April 5, 2021

Prostate Cancer: To Screen or Not To Screen? The Question Is Complicated

Considerations to help guide patients through the decision-making process

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By Timothy Gilligan, MD

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Editor’s note: This article was originally published in the Cleveland Clinic Journal of Medicine.

Whether to screen for prostate cancer remains controversial due to the complexity of balancing the harms and benefits. Prostate cancer is the most common cancer in men and the second-leading cause of male cancer deaths. An estimated 192,000 men received the diagnosis during 2020, and 33,000 died from the disease. In contrast, lung cancer was diagnosed in about 116,000 men, and more than 72,000 died of it.1

The problem of prostate cancer overdiagnosis can be appreciated from autopsy studies. A review of 19 studies of autopsy-detected prostate cancer reported that in men age 70 to 79 who died of unrelated causes, 36% of white men and 51% of Black men were found to have malignant tumors in their prostate.2 Similarly, the Prostate Cancer Prevention Trial reported that biopsies reveal prostate cancer in 15% of men who had normal findings on digital rectal examination, normal prostate-specific antigen (PSA) levels, and no symptoms of the disease.3 Clearly, most cases of prostate cancer are not deadly, and yet tens of thousands of American men die of it each year.

Balancing the harms and benefits of screening

Decisions about screening are difficult mainly due to the adverse effects of treatment, which include urinary incontinence and erectile dysfunction. Men undergoing radiation therapy are also at risk for rectal bleeding from radiation proctitis and secondary (radiation-induced) cancers. Men who are treated and then develop a rising PSA without evidence of metastatic disease may then be treated with hormonal therapy, which, in that setting, has known side effects and harms but no proven benefit. In other words, a screening test can lead to a cascade of treatment decisions and consequences. Balancing harms and benefits depends, in part, on the individual man’s priorities and values; hence, shared decision-making is widely advocated.

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First, there is strong evidence of a disease-specific mortality benefit from screening. The European Randomized Study of Screening for Prostate Cancer reported that with 16 years of follow-up, there was roughly a 20% reduction in the risk of death from prostate cancer (hazard ratio 0.80, P < .001).4 Based on the study results, 570 men would need to be invited to undergo screening to prevent one death from prostate cancer. Similarly, one death was prevented for every 18 cases diagnosed.

Second, decision-making has become more sophisticated and individualized about whom and when to biopsy, how to perform the biopsy, and, if cancer is diagnosed, which cancers need active treatment. These changes have mitigated the cascade from elevated PSA to biopsy to surgery or radiation therapy. The trend is toward reducing the burden of overdiagnosis by being more selective regarding who gets biopsied and who gets treated.

It’s also worth noting that worrisome changes in prostate cancer epidemiology have occurred since the use of PSA screening tests became less common after the US Preventive Services Task Force recommended against screening.5 With less screening, the diagnosis of clinically localized disease has declined while the incidence of locally advanced and metastatic disease has increased.6 For instance, between 2010 and 2016, the incidence of metastatic prostate cancer in men over age 75 increased 5% per year on average.7 The implication of the rising number of men with metastatic disease at diagnosis, given that metastatic prostate cancer is incurable, is that prostate cancer mortality may start to increase after decades of decline. Thus, while the problem of overdiagnosis has been reduced, the cost of that progress is likely to be more prostate cancer deaths.

The answer? Continue to improve screening tools

The best path forward is not more screening or less screening, but rather to continue to develop better screening tests and algorithms for deciding who stands to benefit from early diagnosis and treatment. In the meantime, shared decision-making remains appropriate. Prostate cancer screening reduces prostate cancer deaths, but at a cost. Different men will weigh the harms and benefits differently.

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References

  1. Howlader N, Noone AM, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975–2017, National Cancer Institute. Bethesda, MD, based on November 2019 SEER data submission, posted to the SEER website April 2020. https://seer.cancer.gov/csr/1975_2017. Accessed December 15, 2020.Google Scholar
  2. Jahn JL, Giovannucci EL, Stampfer MJ. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the prostate-specific antigen-era. Int J Cancer 2015; 137(12):2795–2802. doi:10.1002/ijc.29408CrossRefPubMedGoogle Scholar
  3. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349(3):215–224. doi:10.1056/NEJMoa030660CrossRefPubMedGoogle Scholar
  4. Hugosson J, Roobol MJ, Mansson M, et al.ERSPC Investigators. A 16-yr follow-up of the European Randomized Study of Screening for Prostate Cancer. Eur Urol 2019; 76(1):43–51. doi:10.1016/j.eururo.2019.02.009CrossRefPubMedGoogle Scholar
  5. Lee DJ, Mallin K, Graves AJ, et al. Recent changes in prostate cancer screening practices and epidemiology. J Urol 2017; 198(6):1230–1240. doi:10.1016/j.juro.2017.05.074CrossRefGoogle Scholar
  6. Sheng IY, Wei W, Chen Y-W, et al. Implications of the United States Preventive Services Task Force recommendations on prostate cancer stage migration. Clin Genitourin Cancer 2020 Jul 11; S1558–7673(20)30145–2. doi:10.1016/j.clgc.2020.06.006CrossRefGoogle Scholar
  7. Jemal A, Culp MB, Ma J, Islami F, Fedewa SA. Prostate cancer incidence 5 years after US Preventive Services Task Force recommendations against screening. J Natl Cancer Inst 2020 May 20;djaa068. doi:10.1093/jnci/djaa068CrossRefGoogle Scholar

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