• References [2,3,5,6]
KNOWN RISK FACTORS FOR PROSTATE CANCER
Risk factor Comments
Age
  • Age is the number one risk factor for prostate cancer
  • Prostate cancer is rare in men under age 40
  • The incidence of prostate cancer rises rapidly after age 50
Race
  • African-Americans have the highest risk of prostate cancer. They also tend to have more aggressive cancers.
  • White men have a moderate risk for prostate cancer
  • Asian-Americans and Hispanics have the lowest risk of prostate cancer
Family history
  • Family history of prostate cancer is a risk factor for prostate cancer
  • Since a large number of men develop prostate cancer as they age, the number of affected relatives and the age of onset are important factors in quantifying the risk
  • Men with three or more affected relatives or at least two relatives who were diagnosed before the age of 55 are at greatest risk
BRCA2 mutations
  • BRCA2 mutations occur in families with a high incidence of breast and ovarian cancer. See BRCA gene testing for more.
  • BRCA2 mutations also confer a higher risk of prostate cancer
  • BRCA1 mutations likely increase the risk, but this is less clear
POSSIBLE RISK FACTORS FOR PROSTATE CANCER
Risk factor Comments
Environment/
Geography
  • Environmental factors appear to play a role in prostate cancer risk
  • Prostate cancer is more common in certain parts of the world (e.g. North America, northwestern Europe, Australia) and less common in others (e.g. Asia, Africa, Central America, South America). The reason is unclear, but screening frequency and longer life expectancy likely contributes to the measured differences.
Diet
  • A number of studies have looked at a link between prostate cancer and different dietary components (e.g. dairy, fat, alcohol, red meat, vitamin D, etc.). Results from these studies are often conflicting and no definitive link has been confirmed.
Agent Orange
  • Agent Orange was a defoliant chemical used in the Vietnam War
  • Some studies have suggested a link between Agent Orange exposure and prostate cancer while others have not


  • Men in the cohort had PSA screening every 2 years
  • Cohort size was 1756 men
  • References [7]
CUMULATIVE INCIDENCE OF PROSTATE CANCER OVER 15 YEARS BASED ON BASELINE PSA AT AGE 60 YEARS
PSA at 60 years old (ng/ml) 15-year incidence of prostate cancer (%)
0 - 0.99 3.6
1 - 1.99 16.6
2 - 2.99 37.5
≥ 3 49.5











  • Reference [6]
USPSTF Recommendations (2017 draft)
Age group Recommendation
55 - 69
  • Average-risk men - physicians should discuss the benefits and harms (see below) of screening with each patient and the decision to screen should be an individual one
  • African-Americans - recommendation is the same as average-risk men with the acknowledgement that screening in African-American men may have greater benefit and potentially greater harm than screening in average-risk men. Data from available trials is insufficient to draw conclusions either way.
  • Patients with family history - recommendation is the same as average-risk men. Men with the following family histories are most likely to benefit from screening although this has not been proven in clinical trials:
    • Multiple first-degree relatives with prostate cancer
    • First-degree relative who had advanced prostate cancer at diagnosis
    • First-degree relative who developed metastatic prostate cancer or who died from prostate cancer
  • Screening interval - USPSTF makes no recommendation
≥ 70
  • DO NOT SCREEN
AUA Recommendations (2013)
< 40
  • DO NOT SCREEN
40 - 54
  • Average-risk men - DO NOT SCREEN
  • African-Americans and patients with a family history - physicians should discuss the benefits and harms (see below) of screening with each patient and the decision to screen should be an individual one
55 - 69
  • All men - physicians should discuss the benefits and harms (see below) of screening with each patient and the decision to screen should be an individual one
  • Screening interval - every two years is the preferred interval
  • Digital rectal exam - does not recommend for screening
≥ 70
  • DO NOT SCREEN
EAU Recommendations (2017)
All men
  • Physicians should discuss the benefits and harms (see below) of screening with each patient and the decision to screen should be an individual one
  • DO NOT SCREEN men with a life-expectancy of < 15 years
  • Offer PSA screening to men at elevated risk
    • Elevated risk is defined as any of the following:
      • Men > 50 years of age
      • Men > 45 years of age with a family history of prostate cancer
      • African-Americans > 45 years of age
      • Men with a PSA level of > 1 ng/mL at 40 years of age
      • Men with a PSA level of > 2 ng/mL at 60 years of age
Follow-up screening
  • Follow-up screening should be based on the initial PSA value
    • Recheck PSA every 2 years in the following patients:
      • Men with a PSA level of > 1 ng/mL at 40 years of age
      • Men with a PSA level of > 2 ng/mL at 60 years of age
    • Recheck PSA in 8 years in all other men


