Prostate cancer screening - Worth a revisit?
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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?

Prostate 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 benefits.
So what’s the issue here?




1. Worrying trend

Emerging 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.


2. Misinterpretation of existing randomized data?


The 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)
It 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 (5).

3. Insufficient follow up time


16 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.


4. Lower metastatic rates, lower morbidity rates


12-year 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.



Conclusion


Considerations 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.
It 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.


 References:
  1. 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: 10.1056/NEJMsb2000250
  2. 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.
  3. 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.
  4. 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
  5. 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.
  6. Johansson JE, Andrén O, Andersson SO, et al. Natural history of early, localized prostate cancer. JAMA 2004; 291: 2713-9.
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Originally published 05 July 2020 , updated 05/07/2020

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