickers et al. note that the decision to biopsy a man with a PSA > 3 ng/m should take account of at least the following factors:

  • A repeat blood draw for confirmatory testing of the PSA level
  • DRE results, and
  • Work-up for risk of benign disease

They also note the potential of additional testing to assess risk, including such methods as

  • The free-to-total PSA ratio
  • The Prostate Health Index
  • The 4Kscore, and/or
  • The PCA3 value

The authors argue that

The best evidence suggests that more restricted indication for prostate biopsy and a more focused approach to pursue screening in men at highest risk of lethal cancer would retain most of the mortality benefits of aggressive screening schema, while importantly reducing harms from over-detection and over-treatment.

The sad truth remains a simple one. We still need much better testing methods to be able to identify the men who are at real risk for clinically significant prostate cancer so that we can decide to treat them. We need much better treatments for localized prostate cancer so that we aren’t destroying patients’ quality of life along the way. We also need much better testing methods to be able to identify and then monitor the men with low-risk and favorable, intermediate risk prostate cancer so that we can avoid treating them for as long as possible while being able to determine when treatment has probably become a necessary evil.

4 Responses

  1. Your final sentence applies to me: in treatment for almost 10 years, five or six biopsies, one positive core of Gleason 6 found several years ago. A see-saw PSA that’s been as high as 17. Intermediate level numbers for the last 2 years. Cancer has been labeled “indolent” and I’m now limited to two PSA checks a year by my urologist. “Not enough!” I want to scream. But no one’s listening. Thanks to the anti-PSA folks, this minimally invasive, minimally expensive test (the janitor can result it in his broom closet) is minimally available to those who likely need it most. Shame on all of you!

  2. “But let us be very clear that many men treated in what appears to be a timely manner for these types of prostate cancer still progress to have metastatic disease, so we aren’t necessarily curing all of those patients who are diagnosed each year (or anything like).”

    You could at least have said that probably most of the men who would have died without immediate treatment will still die from prostate cancer anyway. Use of the word “most” is not being as clear as you could easily be about the level of benefit of immediate treatment and it’s somewhat misleading.

    “with the goal of reducing risk for prostate cancer-specific mortality”

    Laudable goal that reducing risk for prostate cancer-specific mortality is, it is not the ultimate goal. Not by a long shot. The ultimate goal is overall survival. I’m surprised that a medical professional emphasizes the former but not the latter in the context of a strategy with a very high rate of over-treatment.

  3. Dear David:

    (1) If you can tell me with any degree of accuracy what percentage of men diagnosed since about 2000 with unfavorable intermediate-risk or high-risk prostate cancer have (a) gone on to have metastatic disease and/or (b) died of prostate cancer, please do so. I am not aware of any really accurate data to answer that question.

    (2) Treating prostate cancer effectively and safely can at best only reduce risk for prostate cancer-specific mortality. It may or may not actually increase or lower overall mortality rates depending on the type of treatment used and the set of patients being treated. Of course if one treats prostate cancer badly it may increase risk for prostate cancer-specific and overall mortality!

    (3) When you suggest that I should have said “that probably most of the men who would have died without immediate treatment will still die from prostate cancer anyway” I have no idea what you are talking about. Most men diagnosed with prostate cancer today do not need immediate treatment and do not die of prostate cancer!

  4. I feel that the recently approved 4KScore test by OPKO is a reliable solution to many of these men’s prostate concerns.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: