EURURO Vol. 71 No. 4

620 692

The 2014 ISUP Gleason Grading Conference on Gleason
Grading of Prostate Cancer adopted the concept of
grade groups of PCa to align PCa grading with the grading of
other carcinomas, eliminate the anomaly that the most
highly differentiated PCas have a GS 6 and highlight the
clinical differences between GS 7 (3 + 4) and 7 (4 + 3)
).
3. Screening and early detection
Screening for PCa remains one of the most controversial
topics in the urologic literature. A Cochrane review
suggests that PSA screening is associated with an increased
diagnosis rate (relative risk [RR]: 1.3; 95% confidence
interval [CI], 1.02–1.65), the detection of more localised
(RR: 1.79; 95% CI, 1.19–2.70) and less advanced disease (T3–
4, N1, M1) (RR: 0.80; 95% CI, 0.73–0.87). However, neither
overall survival (OS; RR: 1.00; 95% CI, 0.96–1.03) nor
cancer-specific survival (CSS) benefit were observed (RR:
1.00; 95% CI, 0.86–1.17). Moreover, screening was associat-
ed with overdiagnosis and overtreatment. All these
considerations have led to a strong advice against system-
atic population-based screening in Europe and the United
States. And yet the population-based European Randomised
Study of Screening for Prostate Cancer (ERSPC) showed a
reduction in PCa mortality in the screening arm (RR: 0.8;
95% CI, 0.65–0.98) after a median follow-up of 9 yr. Updated
results from the ERSPC at 13 yr of follow-up showed an
unchanged cancer-specific mortality reduction but the
number needed to screen and to treat to avoid one death
fromPCa decreased and is now below the number needed to
screen in breast cancer trials . But an OS benifit
is still lacking. The uptake of the current US Preventive
Services Task Force recommendations has been associated
with a substantial number of men with aggressive disease
being missed . Finally, a comparison of systematic and
opportunistic screening suggested overdiagnosis and mor-
tality reduction by systematic screening versus a higher
overdiagnosis with at best a marginal survival benefit after
opportunistic screening .
Targeting men at higher risk of PCa might reduce the
number of unnecessary biopsies. These include men aged
>50 yr (>45 yr in African American men) or with a family
history of PCa. In addition men with a PSA >1 ng/ml at age
40 yr and >2 ng/ml at age 60 yr are at increased risk
of PCa metastasis or death several decades later. Risk
calculators developed from cohort studies may also be
useful in reducing the number of unnecessary biopsies.
None has clearly shown superiority over each other or can
be considered as optimal
Optimal intervals for PSA testing and digital rectal
examination (DRE) follow-up are unknown. A 2-yr interval
for men at increased risk, while it could be expanded up to
8 yr for those not at risk. The age at which to stop early
diagnosis should be based on individual’s life expectancy,
where comorbidity is at least as important as age . Men
who have <15 yr of life expectancy are unlikely to benefit.
All the available tools will still lead to some overdiagno-
sis. Breaking the link between diagnosis and active
treatment is the only way to decrease the risk of
overtreatment while maintaining the potential benefit of
individual early diagnosis for men requesting it ).
4. Diagnosis
PCa is usually suspected on the basis of DRE and/or an
elevated PSA. Definitive diagnosis depends on histopatho-
logic verification. Abnormal DRE is an indication for biopsy,
but as an independent variable, PSA is a better predictor of
cancer than either DRE or transrectal ultrasound (TRUS).
Table 3 – Follow-up data from the European Randomised Study of
Screening for Prostate Cancer study
Years of
follow-up
Number needed
to scree
Number needed
to trea
9 1410 48
11 979 35
13 781 27
* Number of men needed to screen or treat to avoid the death of disease of
one man.
Table 4 – Guidelines for screening and early detection
Recommendation LE GR
Do not subject men to PSA testing without counselling
them about the potential risks and benefits.
3 B
Offer an individualised risk-adapted strategy for early
detection to a well-informed man with a good
performance status and a life expectancy of at least
10–15 yr.
3 B
Offer PSA testing in men at elevated risk of having PCa:
Men aged >50 yr
Men aged >45 yr and a family history of PCa
African American men aged >45 yr
Men with a PSA level >1 ng/ml at age 40 yr
Men with a PSA level >2 ng/ml at age 60 yr
2b A
Offer a risk-adapted strategy (based on initial PSA level),
with follow-up intervals of 2 yr for those initially at risk:
Men with a PSA level >1 ng/ml at age 40 yr
Men with a PSA level >2 ng/ml at age 60 yr
Postpone follow-up to 8 yr in those not at risk.
3 C
Decide on the age at which early diagnosis of PCa should
be stopped based on life expectancy and performance
status; men who have a life expectancy <15 yr are
unlikely to benefit.
3 A
GR = grade of recommendation; LE = level of evidence; PCa = prostate
cancer; PSA = prostate-specific antigen.
Table 2 – International Society of Urological Pathology 2014 grade
group
Gleason score Grade group
6 (3+3 or 3+2 or 2+3 or 2+2) 1
7 (3 + 4) 2
7 (4 + 3) 3
8 (4+4 or 3+5 or 5+3) 4
9–10 5
* Grade groups can now be reported in addition to the overall or global
Gleason score of a prostate biopsy or radical prostatectomy.
E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 6 1 8 – 6 2 9 620