Cancer in the prostate gland is quite common in men as they age. But it is also one of the most controversial types of cancer in many aspects.
It is different from most because it grows very slowly, and not all patients with cancer display symptoms.
Screening is different because not all men are supposed to search for cancer actively. Moreover, the screening methods may vary from one country to the other. But most of them use serum PSA levels.
PSA stands for Prostate-Specific Antigen. It is an enzyme secreted by the prostate, and it is meant to run in the semen. However, a small portion of PSA leaks to the blood circulation. We can measure blood PSA and get an indirect assessment of the prostate gland.
An enlarged prostate will leak more PSA into the blood. Inflammation in the prostate tissue (prostatitis) and other prostate ailments can also lead to an increase in PSA. This is precisely the problem of PSA as a screening method. You can have higher or lower readings depending on too many factors. One of them is the oral medications you’re taking.
For some time now, we know that medicine prescribed for an enlarged prostate can change your PSA levels. For example, 5-alpha reductase inhibitors are one of those drugs. They release the tension in the smooth muscle of the urethra, improving the flow of urine.
In contrast, 5-ARIs are useful because they relieve urinary symptoms in benign prostatic hyperplasia. But people with BPH can also have prostate cancer. If they are taking BPH medications, are they at risk of not being adequately diagnosed with prostate cancer?
According to recent research, that might be the case. In this article, we’re reviewing the evidence and telling how to avoid this problem.
What the research says
The acclaimed journal, JAMA Internal Medicine, published this research in May 2019. The study was led by Dr. Reith Sarkar from the Department of Radiation Medicine and Applied Sciences at the University of California San Diego.
The researchers were investigating patients screened for prostate cancer through PSA. They raised the question of whether or not BPH medicine can delay the diagnosis of prostate cancer. If so, this could increase the risk of death in susceptible or high-risk populations.
The study used data from over 80,000 men with prostate cancer. The researchers determined who used BPH medicine before diagnosing prostate cancer and included them in a separate group. They included patients who consumed dutasteride or finasteride for at least 1 year before their diagnosis of prostate cancer.
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After comparing the group with and without BPH medications, Dr. Reith Sarkar and collaborators reported significant differences:
- The time it took to diagnose prostate cancer extended
- PSA level at the moment of diagnosis was higher
- There were higher mortality levels and a higher rate of advanced disease
Firstly, the time it took to diagnose prostate cancer was extended. People who didn’t use 5-alpha reductase inhibitors took a median of 1.4 years to get diagnosed. Users of BPH medicine took a median of 3.6 years to obtain a prostate cancer diagnosis. This is a delay of 2 years in which doctors could have started early treatment for prostate cancer. This happens for multiple reasons. One of them is that the PSA levels are lower than they should be.
Additionally, BPH is a confounder because it raises the patient’s PSA level. As a result, steep rises due to prostate cancer are masked, and higher PSA levels are thought to be caused by BPH and not prostate cancer.
Secondly, the PSA level at the moment of diagnosis was higher. Non-users had a median of 6.4 ng/dL at the time of their first biopsy. Males who used 5-alpha reductase inhibitors had a median of 13.5 ng/mL. That is more than double the measure of PSA. One of the reasons is that we expect BPH patients to have higher PSA levels. Thus, a urologist would be led to believe that a higher PSA is due to BPH and not prostate cancer. Therefore, the use of 5-alpha reductase inhibitors could be playing a secondary role here.
Thirdly, there were higher mortality levels and a higher rate of advanced disease. This was measured in the study through the Gleason score and the clinical stage. 5-alpha reductase inhibitor users were more likely to have a higher Gleason grade. In non-users, the rate of Gleason grade 8 and higher was 17%. It was 25.2% in patients who received BPH medications. On the other hand, the clinical stage measures the size of the tumor (T), whether it takes lymph nodes (N), and the evidence of metastasis (M).
Tumors were bigger, were more likely to take lymph nodes, and metastasis was more likely in patients receiving BPH medications. This effect resulted from a more extended period of diagnosis and a larger tumor at the time of the diagnosis.
Key points and relevance of the research
This was one of the most extensive studies of prostate cancer patients with and without prediagnostic use of BPH medicine. It demonstrates that patients taking drugs to relieve BPH symptoms have a delay in the diagnosis of prostate cancer. This delay is higher than 2 years and increases the rate of disease progression.
