Medications for Prostate Cancer that Might Help and Probably Won’t Hurt

BY MARK SCHOLZ, MD

Do we have confidence in our prescription pills?  How can we really know that they are helping?   It partly depends on whether or not there is a benefit.  Fever disappears soon after starting an antibiotic.   PSA declines in men with prostate cancer who undergo hormone blockade.  Blood pressure is better after starting a new blood pressure medication.

We have confidence in these medications because there is a measurable benefit.  Seeing a benefit offsets our suspicions about potential side effects. Medication choices really boil down to a simple equation: balancing the benefit against the risk of side effects.

But sometimes it’s difficult to see the benefit, especially if the medication is being used because of the benefits were only reported in a population study showing and advantage of one group of people over another.  Baby aspirin is a good example. How do you really know that the pill you took today helped you dodge a heart attack?

Science and the Media
Interpreting scientific studies requires skill and training. But these days, the challenge is even greater because scientific studies are primarily reported in the media.  Unfortunately, media experts face tremendous temptations to make their stories more interesting. So they tend to overstate their importance.  As a result the general public is becoming very wary of supposed scientific finding.   

Considering Risk, What about Low Risk Medications that “Might” Work?
Few people have the time or skills to do their own research. But deciding “yea” or “nay” on a new medication can also be based on its perceived risk. If a medication is considered relatively safe, people with a chronic illness like prostate cancer may start thinking along the following lines: “I can’t be sure it will help, but at least it won’t hurt.”  This is a common mindset with vitamins and supplements because they are generally perceived to be harmless.*

Modifying the Down-Side Risks
This “why not” mindset comes into play when considering certain common generic medications that have been on the market so long their potential side effects are well known.  Specifically I am referring to four medications—aspirin, metformin (a diabetes medication), 5-alpha-reductase inhibitors like Avodart and Proscar, and Lipitor (a cholesterol drug).

In previous blogs I have presented arguments in favor of aspirin, Avodart and Proscar. In my next blog I’ll review some of the arguments for using metformin and Lipitor in patients with prostate cancer.

However, in the remainder of this blog I would like to outline an approach for reducing the risk of experiencing serious side effects:

1)     The greatest vigilance is necessary in the first few weeks after a new medicine is started.  When a medication causes side effects they usually appear fairly quickly.

2)     Generally, there is no rush. So why not begin at half dose? If after a few weeks or a month there are no negative side effects, the dosage can be gradually increased.

3)     Medication side effects follow specific patterns. Aspirin, for example, can cause intestinal bleeding.  So patients need to be carefully informed about the significance of any new symptoms of heartburn and the meaning of having black stools should they appear.

4)     Some side effects are only detected with blood tests.  Everyone who starts a cholesterol drug—Lipitor for example—needs to have liver function tested within a month or so.  Liver problems heal quickly if the side effects are detected and the medication is stopped in a timely fashion. It can be dangerous if negative effects persist undetected.       

*Ironically, in the absence of overt deficiency, when vitamin supplementation is subject to careful testing it sometimes has been shown to be deleterious.   Vitamin E is one good example. In a large randomized, double-blind placebo-controlled trial, prostate cancer mortality was higher in the men who took vitamin E compared to those who took a placebo. 

Remember: In BPH, the “B” stands for “Benign”

BY RALPH BLUM

The prostate gland is the only organ in our body that keeps growing as we get older; all our other organs shrink and atrophy over time. A healthy prostate gland weighs around half an ounce (15 grams) in young men, and an ounce (30 grams) or more in men who are 50 or older. However, the prostate can weigh over 100 grams, in some cases causing problems with urination.

Although an enlarged prostate doesn’t inevitably lead to problems, one-third of all men older than 60 have benign prostatic hyperplasia (BPH) that causes urinary symptoms. The most common urinary symptoms are:
 
— Frequent urination.             
— A slow, weak stream of urine—there may be a lot of stopping and starting.
— A feeling of urgency when you feel like voiding.
— Painful, almost total blockage (this requires immediate medical treatment).

If you are having any of these urinary symptoms, in addition to a urine test to rule out a bladder infection, you will need an ultrasound scan to measure the size of your prostate gland, and to determine the nature and seriousness of the problem.

