SIU 2019: An Epidemiologist’s View of Prostate Cancer Screening

Athens, Greece (UroToday.com) Dr. Carlsson gave an encompassing presentation on prostate cancer screening from the perspective of an epidemiologist.

She began discussing the factors that affect prostate cancer mortality. Three distinct factors can reduce the mortality of prostate cancer. These include:

1. Removal of carcinogens
2. Better treatments
3. Screening

The World Health Organization (WHO) defines screening as the presumptive identification of unrecognized disease in an apparently healthy, asymptomatic population by means of tests, examinations or other procedures that can be applied rapidly and easily to the target population. For prostate cancer, there are two main screening tests – digital rectal examination (DRE) and prostate-specific antigen (PSA) test.

The use of PSA as a disease marker was initialized in 1987-1991 in the USA and Europe. The level of PSA in early midlife was found to identify men at an increased risk for prostate cancer metastases. It was shown that if PSA was at the top 10% (>=2.4 ng/ml) in young men (40-55 years) there was a 5% risk of metastases after 20 years.¹ This risk dropped to 0.3% if PSA was below the median (<0.9 ng/ml.)¹

There have been three large randomized trials assessing prostate cancer PSA screening:

1. 18 years ago - the Goteborg randomized trial²
2. 17 years ago – the PLCO trial³
3. 16 years ago – the ERSPC trial⁴

The ERSPC trial, assessing men aged 50-70 years, showed that standard PSA screening every 2-4 years reduces prostate cancer mortality by 20% after 16 years with a relative risk of (RR 0.8 [95% CI 0.72-0.89, P<0.001]).⁴ The PLCO trial provided similar evidence.

PSA screening has some benefits including a reduction in metastases rate and prostate cancer-specific death. On the other hand, the harms of PSA screening include false-positive results, overdiagnosis, and overtreatment. However, Dr. Carlsson notes that is important to remember that potential benefits and harms of screening ultimately depend on the geographic location of the patient. A good example is that in Northern Europe the incidence and mortality are higher compared to that of Mediterranean countries.

Prostate cancer is the second most frequent cancer and the fifth leading cause of cancer death in men (Figure 1), with lung cancer remaining the leading cause of cancer incidence and mortality worldwide.

 Figure 1 – Ten most common cancers in males in 2018:

Importantly, prostate cancer is the most frequently diagnosed male cancer in more than half of the countries of the world (105 out of 185) (Figure 2). In Sweden and Greece for example, the yearly incidence rate is 95.5 and 16.2, respectively, per 100,000 men, showing the significantly higher rate of Northern European countries. 

 Figure 2 – Highest incidence of cancers in the world in 2018

 Prostate cancer has also been shown to be the leading cause of cancer death among men in 46 countries, with 359,000 deaths reported in 2018 (Figure 3). 

 Figure 3 - Cancers with the highest mortality rates worldwide in 2018:

The mortality rate of prostate cancer has been increasing in some countries (Central and South America, Central and Eastern Europe, Asia) while decreasing in other countries (Northern America, Northern, and Western Europe, developed countries of Asia, and Oceania). The highest prostate cancer incidence and mortality rates have been reported in Guadeloupe and Barbados (Figure 4).

 Figure 4 – Worldwide incidence and mortality rates reported in 2018:

Dr. Carlsson moved on and summarized several of her reflections on the epidemiology of prostate cancer screening. First, prostate cancer screening can reduce prostate cancer mortality – this has been proven many times. However, screening can also cause harm (overdiagnosis, overtreatment). Importantly, we have the knowledge to screen in a “smarter” manner, which keeps the benefits and reduces the harm. Screening could be regarded as a public health need, but it depends on the setting/country of the patient, burden of prostate cancer, life expectancy in the specific country and available resources.

Dr. Carlsson continued and described the 5 golden rules that she recommends regarding prostate cancer screening:

1. Always get consent from the patient whether to perform screening (using shared decision making and discussing benefits and harms)
2. Do not screen men who will not benefit from screening such as those with multiple comorbidities and short life expectancy 
3. Do not perform a prostate biopsy without a compelling reason – as biopsies can lead to significant infectious complications
4. Do not treat low-risk prostate cancer disease – make sure you utilize the strategy of active surveillance if appropriate
5. If you have to treat, refer men to a high-volume provider, as data show that radical prostatectomy performed by experienced surgeons can have a significant impact on oncological and functional outcomes⁵

Dr. Carlsson concluded her talk mentioning the addition of the multiparametric MRI (mpMRI) into the diagnosis of prostate cancer. mpMRI improves the detection of significant prostate cancer, decreases the number of unnecessary biopsies, and reduces overdiagnosis.⁶ However, a negative mpMRI does not obviate the need for systematic biopsy, as a negative mpMRI can miss 9-20% of clinically significant prostate tumors.⁷ Importantly, the negative predictive value of mpMRI depends on the disease prevalence. Moreover, all published studies on mpMRI performed in biopsy-naive patients have been conducted in specialized centers only, not necessarily manifesting the results of most centers, that consist of lower volumes. In order to be successful, the concept of mpMRI in biopsy-naïve patients requires access to high- quality mpMRI studies, optimal reading of scans, a robust training program for radiologists, and access to high-quality mpMRI- targeted biopsy. 

Dr. Carlsson ended her talk mentioning the highlight points of her talk:

1. Prostate cancer incidence and mortality vary greatly across the globe
2. Male life expectancy and health care resource vary globally as well
3. Prostate cancer is a heterogeneous disease
4. Screening may or may not do more good than harm
5. “One size” screening does not fit all

Presented by: Sigrid Carlsson, MD, Ph.D., MPH, Assistant attending Epidemiologist at the Memorial Sloan Kettering Cancer Center,  New York, NY

Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan at the 39th Congress of the Société Internationale d'Urologie, SIU 2019, #SIUWorld #SIU2019, October 17-20, 2019, Athens, Greece

References: 

1. Vickers AJ, Ulmert D, Sjoberg DD, et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study. BMJ : British Medical Journal 2013; 346: f2023.

2. Hugosson J, Godtman RA, Carlsson SV, et al. Eighteen-year follow-up of the Goteborg Randomized Population-based Prostate Cancer Screening Trial: effect of sociodemographic variables on participation, prostate cancer incidence and mortality. 2018; 52(1): 27-37.

3. Pinsky PF, Prorok PC, Yu K, et al. Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years. Cancer 2017; 123(4): 592-9.

4. Hugosson J, Roobol MJ, Månsson M, et al. A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer. European Urology 2019; 76(1): 43-51.

5. Eastham JA. Do high-volume hospitals and surgeons provide better care in urologic oncology? Urologic oncology 2009; 27(4): 417-21.

6. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. New England Journal of Medicine 2018; 378(19): 1767-77.

7. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017; 71(4): 618-29.