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"Prostatic
Intraepithelial Neoplasia (PIN) - When stuck with PIN what should be
done?" (March 2003)
Prostatic intraepithelial neoplasia
(PIN) presents a vexing problem for risk prediction and evidence based
management. It also raises challenging issues relating to the genesis of
prostate cancer. It has been much studied, but satisfactory answers to the
questions it poses await a more complete understanding of its basic
biology.
High grade PIN (HGPIN), the lesion of interest in this discussion,
consists of an abnormally compact cluster of small glands in which the
organization of the epithelial cells is irregular; the cells are not
consistently uniform in size and have abnormal nuclear features; and the
basal cell layers of the glands (acini) are often disrupted. HGPIN can be
present in the prostate in a spectrum ranging from focal to extensive. The
key issue is whether this lesion is an obligate precursor of prostate
cancer - a sort of stage 1/2 -, or a worrisome marker for the likelihood
of recognizable prostate cancer occurring simultaneously or subsequently.
It's deemed quite possible that both processes result from some not yet
clearly identified "field effect" predisposing a prostate to both cancer
and PIN. Optimal management of a patient with HGPIN depends on resolving
this issue. Uncertainty in this area impacts the practical question of
when and whether to conduct follow-up prostate biopsies.
Two major areas of study have been: 1), understanding the relationship of
PIN to cancer; and 2), what is the best re-biopsy strategy. Regarding the
first issue I'll focus on work of Dr. Wael Sakr, who along with Dr. Alan
Partin, updated many years of work in the article "Histological Markers of
Risk and the Role of HGPIN" (UROLOGY 57, Supplement 4A, April 2001. pp
115-120). They report the culmination of their very careful studies of
prostate glands from autopsies of 652 men ( 20 to 80 years of age) who
died from non-prostate cancer causes. The prevalence of HGPIN (in 211
caucasian men) from the third to eight decade was 8%, 23%, 29%, 49%, 53%,
and 67% (in African American men the prevalence was higher). Extensive
involvement (third - sixth decades) was 0%, 2%, 5% and 12%. PIN was found
in 63% of men in whom prostate cancer was discovered and in 25% with no
evidence of concomitant PC. Other autopsy studies report PIN in
association with cancer in 63% to 94%, whereas in benign prostates HGPIN
was present 25% to 43%. When Sakr classified HGPIN as extensive,
intermediate, or focal, an association with cancer occurred in 76%, 51%,
and 36% respectively. Clearly the work of Sakr and many others establish
the frequent association of HGPIN with PC. However, whether this lesion is
a true presursor of PC, i.e "premalignant", is still not known.
How should this information affect management of a patient "stuck with
PIN"? For this discussion I'll refer to the work of Dr. Gary Lefkowitz,
New York University Medical Center, who has very carefully addressed this
issue over years and summarizes his work in "Follow-up Interval Prostate
Biopsy 3 Years After Diagnosis of HGPIN Is Associated With High Likelihood
Of Prostate Cancer, Independent Of Change In PSA Levels" (The JOURNAL OF
UROLOGY,Vol 168, October 2002, pp 1415-1418). The important feature of his
work is that all data is based on 12 core sampling. The study reviewed
1223 biopsies performed because of a suspicion of PC due to an abnormal
PSA or DRE. 119 (9.7%) showed HGPIN. The 72 men who had initial 12 core
biopsies showing HGPIN also had followup biopsies during the following
year. The mean baseline PSA was 6.88 ng/mL. At the repeat biopsy cancer
was found in 2.3%; 45% continued to show PIN, and 48% showed no disease.
The mean PSA for all men at repeat biopsy was 9.7 ng/ml, an insignificant
change. This study is unique in presenting 3 year followup data on the
group that showed PIN on the study entry biopsy. At 3 years 25.8% showed
PC, 35% PIN only, and 38.7% no disease. Lefkowitz noted as have others
that HGPIN is frequently multifocal in distribution. Lefkowitz recommends
re-biopsy at least by three years after an initial diagnosis of HGPIN. He
acknowledged that his data did not allow a recommendation for re-biopsy at
an earlier time. The Lefkowitz study is at varience with other studies
that show 30%, 44%, and as much as 50% PC at intervals usually up to one
year after an initial finding of HGPIN. In this discussion I have,
however, focused on Lefkowitz's work because of the thoroughness of
analysis, consistency of pathological diagnosis, and the three year
follow-up. Interestingly, one study from a Netherlands group (CANCER
August 1, 2001 pp 524-534) reported finding HGPIN in .8% of 4057 men who
had participated in a popoulation-based screening study in which biopsies
were done for abnormal PSAs and DREs. When men with HGPIN were rebiopsied
at one year cancer was found in 10% (3 of 30). Re-biopsy of men who had
initially shown no biopsy abnormalities showed PC in 11% (51 of 452). They
concluded that rate of PC development for men initially showing HGPIN was
the same as the de-novo presentation of PC.
Bottom Line: After much study a good deal has been learned, but it would
be helpful to be able to determine at the outset which HGPIN is going to
be a troublemaker (other than those with an extensive and mutlifocal
presentation). Possibly the discussion presented below will be a start in
that direction.
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