Clinical presentation and diagnosis of prostate cáncer

Authors
Philip W Kantoff, MD
Mary-Ellen Taplin, MD
Joseph A Smith, MD
Section Editors
Nicholas Vogelzang, MD
W Robert Lee, MD, MS, MEd
Jerome P Richie, MD, FACS
Deputy Editor
Michael E Ross, MD
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Mar 2015. &#124 This topic last updated: Jan 15, 2015.

INTRODUCTION — Prostate cancer is the second most common cancer in men worldwide, with an
estimated 1,100,000 cases and 307,000 deaths in 2012 [1]. In the United States there will be an
estimated 221,000 cases and 27,500 deaths in 2015 [2]. The clinical behavior of prostate cancer
ranges from a microscopic, well-differentiated tumor that may never be clinically significant to an
aggressive, high grade cancer that ultimately causes metastases, morbidity, and death.

The frequency of a diagnosis of prostate cancer has increased, due largely to the widespread use
of serum prostate specific antigen (PSA) screening. Following the introduction of PSA testing, the
incidence or prostate cancer peaked in 1992, declined between 1992 and 1995, and has risen since
then at a rate of about 1 percent per year. The reasons for this increasing incidence are not
known; both genetic and environmental factors have been implicated. The incidence is higher in
blacks than in whites in the United States (figure 1). (See "Risk factors for prostate cancer" and
"Screening for prostate cancer".)

An overview of the clinical presentation and initial diagnosis of men with prostate cancer is
presented here. The staging system used for prostate cancer, the initial staging evaluation, and
management approaches based upon risk are presented separately.

●(See "Initial staging and evaluation of men with newly diagnosed prostate cancer", section on
'Introduction'.)

●(See "Prostate cancer: Risk stratification and choice of initial treatment".)

●(See "Initial approach to low- and very low-risk clinically localized prostate cancer".)

●(See "Initial management of regionally localized intermediate, high, and very high-risk prostate
cancer".)

CLINICAL PRESENTATION — Almost 80 percent of men currently diagnosed with prostate cancer

undergo a biopsy because of a suspicious serum prostate specific antigen (PSA). However, digital
rectal examination retains an important role for early detection as 20 percent of cases have a
prostate nodule that prompts the biopsy.
PSA screening — PSA is a protein made solely by prostate cells so the antigen is highly specific for
the prostate. However, it is not prostate cancer specific and other prostate conditions such as
benign prostatic hyperplasia (BPH) or prostatitis can affect PSA levels. The lack of specificity for
prostate cancer has led to considerable controversy about the role of routine PSA testing. The
controversy is compounded by the knowledge that not all cancers detected by routine screening
require treatment. (See "Measurement of prostate specific antigen", section on 'Causes of an
elevated serum PSA' and "Screening for prostate cancer", section on 'Prostate specific antigen
(PSA)'.)

The fact that PSA screening detects more cancers is not debated. The incidence of a prostate
cancer diagnosis increased substantially after the advent of PSA testing in the late 1980’s.
Originally, reference ranges were established as cut points for a “normal” PSA. More recent
knowledge shows that PSA levels correlate with a continuum of increasing risk with no level below
which a man can be declared to not have prostate cancer nor is there a level above which the PSA
level definitively indicates prostate cancer.

Multiple methods are used to increase the accuracy of PSA testing:

●Age related reference range – PSA levels generally increase as men age so that a single value
must be benchmarked against the norm for a specific age group.

●PSA density – AS the size of the prostate increases, the amount of PSA produced by benign
prostate cells may increase correspondingly. PSA density calculates the ratio of prostate size to
PSA. Digital rectal examination is inaccurate in determining prostate volume although there is
some merit in the understanding that a large prostate size on examination may be associated with
a higher PSA. Accurate calculation of PSA density depends upon measurement of prostate volume
of ultrasound, CT, or MRI.

●Fractionated PSA – PSA can be measured in two serum components, either conjugated or free.
The percentage of free PSA relative to the total PSA can be informative as a high ratio (>30
percent) is considered favorable while a low ratio (<10 percent) is more commonly associated with
prostate cancer.

