Diagnostic ultrasound ( PDFDrive )

CHAPTER 10 The Prostate and Transrectal Ultrasound 395
To complicate matters further, no consensus has emerged for
the optimal treatment of clinically localized disease, which has
become the most common presentation in the United States
(91% of cases) since the advent of PSA screening in 1991. 68
Epidemiology
Prostate adenocarcinoma is the most frequently diagnosed
cancer in men, two to three times more than lung and colorectal
cancer. It is a disease seen primarily in men older than 50. It is
the fourth most common male malignancy worldwide. he rates
are highest in Scandinavia and North America, especially in
African Americans (272 per 100,000), and lowest in China (1.9
per 100,000), but rates are increasing in those countries. 19,69
Genetics and environment, including a fatty diet, play roles in
prostate cancer incidence. he risk doubles with a single afected
relative and is even higher with multiple afected relatives. he
incidence and stage at diagnosis have been decreasing since the
early 1990s, partly because of the introduction of PSA screening.
70,71 More than 95% of primary malignant tumors of the
prostate are adenocarcinomas. Rarely other primary neoplasms
are found, including prostate transitional cell carcinoma, sarcomas,
lymphomas, and neuroendocrine tumors. 72 he prostate can be
secondarily afected by tumors of regional structures, including
the bladder and rectum.
It has been reported that 24-year median follow-up of clinically
localized prostate cancer and showed that cause-speciic mortality
increases with Gleason score and age at diagnosis. With Gleason
score of 6 or lower, comorbidities are a more likely cause of
mortality, but with higher scores cancer-related death is likely,
especially in the 50- to 64-year age group, in which cause-speciic
mortality approaches 80% to 90% at 15 to 20 years. 64 Of interest,
most pathologists currently do not report Gleason score below
6 as cancer, and there is discussion that perhaps even Gleason
3 + 3 = 6 does not represent aggressive life-threatening cancer
that needs immediate radical therapy. 9,10,59,73
Prostate Cancer: Key Facts
Most common cancer diagnosed in men
The second leading cause of cancer deaths in men (after
lung cancer)
The fourth most common male malignancy worldwide
Many and varied treatments that are personalized to
patient situation
Treatments are associated with quality-of-life issues
Many men have low-grade tumors that may not need
treatment or affect longevity
Prostate-Speciic Antigen and Variants
PSA is the most commonly used tumor marker to detect prostate
cancer and follow patients ater therapy. 74,75 PSA is a normally
occurring enzyme in the kallikrein family driven by androgen
and secreted by the epithelial cells of prostate ducts and functions
to liquefy the ejaculate. he prostate epithelium is the main source
of PSA and only trace amounts are found in other tissues in
men and women. Intact tissues allow only small amounts to leak
into the blood where it is partly unbound (free) and partly bound
to proteins such as alpha-1-antichymotrypsin. Serum PSA levels
are a nonspeciic indication of prostate abnormality or irritation
that allows excess leakage of this normal enzyme into the blood.
Free PSA is composed of three isoforms: pro-PSA, BPH-associated
PSA, and intact free PSA. Elevated total PSA levels can occur
with cancer but also are variably seen with benign conditions
including BPH and inlammation and ater ejaculation, prostate
manipulation, biopsy, and cystoscopy. In general, DRE and TRUS
without biopsy do not elevate PSA signiicantly, but it is prudent
to draw the blood before disturbing the prostate. PSA levels can
be artiicially reduced by a factor of 2 with antiandrogenic
medications such as inasteride (Proscar) and dutasteride
(Avodart). Unpredictably reduced levels are found with herbal
medications such as palmetto and PC SPEC. With cancer the
proportion of bound PSA increases resulting and can decrease
the ratio of free to total PSA (percent free PSA, %fPSA). 75
Although PSA is accepted as a prostate cancer marker, there
are issues with its use. It is organ speciic but not cancer speciic,
and levels overlap in benign conditions and cancer. Also, not all
cancer elevates PSA and cancer can be found in 6.6% of men
with low PSA (<0.5 ng/mL). he discriminatory level is uncertain.
Initially 4 ng/mL was considered the threshold for consideration
of biopsy, but this has decreased to as low as 2.6 ng/mL. It is
generally agreed that unexplained PSA over 10 ng/mL is an
indication for biopsy and has a positive predictive value (PPV)
of about 80%. Biopsy of men in the problematic 4- to 10-ng/mL
range inds cancer in about 40%. his highlights the problem
with PSA testing: PSA of 4 ng/mL has a sensitivity of about 79%
but a low speciicity of 59%. he low speciicity means that many
men without signiicant cancer would be subjected to the risks
of biopsy and overdiagnosis and overtreatment. hese issues
have led to controversy in the use of PSA for screening. 58,76
However, screening aside, PSA remains the optimal tool to follow
men for recurrence ater curative therapy.
Several approaches have been considered to try to improve
both sensitivity and especially speciicity so that in the 2.6- to
10-ng/mL gray area initial and repeat biopsy are performed only
in men at risk for signiicant aggressive cancer and can be avoided
in men at low risk or at risk for just indolent cancer. Most urologists
feel that their clinical acumen, which takes into consideration
PSA, family history, patient clinical status and history, prior
biopsy results, and discussion with the patient, remains the
mainstay of determining need for both initial and repeat biopsy.
Although PSA and its variants remain the dominant test, there
is a rapidly increasing catalog of additional blood, urine, and
tissue tests that may be taken into consideration and may provide
supporting information regarding diagnosis, prognosis, and need
for enhanced therapy. 74,75,77
With cancer the proportion of bound PSA increases, resulting
in a decrease in the ratio of free to total PSA (percent free PSA,
%fPSA). 75 Using a ratio of 25%, Catalona and colleagues detected
95% of cancers and avoided 20% of biopsies. 78 here is no general
agreement on cut points, which range from about 15% to 25%
(or ratio 0.15-0.25). he instability of fPSA (free PSA) ater
phlebotomy unfortunately has limited its use for general
screening. 75
PSA density (PSAd) is the ratio of PSA to prostate volume.
his test assumes prostate cancer makes more PSA than benign