Men's Health Center - Issues Including Male Sexual Health

December 22, 2004

Men's Health

PSA - It's the Rate of Increase That Counts

Summarized by Robert W. Griffith, MD
September 3, 2004

Introduction
Doubt has been thrown recently on the value of prostate
specific antigen (PSA) tests in diagnosing prostate cancer.
Some men have raised values but have no cancer, or only an
extremely slow-growing one, while others have values below
4 ng/mL and still have prostate cancer. What's to be done?
'Watchful waiting' has been advocated for some men who have
localized prostate cancer when it's agreed that the likely
benefits of treatment are outweighed by the adverse effects
of that treatment. The decision may be helped by a new
analysis of repeated PSA determinations.

The report published in the New England Journal of Medicine
is summarized here.

What was done?
Most men with prostate cancer have a non-palpable tumor,
and are diagnosed as possible cancer by a raised PSA level.
This study was planned to see whether the rate of rise in
the PSA during the year before diagnosis, the PSA level at
diagnosis, the Gleason score (a way of expressing the
severity of the cancer on microscopy) and the tumor stage
could identify those men at risk of death from prostate
cancer.

This sort of information was available for 1804 men treated
by radical prostatectomy at the Barnes-Jewish Hospital in St
Louis from January 1989 to June 2004. After exclusion of
those who were found to have lymph node metastases, those
who received radiotherapy, and those who had only one PSA
level determination before surgery, there were 1095 men
left for evaluation in the study. Their average age was 65,
and their average PSA was 4.3 ng/mL.

Clinical tumor staging was done pre-operatively, and Gleason
scores were assigned on prostate biopsy and prostatectomy
specimens.  Follow-up lasted, on average, for 5 years after
prostatectomy.

During this time PSA levels were measured every 6 months and
digital rectal exams every year. The PSA values were used to
calculate the rate of PSA increase during the year before
diagnosis. The rates were compared with the lymph-node
status, the clinical stage, the Gleason scores, the time
to recurrence, death from prostate cancer, and death from
any cause.

What was found
There were no changes in the time to recurrence, death from
prostate cancer, or death from any cause when the rate of
PSA increase was below 2.0 ng/mL per year. However, at rates
above 2.0 ng/mL there was a significant increase in all
three of these 'endpoints'.  In addition, a PSA increase
rate of more than 2.0 ng/mL per year was linked to lymph
node metastases, a higher clinical stage and a higher
Gleason score, when compared with lower rates.

What does this mean?
Men with a PSA that increases at more than 2.0 ng/mL a
year who are otherwise healthy should consider radical
prostatectomy along with some form of anti-hormonal
therapy. Watchful waiting is not a particularly good
option for these men.

In men who have had a prostatectomy, different guidelines
apply; if there is a doubling of the PSA within a given
period - 3 to 10 months, according to different authorities
- the prognosis is significantly worse.1

There have been recent reports suggesting that a PSA below
4.0 ng/mL is no longer a 'safe' level, carrying no risk of
prostate cancer. The response to these new findings should
be: have an annual check-up by your physician from 55
onwards, making sure it includes a digital rectal exam and
a PSA test. If the level is above 4.0 ng/mL or it has
increased 2.0 ng/mL over the previous year's value, have
further investigations done by a qualified urologist.

Source
Preoperative PSA velocity and the risk of death from
prostate cancer after radical prostatectomy.
AV. D'Amico, M-H. Chen, KA. Roehl, WJ. Catalona,
N Engl J Med, 2004, vol. 351, pp. 125--135

Footnotes
1. Progress toward identifying aggressive prostate cancer.
M. Eisenberger, A. Partin, Editorial. N Engl J Med, 2004,
vol. 351, pp. 180--181