So your PSA is elevated: What next?

You just received your lab results and found out that your PSA is elevated. You have heard how important it is to screen for prostate cancer. You asked your doctor for the test and now what?


Prostate specific antigen (PSA) 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. An elevated PSA is a red flag and an indication to undergo further testing to determine the cause.

Often times the level will be repeated, along with a referral to a urologist. Workup includes a complete physical exam including a digital rectal exam to evaluate the prostate. This was most likely done when your PSA was checked. Depending on the PSA level and other risk factors, an imaging study, such as an ultrasound, and biopsy may be performed.

New diagnostic techniques are available which can yield additional information and can help in the decision of whether to perform a tissue biopsy. 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.

One of the newest and most promising techniques for further evaluating the prostate is the UroNav MR/Ultrasound Fusion Biopsy System. Fusion biopsy is a more effective method for detecting and diagnosing high risk and aggressive prostate cancers and results in less false negatives. MRI biopsy is likely to become an important tool in the evaluation of prostate cancer since the traditional random biopsy may miss tumor or in 30% of the time, underestimate the Gleason score of tumor.

Then what?

If a biopsy is done, a pathologist will evaluate the biopsy under a microscope and make a diagnosis. The most important feature to know about the cancer is the Gleason score. This is a grading system that a pathologist assigns to the tumor. A higher score suggest a more aggressive tumor. Other features that are assessed for include: the amount of tumor, the percentage of tumor in each biopsy sample, tumor length and whether tumor invades small nerves of the prostate. All of these will be recorded in the pathology report. Get a copy of your report.

Other important diagnoses that might be encountered are:

Atypical small acinar proliferation (ASAP) – This is an area that has microscopic finings equivocal for cancer, i.e. suggestive but not diagnostic. It is predictive of cancer and often an indication for repeat biopsy.
Prostatic intraepithelial neoplasia (PIN) – This is another finding that has microscopic features worrisome for cancer. It carries a 20% risk of cancer on repeat biopsy. Like ASAP, it warrants close follow up.

The biopsy is positive for cancer, now what?

The overdiagnosis and overtreatment of indolent cancers has received a lot of scrutiny recently. As a result additional tests may be performed to help assess the aggressiveness of the tumor and decide whether or not treatment is indicated. Different types of genetic testing may be performed to give information on the tumor’s growth rate, aggressiveness and risk of morbidity. Such tests include Prolaris, OncotypeDX and ProstaVysion. Many more tests are in development.

The pathology report, imaging studies and physical exam are all used to assign a stage. Stage is the extent of tumor within the prostate and whether tumor extends to other structures such as the seminal vesicles, lymph nodes or distant sites (metastases).

The genetics of prostate cancer are being deciphered. It is now known that one of the most important genes in breast cancer is also involved in prostate cancer, the BRCA gene. Genetic testing for this gene and others may be appropriate in high risk patients. In fact, the same treatments that have been shown effective in other BRCA driven cancers shows promise in prostate cancer. Recent studies have found that genetic testing may help predict the risk of developing prostate cancer.

This deep understanding of the genetic basis of cancer and harnessing that knowledge to predict cancer or target a patient’s unique tumor characteristics is termed personalized or precision medicine. It has dramatically changed our approach to cancer care. Pathologists have been instrumental in this process, allowing the selection of the right drug for the patient. Many such targets were recently discovered for advanced prostate cancer.

As a pathologist and a member of the care team, I know the strongest weapon in the fight against cancer is an educated patient. Be proactive in your care. Get a copy of your pathology report. Ask about the pathologist involved in your care. We want to help you.



Dr. Michael Misialek currently serves as Associate Chair of Pathology at Newton-Wellesley Hospital, Newton, MA. He is the Medical Director of the Vernon Cancer Center, Chemistry Laboratory and Point of Care Testing. He practices in all areas of pathology in a busy community hospital. Holding an academic appointment at Tufts University School of Medicine as a clinical assistant professor of pathology, he regularly instructs medical students and pathology residents. Dr. Misialek is a strong advocate for pathology and is very active in the College of American Pathologists (CAP), serving on the Personalized Healthcare Committee, the political action committee PathPAC, the CAP Foundation and as chair of the Massachusetts delegation in the CAP House of Delegates. He is an inspector with the CAP and has conducted several domestic and international hospital laboratory inspections.

He received his MD from the University of Massachusetts, did an internship in internal medicine at Boston Medical Center and completed his residency in anatomic and clinical pathology at the University of Massachusetts Medical Center. He did a fellowship in general surgical pathology at the University of Florida and is board certified in Anatomic and Clinical Pathology.