In most cases BPH can be treated with a category of medications, known as alpha blockers, that relax the prostate and make urinating easier. The best known of these is Flomax (generic name: tamsulosin). Another standard treatment is Proscar (generic name: finasteride) that works to shrink the size of the gland and, therefore, reverse the problem of slow urination from prostate enlargement.

However, if your symptoms are severe and/or multiple, you may require treatments using microwave, laser or electrical energy. Or if total blockage occurs, your urologist will perform transurethral resection of the prostate (TURP), a surgical procedure that removes the prostate tissue that is blocking the flow of urine.  This procedure is sometimes referred to as a “rotor-rooter job.”

BPH is the most common reason for urinary problems in older men. But equally important is the fact that an enlarged prostate causes a rise in PSA. The reason for this elevation is because the level of PSA measured in the blood is not only proportionate to the number of cancer cells in the prostate gland, but also to the size of the gland. If, therefore, the PSA level is appropriate for the size of the prostate, and if ultrasound imaging fails to reveal any sign of cancer, chances are the PSA elevation originates from BPH. In which case, active surveillance with regular PSA testing and occasional prostate imaging is, without a doubt, preferable to biopsy.

 

But the overwhelming concern of most doctors is that they might miss cancer in their patients. That concern, plus our own fear of the disease, far too often makes us jump to an immediate, unnecessary biopsy. And here’s a fact to tape to your shaving mirror:

 

--More than half the prostate biopsies performed annually

in the U.S. are done for evaluation of an elevated PSA

caused by Benign Prostatic Hyperplasia.

 

Isn’t it time we got smarter and started acting out of knowledge, instead of out of panic? And to remember what the “Benign” in BPH stands for?

 

VIDEO: Learn more about High PSA, Multiparametric MRI and random biopsies  http://youtu.be/6QgcfVBzFNs

 

 

Avodart & Proscar

BY MARK SCHOLZ, MD

Frequently I am asked about Proscar and Avodart, two medications that are FDA approved to reduce urinary side effects from prostate enlargement (BPH).  It turns out that these medications have a much wider spectrum of application than simply treating BPH. They function by blocking a type of testosterone called dihydrotestosterone (DHT) that occurs primarily inside the prostate. A short blog can’t summarize this vast field.  However, I think even a brief review might be helpful.  Here is a list of their potential applications:

• Lower the risk of being diagnosed with prostate cancer
• Improve the detection rate of high-grade prostate cancer
• Cause Gleason 6 cancer to regress or be suppressed
• Synergize with other hormone therapy medications (such as Casodex)
• Help maintain men on active surveillance to avoid surgery or radiation
• Prolong the “holiday period” in men on intermittent hormone therapy
• Reduce male pattern baldness
• Delay orgasm in men with premature ejaculation

The occasional side effects that can occur, such as reduced libido, impotence and breast enlargement, are manageable or preventable as long as the medication is stopped in a timely fashion when side effects occur.

In a randomized study comparing Proscar with placebo, 10,000 men underwent a prostate biopsy. The Proscar-treated men were diagnosed with cancer 25% less frequently compared to placebo. However, enthusiasm for the routine use of Proscar to prevent cancer was dampened when the same study reported a 1% increased incidence of diagnosing high-grade prostate cancer. Even though many experts hypothesized that Proscar was increasing the detection rate, not causing high-grade disease, Peter Scardino, a prominent urologist from Memorial Sloan Kettering published an opinion that Proscar could be causing high-risk cancer, raising all kinds of consternation and inciting the FDA to place a warning. Fortunately, subsequent follow up published in the August 15, 2013 issue of the New England Journal of Medicine showed that after 18 years of observation there was no increased prostate cancer mortality from Proscar.

Much of what is known about Proscar can also be said about Avodart. Both agents block 5- alpha reductase (5-AR), an enzyme that converts testosterone into DHT.  A possible advantage of Avodart is that it blocks two of the three forms of 5-AR whereas Proscar only blocks one.  No clinical trials, however, have been performed to compare clinical efficacy of the two agents.  In our in-house trials we have found that DHT blood levels are lower with Avodart than Proscar.

