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"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals 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 usually diagnosed after a referral from a primary care physician to a urologist. Many prostate cancers do not need immediate treatment. For example, patients with low-risk tumors can be closely followed on "active surveillance" and undergo treatment only if warranted. For those at higher risk, earlier screening is recommended.

After a digital rectal exam and a prostate-specific antigen (PSA) test, some patients are referred for additional testing. Patients are referred to a urologist for consideration of a biopsy if they have a worrisome finding on the digital rectal exam or a persistently elevated PSA that is not explained by other possibilities, such as benign prostatic hypertrophy or prostatitis.

Patients with a strong family history, an inherited mutation that increases the risk of prostate cancer, or those of African descent should consider evaluations at a younger age. Advanced molecular tests and imaging may also be needed to diagnose prostate cancer.

"Patients should work in collaboration with their medical team. Information gleaned from screening tests can be very helpful in making informed decisions on next steps," said William L. Dahut, MD, chief scientific officer for the American Cancer Society in Atlanta.

PSA Screening

PSA screening has been shown to at an early stage, and has been clearly shown to improve the chance of a cure. PSA-based screening has led to a dramatic shift from mostly incurable to mostly curable disease along with a more than 50% reduction in the U.S. prostate cancer mortality rate. However, concerns have arisen about overdiagnosis and treatment of screen-detected indolent tumors.

Presently, 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 American Cancer Society 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 the age of 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 are BRCA mutation carriers.

Traditionally, the aggressiveness of prostate cancer has been graded according to the , which is used to help plan treatment and determine prognosis. The Gleason score is calculated by adding together the two grades of cancer cells that make up the largest areas of the biopsied tissue sample. A Gleason score of 6 is low-grade, 7 is intermediate-grade, and a score of 8 to 10 is classified as high-grade cancer.

Genomic testing to analyze the presence of genetic mutations in prostate cancer cells may also provide more information about prognosis. However, it is unclear which patients benefit the most from this information, so these tests are not in wide use as yet.

Active Surveillance

that should be offered to patients with low-risk prostate cancer. Active surveillance may be recommended for patients with a low-risk tumor instead of treating it with immediate surgery or radiation therapy.

During active surveillance, patients are carefully followed for any suspected progression of prostate cancer. Men with low-risk disease who choose active surveillance typically have follow-up PSA tests every 3 to 6 months and follow-up MRI and biopsies at intervals determined for each individual patient. Compliance with surveillance generally increases when men are told whether they are at high, intermediate, or low risk and know about their need for subsequent testing.

If a surveillance biopsy suggests that the cancer is progressing, immediate treatment is generally advisable. The number of men on active surveillance who eventually get treated with surgery or radiation varies. In a large observational study involving 8,541 men, within 5 years.

New Diagnostic Tests

New and molecular imaging may help further refine a prostate cancer diagnosis. Among the new diagnostic tests are the following:

• 4Kscore test: This follow-up blood test after abnormal screening scores the risk of aggressive prostate cancer and can help patients avoid an unnecessary prostate biopsy

• Prostate Health Index: A combination of three blood tests provides information about the chances of finding cancer with a biopsy after an elevated PSA level

• A urine test can find PCA3, a gene that is specific to prostate cancer that is found in more than 90% of prostate cancer tissue, but not normal tissue. This test helps determine whether a patient with a negative prostate biopsy should have another biopsy

• ConfirmMDx test is performed on prostate biopsy samples that did not show cancer, and can help in determining whether to repeat a biopsy

• Several genetic tests of tissue acquired through prostate biopsy, including Prolaris and Oncotype DX Genomic Prostate Score, can also determine how aggressive the cancer is

Prostate Biopsy

Patients whose PSA values or exam is concerning for prostate cancer should be referred for consideration of a prostate biopsy. The is a needle biopsy. Most urologists now perform a transrectal biopsy using ultrasound guidance. Less frequently, urologists use a in patients who may be at increased risk of complications from a transrectal approach.

Sometimes the biopsy is preceded by a prostate MRI to help guide the biopsy or in some cases defer the biopsy. "Until a few years ago prostate biopsies were not guided by imaging," Dahut noted. "The urologist would biopsy 12 areas in the prostate using an ultrasound probe, but the imaging was not capable of detecting specific abnormal images. Today, using an MRI of the prostate, which is obtained prior to the biopsy, specific abnormalities can be identified."

This image is then fused with images from the ultrasound probe to allow targeted biopsies. In addition, other areas of the prostate are often sampled.

Understanding prostate cancer heterogeneity can add to insights into prostate cancer etiology and progression, noted Timothy R. Rebbeck, PhD, professor of Cancer Prevention at Dana-Farber Cancer Institute in Boston and director of the Zhu Family Center for Global Cancer Prevention at Harvard T.H. Chan School of Public Health. "We have always treated prostate cancer as a single disease, even though we know that there are major differences in the biology of tumors that affects who will have an indolent course of disease and who will die of their disease."

In many cancers -- for example, breast cancer -- tumors are not all the same in terms of etiology, and out of this heterogeneity come different approaches to prevention and treatment.

"The emerging data suggest this is also the case in prostate cancer, but we are early in this field," Rebbeck added. "It is likely that the limited data we have on prostate tumor heterogeneity and our understanding of subtypes of prostate cancer have limited our ability to appropriately diagnose and treat these cancers."

Read Part 1 of this series:

Prostate Cancer: Epidemiology, Diagnosis, and Treatment