The Shifting Prostate Cancer Treatment Paradigm

In the last 2 years, the FDA has approved several new active metastatic prostate cancer therapies. This progress was made after researchers discovered that the available androgen deprivation therapies (ADT) had failed patients and that castration-resistant prostate cancer (CRPC) is not actually resistant to hormonal manipulation. Rather, ADT reduces levels of circulating hormones by 95%, but only by 75% within the prostate. Advanced prostate tumors are adept at making their own testosterone. Therefore, tumors seemingly resistant to androgen deprivation remain dependent on androgen receptor signaling for their growth—these tumors still rely on hormone signaling.

About 70 years ago, researcher Charles B. Huggins discovered that male hormones (androgens) are important for the growth and survival of prostate cancer tumors. In 1966, Huggins was awarded the Nobel Prize for Physiology or Medicine for his work on using hormones to control prostate cancer. In the last 10 years, studies have shown that castrate-resistant prostate tumors can continue to make their own hormones and can also increase the expression of androgen receptors on prostate cancer cells. This continued hormone signaling allows for continued tumor growth and cancer progression.

New oral androgen receptor signaling therapies have taken advantage of this latest research, targeting either hormones themselves or their receptors. These drugs provide new opportunities for patients who, just a few years ago, would have run out of treatment options. Continue reading…

Tracking PSA Levels Over Time Could Identify More Aggressive Prostate Cancers

A very large, retrospective study analyzing the 10-year health records of almost 220,000 men over age 45 years suggests that measuring levels of prostate-specific antigen (PSA) can help improve detection of aggressive prostate cancer.

PSA is made by the prostate and is found in the blood. Generally, higher PSA levels suggest something is wrong with prostate function, but specific PSA levels depend on a man’s age, conditions, race, and other factors. A PSA screening test is currently the most common way to screen for prostate cancer and to monitor patients who have been diagnosed with the disease. But, this screening is controversial.

Prostate cancer mortality data suggest that there is not enough benefit from PSA screening to justify it. Prostate cancer screening guidelines from the American Society of Clinical Oncology (ASCO) say that men with life expectancies of over 10 years should receive PSA tests, but that those with life expectancies of less than 10 years do not benefit from screening. These guidelines are based on PSA screening trials in both the U.S. and Europe including the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. In July of 2012, the U.S. Preventive Services Task Force also reviewed the evidence and released a statement against PSA-based screening for all men in the U.S., as long as a patient has no prostate cancer symptoms. Although the overall message is not to screen, the task force recommendation does include a statement that a man should discuss PSA screening with his clinician to make an individual decision. Continue reading…