Since both Proscar and Avodart lower PSA by about 50%, the question arises, “Are they masking the capacity of PSA to signal cancer progression?”  Briefly, the answer is no. These medications do not stop a PSA rise in men with progressive cancer. However, after starting Proscar or Avodart the PSA baseline does reset 50% lower. On average, a man with a PSA of 6.0 before starting Proscar will drop to 3.0 within a few months. Subsequently, if the PSA rises consistently above 3.0, cancer progression should be entertained as a possible cause.

The rationale for concluding these agents are beneficial when added to other hormonal agents is based on the known fact that no pharmaceutical drug by itself can totally eradicate or block testosterone. So logically, the addition of a nontoxic 5-AR inhibitor to further lower DHT is likely to be helpful. Studies show that these agents suppress PSA in men with relapsed disease, delaying the rise in PSA, on average, for a couple of years.  It has also been shown that these agents can double the duration of the “holiday period” in men on intermittent hormone blockade.

Proscar and Avodart—mild agents with mostly reversible side effects—almost never interact with other medications.  They can be taken anytime of the day, with or without food. Proscar is available as a generic called finasteride and is very affordable. There is certainly an important role for these well-tolerated medications though in this era of new, high-powered hormonal agents such as Zytiga and Xtandi, Proscar and Avodart often get forgotten.  

Read another Prostate Snatchers blog written on Avodart & Proscar here:  http://prostatesnatchers.blogspot.com/2011/05/avodart-proscar-for-men-on-active.html
 

Introduction to Hormone Therapy for Prostate Cancer

BY MARK SCHOLZ, MD

Testosterone is the primary male hormone. It comes mostly from the testicles and to a lesser degree, from the adrenal glands. Testosterone causes the common male characteristics such as bigger muscles, facial hair growth and increased sex drive. Testosterone is also essential for prostate cancer to grow.

 

Why Blocking Testosterone Kills Prostate Cancer

The prostate gland, located near the bladder, makes semen. Prior to puberty the gland is only the size of a peanut. However, when the testicles begin making testosterone, the prostate comes to life and grows to the size of a walnut. The cells of the prostate, therefore, require testosterone to proliferate. Since prostate cancer originates from the prostate gland, the cancer also depends on testosterone.

 

Hormonal therapy works by blocking testosterone. When prostate cancer cells are deprived of testosterone they commit suicide in a cell death process called apoptosis.  The amount of cell death in early-stage prostate cancer is usually dramatic.  Not uncommonly, when men are pretreated with potent forms of hormonal therapy, there is no residual cancer after surgery. More typically, there is a dramatic reduction in the number of cancer cells, but not total elimination of the cancer.

 

The mechanism for testosterone to stimulate cancer growth occurs through the activation of a multifaceted protein called the androgen receptor.  Before binding with testosterone the androgen receptor is inactive. Once the receptor comes into contact with testosterone, the activated androgen receptor is transported into the nucleus of the cell where it stimulates DNA.  As a result, a plethora of cell-growth-enhancing proteins are synthesized that stimulate cancer growth and progression.

Hormone Therapy Comes in Many Form
Prior to the advent of modern medications, hormone blockade was accomplished by surgical castration. These days, testosterone is blocked with shots or pills. Agents that block testosterone by inhibiting the pituitary gland are Lupron, Zoladex, Firmagon, Eligard and Trelstar.  Medications that work by interposing themselves between testosterone and the androgen receptor to block its activation are Casodex, Nilutamide or Flutamide.  A third milder type of hormonal agent, the 5-alpha-reductase inhibitors, such as Avodart and Proscar, work by inhibiting the chemical conversion of testosterone into its more potent form, dihydrotestosterone (DHT).

Recently the FDA approved two new, and more potent, hormonal agents, Zytiga and Xtandi. Their increased anticancer efficacy was demonstrated through prolonged survival in men whose cancer became resistant to Lupron. Zytiga and Xtandi work by different mechanisms. Zytiga inhibits cancer cells from making their own testosterone. Xtandi works by blocking the activity of the androgen receptor.