  • Reference [2,8,9]
BENEFITS OF SCREENING FOR PROSTATE CANCER
Study Finding
PLCO trial Prostate cancer-related mortality after 10 years (death rate per 10,000 Person-Years)
  • Screened - 2.7, Control - 2.4 (RR 1.11; 95%CI [0.83 to 1.50])
ERSPC trial Prostate cancer-related mortality after a median of 9 years (death rate per 1000 Person-Years)
  • Screened - 0.35, Control - 0.41 (RR 0.85; 95%CI [0.73 to 1.00])
USPSTF trial review
  • In men 55 - 69 years old, prostate cancer screening may prevent up to 1 to 2 deaths from prostate cancer over approximately 13 years per 1,000 men screened
  • Screening programs may also prevent up to 3 cases of metastatic prostate cancer per 1,000 men screened over 13 years





  • For values ≤ 4 ng/ml, the median age of the cohort was 69 years
  • For values > 4 ng/ml, the average age of the cohort was 63 years
  • Rereneces [10,11]
PSA value Men with prostate cancer on biopsy Men with high-grade prostate cancer (Gleason ≥ 7) on biopsy
≤ 0.5 ng/ml 6.6% 0.82%
0.6 - 1 ng/ml 10% 1.0%
1.1 - 2.0 ng/ml 17% 2.0%
2.1 - 3.0 ng/ml 24% 4.6%
3.1 - 4.0 ng/ml 27% 6.7%
4.0 - 10 ng/ml 26% -
> 10 ng/ml 53% -


  • Data drawn from a sample of 773 men with normal digital rectal exams and a total PSA between 4 - 10 ng/ml
  • Rereneces [13]
% free PSA Probability of cancer
(50 - 64 years old)
Probability of cancer
(65 - 75 years old)
0 - 10 56% 55%
10 - 15 24% 35%
15 - 20 17% 23%
20 - 25 10% 20%
> 25% 5% 9%







  • Reference [6]
TUMOR (T) CATEGORIES
T score Clinical finding
T1
T1 - tumor cannot be felt or seen on imaging
  • T1a - cancer found incidentally on transurethral resection of the prostate (TURP) specimens. Less than 5% of specimens contain cancer.
  • T1b - cancer found incidentally on TURP specimens. More than 5% of specimens contain cancer.
  • T1c - cancer found on biopsy performed because of high PSA
T2
T2 - tumor can be felt on rectal exam or seen on imaging but appears confined to prostate
  • T2a - cancer is confined to one half or less of one side (left or right) of the prostate
  • T2b - cancer is in more than one half of one side of the prostate
  • T2c - cancer is in both sides of the prostate
T3
T3 - cancer has grown outside of the prostate
  • T3a - cancer is outside the prostate but not in the seminal vesicles
  • T3b - cancer has spread to the seminal vesicles
T4
T4 - cancer has grown into tissue outside the prostate (other than the seminal vesicles)
  • Other tissue may include urethral sphincter, rectum, bladder, and/or wall of the pelvis.
NODE (N) CATEGORIES
N score Clinical finding
NX NX - regional lymph nodes were not assessed
N0 N0 - no cancer found in regional lymph nodes
N1 N1 - cancer found in one or more regional lymph nodes
METASTASIS (M) CATEGORIES
M score Clinical finding
M0 MO - cancer has not spread beyond regional lymph nodes
M1
M1 - cancer has spread beyond regional lymph nodes
  • M1a - cancer has spread to lymph nodes outside the pelvis
  • M1b - cancer has spread to the bones
  • M1c - cancer has spread to other organs (e.g. lung, liver, brain) with or without bone involvement

