Research digest: Easy
to digest updates on articles published in high impact journals.
Title: Reconsidering the
Trade-offs of Prostate Cancer Screening (1)
Type: Research update
Published: June 18, 2020
Journal: The New England
Journal of Medicine
Prostate Cancer screening – Worth a revisit?
cancer is the most common cancer in men and second most common cause of male
cancer death in the United Kingdom. The advent of prostate-specific antigen
(PSA) testing in the early 1980s resulted in a surge of prostate cancer
diagnosis, but its use for prostate cancer screening has fallen out of favor
over the years, replaced by a general consensus that the harms outweigh the
what’s the issue here?
1. Worrying trend
data suggests that the incidence of metastatic prostate cancer at diagnosis is
on the rise despite having been on a decrease up till 2010 (2). This could have
been associated with the decreased efforts in screening, therefore reduction in
diagnoses made in earlier stages of prostate cancer.
of existing randomized data?
Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial and European
Randomized Study of Screening for Prostate cancer (ERSPC), arguably forms the
basis of the current opinion regarding prostate cancer screening. PLCO found no
significant difference in mortality rates while ERSPC reported a 21% reduction in
the intervention i.e. screening arm (3, 4)
is suggested that the evaluation of screening efficacy (versus no screening),
may not be appropriate in the PLCO trial as a large proportion (~90%) in the
control group had undergone PSA testing. The possibility of a selection bias of
‘prostate cancer-free’ individuals in the control group cannot be ignored, as
it may result in a narrower margin of overall survival advantage in the
screening group. The conflicting results between both trials may be due to
differences in demographics, design and practice settings among many (5).
However, a recent analysis that accounted for the difference in implementation
and practice settings, found that there was no difference in screening efficacy
(relative to no screening) between both trials and this common effect of
screening was a significant reduction in the risk of prostate cancer mortality
follow up time
years of follow up from randomization in the ERSPC trial may be insufficient to
evaluate the survival advantage of screening, given that screening in men
happens around the age of 50 but the median age of death from prostate cancer
is 80 years old. Results from a 21-year follow up trial in men with clinically
detected prostate cancer showed that the absolute number of person-years
mortality from prostate cancer tripled in the period after the first 15 years post-diagnosis
(6). Therefore the magnitude of long term benefit is still unclear and may well
be greater than is observed in the 16-year follow up of the ERSPC trial.
metastatic rates, lower morbidity rates
data from centers participating in the ERSPC showed an absolute risk reduction
of metastatic disease incidence as a result of screening. The quality of life
in individuals with metastatic disease is much poorer than those of earlier
stages in many aspects. Therefore, screening could have an additional benefit
of reducing morbidity associated with prostate cancer by preventing a portion of
individuals from progressing to advanced stages.
involved in the entire picture of prostate screening is of course of a higher complexity
than discussed here. Among them is the cost of screening and detection. Perhaps
the biggest concern is regarding the impact of physical, emotional and social
well-being of the patient as a result of cancer over-diagnosis and over-treatment.
However, these issues may potentially be overcome in the future as seen in
recent promising refinements in diagnosis and management strategies.
is possible that the balance of benefit versus harm in prostate cancer
screening could be more favorable than as currently appreciated, especially
after taking into account the fast-paced advancements made in medicine. Continuous
exploration in search for a conclusive result would be vital given the impact
it will have on regular clinical practice.
Jonathan E. Shoag, Yaw A. Nyame, Roman Gulati, Ruth Etzioni et al.
Reconsidering the Trade-offs of Prostate Cancer Screening. N Engl J
Med 2020;382:2465-2468. DOI:
Hu JC, Nguyen P, Mao J, et al. Increase in prostate cancer distant
metastases at diagnosis in the United States. JAMA Oncology 2017; 3: 705-7.
Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer
mortality: results of the European Randomised Study of Screening for Prostate
Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384: 2027-35.
Andriole GL, Crawford ED, Grubb RL 3rd, et al. Prostate cancer screening
in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening
Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst.
2012;104 (2):125-132. doi:10.1093/jnci/djr500
Tsodikov A, Gulati R, Heijnsdijk EAM, et al. Reconciling the effects of
screening on prostate cancer mortality in the ERSPC and PLCO trials. Ann Intern
Med 2017; 167: 449-55.
Johansson JE, Andrén O, Andersson SO, et al. Natural history of early, localized
prostate cancer. JAMA 2004; 291: 2713-9.
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