Page 3 - Canadian Urological Association recommendations on prostate cancer screening and early diagnosis

Rendon et al

reduction in prostate cancer mortality was seen at up to imperative that we not only separate the diagnosis of prostate
18 years of followup, with a relative risk reduction of 42% cancer from the treatment of prostate cancer, but that we
and 139 patients being invited for screening to prevent one institute improved screening and early detection practices to
17
prostate cancer death. Although there was also contami- decrease the risk of detecting clinically insignificant disease.
nation of the control arms in both the ERSPC and Goteborg The CUA recognizes that PSA screening may not be the
trials, the estimated proportion of control patients receiving best option for all men. Balancing the known benefits and
PSA testing is significantly lower than those in the PLCO risks of PSA screening is difficult and is significantly influ-
trial. 11,18,19 Overall, based on currently available evidence enced by personal values. As such, the decision of whether
from randomized, controlled trials, it appears as though or not to undergo prostate cancer screening is, and will likely
organized PSA screening results in a reduction in pros - remain, an individualized decision. In order to reach this
tate cancer mortality. To add to these currently available decision, the CUA recommends that healthcare providers
studies, the initial results from the cluster randomized trial engage in a thorough discussion on the potential risks and
of PSA testing for prostate cancer (CAP trial), a large ran- benefits of PSA screening with their patients and that shared
domized trial including over 400 000 patients in the U.K. decision-making be performed.
randomized to PSA screening or standard care, will likely
provide further information on the effects of PSA screening Best screening practices
in the near future. 20
There is also weaker evidence from epidemiological stud- When prostate cancer screening is performed, the overarch-
ies on the effect of PSA screening. Prostate cancer mortal- ing goal should be the early detection of clinically significant
ity has declined since the introduction of PSA screening in prostate cancer in healthy men while minimizing the detec-
North America. 21-23 While we cannot know with certainty tion and treatment of low-risk disease. Screening studies
why mortality has declined, modelling studies indicate that are challenging to conduct because of the large numbers
the most plausible and largest contribution to mortality of participants required, risk of contamination, loss to fol-
reduction is from screening. 23-27 Additionally, there has been lowup, and many other pitfalls. It is not feasible to evalu-
a decrease in the incidence of prostate cancer diagnosis in ate most questions regarding timing and administration of
recent years in the U.S., which is likely a result of decreased PSA directly. In this context, the CUA provides the follow-
screening use. 28-30 This has been associated with a stage ing recommendations based upon the inclusion criteria of
migration towards higher stage and more frequent meta- randomized trials and high-quality observational studies to
static disease. 30,31 While more time is required to determine encourage “smart” screening. Our aims are to maintain ben-
whether this recent stage migration will result in an increase efits and mitigate potential harms associated with screening.
in prostate cancer mortality, we believe that reducing the 2. For men electing to undergo PSA screening, we sug-
morbidity of advanced and metastatic prostate cancer is in gest starting PSA testing at age 50 in most men and
itself an important outcome. Although these observations at age 45 in men at an increased risk of prostate
were not directly used by the guideline panel when consid- cancer (Level of evidence: 3; Grade of recommen-
ering recommendation for PSA screening, the underlying risk dation: C).
of under-diagnosis of high-risk disease remains a concern. Justification: Although the optimal age for starting PSA
Although the available evidence suggests there are ben- screening has not been vigorously studied, our recommen-
efits to prostate cancer screening in terms of reduction in dation for starting PSA screening at age 50 comes from the
mortality, there are also significant potentials harms of over- Goteborg trial, which provides randomized data on the
11
diagnosis and over-treatment. Indeed, up to 67% of men benefits of screening in men starting at this age; however,
diagnosed with prostate cancer by screening will be identi- evidence from observational studies suggests that certain
fied as having clinically insignificant prostate cancer, which, men may benefit from PSA screening at an earlier age, with
if never detected, would be unlikely to lead to increased a nearly 5% risk of developing lethal prostate cancer within
morbidity or mortality. 32-36 Thus, if screened, men with insig- 15 years for men aged 45 ‒49 with a PSA >4 ng/ml. 38,39
nificant disease may be unnecessarily exposed to the poten- Although it remains unclear which men will benefit from
tial harms of both prostate biopsy and treatment in addition early PSA screening, family history imparts a substantially
to the psychological effects accompanying a prostate cancer increased risk of prostate cancer diagnosis at a younger age.
diagnosis. The increased use of active surveillance for low- Particularly, men aged <50 with a family history of prostate
risk prostate cancer in Canada has been an important step cancer in a first- or second-degree relative have an approxi-
in reducing the over-treatment of prostate cancer; however, mately five-fold and two-fold increased risk of receiving a
active surveillance does not eliminate the issue of over- prostate cancer diagnosis, respectively. 38
diagnosis and itself is associated with significant potential The potential benefits and harms of PSA screening for
37
detriments to quality of life. With these risks in mind, it is men less than age 45 has not been prospectively studied;

300 CUAJ • October 2017 • Volume 11, Issue 10