The Nitty Gritty of Treatment Selection
The most potent anticancer action is achieved through complete blockade with agents from different functional classes administered together for a prolonged period of time. Therefore, the variables that affect the intensity of hormone blockade treatment are:  1. the type of medicine; 2. how many medicines are used; and 3. how long the medications are continued.  Of course, medical skill and experience is required to fine-tune the selection and duration of therapy.  Nevertheless, here is a brief presentation of some rough guidelines.
 

1.    A short course, say three to four months, to shrink the prostate or to improve cure rates in men with intermediate-risk disease (Teal Shade of Blue) undergoing radiation

2.    A short course of four months to improve cure rates with radiation in men with intermediate-risk disease (Teal Shade of Blue)

3.    An intermediate course (6-12 months) for treatment for intermediate-risk disease (Teal Shade of Blue) as a sole form of therapy

4.    A long course (18-24 months) to improve cure rates in men with high-risk (Azure Shade of Blue) prostate cancer undergoing radiation

5.    An intermediate to long course in conjunction with radiation to improve cure rates in men with a rising PSA after surgery (Indigo Shade of Blue) who are undergoing salvage radiation

6.    Intermittent use to suppress a rising PSA after surgery or radiation (Indigo Shade of Blue)

7.    Intermittent or continuous use to treat men with metastatic disease (Royal Shade of Blue)

8.    Salvage treatment with Xtandi or Zytiga to control disease in men on Lupron who have progressive disease (Royal Shade of Blue) 

Over the last ten years the medical community has been roiled by the discovery that some forms of prostate cancer are truly harmless, raising a serious concern about men receiving surgery and radiation they don’t need. However, overtreatment with hormone therapy also occurs. The overriding goal is to use a hormone therapy approach that achieves a maximum anticancer benefit while minimizing side effects as much as possible. Treatment always has to be personalized so the intensity and duration of treatment is appropriate for each individual’s specific situation.

Hormone Therapy: Earlier is Better than Later

BY MARK SCHOLZ, MD

Prostate cancer is by far the most hormonally sensitive cancer. Practically all other types of cancer, except breast cancer, are totally immune to testosterone blockade. Just as normal cells need oxygen, prostate cells, cancerous or otherwise, depend on testosterone. Cells originating in the prostate are by nature very sensitive to testosterone blockade. This sensitivity can be exploited as a treatment. When a cancer cell is deprived of testosterone it initiates a suicide sequence called apoptosis. Low testosterone is acting like a signal, sending a biochemical message to the cell, telling it to release destructive intracellular enzymes, causing it to die.

Within a few months of blocking testosterone, cancer regression is usually dramatic. For example, one study used Zytiga prior to surgery. The surgically removed prostate glands were fine-sliced and examined under a microscope.  Some men showed no residual cancer in their prostates.

The testosterone inactivating pharmaceuticals (TIP) that block testosterone are listed below in order of ascending potency:

 

1.    5-alpha reductase inhibitors: Avodart (dutesteride), Proscar (finasteride):

2.    Anti-Androgens: Casodex (Bicalutamide), Eulexin (flutamide), Nilandron (nilutamide)

3.    Orchiectomy: Surgical removal of the testicles

4.    LHRH agonists and antagonists: Lupron, Zoladex, Eilgard, Firmagon

5.    Estrogen: Works basically the same way as #3, by suppressing luteinizing hormone (LH). In addition, however, there also may be some direct anticancer effects from estrogen.

6.    Cyp17 Inhibitors: Zytiga (abiraterone), Nizoral (ketoconazole):

7.    Multimodality androgen receptor inhibition: Xtandi (enzalutamide)

While categories 6 and 7 are clearly the most potent, as yet there is no conclusive evidence that either of these two categories is more potent than the other. However, a variety of studies have demonstrated that a combination of agents is more potent that agents used by themselves.

 

Also, a number of studies have shown that men live longer when they are treated with TIP at an earlier stage—that is, at the time of diagnosis—rather than at the time of relapse when the disease has become more entrenched:  In August 1997, The New England Journal of Medicine published a study comparing two groups of 200 men each, all of whom were treated with radiation for high grade prostate cancer (Gleason 8, 9, or 10 or a large tumor felt on digital rectal exam). The five-year death rate from prostate cancer was reduced by 80% in the men who received radiation plus TIP compared to radiation alone.

