Download MOD_GUAZZARONI_D`URSO_SIMONETTIi

Manlio Guazzaroni, Sara D’Urso, Giovanni Simonetti
PROSTATE CANCER DIAGNOSIS
ULTRASOUND
Prostate cancer is the most commonly diagnosed solid tumor in men older than 50 years and is not
amenable to primary prevention.
It represents 23% of all new cancer cases and 12% of all cancer death.
Because the median age at diagnosis is 72 years, many patients - especially those with localized
tumors - may die of other illnesses without ever having suffered significant disability from their
cancer and postmortem studies confirm the aphorism that “more men die with prostate cancer than
of it” [1].
Screening achieves great diagnostic anticipation because it has increased the number of men
diagnosed with organ confined, potentially curable disease.
The principal screening tests for detection of asymptomatic prostate cancer are the digital rectal
examination (DRE) and measurement of the serum tumor marker prostate specific antigen (PSA)
[2]. Transrectal ultrasound (TRUS) is no longer considered a first-line screening test for prostate
cancer, but plays a role in the investigation of patients with abnormal DRE or PSA.
Tumours are mostly slow growing and it is not possible to distinguish with certainty between nonfatal lesions, which probably require no treatment, and fast growing tumours that metastasise
quickly. Although high grade tumours tend to behave aggressively, there are uncertainties about the
effectiveness of early treatment.
Each of the main treatments - radical prostatectomy, radiation therapy, and monitoring - has risks.
Radical treatments offer the potential for cure, but can have serious side effects, including pain,
hospitalisation, varying levels of incontinence and impotence, and, rarely, death. With monitoring,
men have to live with the knowledge that they have untreated cancer and the risk of progression that
in a few cases may be fatal.
PSA testing offers the prospect of early detection and treatment of the disease, but has not been
shown conclusively to lead to observable improvements in mortality from prostate cancer [1]. Two
large-scale randomized clinical trials currently are underway in North America and Europe to
examine this question but they have not been completed.
PSA testing: A PSA of greater than 4.0 ng/ml, the accepted threshold for further diagnostic
evaluation, has been reported to be over 80% sensitive in detecting prostate cancer. PSA appears to
have increased sensitivity for aggressive cancers and those with histopathologic features associated
with progression: large volume, poorly differentiated cells, extracapsular penetration. PSA,
produced by both non- and malignant epithelial cells, has limited specificity because elevations also
occur in men with benign disease (e.g., prostatic hypertrophy, prostatitis). The reported positive
predictive value of PSA in asymptomatic men is 28%-35%. The specificity and/or positive
predictive value of PSA may be enhanced by measuring PSA density (PSA value divided by gland
volume measured by transrectal ultrasound), PSA velocity (annual rate of change of PSA), the free
PSA ratio, age-adjusted PSA reference ranges, or increasing the cut-off value [3]. Combining PSA
with DRE increases the positive predictive value to 49%.
DRE findings: Although relatively cheap and easy to perform, the DRE has significant limitations
for the detection of prostate cancer. The DRE is a subjective, operator-dependent test with high
variability. In addition, an abnormal DRE may be caused not only by prostate cancer but also by
benign processes, such as prostatic enlargement or asimmetry, calcifications, cystic lesions, or
chronic inflammatory conditions.
Since the DRE mainly evaluates the posterior and lateral portion of the prostate, tumors occurring
anterior to the midline, which comprise about 40-50% of all cases of prostate cancer, are usually not
detected.
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DRE has a reported sensitivity of 55%-68% in asymptomatic men, but values as low as 18%-22%
have been reported. The reported positive predictive value of DRE is 6%-33% [1, 4].
Imaging tests: The primary goal of imaging is lesion detection and characterization. Additional
roles of imaging include tumor staging and surveillance.
CT and MR imaging with a body coil have been found to have little value in detecting prostate
abnormalities and are not recommended for the initial evaluation of patients with a prostate
problem.
TRUS: TRUS is routinely used as a diagnostic tool for the detection of localised prostate cancer.
A majority of prostate cancers are presently diagnosed by using transrectal US coupled with guided
biopsy [5].
TRUS is currently used in a number of ways: to estimate the size of the prostate, diagnose prostate
cancer, guide needle biopsies, stage the cancers detected and to monitor disease prior and after
treatment [1, 6]. The evidence for the ability of TRUS in each of these roles varies. In particular, it
is more accurate than DRE in the estimation of prostate size [7] but its sensitivity and specificity in
the detection of prostate cancer are poor in comparison with other measures such as PSA assay [1].
TRUS can document areas of abnormalities in the prostate gland that may be suspect for cancer,
such as a focal hypoechoic lesions (Fig. 1). The sonographic appearance of early prostate cancer is
a hypoechoic lesion in the peripheral zone, contrasted against the relatively hyperechoic texture of
the outer gland. This sonographic appearance is, however, non specific because not all cancers are
hypoechoic and not all hypoechoic lesions are malignant. Sonographic pathologic correlation
studies have shown that approximately 70%-75% of prostate tumors are hypoechoic, 25-30% of
prostate tumors are isoechoic and blend with the surrounding tissues and less than 1% are
hyperechoic.
The positive predictive value that a hypoechoic lesion is cancer increases with the size of the lesion,
the presence of a palpable nodule, and an elevated value of PSA.
Overall, the incidence of malignancy in a sonographically suspect lesion is approximately 20-25%.