  • * PSA density is obtained by dividing the total PSA value by the prostate gland weight. Prostate gland weight is estimated with transrectal ultrasound.
  • Reference [17]
NCCN Prostate Cancer Risk Stratification Groups
Risk group Findings
Very low All of the following must be met:
  • Stage T1c or lower
  • Gleason score ≤ 6
  • PSA < 10 ng/ml
  • Fewer than 3 prostate biopsy cores positive and ≤ 50% cancer in each core
  • *PSA density < 0.15 ng/ml/g
Low All of the following must be met:
  • Stage T1 - T2a
  • Gleason score ≤ 6
  • PSA < 10 ng/ml
Intermediate If any of the following are present, then risk is intermediate:
  • Stage T2b - T2c
  • Gleason score 7
  • PSA 10 - 20 ng/ml
High If any of the following are present, then risk is high:
  • Stage T3a
  • Gleason score 8 - 10
  • PSA > 20 ng/ml
Very high If any of the following are present, then risk is very high:
  • Stage T3b - T4
  • Primary Gleason pattern of 5
  • > 4 cores with Gleason score 8 – 10
Metastatic
  • N1 and/or M1

  • 1Data derived from cohort of 3183 U.S. men who were initially diagnosed in 1994-1995. 74% of subjects received either prostatectomy or radiation treatment.
  • 2Data from the National Cancer Institue SEER data
  • Reference [18,19]
Prostate cancer survival rates based on initial risk group
Risk group Mortality
Low risk1 3%
(14-year prostate cancer-specific mortality)
Intermediate risk1 7%
(14-year prostate cancer-specific mortality)
High risk1 18%
(14-year prostate cancer-specific mortality)
Metastatic2 70%
(5-year overall mortality)





  • Reference [17]
2017 NCCN Prostate Cancer Treatment Recommendations
Risk group Life expectancy Treatment recommendation
Very low risk ≥ 20 years One of the following:
10 - 20 years
< 10 years
  • Observation
Low risk ≥ 10 years One of the following:
< 10 years
  • Observation
Intermediate risk ≥ 10 years One of the following:
  • Radiotherapy ± ADT
  • Radical prostatectomy
< 10 years One of the following:
  • Radiotherapy ± ADT
  • Observation
High risk Does not apply One of the following:
  • External beam radiation + ADT
  • External beam radiation + brachytherapy ± ADT
  • Radical prostatectomy
Very high risk Does not apply One of the following:
  • External beam radiation + ADT
  • External beam radiation + brachytherapy ± ADT
  • Radical prostatectomy
  • ADT or observation
Regional metastasis
(N1, M0)
Does not apply One of the following:
  • External beam radiation + ADT
  • ADT
Metastatic
(M1)
Does not apply
  • ADT


  • 1Data from ProtecT study. Average age in the study was 62 years. External-beam radiation included neoadjuvant ADT for 3 to 6 months before and concomitantly with therapy. After 6 years of follow-up, ∼ 40% of patients in the active surveillance group had undergone prostatectomy or radiation.
  • 2Data from prospective cohort study. Median age in the cohort was 65 years. About 7% of the patients received ADT.
  • Reference [20,21]
Proportion of men with erections not firm enough for intercourse
Treatment Baseline
(before treatment)
6 months 1 year 2 years 5 years
Prostatectomy1
(N=553)
34% 88% 85% 81% 80%
External-beam radiation therapy1
(N=545)
32% 78% 62% 66% 73%
Brachytherapy2
(N=306)
36% 58% 54% 56% -
Active surveillance1
(N=545)
32% 48% 51% 53% 65%


