Background

Question 1

What proportion of men will develop prostate cancer and what is the annual incidence and mortality in the United States?

Answer 1

1 in 7 men corresponding to 160,000 Dx of and 26,000 deaths from prostate cancer annually.

Question 2

What are the 4 zones of the prostate?

Answer 2

Zones of the prostate:

Peripheral zone
Central zone
Transitional zone
Ant fibromuscular stroma

Question 3

Prostate cancers develop most commonly in which zone?

Answer 3

Two-thirds of prostate cancers arise in the peripheral zone.

Question 4

Benign prostatic hypertrophy (BPH) develops in which zone?

Answer 4

BPH develops primarily in the transitional zone.

Question 5

What does median lobe hypertrophy refer to?

Answer 5

Median lobe hypertrophy refers to a characteristic transitional zone hypertrophy (BPH) that mushrooms superiorly into bladder lumen.

Question 6

What tissues likely mediate erectile dysfunction (ED) after prostate RT?

Answer 6

ED likely results from RT injury to the neurovascular bundles, internal pudendal arteries, corpora cavernosa and possibly the penile bulb. (Spratt DE et al., European Urology 2017)

Question 7

Name the 3 histologic cell types seen in the normal prostate.

Answer 7

Secretory cells (produce PSA)
Basal cells (flattened basement membrane where stem cells that repopulate the secretory layers reside)
Neuroendocrine cells

Question 8

Describe the GS and what it represents.

Answer 8

A sum of pathologic grades assigned to prostate cancer that reflect aggressiveness based on the tumor’s resemblance to normal glandular tissue. A primary (or predominant) pattern is recorded f/b a secondary or lesser pattern, which are summed to give the overall GS (e.g., 3 + 4).

Question 9

How do the Gleason Grade Group definitions correspond to the GSs?

Answer 9

Group 1: GS ≤6
Group 2: GS 3 + 4 = 7
Group 3: GS 4 + 3 = 7
Group 4: GS 4 + 4 = 8; 3 + 5 = 8; 5 + 3 = 8
Group 5: GS 9–10

Question 10

How often is higher-grade Dz diagnosed in a radical prostatectomy specimen (upstaging) than that seen in the initial Bx specimens?

Answer 10

One-third

Question 11

What racial groups are associated with the highest and lowest risks for prostate cancer?

Answer 11

Black men are at highest risk for the development of prostate cancer (and their Dz presents more aggressively [higher GS, 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 b/t native Asians and black men. (Ross R et al., Cancer 1995)

Question 12

Define the incidence of adenocarcinoma of the prostate on autopsy studies as a function of age.

Answer 12

Incidental finding of prostate adenocarcinoma on autopsy studies increases with age, with the average GS b/t 6 and 7. In 1 study, the following incidences of prostate cancer were found:

Age 50–59: 23.4%

Age 60–69: 34.7%

Age 70–81: 45.5%

(Ming Y et al., J Urol 2008)

Question 13

How does finasteride use impact prostate cancer incidence, aggressiveness, and mortality?

Answer 13

In a phase III trial comparing finasteride vs. placebo, finasteride reduced the incidence of prostate cancer (30.6% vs. 18.6%), but increased the risk of more aggressive (Gleason 7–10) tumors (37% vs. 22%) (Thompson IM et al., NEJM 2003). Finasteride likely does not impact grade, but rather shrinks the prostate, making high-grade Dz more easily detected (Lucia MS et al., JNCI 2007). There is no impact of finasteride on OS. (Thompson IM et al., NEJM 2013)

Question 14

Describe 5 factors that can increase the level of PSA.

Answer 14

Prostate cancer
Prostate manipulation (prostate Bx or DRE)
Infection (prostatitis)
Ejaculation shortly before PSA testing
BPH

Question 15

Define the risk of prostate cancer as a function of total PSA level.