●PCa3 measurement is obtained on a urine specimen collected after a digital rectal examination
and prostatic massage. This test can provide supplementary information to the PSA level in some
clinical situations. (See "Screening for prostate cancer", section on 'PCA3'.)

●PSA velocity – Changes in PSA over time, sometimes termed PSA velocity, can be highly
informative. Although some increase with age is expected, a substantial change is worrisome. A
change of >0.35ng/ml may prompt a biopsy if the PSA value is between 2.5 and 4 ng/ml while a
greater than 0.75ng/ml change within a year may prompt investigation with a PSA over 4.0ng/ml.

Generally, PSA should be repeated before a biopsy is recommended since almost a third of
patients will have a decrease to baseline levels if PSA is repeated a month or so later. Giving
antibiotics to asymptomatic men with no evidence of a urinary tract infection or prostatitis is not
helpful.
Summary — Considerable controversy remains about PSA screening. Although more cancers are
found through PSA screening, many men undergo a biopsy which may prove to be negative or are
subjected to treatment and its side effects for a cancer that may not be life threatening. Targeting
screening to the most optimal population (those with at least 10 years of life expectancy) and a
straightforward discussion of the merits of treatment for a cancer that is detected temper some of
the concerns surrounding PSA screening.

The issues surrounding PSA screening for prostate cancer are discussed in detail separately. (See
"Screening for prostate cancer".)

Digital rectal examination — On digital rectal examination, asymmetric areas of induration or frank
nodules are suggestive of prostate cancer. In contrast, symmetric enlargement and firmness of the
prostate are more frequent in men with benign prostatic hyperplasia (BPH). (See "Clinical
manifestations and diagnostic evaluation of benign prostatic hyperplasia".)

A prostate biopsy is indicated in men with a digital rectal examination that is suspicious for cancer,
regardless of the serum PSA. All men with significant asymmetry, induration, or palpable
nodularity of the prostate gland require further diagnostic studies to rule out prostate cancer,
particularly if they are over the age of 45 or have other risk factors for the disease. (See "Risk
factors for prostate cancer".)

Digital rectal examination can detect tumors in the posterior and lateral aspects of the prostate
gland. Tumors not detected by digital rectal examination include the 25 to 35 percent that occur in
other parts of the gland, and small, T1, cancers that are not palpable (table 1) (see "Initial staging
and evaluation of men with newly diagnosed prostate cancer", section on 'Staging system').

The serum PSA level should be measured prior to biopsy in men with an abnormal digital rectal
examination for prognostic purposes. Although serum PSA concentrations may rise slightly during
the first several hours after a rectal examination [3], the rise is small enough that the blood sample
for PSA testing can be obtained at any time prior to biopsy. (See "Measurement of prostate
specific antigen", section on 'Causes of an elevated serum PSA'.)

Transrectal ultrasonography (TRUS) is often used to evaluate abnormalities detected by digital

rectal examination and to guide sites for prostate biopsy. However, prostate biopsy is
recommended regardless of the results, since TRUS misses a substantial number of tumors [4,5].
Cancers typically appear hypoechoic, but some may be hyperechoic or isoechoic, leading to false
negative studies.

Symptoms — Most men with early stage prostate cancer have no symptoms attributable to the
cancer.

Urinary frequency, urgency, nocturia, and hesitancy are seen commonly but are usually related to
a concomitant benign prostate enlargement. (See "Clinical manifestations and diagnostic
evaluation of benign prostatic hyperplasia".)

Hematuria and hematospermia are uncommon presentations of prostate cancer but their
presence in older men should prompt consideration of prostate cancer in the differential
diagnosis. These symptoms are also present in men with benign prostatic hyperplasia (BPH) and
are more likely to be caused by BPH than cancer. (See "Clinical manifestations and diagnostic
evaluation of benign prostatic hyperplasia".)