Urologists knew before this study that BPH medications lower PSA levels. There was speculation that many cases of prostate cancer were masked, but no study proved it. This study provided objective data to show that this is happening in real life. Not all doctors are taking into consideration PSA lowering as a side effect of BPH medications. Not doing so could delay prostate cancer screening and diagnosis.
This study and its researchers are not against BPH medications. They mention that these drugs are not inherently unsafe. It does not mean that PSA screening is not effective in these patients, either. Instead, this research is a wake-up call for doctors and patients for different reasons:
- Doctors should not underestimate the lowering effect of 5-alpha reductase inhibitors in PSA levels.
- Patients should not neglect their condition just because they feel relieved from their urinary symptoms.
Is there any solution?
After studies like this, we often need more research before translating the results into medical decisions and clinical behavior. It is doubtful that BPH medicine triggers or worsens prostate cancer. However, more research will shed some light to rule out this possibility. In the meantime, the safety of BPH medicine is proven in studies that show no reduction in survival rate when prostate cancer patients use them.
The real solution is in our hands, and we could suggest the following steps for doctors and their patients:
Doctors should combine screening methods
PSA is not the only one screening method for prostate cancer. The digital rectal examination also has an essential role in diagnosing this ailment. For a skilled physician, BPH feels different in a digital rectal exam than prostate cancer. The patient’s symptoms are also relevant, and any sudden change in urinary symptoms should be recorded. PSA screening should also include more advanced PSA parameters. For example, PSA density and velocity. This increases the sensitivity and specificity of the exam. Imaging studies are also relevant to diagnose prostate cancer because it looks different from BPH in transrectal ultrasound scans and MRI scans.
Understanding risk factors
Assessing risk factors is essential to understand who needs screening and who doesn’t. In patients with BPH, doctors should be conscientious about looking for high-risk patients. Patients should also understand their personal risks and act accordingly. African American patients and those with a family history of prostate cancer should take special considerations.
Patients should report changes in urinary symptoms:
Patients taking BPH medications feel relief from their urinary symptoms. They could neglect minor changes in their urinary symptoms, leading to a delay in their referral to the urologist. By reporting changes in urinary symptoms and keeping in contact with the urologist, patients would avoid delays in diagnosing prostate cancer. This is particularly relevant in patients older than 60 years.
Do not underestimate further workup
A common cause of delay in the diagnosis is that patients decline further workup and treatment. They feel better from their BPH symptoms and may experience significant improvements after using 5-alpha reductase inhibitors. Thus, they might not understand the importance of further tests and other steps in the diagnostic process. By trusting their urologist in this regard, patients could avoid delays in the diagnosis of prostate cancer.
Consider your alternatives
There are alternatives to the treatment with 5-alpha reductase inhibitors. Most of them include herbal prostate remedies and complementary therapy. For example, Pygeum africanum and Saw palmetto. Lifestyle changes can also improve your urinary symptoms by simply exercising, controlling your weight, and limiting your caffeine and alcohol intake. These measures could help you reduce the need for BPH medications. However, always remember to ask your doctor before including any modification in your lifestyle and treatment.
Medications to treat prostatic hyperplasia are known as 5-alpha reductase inhibitors. They are also known as 5a reductase inhibitors or 5-ARI.
One example is tamsulosin. They should not be confused with phosphodiesterase-5 inhibitors like sildenafil (Viagra). The former acts in the urinary tract smooth muscle. It is used for prostate enlargement and lower urinary tract symptoms. The latter acts in the penile blood vessels. It is used to treat sexual dysfunction.
5-ARIs relieve patients with BPH from annoying urinary symptoms. However, by controlling their symptoms, these patients and the doctor may neglect other prostate conditions. More specifically, prostate cancer. By delaying the diagnosis of this disease, it would also delay prostate cancer treatment. In patients who would benefit from radical prostatectomy and radiation therapy, delaying treatment could make prostate surgery insufficient to treat metastatic disease. Then, hormone therapy and chemotherapy would remain the only alternatives.
If we don’t want to face delays in patients with BPH who take 5-ARI medications, we need to follow a few steps. First, it is essential to use multiple screening methods and not only PSA. Second, it is important to evaluate the patient’s risk factors and act accordingly. Third, patients should report any change in their urinary symptoms. Fourth, patients should not neglect other exams when recommended by the doctor.
Finally, we can use alternative treatments that do not cause alterations in PSA levels but always follow the urologist’s recommendations.