Finasteride shown effective in reducing prostate cancer risk in Prostate Cancer Prevention Trial

More than 52,000 new cases of prostate cancer are diagnosed every year in the UK. Almost 12,000 of them die from prostate cancer. Prostate cancer is the most common cancer in males and the 2nd most common cause of cancer deaths for males in the UK. Accounting for 13% of all cancer deaths for men in the UK.

Recent research has shown that treatment with finasteride can reduce the risk of prostate cancer by 25%.^[1] Despite the recent findings, finasteride is rarely used for prostate cancer prevention. In this article, we explain what these studies mean.

What is finasteride?

Finasteride, known by the brand name Propecia, is a drug used to treat hair loss in men. It is also used to treat Benign Prostate Hyperplasia (BPH) - an enlarged prostate. A condition that occurs mainly in men aged 50+.

For the treatment of hair loss, finasteride is used at a dose of 1 mg. For the treatment of BPH, the dose is 5 mg.

What does finasteride do?

Finasteride is what they call a 5-α-reductase inhibitor; a medicine that inhibits the enzyme 5-α-reductase. This enzyme is involved in the conversion of testosterone to dihydrotestosterone (DHT). By inhibiting this enzyme, finasteride blocks the conversion of testosterone to DHT. In other words, finasteride reduces the amount of DHT.^[2]

This is important because DHT is the main cause of hair loss in men. A hormone present in the scalp that damages hair follicles. DHT disrupts the hair growth cycle, causing hair to shorten, fall out more easily and grow back more difficultly. Finasteride works by reducing the production of DHT by 70%, which prevents further hair loss in about 80% of men.^[3]

In addition, finasteride also reduces the amount of DHT in the prostate. A single dose of 1 mg of finasteride reduces plasma DHT in the prostate by 65%.^[4]

What is the role of DHT in prostate cancer?

The role of DHT in the development of prostate cancer is not entirely clear. What is interesting, however, is that men born with a deficiency of 5-alpha reductase do not develop prostate cancer.^[5]

This led people to suspect that finasteride might reduce the risk of developing prostate cancer. It is this suspicion that eventually led to the Prostate Cancer Prevention Trial. A study involving more than 18,000 men.^[6]

De Prostate Cancer Prevention Trial

De Prostate Cancer Prevention Trial (PCPT) was a study designed to see whether finasteride lowered the risk of getting prostate cancer. The PCPT randomnised 18,882 men to receive either placebo (= sugar pill) or finasteride. The study started in October 1993 and was planned to continue until May 2004. However, due to overwhelming evidence that finasteride reduced the risk of prostate cancer by 25%, the trial was closed early in June 2003. Additional analysis published in 2013 with more follow-up data showed a risk reduction for developing prostate cancer of 28%.^[7]

Paradoxically, the same study results published in 2003 showed finasteride to increase the risk for getting high-grade prostate cancer by 20%. At this point you might wonder “How can finasteride lower the overall risk of prostate cancer by 25% but increase the risk of high-grade prostate cancer by 20%?”. Well, that’s an excellent question.

Finasteride and high-grade prostate cancer

Despite the possible benefit of finasteride in reducing the risk of prostate cancer by 25%, the increase in high-grade tumors dampened public interest for using finasteride.

Since the original PCPT report in 2003, researchers identified several causes that might have led to the increased high-grade cancer rate in the finasteride group:^[8]

• Finasteride enhances overall and high-grade prostate cancer detection rate.
• Finasteride increases the sensitivity of the prostate-specific antigen.

Enhanced detection of overall and high-grade prostate cancer

Like we said before, finasteride is used for treating Benign Prostate Hyperplasia. Treatment with finasteride decreases the prostate gland by approximately 25%.^[9] It stands to reason that if there were a small tumor in the prostate, it would be more readily diagnosed in a participant who had received finasteride.

To clarify: if there is a high-grade cancer present, striking this tumor with the biopsy needle is easier in a 25.5 cm³ average size gland (finasteride) compared to a 33.6 cm³ average size gland (placebo).

Enhanced sensitivity of prostate-specific antigen (PSA) for detecting prostate cancer

Research has shown that the use of finasteride increases the sensitivity of PSA for detecting cancer, particularly high-grade cancer.^[10] When a PSA-test is done they measure the amount of PSA you have in your blood - a protein produced by cells in the prostate. A normal PSA level falls between 1.0 and 1.5 ng/ml, but these levels are elevated in men with prostate cancer.

In men taking finasteride, PSA levels seems to respond more rapidly to high-grade prostate cancers compared to placebo. In other words: it’s more likely that you’ll detect abnormal high PSA levels as a result of high-grade tumors in men taking finasteride.

What’s important to know is that abnormal high PSA levels are used as a trigger for performing a biopsy. Since finasteride increases the sensitivy of PSA, more men in the finasteride group received a biopsy as a result. Researchers argued that this effect increased the likelyhood of high-grade tumors to be detected.

The true risk of high-grade prostate cancer

An scientific paper that incorporated adjustments for the above-mentioned biases concluded the following:

• Estimated overall prostate cancer rates of 14.7% (finasteride) and 21.1% (placebo).
• Estimated high-grade prostate cancer rate of 6.0% (finasteride) and 8.2% (placebo).

These results translate into a relative risk reduction of 30.3%(!) for overall prostate cancer and a risk reduction of 27% for high-grade prostate cancer.^[11] In other words: men taking finasteride had a 30.3% lower risk for getting prostate cancer and a 27% lower risk for getting high-grade prostate cancer.

In summary: what does it all mean?

The central finding of this analysis is that finasteride decreased the overall risk of developing prostate cancer by around 30%. Secondly, finasteride increased the sensitivity of PSA testing for detecting overall and high-grade prostate cancer.