Prostate Cancer Today: A 2-Minute Update for Physicians

By Eric Klein, MD

It’s not your father’s Oldsmobile when it comes to today’s prostate cancer diagnosis and treatment.

Innovative diagnostic tools and treatments introduced within the last six to eight years have ushered in a new era. They are refining our ability to identify which patients need biopsy, improving the quality of biopsy and assessing the biology of prostate cancer. All developments are helping clinicians and patients make more informed, better treatment decisions.

A quick history

Prior to prostate-specific antigen (PSA) testing in 1987, half of men newly diagnosed with prostate cancer had incurable disease at diagnosis. Treatment was castration to remove the testosterone that fueled the cancer.

Five years after PSA was introduced, the rate of incurable prostate cancer at diagnosis dropped from 50 percent to 5 percent. PSA allowed clinicians to diagnose cancers far earlier at a curable stage. For about 20 years after PSA testing was introduced, however, physicians believed that every cancer detected had to be treated.

Over time, the medical community found that PSA screening detected a lot of low-grade cancer that did not need treatment. We also discovered that the most common reason for a worrisome PSA level in the bloodstream was noncancerous prostate enlargement.

The challenge is that PSA is prostate-specific, but not cancer-specific. The PSA test measures PSA levels in the bloodstream, but a number of benign conditions — including prostate enlargement (known as benign prostatic hyperplasia or BPH) — can raise PSA levels. It’s a major limitation in the use of PSA, leading to overdetection and overtreatment of low-grade cancers.

In 2012, the U.S. Preventive Services Task Force discouraged the use of PSA as a screening tool for prostate cancer, citing the harm it caused through overdetection and overtreatment. That decision led to a marked reduction in the number of patients screened, which led to an increase in men presenting with advanced cancer again.

The task force refined its recommendations in 2018, stating men aged 55 to 69 should make an individual decision on whether or not to be screened based on conversations with their doctors. Men 70 and older, the recommendations state, should not be screened because the harm caused by a false-positive test outweighs the benefits.

A new era

In the last six to eight years, there have been a number of important findings that opened up a new era in screening, diagnosis and management of prostate cancer:

1. European Randomized Study of Screening for Prostate Cancer (ERSPC) — Initiated in the early 1990s, the ERSPC was the largest-ever randomized study on screening for prostate cancer, providing the first evidence that PSA benefitted patients. The ERSPC revealed that men screened with PSA had an almost 30 percent reduction in the risk of dying of prostate cancer, and a 35 percent reduction in the risk of developing metastatic cancer. This translated into a reduction in the need for palliative treatment of prostate cancer. After publication of this trial, there was no longer any argument about whether PSA screening improved mortality rates for prostate cancer. Men screened are less likely than unscreened men to die of prostate cancer or need treatment for metastatic prostate cancer.
2. Large scale adoption of active surveillance (AS) — AS in prostate cancer is a management strategy that recognizes that not all low-grade cancers require treatment. New genomic tools that directly measure the biology of cancer are changing the way prostate cancers are classified. Treatment decisions can now be based on true biology rather than what cells looks like under a microscope. Genomic tests also can tell a lot about resected tumors, such as recurrence potential, whether additional treatment is necessary, and in some instances which treatments are most likely to be beneficial.
3. Magnetic resonance imaging (MRI) and targeted biopsy — In the past, prostate biopsy using transrectal ultrasound randomly sampled prostate tissue. But its reliability was limited. MRI technology substantially improved, and a new generation of MRI devices along with other technological advances in contrast enhancement and special processing, now provide more accurate tumor location, allowing for more tailored and accurate biopsy. MRI also revealed prostate cancers in areas typically not targeted by transrectal ultrasound biopsy.
4. Improved PSA tests — PSA screening, while it reduces prostate cancer-related deaths, leads to a lot of false positive tests and unnecessary biopsies. This leads to overdiagnosis and overtreatment of low grade cancers. New PSA tests on the market are more accurate and commercially available, providing better accuracy and sensitivity in identifying high grade cancer. Among them are the Prostate Health Index, which combines three forms of PSA into a single score, and OPKO Health’s 4Kscore Test, a blood test looking at protein biomarkers and other clinical information. Another test – IsoPSA from Cleveland Diagnostics, a subsidiary of Cleveland Clinic – is a novel blood test that provides a more accurate identification of high-risk prostate cancer and has been shown to reduce the need for biopsies.
5. Targeted therapy — Patients with metastatic prostate cancer also are seeing the benefits of new treatments approved by the U.S. Food and Drug Administration within the last five years. With these newer diagnostic tools, we have a better understanding of the biology of cancers, allowing us to perform targeted therapies for personalized medicine.

Just as cars are evolving beyond the Oldsmobile with the introduction of hybrid and driverless technology, prostate cancer detection and treatment continues to evolve to improve the decision-making process.