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Section - III. Genitourinary Cancer
Prostate Cancer
Prostate cancer is the most common solid tumor among males. Although
prostate cancer has a long natural history, it is the second most common cause of
cancer death in males.
Adenocarcinoma counts by more than 95% of cancers of the prostate gland.
Genitourinary pathologists according to the Gleason scoring system, which is
based on 10 points, grade the tumor.
The majority of prostatic cancer is usually asymptomatic and can be detected as
a result of routine digital rectal examination (DRE).
TRUS-guided true-cut biopsy is the standard method to diagnose prostate
cancer.
A twelve-core set is taken by sampling the base, apex, and midgland on each
side of the gland along two parallel lateral lines.
The probability of a positive scan is extremely low when the PSA is <10 ng/mL
or symptoms are absent.
CT scans and MRI are used to assess tumor spread into lymph nodes or the
pelvis. These studies are warranted only in high-risk patients who have a tumor
that is confluent with the pelvic side wall on DRE, a high Gleason’s score, or
PSA >20 ng/mL.
The treatment options for men with prostate cancer include radical pros-
tatectomy (RP), external beam radiation therapy (EBRT), brachytherapy, and
active surveillance.
Management of locally advanced prostate cancer is often with EBRT combined
androgen deprivation therapy (ADT).
Chapter 10
Abstract
Introduction
Prostate cancer is the most common solid tumor among males. Although prostate cancer
has a long natural history, it is the second most common cause of cancer death in males.
Currently, up to 50% of patients with prostate cancers are asymptomatic at diagnosis.
Generally, diagnosis in such cases is based on abnormalities in a screening prostate-specific
Gustavo Arruda Viani
144
antigen (PSA) level or findings on digital rectal examination. Standard treatments for
clinically localized prostate cancer include radical prostatectomy (RP), external beam
radiotherapy (EBRT), brachytherapy (BT), or active surveillance. Management of locally
advanced prostate cancer is often with EBRT combined androgen deprivation therapy (ADT).
1. Epidemiology
• Prostate cancer is the most commonly diagnosed cancer in men. Prostate cancer
crossed the line of 100 cases per 100,000 in 1987.
• The peak incidence was observed in 1992. The incidence declined from 1992 to
1995, and then leveled off.
• The rise in incidence is basically explained by improved detection, mainly, using
prostate-specific antigen (PSA) and transrectal ultrasound (TRUS) to aim prostate
biopsies.
• The lifetime risk of a diagnosis of prostate cancer is about 1 in 6, while the lifetime
risk of death from prostate cancer is on the order of 1 in 35.
• However, the rate of this latent or autopsy cancer is much greater than that of clinical
cancer. In fact, it may be as high as 80% by age 80 years.
References
American Cancer Society. Cancer Facts and Figures 2012. Available at http://www.cancer.-
org/acs/groups/content/@epidemiologysurveilance/documents /document/acspc-026238.
pdf. Accessed may 19, 2012.
2. Anatomy
Prostate gland consists of the peripheral zone (70% of glandular prostate), the central
zone (25% of the glandular prostate), the transition zone (surrounding the urethra and the site
of BPH), and the anterior fibromuscular stroma. Approximately 80% of tumors involve the
prostate apex, and almost 85% of patients have multifocal disease (figure-1).
Prostate Cancer
145
Demography
The risk for prostate cancer is highest in Sweden, intermediate in the United States
and Europe, and lowest in Taiwan and Japan.
Blacks are afflicted 30% more often than are whites.
Familial history
Positive history of the father or brother increases the risk sevenfold over the general
population if the affected relative was diagnosed by 50 years of age.
When the first-degree relative has the diagnoses after 70 years of age, the relative
risk declines to fourfold.
Hormones
Altered estrogen and androgen metabolite levels have been suggested as a causative
mechanism leading to prostate cancer occurrence.
Obesity
Prospective studies have failed to consistently show that obesity is related to the
incidence of prostate cancer.
However, recent data shows that men with higher body mass index have an
increased risk of prostate cancer death as compared with men with a lower body
mass index.
Age
Age is the single most important factor associated with prostate cancer.
The rate of clinical detection of prostate cancer is a direct function of age.
3. Risk Factors
Several factors are associated with an increased risk (table-1).
Table1. Risk factors for developing prostate cancer
Figure 1. Prostate anatomy.
Gustavo Arruda Viani
146
References
Hsing AW, Comstock GW. Serological precursors of cancer: serum hormones and risk of
subsequent prostate cancer. Cancer Epidemiol Biomarkers Prev. Jan-Feb 1993;2(1):27-
32.