Bone pain may be the presenting symptom in men with metastatic disease but an initial diagnosis
when bone metastases are present has become unusual [6]. (See "Bone metastases in advanced
prostate cancer: Clinical manifestations and diagnosis", section on 'Clinical manifestations' and
"Initial staging and evaluation of men with newly diagnosed prostate cancer", section on
'Evaluation for distant metastases'.)

DIAGNOSIS — Men with abnormal prostate exams (nodules, induration, or asymmetry) should be

referred to a urologist for a prostate biopsy, with a the histologic diagnosis based upon tissue
obtained from the biopsy. A prostate biopsy may also be indicated based upon abnormal PSA
values. (See "Screening for prostate cancer", section on 'Referrals for biopsy'.)

A transrectal biopsy typically is performed with transrectal ultrasound (TRUS) guidance. TRUS may
image prostate cancer as a hypoechoic area but the test is used to direct prostate biopsy rather
than as a diagnostic modality. A transperineal route may also be used for biopsy. This approach
may require general anesthesia or, at least, sedation, but also is associated with a lower risk of
infection.

MRI targeted prostate biopsy is being evaluated as a method to improve the accuracy of TRUS
biopsy [7,8]. Clinical settings in which this approach may have utility include patients with a rising
PSA and several negative biopsies, and those men with prostate cancer who will be managed with
active surveillance. MRI guided biopsy may also have a role when patients are being considered for
salvage prostatectomy. (See "Prostate biopsy", section on 'MR-targeted biopsy'.)

If a biopsy is to be performed based upon the finding of an elevated serum PSA, confirmation of
the elevated serum PSA is advisable prior to proceeding to prostate biopsy. The measurement of
serum PSA is also important for prognostic purposes. Although serum PSA concentrations may rise
slightly during the first several hours after a rectal examination [3], the rise is small enough that
the blood sample for PSA testing can be obtained at any time prior to biopsy.

The technique involved in prostate biopsy, including preparation, complications, and the extent of
sampling (a minimum of 12 cores in most situations) are discussed separately, as is pathologic
interpretation of the prostate biopsy. (See "Prostate biopsy" and "Interpretation of prostate
biopsy".)

A negative biopsy does not exclude the diagnosis of prostate cancer. Biopsy is a sampling
technique with a substantial potential for misdiagnosis. Repeat biopsy may be indicated if the PSA
level increases further. (See "Prostate biopsy", section on 'Need for repeat biopsy'.)

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Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a variety
of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient information: Prostate cancer (The Basics)")

●Beyond the Basics topics (see "Patient information: Prostate cancer screening (Beyond the
Basics)" and "Patient information: Prostate cancer treatment; stage I to III cancer (Beyond the
Basics)" and "Patient information: Treatment for advanced prostate cancer (Beyond the Basics)")

SUMMARY

●Most patients who undergo prostate biopsy do so because of a PSA determination despite the
controversy surrounding PSA screening. (See 'Clinical presentation' above.)

●Although the risk for having a biopsy positive for prostate cancer increases as the PSA level rises,
there are no absolute numbers used as a threshold to determine a need for biopsy. (See 'PSA
screening' above and "Screening for prostate cancer", section on 'Prostate specific antigen (PSA)'.)

•Patient age, prostate volume, digital rectal examination findings, and family history must all be
considered. A PSA level substantially above normal for a certain age may be an indication for
biopsy.

•A change from prior values (more than 0.35ng/ml/year for a PSA of <4.0 or 0.75ng/ml if the PSA
is >4.0) should be considered suspicious.

●An abnormal digital rectal exam, especially asymmetry, nodularity, or induration, should prompt
a biopsy regardless of the serum PSA level. (See 'Digital rectal examination' above.)

●Symptoms are an unusual presentation for men with prostate cancer and may be difficult to
differentiate from symptoms due to benign prostate disease. (See 'Symptoms' above.)

●The diagnosis of prostate cancer requires tissue. This is usually obtained by biopsy with guidance
of transrectal ultrasound, which should be preceded by measurement of serum PSA. (See
"Prostate biopsy" and "Interpretation of prostate biopsy".)

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