Answer 15

Prostate cancer risk increases as the total PSA level increases:

PSA ≤4 ng/mL: 5%–25%

PSA 4–10 ng/mL: 15%–25%

PSA ≥10 ng/mL: 50%–67%

Question 16

Screening programs for prostate cancer include what 2 clinical assessments?

Answer 16

Screening for prostate cancer includes DRE and a serum PSA.

Question 17

Describe 4 variants of absolute PSA that can be helpful in assessing a man’s risk of prostate cancer.

Answer 17

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

Question 18

Describe the upper limits of normal PSA values as a function of age.

Answer 18

PSA values in men without prostate cancer will increase with age:

40–49 yrs: 1.5–2.5 ng/mL

50–59 yrs: 2.5–4 ng/mL

60–69 yrs: 4–5.5 ng/mL

70–79 yrs: 5.5–7 ng/mL

Question 19

What is prostate-specific antigen velocity (PSAV), and how is it used in prostate cancer screening?

Answer 19

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)

Question 20

What is prostate-specific antigen density (PSAD), and how is it used in prostate cancer screening?

Answer 20

PSAD is the total serum PSA value divided by the volume of the prostate gland. A PSAD of ≥0.15 ng/mL/cm3 identifies men with a higher risk of detecting prostate cancer on a screening Bx.

Question 21

What is the relationship b/t prostate cancer and the ratio of serum free-to-total PSA?

Answer 21

The end product of normal PSA biosynthesis within the prostate epithelium and ducts is inactive “free PSA,” an fx 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. 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.

Question 22

What are population-based screening recommendations by the American Cancer Society (ACS) for prostate cancer? U.S. Preventive Services Task Force (USPSTF)?

Answer 22

The ACS (2010) recommends that physicians discuss screening with men aged (1) ≥50 yrs at avg risk expected to live ≥10 yrs, (2) ≥45 yrs at high risk (African Americans, 1st-degree relatives diagnosed prior to 65), (3) ≥40 yrs at very high risk (>1 1st-degree relative diagnosed prior to 65 yrs). The USPSTF (2017) acknowledges a small potential mortality benefit with PSA screening that should be discussed with men aged 55–69 yrs of age (C recommendation).

Question 23

Is there evidence of a mortality benefit with prostate cancer screening?

Answer 23

Yes. The European Randomized study of Screening for Prostate Cancer study with 13 yrs of f/u showed an SS 21% decreased risk of prostate cancer mortality with PSA screening. The number needed to screen to prevent 1 death in this study was 781. (Schröder FH et al., Lancet 2014)

Question 24

What has annual DRE and PSA screening in the US population shown in terms of prostate cancer and deaths?

Answer 24

In the U.S. Prostate, Lung, Colorectal, and Ovarian Cancer screening trial, 76,685 men were randomized to (1) annual PSA × 6 yrs + annual DRE × 4 yrs or (2) usual care in which opportunistic screening with PSA or DRE was allowed. After 13 yrs of f/u, the incidence of prostate cancer was higher with PSA testing (108 vs. 97 cases/10,000 person-yrs). The incidence of death was similar b/t the groups (3.7 vs. 3.4 cases/10,000 person-yrs) (Andriole GL et al., JNCI 2012). However, control group participants reported higher rates of PSA screening (∼90%) than those in the intervention group (Shoag JE et al., NEJM 2016) making it difficult to draw conclusions from this trial.

Question 25

What is the most common presentation of prostate cancer?

Answer 25

In the PSA era, most pts present with an abnl PSA and no associated Sx.

Question 26

In men with symptomatic prostate cancer, what local Sx may arise at Dx?

Answer 26

Lower urinary tract Sx such as urgency, frequency, nocturia, and dysuria
Hematuria
Hematochezia, constipation, intermittent diarrhea, reduced stool caliber
Renal impairment from bladder outlet obstruction

Question 27

What is the most common site of metastatic spread of prostate cancer?

Answer 27

Bone is the most common site of metastatic spread. Blastic > lytic lesions.