Low-Risk Prostate Cancer
Background
What is the annual incidence and mortality of prostate cancer in the U.S.?
~230,000 Dx of and ~27,000 deaths from prostate cancer annually in the U.S.
1 in how many American men will develop prostate cancer during his lifetime?
~1 in 6 American men will be diagnosed with prostate cancer during his lifetime.
What are the 4 zones of the prostate?
Zones of the prostate:
Peripheral zone
Central zone
Transitional zone
Anterior fibromuscular stroma
Prostate cancers develop most commonly in which zone?
Two thirds of prostate cancers arise in the peripheral zone.
Benign prostatic hypertrophy (BPH) develops in which zone?
BPH develops in the transitional zone.
What is median lobe hypertrophy?
Median lobe hypertrophy refers to a characteristic transitional zone hypertrophy (BPH) that mushrooms superiorly into the rest of the prostate and bladder. The term does not refer to enlargement of the central zone, which is typically small and compressed in older men.
What is the name for the nerves responsible for penile erections, and where are these nerves located with respect to the prostate?
The neurovascular bundles are paired nerves located along the posterolat edge of the prostate and are responsible for penile erection.
Name the 3 histologic cell types seen in the normal prostate.
Histologic cell types seen in the normal prostate:
Secretory cells (produce PSA and involute with hormonal deprivation)
Basal cells (flattened basement membrane where stem cells that repopulate the secretory layers reside)
Neuroendocrine cells
Describe the Gleason score and what it represents.
The Gleason score is a grade assigned to prostate cancer specimens that reflects the degree of aggressiveness based on the tumor’s resemblance to normal glandular tissue. A primary (or predominant) pattern is recorded followed by a secondary or lesser pattern. The Gleason score is the sum of the primary and secondary pattern values and can be between 2 and 10.
Grade 1: small, well-formed glands, closely packed
Grade 2: well-formed glands, but more tissue between them
Grade 3: darker cells, some of which have left the gland and are invading the surrounding tissue
Grade 4: few recognizable glands with many cells invading the surrounding tissue
Grade 5: no recognizable glands; sheets of cells throughout the surrounding tissue
How often is higher-grade Dz diagnosed in a radical prostatectomy specimen (upstaging) than that seen in Bx specimens?
One third of cases are higher grade in post-prostatectomy specimens than that diagnosed in Bx specimens.
What racial groups are associated with the highest and lowest risks for prostate cancer?
Black men are at highest risk for the development of prostate cancer (and their Dz presents more aggressively [higher Gleason score, more advanced stage]). Asians are at the lowest risk for the development of prostate cancer. A 30- to 50-fold difference in the incidence of the Dz is observed between native Asians and black men (Ross R et al., Cancer 1995).
Describe 5 clinical factors associated with the Dx of prostate cancer.
Clinical factors associated with the Dx of prostate cancer:
Advanced age
African American race
Past prostate Bx showing prostatic intraepithelial neoplasia (PIN; especially high-grade PIN)
Obesity
High dietary intake of fats
Is there a causative relationship between vasectomy and subsequent development of prostate cancer?
No. Studies show no consistent trend between vasectomy and subsequent development of prostate cancer. The National Institutes of Health has concluded that information regarding a relationship between them is not convincing and that a causative relationship has not been established. (Healy B et al., JAMA 1993)
Define the incidence of high-grade PIN or adenocarcinoma of the prostate on autopsy studies as a function of age.
Incidental finding of prostate adenocarcinoma on autopsy studies increases with age, with the avg Gleason score between 6 and 7. In 1 study, the following incidence of either high-grade PIN or prostate cancer was found:
Age < 39: 0.6% (cancer: 0.6%)
Age 40–49: 19.2% (cancer: 0%)
Age 50–59: 40.3% (cancer: 23.4%)
Age 60–69: 61.2% (cancer: 34.7%)
Age 70–81: 45.5% (cancer: 45.5%)
(Ming Y et al., J Urol 2008)
Does finasteride decrease the incidence of prostate cancer?
Yes. In a phase III trial comparing finasteride vs. placebo given for 7 yrs to test the role of finasteride as a chemoprevention agent in men age ≥55 yrs (without evidence of prostate cancer), finasteride reduced the incidence of prostate cancer by 25% (30.6% vs. 18.6%) but increased the risk of more aggressive (Gleason 7–10) tumors (37% of tumors on the finasteride arm vs. 22% of tumors on the placebo arm) (Thompson IM et al., NEJM 2003). Follow-up studies suggest that finasteride likely does not affect grade but rather shrinks the prostate, making high-grade Dz more easily detected on subsequent Bx (Lucia MS et al., JNCI 2007).
Describe 5 factors that can increase the level of PSA.
Factors that can increase PSA levels in the body:
Prostate cancer
Prostate manipulation (prostate Bx or DRE)
Infection (prostatitis)
Ejaculation shortly before PSA testing
BPH
Define the risk of prostate cancer as a function of total PSA level.
Prostate cancer risk increases as the total PSA level increases:
PSA < 4: 5%–25%
PSA 4–10: 15%–25%
PSA > 10: 50%–67%
Screening programs for prostate cancer include what 2 clinical assessments?
Screening for prostate cancer includes DRE and a serum PSA.
Describe 4 variants of absolute PSA that can be helpful in assessing a man’s risk of prostate cancer.
Variants of absolute PSA that identify prostate cancer risk:
PSA as a function of age
PSA velocity
PSA density
ratio of free to total PSA
Describe upper limits of normal PSA values as a function of age.
Normal PSA values in men (without prostate cancer) will increase with age.
Upper-limit normal PSA values by age:
40–49 yrs: 1.5–2.5
50–59 yrs: 2.5–4
60–69 yrs: 4–5.5
70–79 yrs: 5.5–7
What is prostate-specific antigen velocity (PSAV), and how is it used in prostate cancer screening?
PSAV is a measure of the rate of change of the total PSA annually. A PSA velocity ≥2 ng/mL/yr is associated with a higher risk of finding Gleason ≥7 prostate cancer on prostatectomy (Loeb S et al., Urology 2008).
What is prostate-specific antigen density (PSAD), and how is it used in prostate cancer screening?
PSAD is the total serum PSA value divided by the volume of the prostate gland (ellipsoid volume = length × width × height × 0.52). A PSAD of ≥0.15 ng/mL/cm3 identifies men with a higher risk of detecting prostate cancer on a screening Bx.
What is the relationship between prostate cancer and the ratio of serum free-to-total PSA?
The end product of normal PSA biosynthesis within the prostate epithelium and ducts is inactive “free PSA”, a fraction of which diffuses into the circulation. In prostate cancer, tumors disrupt the prostate basement membrane and allow precursor forms of PSA to leak into the circulation, which decreases the relative proportion of free PSA. Hence, the ratio of free-to-total PSA will be lower in men with prostate cancer. A ratio of <7% is highly suspicious for prostate cancer, whereas a ratio of >25% is rarely associated with malignancy.
What are population-based screening recommendations by the American Cancer Society (ACS) for prostate cancer? United States Preventive Services Task Force (USPSTF)?
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