• Michael Misialek, MD

Pathologist offers insight to help men understand need for prostate cancer screening

Consider these facts on prostate cancer. More than 200,000 men will develop prostate cancer this year, making it the #1 cancer in men after skin cancer. Almost 30,000 men will die of prostate cancer, second only to lung cancer. Detecting and treating prostate cancer early is the key to cure.

Published in the current issue of the Journal of the American Medical Association (JAMA), are two studies that look at the incidence of prostate cancer diagnosis since the introduction of the 2012 United States Preventive Services Task Force (USPSTF) recommendations. The USPSTF recommends that men not be screened for prostate cancer, citing the benefits do not outweigh the harms of early detection. The studies found that the incidence of early-stage prostate cancer and rates of PSA screening have declined since the 2012 USPSTF recommendations. However, longer follow-up is needed to see whether there is an associated trend in mortality.

PSA screening recommendations can be confusing. There is no consensus among the societies about the right age a man should start PSA screening.

Elevated PSA doesn’t always mean you have cancer

PSA (prostate specific antigen) is a protein secreted by the prostate. It is elevated in 80% of prostate cancers but also can be seen due to benign causes. These include common conditions such as benign prostatic hyperplasia (BPH, prostate enlargement) and inflammation. Since the introduction of the PSA test, there has been a steady decrease in prostate cancer mortality and metastatic disease. An elevated PSA is a red flag and an indication to undergo further testing to determine the cause.

New tests

While PSA is among the best tests for prostate cancer available now, newer tests are in the pipeline that might be more effective. The Prostate Health Index (PHI) test is a combination of three forms of the PSA protein. The results are used to provide a probability of cancer. The 4K score is a blood test measuring 4 different prostate related proteins that provides a percent risk score of having an aggressive prostate cancer. Another test is the Prostate Cancer Gene 3 test (PCA3) which is a gene based test carried out on urine. The higher the level, the more likely the chance cancer is present.

Active surveillance

As mentioned in the JAMA, “active surveillance” (AS) is an important management option for men diagnosed with low-risk prostate cancer. With active surveillance, patients undergo regular visits and PSA tests and repeated prostate biopsies rather than aggressive treatment. This differs from “watchful waiting”, in which treatment for localized disease is withheld and palliative treatment for systemic disease is initiated.

AS is a reserved for patients with low grade, low volume cancer. Specific criteria often vary but usually include age, PSA density (PSA/prostate volume), percentage of positive biopsy cores, the extent of prostate cancer in any core, and measures of PSA kinetics, such as PSA velocity. Patents undergo regular visits, PSA testing and repeat biopsies instead of upfront aggressive treatment. It is different than “watchful waiting” which is typically offered to older patients with significant comorbidities where life expectancy is not expected to be impacted by treatment.

Intervention will occur if there is evidence of tumor progression. This can include PSA change, changes in clinical staging or imaging, and findings on repeat biopsy that are indicative of a larger or higher-grade cancer, i.e. increased Gleason score or increased volume of tumor in the core biopsies.

Pathologists—diagnostic experts on multi-specialty care teams—are the physicians who help determine patient eligibility for active surveillance. They ensure criteria are reproducible so that reporting is consistent and accurate.

Genetic testing

Genetic testing may be appropriate for prostate cancer. Here, your pathologist is critical.

New research has shown that mutations of such genes as BRCA1 and BRCA2 may be linked to early onset prostate cancer. These are the same genes known to play roles in some breast and ovarian cancers.

A recent study out of UCSF-Kaiser Permanente studied 7,783 men with prostate cancer, comparing them to 38,595 without cancer. Researchers looked at 105 different DNA variants and found certain combinations of these variants that predicted which men would develop prostate cancer. In fact, men at the highest risk had a cancer risk comparable to women’s breast cancer risk carrying the well known BRCA gene mutations.

This comes on the heels of another study identifying potential actionable targets for prostate cancer and shedding light on what drives prostate cancer. An international group of researchers looked at 150 men with metastatic, advanced prostate cancer that had become resistant to treatment. They found almost two thirds had mutations in the male hormone androgen receptor. Nearly a quarter had mutations in DNA repair genes including BRCA. This may allow for drugs approved in other BRCA driven cancers to be used in patients with advanced prostate cancer. Additionally, eight percent of patients had a heritable mutation, raising the possibility that some forms of prostate cancer are inherited and genetic counseling may be of benefit.

What can you do?

Talk with your physician about factors that impact your level of risk for prostate cancer and your need for early, regular PSA testing. Risk factors include:

Family history: Depending on whether you have a family history of cancer, you may not need to be screened immediately, but if you’re an average man over 40, it’s time to begin a conversation with your doctor about prostate cancer screening.

Your general health: For example, obesity may not increase your risk, but it can make prostate cancer harder to detect through PSA testing.

Race: Clinical studies find that PSA levels and tumor loads vary distinctly between black and white prostate cancer patients.

Your physician should also explain what the test might show and help you prepare to consider options if PSA levels are elevated. Ask about the pathologist behind your care. The best treatment is that of a multidisciplinary team approach. Through shared decision making with your doctor, and in particular, understanding your pathology report, you will be assured of the best care.

#pathology #prostatecancer #PSA #cancerscreening

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