Parker PM, Rice KR, Sterbis JR, Chen Y, Cullen J, McLeod DG, Brassell SA. Prostate cancer
in men less than the age of 50: a comparison of race and outcomes. Urology.
2011;78(1):110.
Chan JM, Gann PH, Giovannucci EL. Role of diet in prostate cancer development and
progression. J Clin Oncol. 2005;23(32):8152.
Stewart SB, Freedland SJ. Influence of obesity on the incidence and treatment of
genitourinary malignancies. Urol Oncol. 2011;29(5):476.
4. Pathology
• Adenocarcinoma counts by more than 95% of cancers of the prostate gland. Less
common histologies are ductal adenocarcinoma, neuroendocrine tumors, mucinous
carcinoma, sarcomatoid carcinoma, endometrioid tumors, adenoid cystic carcinoma,
sarcomas, carcinosarcoma, and primary lymphoma.
• Genitourinary pathologists according to the Gleason scoring system, which is based
on 10 points, grade the tumor.
• This consists of two numbers, with the first number representing the predominant
Gleason pattern (scored out of 5) and the second number representing the second
most common Gleason pattern (figure-2).
Figure 2. The Gleason score is generated by adding the sums of the two most common patterns of
tumor cells observed, each assigned a grade from 1 to 5.
Prostate Cancer
147
Symptoms
The majority of prostatic cancer is usually asymptomatic and can be detected as a
result of routine digital rectal examination (DRE).
Prostate cancer can also be discovered by serum PSA measurement or, rarely, during
Symptoms includes hesitancy, urgency, nocturia, poor urine stream, dribbling, and
terminal hematuria.
Physical
examination
Check for induration or nodularity of the prostate, which are typically stony hard and
not tender.
Examine lateral sulci and for palpable (abnormal) seminal vesicles.
Evaluate for distant metastases by palpating the skeleton and by performing an
oriented neurologic examination looking for spinal cord compression.
Acute prostatitis
Bacterial infection causes dysuria, pain, and often fever.
The prostate is tender and enlarged but not hard. Examination and culture of
prostatic fluid obtained by prostate massage may reveal the infectious agent.
Chronic and
granulomatous
prostatitis
Bacterial, tuberculous, fungal, or protozoan infection may produce a mass that
cannot be clinically distinguished from cancer.
Nodular hyperplasia
Benign prostatic hypertrophy is found in men >30 years of age and in 80% of
men by 80 years of age.
Urinary obstructive symptoms are common. Palpable nodules that are
indistinguishable from cancer necessitate biopsy.
Reference
Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by
combined histological grading and clinical staging. J Urol. 1974;111(1):58.
5. Diagnosis and Evaluation
5.1. Symptoms and Signs
Currently, most patients with prostate cancer are asymptomatic at diagnosis. The
symptoms findings from physical examination are summarized in table-2.
Table 2. Symptoms and physical examination of prostate cancer
5.2. Differential Diagnosis
Table 3. Differential diagnosis from prostate cancer
5.3. PSA Tools
The acceptable limit for serum prostate-specific antigen (PSA) is 4.0 ng/mL. But, 20% of
prostate cancer cases have PSA levels below of 4.0 ng/mL, and only 25% of cases with serum
PSA levels of 4–10 ng/mL have prostate cancer in a biopsy (table-4).
Gustavo Arruda Viani
148
PSA
PSA is a serine protease that serves as a marker unique to the prostate.
Around 15% of patients with nodular hyperplasia have elevated PSA levels.
PSA values can also be increased with prostatic inflammation, surgery, or endoscopy,
but not with rectal examination. After a prostate biopsy, PSA is reported to be elevated
for at least 6 to 8 weeks.
Free PSA
A decreased ratio of free PSA to total PSA is associated with increased probability of
prostate cancer.
It is recommended to proceed with watchful waiting after one negative biopsy if the
free-to-total PSA ratio >25%.
PSA density
The indices adjust serum PSA levels for the prostate gland volume (PSA density =
PSA/gland volume) or for the TZ volume (PSA TZ = PSA/TZ volume).
These indices were found to improve positive-predictive and negative-predictive
values in patients with total PSA levels of 4 to 10 ng/mL.
PSA velocity
The rate of PSA change over time (the PSA velocity). A PSA velocity cutoff of 0.75
ng/mL per year distinguished patients with prostate cancer from those with either BPH
or no prostate disease with a specificity of 90 and 100%, respectively.
