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Prostate Cancer: Epidemiology, Diagnosis, and Treatment

— Introductory overview about the second most common cancer in men worldwide

MedpageToday
Illustration of the letter i on a piece of paper over a hand over a prostate with cancer
Key Points

"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 cancer is the in men worldwide. An estimated 288,300 will be diagnosed in the U.S. in 2023 and 34,700 men will die from the disease, according to the American Cancer Society (ACS). The incidence of prostate cancer is more than 70% higher in Black men than in white men, for as yet unknown reasons.

The in the U.S. is 112.6 per 100,000 men, according to data from the NCI's Surveillance, Epidemiology, and End Results Program. In the U.S., a man's lifetime risk of the disease is estimated to be 11.2%, with a median age of diagnosis of 67. Prostate cancer is rarely diagnosed before age 45, although the incidence rises steadily from age 45 through 70, and then declines after 70.

Incidence rates of prostate cancer in the U.S. almost doubled from the late 1980s into the early 1990s with the introduction of prostate-specific antigen (PSA) testing, which mostly detects early-stage disease. The from 2007 to 2014, coinciding with reduced PSA testing due to a revision in the screening recommendations of the U.S. Preventive Services Task Force.

The 2023 ACS report on cancer statistics shows that after two decades of decline, from 2014 to 2019 and by about 5% per year for advanced-stage diagnoses.

Prostate cancer mortality has been trending down. The death rate peaked in 1993 (39.3 per 100,000 men) and was cut in half by 2013 (19.3 per 100,000 men), largely due to earlier detection through PSA testing and advances in treatment. The pace of decline has since slowed -- most likely related to an increase in diagnosis of advanced-stage disease. From 2016 to 2020, the by 0.6% per year, from 19.4 to 18.5 per 100,000 men.

"Prostate cancer is a disease that is very survivable when diagnosed early. Screening is the best way to find cancer early, but for prostate cancer we need to focus on finding and managing potentially fatal disease," said Timothy R. Rebbeck, PhD, professor of Cancer Prevention at the Harvard T.H. Chan School of Public Health and professor of Medical Oncology at Dana-Farber Cancer Institute in Boston. "Because Black men suffer disproportionately from fatal prostate cancer, special attention needs to be paid to their screening and management."

Risk Factors

The risk factors for prostate cancer include older age, African American ancestry, family history of the disease, and certain inherited genetic conditions, such as Lynch syndrome and BRCA1 and BRCA2 mutations. Smoking and excess body weight may increase the risk of aggressive or deadly disease.

Genetics plays a central role in prostate cancer risk and outcomes, contributing to more than half of all prostate cancers. "Prostate cancer has very few non-genetic risk factors, and is probably the most genetically driven of all common cancers," said Rebbeck, who is also director of the Zhu Family Center for Global Cancer Prevention at the Chan School of Public Health. "There are now a number of 'high penetrance' prostate cancer genes -- for example, BRCA2 -- and over 450 'low penetrance' prostate cancer genes. And family history is one of the major prostate cancer risk factors."

Men with a close relative with prostate cancer may be , and those with two or more relatives have nearly four times the incidence. The risk rises if family members were diagnosed before age 65.

Genetic variation also differs substantially by race/ethnicity. Black men in the U.S. and the Caribbean have one of the highest documented prostate cancer incidence rates in the world. "However, when we think about disparities, it is not yet clear how much genetics contributes. More likely, social determinants play a prominent role, but research is required to understand the relative contribution of genetics/biology compared with non-genetic causes," he said. Black men are vastly underrepresented in clinical trials for prostate cancer.

"Where someone lives is a factor: your neighborhood can impact stress and access to healthcare, and is a reflection of social position in our society," Rebbeck noted. He is co-leading a study to investigate what it is about neighborhoods that may increase a Black man's risk of dying from prostate cancer. Use of nationwide cancer registry and patient survey databases will allow researchers to identify generalizable predictors of screening use and survival, while also allowing them to dig deeper into the local neighborhood, behavioral, and sociodemographic characteristics that influence access and risk of prostate cancer in Black men.

"By understanding the influence of neighborhood factors on prostate cancer, we may be able to understand -- and then change -- the circumstances that affect prostate cancer risk differently across racial and ethnic groups," Rebbeck explained.

Early Detection

Currently no major medical organization endorses routine screening for men at average risk of prostate cancer in order to avoid the potential of overdiagnosis and the serious side effects associated with prostate cancer treatment. The ACS recommends that , men who are at average risk of prostate cancer and have a life expectancy of at least 10 years discuss the benefits and limitations of PSA testing with a physician.

This informed decision-making should begin at age 45 for Black men and those with a close relative diagnosed with prostate cancer before age 65, and at age 40 for those at even higher risk, including men with a close relative who was diagnosed at an early age and men who are BRCA mutation carriers.

Signs and Symptoms

Early-stage prostate cancer usually causes no symptoms. The first sign of prostate problems is often found during a routine screening exam.

Prostate cancer screening tests include digital rectal examination and PSA testing. A high PSA score may increase the suspicion of prostate cancer; further testing usually includes imaging and a biopsy to determine the presence of cancer. Blood and urine tests are available that may provide additional information.

Uncommonly, prostate cancer may present with nonspecific lower urinary tract symptoms (LUTS), hematuria, or hematospermia. In particular, LUTS such as frequency, urgency, nocturia, and hesitancy are more often related to benign conditions such as benign prostatic hyperplasia rather than prostate cancer. These symptoms may also be due to bladder outlet obstruction, urinary tract infection, prostatitis, interstitial cystitis, or chronic pelvic pain syndrome.

Late-stage prostate cancer commonly spreads to the bones, which can cause pain in the hips, spine, ribs, or other areas.

Treatment Approaches

Many advances in prostate cancer treatment have been made over the past 20 years due to improved tumor characterization and disease management. The approach to treatment is influenced by age and coexisting medical conditions. Side effects, including urinary and erectile difficulties, of various forms of treatment should be considered in selecting appropriate management.

Many patients simply require careful monitoring of the disease (active surveillance) -- particularly patients with early-stage disease and less aggressive tumors, and those who are older. New biologic markers for prostate cancer can help identify which early-stage cancers are less likely to progress if left untreated.

The most common treatment options for early-stage disease include surgery, external-beam radiation, and brachytherapy (radioactive seed implants). Focal therapy ablates small tumors located in only one area of the prostate. In locally advanced disease, hormonal therapy may be appropriate, along with surgery or radiation.

Late-stage prostate cancer may require systemic therapies, including hormonal therapy, chemotherapy, and immunotherapy. Some men with advanced prostate cancer who no longer respond to hormonal therapy may be candidates for a cancer vaccine designed to stimulate the immune system to attack prostate cancer cells specifically.

Targeted drugs, such as PARP inhibitors, may be prescribed for men with BRCA mutations. Treatment with bisphosphonates or denosumab can help prevent complications related to bone metastases, such as fractures. Bone metastases occur in 85-90% of metastatic cases.

Long-term Survival

Prostate cancer tumors may grow very slowly or moderately rapidly, and some patients may have prolonged survival even after their cancer has metastasized to distant sites, such as the bone. Many men, particularly those with localized tumors, may eventually die of other illnesses.

The 5-year relative survival rate for men diagnosed in the U.S from 2012 to 2018 with local or regional disease was , and the rate for distant disease was 32%. For all stages combined, the is 98%.

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    Mark Fuerst is a Contributing Writer for ľֱ who primarily writes about oncology and hematology.