A Publication of the James Buchanan Brady
Urological Institute Johns Hopkins Medical Institutions
Volume VI, Winter 2003
What Should You Do?
which men is surgery necessary, and which men can safely forego
Twenty years ago, most men diagnosed with prostate
cancer had advanced disease. Only about 25 percent of men were
diagnosed with cancer that appeared to be confined within the
prostate—and of those, only about half actually had curable disease.
Today, the story is nearly reversed: 75 percent of men diagnosed
with prostate cancer have clinically localized disease, and at
least 80 percent of them are curable.
PSA testing has been a godsend for men with prostate
cancer. It’s been hugely successful at spotting cancer in its
earliest, most curable stages. However, as with every other screening
test (with breast cancer, for example), as cancers are detected
earlier than ever, some are detected at such an early stage, and
are so small and slow-growing, that they don’t need to be treated.
Today, some men are found to have minuscule amounts
of cancer—smaller than 0.2 cubic centimeters, about the size of
a pinpoint, captured by sheer chance during a biopsy. For some
men, these are cancers that will never cause harm, and ideally,
should never have been diagnosed. Which leads to a treatment dilemma:
If this kind of small-volume cancer is diagnosed, what should
happen? To treat, or not to treat? What should a man do?
some men, these are cancers that will never cause harm, and
ideally, should never have been diagnosed.
This is the kind of problem urologists —who,
for so many years, could only diagnose prostate cancer when the
chance of cure had become uncertain—have always dreamed of having.
It’s also, increasingly, a clinical challenge. Exactly which kind
of cancer is it—the “good” kind, that seems content to remain
in the prostate and never causes harm, or the kind that will be
less indolent over time, and needs to be nipped in the bud? “To
what extent are we diagnosing and treating a disease that would
progress very slowly, and never threaten a man’s life?” asks urologist
H. Ballentine Carter, M.D., who is also a professor of oncology
at the Kimmel Cancer Center. “For which men is surgery necessary,
and which men can safely forego treatment?”
Fortunately, there are guidelines, developed by
Jonathan Epstein, M.D., Rose-Lee and Keith Reinhard Professor
of Urologic Pathology (see Epstein’s criteria).
There’s also the matter of a man’s age, Carter notes. “In a very
young man (in his thirties, forties or fifties), a very small
tumor might be significant. But in an older man, a very small
tumor probably isn’t significant, because of the time it takes
for that tumor to grow and become dangerous.” Even without treatment,
cancer that is fairly well-differentiated (to the pathologist,
this kind of cancer cell looks fairly normal, or not terribly
abnormal) Gleason 6 or below, and localized to the prostate, takes
more than 10 years to spread and cause harm.
Thus, “for men who are in their sixties or older,
we feel that if we can identify who has low-volume disease, then
expectant management may well be a rational approach.” For the
last few years, Carter and Epstein have been studying this strategy
in men with stage T1c disease. Their results, published in the
Journal of Urology with Patrick C. Walsh, M.D., and Patricia Landis,
were so encouraging that a larger trial, involving several institutions,
is in the works.
In this study, 81 men who fulfilled the criteria
for low-volume disease were followed. At an average of two years’
followup, 25 (31 percent) had progression of disease. In 22 of
these men, every followup biopsy showed cancer. In the men who
had progression of cancer, PSA density was significantly higher,
and free PSA was lower. Thirteen of these men underwent radical
prostatectomy, and 12 (92 percent) had curable disease.
Significant or Not? Epstein’s
Criteria for Stage T1c Treatment
If you’re a healthy man under
the age of 60, you should strongly consider curative treatment
for low-volume stage T1c cancer. But if, for reasons of age
or health, your projected life expectancy is not more than
15 years and there is evidence of small-volume stage T1c prostate
cancer, your cancer may never become significant, and may
never need to be treated. Pathologist Jonathan Epstein, M.D.,
has developed criteria that can help predict which men should
consider the option of expectant management.
T1c cancer is significant if…
- It’s found in three biopsy
needle cores, OR
- It’s present in greater than half of any one biopsy needle
- If the Gleason score is 7 or higher, OR
- If the PSA density is greater than 0.1-0.15, OR
- If the free PSA is less than 15 percent.
T1c cancer is probably NOT significant if…
- It’s found in only one or two needle cores, AND
- It makes up less than half of each needle core, AND
- The Gleason score is 6 or lower, AND
- The PSA density is less than 0.1-0.15, AND
- The free PSA is greater than 15 percent.
Most importantly, Epstein says, the Hopkins research
shows that “there is no evidence that prostate cancer grade worsens
significantly during a one and a half-to two-year period after
biopsy. If a tumor grade changes relatively soon after biopsy,
it’s most likely not because the tumor evolved, but because the
higher grade component of the cancer was missed.” Based on this
study, what should men do? “If a man is interested in this approach,
the first thing we do is have his pathology slides re-read here
at Hopkins (by Epstein), and if we think he is still a candidate,
we repeat the biopsy, taking at least 12 samples,” says Carter.
Then, if the repeat biopsy confirms that the cancer
is low-volume, the man returns to Hopkins every six months for
a PSA test and rectal exam, and undergoes a follow- up biopsy
once a year. Epstein has found that if the repeat biopsy is negative,
it almost certainly means that the cancer truly tiny, and the
initial biopsy just happened to hit some of its few cells. “An
important message of this paper is that as we accumulate biopsy
history on these men, and the biopsies continue to be negative,
it’s more evidence that what was found initially was small-volume
disease,” he says. The study has now expanded to include more
than 200 men. “Another thing we’ve learned,” notes Carter, “is
that there’s a lot of variability in men’s comfort levels. Some
men end up getting treated, even though there is no evidence of
serious cancer, because they learn something about themselves—they
don’t like the uncertainty. They worry, and that decreases their
quality of life. Then there are other men who appear to be incredibly
comfortable with this approach, and for them, it’s the best decision.”
Carter and Epstein point out that these results
are short-term, because the entity of T1c cancer has been recognized
for less than a decade. “Because the follow-up is short-term,
we can’t say that this is an absolutely safe approach,” says Carter.
“We think it is, but we’re still trying to learn. What we do know
is that the potential here is very exciting, because we may save
a lot of men from surgery that they don’t need.”