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Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Prostate-specific antigen (PSA) testing can identify early prostate cancer, and when , prostate cancer is almost always curable. But the incidence of prostate cancer has increased by about 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases. This comes on the heels of steep declines in previous years.

According to that latest from the American Cancer Society (ACS), the incidence of advanced-stage prostate cancer has increased by 4-5% annually since 2011. In 2019, 8% of cases had distant stage disease at diagnosis, compared with 4% in 2011, and 14% had regional stage disease at diagnosis, versus 11% in 2011, for a total of 22% of cases with advanced stage disease at diagnosis.

"We have had progress the past few decades in prostate cancer, with steep reductions in incidence and mortality. The new data indicate that progress may be reversing, said Rebecca L. Siegel, MPH, the ACS's senior scientific director of Surveillance Research. "Increased incidence is driven by diagnosis of advanced stage disease, which is more difficult to treat."

Changes in PSA Screening Recommendations

The rise in cases of lethal prostate cancer may be partly linked to recommendations against PSA screening for healthy men. for men ages 75 and older, and .

With recommendations against screening, many physicians stopped having conversations with patients about PSA testing. to informed decision-making in men ages 55 to 69. But the Task Force recommendations against screening led to delayed diagnoses and more prostate cancer cases at advanced stages with higher-grade tumors.

Unlike USPSTF, , advising since 2009 that men age 50 and older have a conversation with their primary care physician about the benefits and harms of PSA testing, as long as they have 10 years of life expectancy (prior to that ACS did recommend both digital rectal examination and PSA testing). Black men and those with a family history of prostate cancer, who are at increased risk, should have the conversation at age 45, the ACS recommendations state.

Overdiagnosis, Overtreatment

The use of PSA screening, however, can lead to both overdiagnosis and overtreatment. Many prostate cancers are slow-growing and may never result in harm or shorten life. "Finding these cancers represents an overdiagnosis as it likely never would have become clinically evident on its own," explained Samuel Haywood, MD, of the Cleveland Clinic. "Once a prostate cancer has been diagnosed, there exists the risk for overtreatment, where men receiving treatment for prostate cancer experience the side effects of treatment without significant benefit to their life."

At the peak of use of PSA testing, an estimated 40% of new prostate cancer diagnoses were overdiagnoses, said Siegel. PSA testing in and of itself is not a very precise method for detecting prostate cancer. Small anomalies that are diagnosed as cancer may just be part of the normal aging process. "A large percentage of men at autopsy have prostate cancer, but that is not their cause of death. We have not been able to distinguish normal changes that progress to cancer," said Siegel.

In the past, when a patient was diagnosed with early stage, low-risk prostate cancer, the physician recommended treatment. Now active surveillance is recommended. Treating men for low-risk cancer that would not have shortened their lives can lead to long-term side effects and toxicities that can impact quality of life.

"We have to use PSA screening smartly," said Ash Tewari, MD, director of the Department of Urology at the Icahn School of Medicine at Mount Sinai in New York City. "Once we find cancer, not every prostate cancer needs intervention. Not every prostate cancer tested with PSA needs a biopsy, and we can do imaging before biopsy now. It's disappointing that we took PSA testing, part of effective screening, out of physicians' hands, which contributed to the rise in mortality."

Most academic institutions use advanced PSA screening, considering a patient's age and life expectancy, PSA velocity, noting the doubling time, and following PSA sequentially, Tewari added, noting that PSA density is also adjusted for prostate volume.

Increased Screening for Black Men

To increase awareness of PSA screening, Mount Sinai created a program to take screening directly into communities. A mobile screening outreach unit delivers point-of-care PSA testing approved by the New York State Department of Health. The mobile facility has screened approximately 2,140 men for prostate cancer over the past year throughout New York City, Long Island, and Westchester and Orange counties. "With this technology, we can deliver PSA test results in just 20 minutes," Tewari said. "We found that 18% of these men had elevated PSA levels, and 7% of them required surgery, follow-up treatment, and active surveillance."

Taking testing into neighborhoods is particularly important for Black men, Tewari noted. In the new ACS data, than white men. Death rates from prostate cancer were two to four times higher in Black men than men in every other racial and ethnic group.

Over the last few decades, Black men have had twice the mortality from prostate cancer as other men. This is due to a combination of factors, including lack of access to high-quality healthcare, education, and socioeconomic factors, which leads to a dearth of early detection and treatment. "Black men may also have comorbidities, such as diabetes, metabolic disease, obesity, and pulmonary embolism, which increases mortality, and their genomic pathways may be more aggressive to start with," Tewari said. "Prostate cancer tumors in Black men tend to be more inflamed, with more T cells and lymphocytic infiltration."

African ancestry is the strongest risk factor for prostate cancer, for unknown reasons. Many studies show that once diagnosed, Black men are less likely to receive any treatment or high-quality treatment, which results in a greater disparity in mortality. When treatment is equal, Black men have the same or even lower mortality rates compared with white men, said Siegel.

Minimizing Death and Metastatic Disease

Clinicians can minimize the trend toward more death and possibly more metastatic diseases at the time of diagnosis by following screening guidelines for early detection, Siegel said. "When testing is decided upon, take advantage of recent advances in more targeted screening using molecular markers and MRI to target biopsies." It's important to find cancers early on. Once prostate cancer has spread far from the original tumor, the .

If clinicians come across beliefs in patients regarding prior guidelines recommending against PSA screening, they can address this with discussions of current guidelines, said Haywood. "Despite changing guidelines over the past years, PSA testing remains an important cancer screening tool in appropriate men. With rising rates of cancer diagnosis and diagnosis of aggressive cancer, this is an important test to consider for the patient."

The key is shared decision-making, said Tewari. "Discuss the pros and cons of PSA testing. Not every positive PSA result requires an intervention. Explain that we have new treatments that lead to less morbidity so the patient can live longer and better. Most treatments are nerve-sparing, but if the diagnosis is delayed, this may impact a man's sexuality."

Read previous installments in this series:

Part 1: Prostate Cancer: Epidemiology, Diagnosis, and Treatment

Part 2: The Latest on Prostate Cancer Diagnosis