Study: Metastatic prostate cancer cases increased as screening use declined

Contents

STUDY AT A GLANCE

What is this study about?

This study reports on trends in the diagnosis of metastatic prostate cancer between 2004 and 2018. The study authors draw a connection between an increase in cases and a decline in the use of PSA testing for prostate cancer screening. They look at the increase in cases between 2010-11 and 2018 during a time when changes in PSA screening guidance were issued by the United States Preventive Services Task Force (USPSTF).
 

Why is this study important?

Prostate cancer is the most common cancer among men. Approximately 1 in 8 men will develop prostate cancer in their lifetime. Prostate cancer is the second leading cause of death among American men. Black men are more likely to die of prostate cancer than men of other races.

The screening test for prostate cancer is called a prostate-specific antigen (PSA) test. It is a blood test that measures the level of PSA in the blood. PSA is a protein found in both normal cells and cancer cells. A higher PSA level is linked to an increased risk of prostate cancer. The PSA test has been used to screen for prostate cancer since the early 1990s.

Despite the prevalence of prostate cancer, the use of prostate cancer screening is not straightforward for these reasons:

• The results of a PSA test are not always clear there is not one level or number for PSA that confirms cancer.
• Factors other than cancer can cause a high PSA.
• False positives and false negatives occur in PSA testing, and both are a problem. Many people with prostate will have a low PSA score.
  • Only about 25% of people who have a prostate biopsy following a high PSA test are found to have cancer.
  • In the case of a false positive, cancer is often discovered through a biopsy. Prostate biopsies can cause complications although most are not serious.  
• Many (but not all) prostate cancers can be slow growing and may never lead to problems or early death. At the same time, prostate cancer treatment can cause side effects. For this reason, there is concern about the possibility of overtreating prostate cancers.

As a result, PSA screening became controversial. It was not clear if the overall benefit of frequent screenings outweighed the risks. The U.S. Preventive Services Task Force changed its guidance in 2008 to recommend against prostate cancer screening after age 74. In 2012, it expanded this recommendation to include people 45 and older.

This study looks at trends in metastatic prostate cancer diagnosis over a period when use of the screening changed. It attempts to understand how these changes affected the number of men being diagnosed with metastatic disease. This study looked at these trends through 2018. The findings may inform public health guidance around the use of prostate cancer screening in the future.
 

Prostate screening guidelines and changes over time

The USPSTF’s prostate cancer screening guidelines have changed over time and continue to be updated as doctors learn more.

In 2008, the USPTF looked at data on the drawbacks of screening, particularly:

• a high number of false positives leading to unneeded and sometimes harmful biopsies
• overtreatment of people whose high PSA level might not progress to aggressive cancer
• little to no reduction in prostate cancer deaths as a result of screening

Based on this evidence, the USPSTF recommended against screening for men 75 and older. The change led to a decline in prostate cancer cases among older men.

A few years later, the USPSTF extended this guidance to all men over 45. Starting in 2012, annual PSA tests were not recommended for anyone over 45. Fewer people were diagnosed with prostate cancer in the years that followed.
 

The guidelines today

The guidelines for PSA screening focus on shared decision making between patients and clinicians. This chart describes the guidelines issued by three key organizations – the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network, and the American Cancer Society. All three groups support discussion between patients and clinicians about the uncertainties, risks and benefits of screening. The age at which each organization recommends this conversation should start varies.

Study findings

This study looked at trends in prostate cancer diagnosis, specifically in the diagnosis of metastatic or stage 4 prostate cancer. The researchers analyzed data on prostate cancer cases from the Surveillance, Epidemiology, and End Results (SEER) database.

The database includes information on more than 800,000 people with prostate cancer. The study looked at rates of metastatic prostate cancer by two age groups – men ages 45 to 74 years old and those 75 and older.

The data showed an increase in metastatic prostate cancer diagnoses starting in the years 2010-2012. This upward shift in later stage cancer occurred at a time when the overall number of prostate cancer cases was lower. Broken down by age group, the data show:

Among men 45-74 years old:

• The rate of new diagnoses of metastatic prostate cancer was stable in men ages 45 to 74 between 2004 and 2010.
• The rate of new diagnoses of metastatic prostate cancer increased 41% between 2010 and 2018.

Among men 75 and older:

• The rate of metastatic prostate cancer declined between 2004 to 2011.
• The rate of metastatic prostate cancer increased by 43% between 2011 and 2018.

These trends were seen across all races but were especially significant in non-Hispanic white men.

This report suggests that the increase in cases beginning in these years is a result of the changes in screening guidance. Fewer screenings led to delays in diagnosis, resulting in more cases being found at the metastatic stage.
 

Strengths and limitations

Strengths

• The study used data from the Surveillance, Epidemiology, and End Results (SEER) database, an established U.S. population-based data set. SEER tracks cancer cases. It is the only  U.S. population-based data set containing stage of disease at diagnosis information. Data on deaths due to prostate cancer in SEER come through the National Center for Health Statistics.
• Stage of disease was defined using two staging systems (SEER stage and AJCC TMN Staging System) which ensures greater accuracy.
• The large data set includes enough cases for the findings to be statistically significant.
• The study looks at trends over a period of 14 years, a timeframe that allows researches to follow how changes in screening practices affected stage of diagnosis.
   