Prostate cancer may be multifocal and thus multiple hypoechoic areas may be present in an
individual patient. There is a wide differential diagnosis for hypoechoic areas in the peripheral zone
of the prostate: prostatic atrophy, inflammation, focal areas of acute prostatitis, granulomatous
prostatitis, tuberculous prostatitis or prostatic intraepithelial neoplasia (PIN); primary lymphoma of
the prostate occurs rarely but may be found also as a hypoechoic area. Biopsy is needed to estabilish
the diagnosis of a focal hypoechoic area in the peripheral zone [1, 6, 8].
Isoechoic lesions are usually not detected with TRUS unless secondary signs of cancer, such as a
tumor bulge or distortion of periprostatic fat, are present.
A small number of cancer are echogenic or have a heterogeneous echotexture with small echogenic
foci within hypoechoic lesions.
Hyperechogenicity can be due to the degree of stromal fibrosis (that increases in poorly
differentiated cancer), infiltration into surrounding tissues, and radiotheraphy or hormonal treatment
response [9].
The range of reported sensitivities, specificities and PPVs vary widely between studies. The
sensitivity of using TRUS alone ranges from 35% to 96%; specificity from 32% to 94%; and PPV
from 19% to 65%. The PPV increases with the stage of the tumour detected and also increases
when TRUS is combined with other diagnostic tests, such as DRE and PSA assay. The highest
predictive values are achieved when TRUS, DRE and PSA assay are all performed and are all
positive [1].
Color Doppler US has been shown to be an important adjunct to conventional gray-scale transrectal
US, improving the accuracy of cancer detection, especially for isoechoic cancers (Fig. 2). Small
tumors (<2mm) have been reported to be avascular and tumors of at least 1 cm 3 show vascularity
(Fig. 3).
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Results of color Doppler flow studies are conflicting, with problematic overlap between increased
flow detected with cancer, acute or chronic prostatitis, and benign lesions (Fig. 4). Also not every
cancer may demonstrate sufficient flow to be detected with color Doppler flow imaging.
Color Doppler US will not and should not replace gray-scale US, but the findings of color Doppler
flow studies have been used to prompt TRUS guided biopsies that may otherwise not have been
performed. Color Doppler flow studies therefore enable tailoring the biopsy to target isoechoic, yet
hypervascular, areas of prostate gland.
It has also been suggested that color Doppler US is important for recognition of tumors with higher
Gleason grades.
There is an association of increased vascularity at color Doppler US with higher Gleason scores.
Transrectal color Doppler US improved the detection of higher-grade prostate cancer and also
depicted hypervascularity, which appears to be a marker for more aggressive tumors.
Power Doppler US may be helpful in this respect due to its increased sensitivity to flow, which
allows the evaluation of even smaller vessels than is currently possible [8, 10].
Preliminary studies have shown that the recently developed intravenous US contrast agents may
have a possible role in the delineation of subtle prostate cancers with color Doppler flow imaging.
Further research in this area needs to be performed [8, 11, 12].
In addition TRUS has become the routine guidance modality for a biopsy of the prostate (Fig 5).
Until today there has been no other means to diagnose or exclude prostate cancer except by biopsy.
The combination of DRE, PSA and TRUS markedly improves sensitivity and is able to reduce
unnecessary prostate biopsy procedure in 50% of cases.
Abnormal PSA levels or abnormal DRE usually prompt the performance of a TRUS-guided biopsy,
which is simple, safe, and accurately performed with an automatically triggered core-biopsy device.
Focal lesions are targeted, followed by systematic (usually sextant) biopsies of the remainder gland.
There are different protocols describing modifications in the technique of prostate biopsy in order to
cover all regions of the prostate with more than six systematic biopsies [13].
The evidence suggests that random biopsy identifies a significant number of additional tumours that
would have been missed by guided biopsy alone. The proportion of additional tumours detected
varies between studies and , in some cases, the tumours detected are extremely small.
At first, the sextant biopsy technique described by Hodge et al. [14] was considered to be the
standard or routine method. According to this technique, three biopsy cores are taken from each
side (right and left) of the prostate, 1 cm apart along the parasagital area. However, concerns have
arisen that the sextant biopsy method under-samples the prostate, and consequently may fail to
detect a significant proportion of clinically important tumors [15]. The optimum number of biopsy
cores is unknown. Currently, many clinics perform extended prostate biopsy protocols consisting of
10 plus x cores.
The 10 systematic TRUS-guided prostate biopsy showed clinically significant improvement in
terms of prostate cancer detection rate in comparison with sextant systematic biopsy, without
increase in the morbidity.
In addition, staging biopsies of the seminal vescicles, ejaculatory ducts, and the apex can be
performed.
Patients with an initially negative biopsy but with increasing PSA levels usually undergo repeat
biopsies. Some studies have shown an incremental detection rate of cancers on second and even
third biopsies [1, 8, 16].
Conclusion: In summary, a combination of tests is probably the best way to detect prostate cancer:
DRE and PSA measurements, followed by TRUS with or without a biopsy in those patients with
abnormal test results. Biopsy does not have a role in first line screening but remains important for
histological confirmation of the presence of organ-confined prostate cancer.
Targeted biopsy of US-visible lesions alone results in missing almost half of all cancers. Systematic
biopsy coupled with targeting according to transrectal US and color Doppler US findings is the
single best method at present for detection of prostate tumor.
3
Fig. 1: Suspicious hypoechoic
nodule in the peripheral zone
Fig. 2: Occult carcinoma:
Peripheral hypervascular area on
color Doppler. No focal
abnormalities are noted on gray
scale image
Fig. 3 Color Doppler: malignant hypervascular nodule
Fig. 4 Benign hypervascular nodule:
focal areas of acute prostatitis
Fig. 5 Prostate biopsy
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