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From the Summer/Fall 2019 Quest
A new study looked at the relationship between BPH drugs, PSA suppression, and treatment outcomes for prostate cancer patients. The authors of the study are concerned that patients and physicians do not realize that the drugs could mask the progression of prostate cancer.
Turbulent discussion continues in the medical community over potential side effects of BPH drugs. They can suppress a patient's PSA, thus masking the progression of prostate cancer.

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate. The condition affects more than 80% of men 50 years and older and can lead to problems such as frequent or urgent urination. This is because the urethra passes through the prostate, and thus the enlarged prostate puts pressure on the urethra.

Common treatments for BPH are medications called 5-ARIs reductase inhibitors (5-ARIs), including finasteride and dutasteride. These are hormone blocking drugs sold under the trade names Proscar, Propecia, and Avodart. They reduce prostate volume, and thus the urinary problems subside. 5-ARIs are also prescribed for male pattern baldness.

However, some experts and research findings suggest patients and physicians should exercise caution with these drugs due to a possible increased risk of developing high-grade prostate cancer. A new analysis published in JAMA Internal Medicine in May addressed this concern in patients on 5-ARIs who underwent routine PSA screening.

PSA Suppression

5-ARIs suppress PSA concentrations by 20% to 80%. While randomized clinical trials have shown that adjusting the PSA level for men on these medications can be effective for prostate cancer detection, the authors of the new study speculated that the necessary PSA adjustments may not be routinely taken into account. The authors hypothesized that could lead to misinterpretation of PSA values in men taking finasteride and dutasteride, and thus delayed prostate cancer diagnoses and worse outcomes.

Examining the data

The authors looked at data of more than 80,000 men with prostate cancer in the VA health care system. Approximately 10% of the men had been prescribed a 5-ARI for at least one year before their diagnosis of prostate cancer.

Overall, the men taking 5-ARIs had worse outcomes with significantly longer times from elevated (adjusted) PSA to a diagnostic biopsy, higher PSA levels when they were diagnosed with prostate cancer (13.5 ng/mL vs. 6.4 ng/mL), and they were more likely to have a Gleason scores of 8 or higher when they were diagnosed. Not surprisingly, the men taking 5-ARIs were also more likely to have cancer that had already spread out of the prostate, and a greater risk of dying from prostate cancer or other causes.

The authors wrote that increased awareness of PSA suppression in men on 5-ARIs and establishing clear guidelines for early prostate cancer detection would improve care for men taking these drugs.

Previous QUEST articles have addressed other concerns with 5-ARIs. Search "finasteride" on the URF website at www.drcatalona.com.

JAMA Intern Med. 2019 May 6. doi: 10.1001/jamainternmed.2019.0280.


An Expert's Explanation

In an editorial response in Practice Update, noted urologist Patrick C. Walsh, M.D., wrote of the study, "This is an important warning for every physician who prescribes 5α-reductase inhibitors (5-ARIs)… If PSA levels are not monitored or adjusted properly for the effect of the drug, this can spell disaster."

Dr. Walsh's editorial discussed the scientific mechanisms behind the findings, noting that 5-ARIs have "no effect in reducing Gleason 7-10 disease," yet patients may not realize their PSA is being suppressed, and thus "they will not realize they may need a biopsy and may miss the opportunity of being diagnosed with curable disease."

He concluded, "In patients taking a 5-ARI, PSA levels should continue to go down for as long as they are taking them. If their PSA ever goes up at all, the risk of cancer is increased by a factor of 3, and the risk of high-grade disease by a factor of 6.4. I wonder how many of the patients in this study who died from prostate cancer were told by their wellmeaning, but misinformed, urologists that this drug would prevent their disease. If that is what you believe, it's time to understand the truth."

The full editorial is available at www.practiceupdate.com.



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