Proportion of men with any degree of urinary incontinence in the ProtecT study
Treatment Baseline
(before treatment)
6 months 1 year 3 years 5 years
Prostatectomy1 30% 71% 71% 68% 69%
Radiation therapy1 31% 38% 38% 43% 48%
Active surveillance1 28% 39% 42% 47% 47%
  • 1Data from ProtecT study. Average age in the study was 62 years. External-beam radiation included neoadjuvant ADT for 3 to 6 months before and concomitantly with therapy. After 6 years of follow-up, ∼ 40% of patients in the active surveillance group had undergone prostatectomy or radiation.
  • 2Data from prospective cohort study. Median age in the cohort was 65 years. About 7% of the patients received ADT.
  • Reference [20,21]
OTHER URINARY SYMPTOMS
Prostatectomy2
(N=603)
External-beam radiation2
(N=292)
Brachytherapy2
(N=306)
Baseline
(before treatment)
6 months 12 months 24 months Baseline
(before treatment)
6 months 12 months 24 months Baseline
(before treatment)
6 months 12 months 24 months
Dysuria 1% 1% 1% < 1% 1% 5% 1% 1% 1% 11% 11% 5%
Weak stream 12% 6% 3% 4% 13% 11% 12% 10% 7% 26% 18% 11%
Frequency 17% 14% 11% 10% 16% 19% 13% 14% 11% 31% 20% 20%
Incontinence
(> 1 time/day)
4% 23% 16% 14% 6% 9% 8% 7% 5% 9% 6% 10%

  • Data from prospective cohort study. Median age in the cohort was 65 years. About 7% of the patients received ADT.
  • Reference [21]
BOWEL SYMPTOMS
Prostatectomy
(N=603)
External-beam radiation
(N=292)
Brachytherapy
(N=306)
Baseline
(before treatment)
6 months 12 months 24 months Baseline
(before treatment)
6 months 12 months 24 months Baseline
(before treatment)
6 months 12 months 24 months
Urgency 1% 3% 3% 2% 3% 12% 14% 16% 4% 14% 10% 9%
Frequency 1% 2% 1% < 1% 2% 9% 9% 10% 3% 9% 8% 7%
Incontinence < 1% 1% < 1% < 1% < 1% 4% 4% 2% < 1% 6% 4% 5%
Rectal pain 1% 3% 2% 2% 2% 5% 3% 4% 2% 5% 4% 4%

  • References [Manufacturer's PI, 17]
DRUGS USED IN ANDROGEN DEPRIVATION THERAPY
Drug Class Side effects of ADT
Leuprolide (Lupron®)
Goserelin (Zoladex®)
Triptorelin (Trelstar®)
Histrelin (Vantas®)
GnRH agonist
  • GnRH agonists only - Initial increase in testosterone over 2 - 3 weeks which may exacerbate bone pain and/or urinary tract obstruction
  • Hot flashes - up to 73%
  • Erectile dysfunction - may worsen
  • Gynecomastia / breast pain
  • Osteoporosis - Use FRAX tool with "secondary osteoporosis" checked to determine risk
  • Increased risk of diabetes or worsening of diabetes
  • Increased risk of cardiovascular disease
  • Increased cholesterol / triglyceride levels
  • Depression / fatigue / weight gain
  • Prolonged QT interval
Degarelix (Firmagon®) GnRH antagonist


  • 1In high-risk men, PSA surveillance as frequently as every 3 months may be necessary to clarify disease status
  • 2In young, healthy men who are candidates for salvage therapy, a recurrence evaluation may be indicated for increases that are < 2 ng/ml
  • Reference [17]
Prostate cancer post-treatment surveillance recommendations
Initial treatment surveillance Recurrence
Prostatectomy or
external-beam radiation
(localized disease)
  • PSA every 6 - 12 months for 5 years then every year1
  • DRE every year, but may be omitted if PSA is undetectable
If patient had radical prostatectomy:
  • Detectable PSA that increases on 2 or more checks
If patient had external-beam radiation therapy:
  • PSA increase by ≥ 2 ng/ml above the nadir PSA2
N1 or M1 on ADT
  • Physical exam + PSA every 3 - 6 months
  • Bone scan initially and for symptoms as often as every 6 - 12 months
  • Further metastasis