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Revisit: Strategy for Re-Biopsy After an Initial Diagnosis of Isolated
HGPIN (January 2005)
The best
strategy as to when to repeat a biopsy and the identification of
predictors that might offer guidance in selecting those men at greatest
risk for subsequent cancer remains a “work in progress”. The
discussion in the March 2003 PCa Commentary (indexed under
“Pathology”) concluded by approvingly citing the work of Lefkowitz who
reported that if only HGPIN were diagnosed on a initial 12 core
biopsy, cancer was found in 2.3% of men on repeat biopsy at one year,
and in 25.8% at three years. Several recent articles, however, have
provided some useful additional clarification.
As
background it should be pointed out that the prevalence of HGPIN is a
moving target and increases with age. This necessarily influences the
interpretation of all the studies, requiring information about the
demographics of the population under study. Two autopsy studies have
documented finding HGPIN in men in their third to eighth decades in 3.6%
and 8%, 8.8% and 23%, 14.3% and 29%, 23.8% and 50%, 31.7% and 60%, and 33%
and 70%, respectively. (Interestingly, the same studies showed that latent
prostate cancer was found in similar numbers decade for decade.) One study
further documented that in autopsy studies multifocal HGPIN was
found in decade three through six in 0%, 2%, 5%, and 12% of men. The
prevalence in African Americans is slightly higher than in Caucasians in
comparable decades. Isolated HGPIN (ie not accompanied by cancer) is found
on average in 5% to 9% of the more than 2 million prostate biopsies done
yearly in the USA, yielding more - possibly many more - than 115,000 new
cases in which the issue of management has to be addressed. Bostwick
combined the figures for prevalence and US male population between ages 40
and 90 and estimated that 16,842,640 men harbor HGPIN!
Clinicians
who try to digest the many articles addressing this subject will likely
find, as did I, that their cerebral hard drive begins to freeze up under
the burden of the plethora of varying results. A summary of 10 published
studies recording the finding of cancer on re-biopsy after an initial
diagnosis of isolated HGPIN ranged from 15% to 79%! Further complicating
management decisions is the fact that in about 20% of repeat biopsies no
HGPIN will be found, possibly due to sampling error. Or could the disease
regress? Dr. Tickman, prostate pathologist, Swedish Hospital, Seattle,
points up the practical reality that even in some “definitive”
analyses of the subject the definition of HGPIN lacks clarity, and
“there is quite a bit of interobserver variability in diagnosis”.
Two 2004
articles are particularly useful in their observations and present an
overall perspective. In “Predictors of Prostate Cancer on Extended
Biopsy in Patients with High-Grade Prostatic Intraepithelial Neoplasia: a
Multivariate Analysis Model”, Abdel-Khalek, BJU INT, 94, 528-533,
evaluated the importance of an extended biopsy in 83 men who had been
diagnosed with HGPIN on an initial six core biopsy (in one core, 30%, in
two cores 22%, and in > 2 cores, 48%). Re-biopsy was premised on
a PSA rise of > 1 ng/mL per year or an abnormal DRE. Cancer was
found in 36% on the extended 11 core biopsy, which added 23% more cancers
to what was discovered by only recording the yield of the 6 core portion
of the extended procedure. The significant predictors for cancer in this
study (each at P <0.001) were age > 65 vs. less (56% vs.
18%); PSAD > 1.5 ng/cc vs less (53% vs 16%); and > 2 cores
with HGPIN on the initial biopsy vs < 2 (56% vs 16%). The PSA
value was not significantly different between the two groups. Similar to
the findings in other studies, subsequent prostatectomy predominantly
showed organ confined disease with Gleason < 7 (28 of 30 men).
“Monofocal
and Plurifocal High-Grade Prostatic Intraepithelial Neoplasia: Factors
Predicting Cancer Detection on Extended Repeat Biopsy”, Roscigno,
UROLOGY June 2004, focuses on the importance of the predictive value of
the volume of HGPIN and reports that a repeat biopsy (10 to 12 cores) at a
median of 11.4 months following the initial HGPIN diagnosis found cancer
in 70% (19 of 27) of men who initially had plurifocal HGPIN as
compared to 10% (2 of 20) with monofocal disease. PSAD was
significant only on univariate analysis. However, the PSAD value for men
showing no cancer was 0.11 +/- 0.05 versus 0.25 +/- 0.04 ng/cc for those
in whom cancer was found. The median PSA for the entire study group was
8.25 ng/mL with no significant difference between the cancer and no-cancer
groups. They reconfirmed the results of other studies and found that
re-biopsy should not be focused only on the site of the original HGPIN,
since in their study 24% of cancers were found at a different site. Of the
14 men who underwent radical prostatectomy organ confined disease was
found in 13 (93%).
Perhaps,
future studies addressing this issue will include the newly available uPM3
test from the Bostwick Laboratory which is based on a “molecular
cytology” in cells in masssage-induced prostatic secretions. (Discussed
in Pca Commentary, October 2003, and indexed under “Diagnostics”.) In
tests of 91 men at high-risk for cancer with PSA values < 4ng/mL a
positive uPM3 test showed a 74% sensitivity and a 87% specificity for
identifying those with cancer on re-biopsy.
Bottom
Line: The management of men with HGPIN remains clinically challenging
requiring considerable clinical judgment, but emerging data is
contributing useful guidance.
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