A further study from the same group found that when PSA was <4 ng/mL, a PSA
velocity >0.35 ng/mL per year measured over several years was associated with a high
risk of death from prostate cancer 15 years later.
Table 4. PSA level and PSA tools to diagnosis prostate cancer
5.4. Biopsy Techniques
5.4.1. TRUS-Guided True-Cut Biopsy
TRUS-guided true-cut biopsy is the standard method to diagnose prostate cancer.
A twelve-core set is taken by sampling the base, apex, and midgland on each side of
the gland along two parallel lateral lines.
Most cancers have a hypoechoic appearance in TRUS, although up to 30% of cancers
may be isoechoic. When the indication for TRUS-guided biopsy is a PSA >4 ng/mL,
the expected yield for diagnosing prostate cancer reaches 24%. When PSA is >4
ng/mL, the DRE is suspicious, and a hypoechoic lesion is imaged by TRUS, the yield
rises to 45%.
Upgrading of biopsy GS from 6 to 7 or from 7 to >7 occurs in approximately 25–
30% of patients who subsequently undergo prostatectomy even with more than 10
biopsy cores.
5.5. Evaluation
Bone Scans
• The probability of a positive scan is extremely low when the PSA is <10 ng/mL or
symptoms are absent.
• The American Urology Association guidelines recommend a bone scan if the PSA is
>10 ng/ml (figure – 3).
• In a review of 23 studies that examined the role of staging bone scans, the detection
rates for men with serum PSA levels of <10, 10.1-19.9 and 20 to 50 were 2, 5, and 16
%, respectively.
Prostate Cancer
149
CT Scans and MRI
• CT scans and MRI are used to assess tumor spread into lymph nodes or the pelvis.
• These studies are warranted only in high-risk patients who have a tumor that is
confluent with the pelvic side wall on DRE, a high Gleason’s score, or PSA >20
ng/mL.
• An MRI with an endorectal coil of the prostate can be suggested for evaluation of
local disease.
• The procedure provides superior soft tissue anatomy as compared to CT scans in
evaluating for extracapsular extension and/or seminal vesicle involvement (figure-4).
• Magnetic resonance spectroscopy imaging (MRSI) can be used in staging and post-
treatment measurement of efficacy. The study has been demonstrated a good efficacy
in numerous prospective radiology studies.
Figure 3. Bone scan showing a compromising of pelvis and all spine.
Figure 4. Same slice of a CT and a MRI showing a superior soft tissue anatomy with MRI.
Gustavo Arruda Viani
150
Primary Tumor (T)
TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
T1a - Tumor incidental histologic finding in 5% or less of tissue resected
T1b - Tumor incidental histologic finding in more than 5% of tissue resected
T1c - Tumor identifi ed by needle biopsy (because of elevated PSA)
T2a - Tumor involves one-half of one lobe or less
T2b - Tumor involves more than one-half of one lobe but not both lobes
T2c - Tumor involves both lobes
T3a - Extracapsular extension (unilateral or bilateral)
T3b Tumor invades seminal vesicle(s)
T4 - Tumor is fixed or invades adjacent structures other than seminal vesicles such as external
sphincter, rectum, bladder, levator muscles, and/or pelvic wall
Regional Lymph Nodes (N)
NX - Regional lymph nodes cannot be assessed
N0 - No regional lymph node metastasis
N1 Metastasis in regional lymph node(s)
Distant Metastasis (M)
M0 - Ausência de metástase a distância
M1a - Nonregional lymph node(s)
M1b - Bone(s)
M1c - Other site(s) with or without bone disease
References
Wolf AM, Wender RC, Etzioni RB, et al. American Cancer Society guideline for the early
detection of prostate cancer: update 2010. CA Cancer J Clin. Mar-Apr 2010;60(2):70-98.
Rosario DJ, Lane JA, Metcalfe C, et al. Short term outcomes of prostate biopsy in men tested
for cancer by prostate specific antigen: prospective evaluation within ProtecT
study. BMJ. Jan 9 2012;344:d7894.
Agency for Healthcare Research and Quality Guideline Clearinghouse. ACR Appropriateness
Criteria® pretreatment staging prostate cancer. Available at http://guideline.gov/content.
aspx?id=15768. Accessed January 26, 2011.
6. Staging
Prostate cancer is clinically staged using the 2010 AJCC TNM system, which is based on
DRE findings (Table-5).
Table 5. TNM for prostate cancer
7. Routes of Spread
• Local extension mainly involves direct extracapsular extension of prostate cancer or
involvement of seminal vesicles