Limitations

• The screening or diagnosis history of respondents with metastatic prostate cancer is unknown. The authors assume that fewer survey respondents were screened after the screening guidance changed.
• SEER data do not reflect the whole U.S. population.
• SEER data do not collect information on inherited mutations that increase the risk for prostate cancer and for more aggressive disease.
• This study only looks at data up to 2018, when screening recommendations changed again. It would be informative to follow prostate cancer screening trends after 2018.
• This study does not look at trends in prostate cancer deaths.
   

Context

This study documents what some in the medical community may have expected – that screening for prostate cancer less often can lead to more cancer cases being found at a later stage. It does not provide information on whether more people will die of prostate cancer because of less screening. In fact, some research has shown that annual prostate cancer screenings do not result in fewer deaths from prostate cancer.

This study looked at cancer cases through 2018. In 2018, the USPSTF updated its recommendation. The revised USPSTF guidance, which still stands, says that men between 55 and 69 years old should decide whether and how often to get screened based on a discussion of the potential benefits and harms with their doctors. Doctors should not order PSA tests for men who do not want to have the test. The recommendation not to do annual PSA screenings of men over 70 currently stands. The American Cancer Society (ACS), the National Comprehensive Cancer Network (NCCN), and the American Urological Association offer similar guidance, with ACS encouraging conversations starting at age 50. Refer to the table for updated screening guidelines, which vary based on risk. People with an inherited mutation in a gene linked to prostate cancer are advised to start screening conversations earlier. Similarly, for Black men, screening usually begins at an earlier age; however, whether this is beneficial requires more research.

PSA testing for average risk men remains somewhat controversial for reasons mentioned earlier. Yet, doctors have been trained to take more care now to balance the risks and benefits of screening and treatment. They seek to avoid possible harm from invasive procedures or unnecessary treatment by following up on a high PSA test with:

• magnetic resonance imaging (MRI) testing to help with diagnosis
• active surveillance in otherwise healthy patients to see how the PSA count changes over time

At the same time, doctors still aim to quickly treat early-stage cancers that could develop into metastatic prostate cancer. This may include gathering additional information, including personal and family health history, biomarker testing of the cancer, and genetic testing for an inherited mutation.

Even though the guidelines focus on informed individual decisions, a new study found that 26% of cancer centers still recommend the PSA test for all men starting around age 50. More than three-quarters of cancer centers (78%) do not recommend an age at which to stop screening.
 

Conclusions

The diagnosis of metastatic prostate cancer is on the rise. The increase began in the years after USPTSF recommended against screening. The assumption of these authors was that doctors likely followed the revised screening recommendations and used PSA testing less often.

Since this study was completed, screening guidance has changed again. The current guidance encourages discussion about screening for men starting at 50 or 55 and ending at age 69. It encourages shared decision making between doctors and patients. More research is needed to see how this approach will affect prostate cancer cases over time. Some research also suggests that doctors do not uniformly follow the guidance of major public health and medical organizations.

In the meantime, prostate cancer screening continues to cause confusion for many This study provides additional perspective on prostate cancer screening but may not answer all your questions.
 

What does this mean for me?

If you are male or were assigned the sex male at birth, you may have questions about whether to get a PSA test. Your doctor may ask you if you are interested in PSA testing. Doctors who follow current guidelines (refer to table), will talk with you about the possible risks and benefits of having or not having the PSA test. Your doctor should assess your personal risk for prostate cancer as part of this discussion.

This conversation can help you decide what to do. If your doctor has not discussed PSA testing with you, you should bring it up. When you talk with your doctor, be sure to share:your personal and family history of cancer on both sides of the family. Having a family history of prostate or other cancers or being Black may increase your risk. Some inherited mutations, including BRCA1 and BRCA2, can also increase the risk for prostate cancer. These genes are also linked to breast, ovarian and pancreatic cancers. Inherited mutations in BRCA2 are linked to an aggressive prostate cancer that is more likely to become metastatic. Depending on the gene, men at increased risk for prostate cancer due to an inherited mutation may have different screening recommendations than men without mutations.

Some doctors recommend a digital rectal exam (DRE) along with a PSA test. In DRE, the doctor exams the prostate area by inserting a finger in the rectum. This exam can be helpful, especially if performed by a skilled doctor, but it also can miss cancers.

If you decide to screen and your PSA screening test shows a high level, talk with your doctor about next steps. Increasingly, doctors recommend keeping an eye on the PSA level and other symptoms in otherwise healthy people before rushing into a biopsy or treatment. Your doctor may call this “watchful waiting” or “active surveillance.”

References

Desai MM, Cacciamani GE, Gill K, Zhang J, Liu L, Abreu A, Gill IS, Trends in incidence of metastatic prostate cancer in the US. Journal of the American Medical Association Network Open. 2022;5(3): e222246.

Hoffman RM, Striking the right balance with prostate cancer screening. Journal of the American Medical Association Network Open. 2022;5(3):222174.

FDA approves Pluvicto for metastatic castration-resistant prostate cancer. U.S. Food and Drug Administration. Accessed April, 2022.

Grossman DC, Curry SJ, Owens DK, et al., Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. Journal of the American Medical Association; 2018; 319(18):1901-1913.

Key statistics for prostate cancer. American Cancer Society. Revised January 12, 2022.

Koh ES, Lee AJ, and Ehdaie B, Comparison of US Cancer Center Recommendations for Prostate Cancer Screening With Evidence-Based Guidelines. Journal of the American Medial Association Internal Medicine; 2022. Published online March 7, 2022.

Prostate cancer screening. National Cancer Institute. Accessed April, 2022.

Surveillance, Epidemiology, and End Results Program. National Cancer Institute. Accessed April, 2022.
 

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests, and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 6/13/22