 

A study published in the British Journal of Urology in February 1997 looked at immediate TIP vs. starting TIP after the cancer was causing symptoms.  Two groups of 400 men were evaluated and compared. Mortality was 25% lower in the group that had early treatment.  A third study was published in the Journal of Urology in June 1998 in which ninety-one men were randomized between radiation alone and radiation with TIP.  The mortality rate was 50% less in the men that were treated with TIP.

 

Another famous study in New England Journal of Medicine authored by Dr. Messing in 1999 looked at the value of starting TIP right after surgery in a 100 men, all of whom had cancer confirmed to have spread into their lymph nodes. Half were randomly allocated to start TIP right after the operation.  The other half started TIP when they had disease recurrence and evidence of progression.  Seven years later the men treated with immediate TIP were eight times less likely to have died of prostate cancer: Two men treated with immediate TIP died of prostate cancer whereas 17 men treated with delayed TIP died of prostate cancer.

 

In this last study TIP was continued for life. Since we know that TIP has more side effects when administered over a longer period, one can’t help but wonder if the same survival advantage could have been achieved with a shorter treatment period, say for two years?

 

The side effects of TIP can indeed be troublesome, especially the lowering of libido.  In our experience 70% of men under age 60 and 90% of men over age 65 lose sexual desire completely—particularly if they are treated with drugs in category three or higher. Category two and category one drugs cause loss of libido in about 50% and 25% of men respectively.

 

It is important to make one thing clear: Libido is not a euphemism for getting an erection. Viagra is powerful enough to restore erections in most men on TIP. Loss of libido means undergoing a loss of sexual interest. After TIP is stopped, younger men recover libido quite nicely though a minority describe their libido as persistently diminished. Some men, particularly the older ones, are more likely to have a persistent reduction in libido.

 

The list of potential side effects from TIP (besides libido problems) is long. Most of the side effects are manageable with expert supervision. Please inquire about a copy of Preventing the Side Effects of TIP for further details. Using a category two drug like Casodex is one way to reduce TIP’s side effects. However, using a less potent agent raises another concern: Some studies have shown reduced anticancer efficacy. Clearly treatment selection depends on weighing the intensity of potential side effects against the expected survival benefit. In some cases, slightly diminished anticancer efficacy may be an acceptable tradeoff if side effects can be substantially reduced.

 

Prostate cancer’s Achilles heel is that it can’t survive without testosterone. While anti-testosterone medications have remarkable anticancer efficacy they can also cause notable side effects. Treatment intensity and timing needs to be varied in accordance with each patient’s individual characteristics. 

Prostate Size Matters

BY MARK SCHOLZ

Having a large prostate is generally considered to be a bad thing because it is associated with urinary malfunction -- slow urination, getting up frequently at night and,  in the worst case scenario, total urinary blockage—an emergency condition that requires insertion of a catheter.

Treating urinary problems such as these is a big business.  A variety of herbal extracts containing ingredients such as saw palmetto as well as medications such as Flomax and Proscar are commonly prescribed and used with varying success. When total blockage occurs the urologists swings into action with lasers, microwave treatments or a good old-fashioned TURP, Transurethral Resection of the Prostate, sometimes referred to by laymen as the “rotorooter job.”

It should be made clear that many large prostate glands cause no urinary symptoms whatsoever.  Also, urinary problems like those described above can occur in men with normal sized glands.  Therefore you need to be aware that the connection between prostate size and urinary symptoms is a loose one.

A normal, healthy prostate gland is a walnut-sized organ that weighs approximately 15 grams in young men and around 30 grams (about an ounce) in men age 50 or older. The prostate gland is the only organ in the body that keeps growing as you get older. Enlarged prostates can weigh as much as 100 grams or more (the size of an orange or small grapefruit), and are more likely to lead to urinary problems.

However, as it turns out, having a large prostate can actually be a good thing, at least as far as prostate cancer concerned. Several studies show that men with big prostate glands tend to have lower Gleason scores. When men with big prostates are treated with radical prostatectomy, studies also show that they are less likely to have cancers that have spread through the capsule or into the seminal vesicles.

No one knows for sure why big (where cancer is concerned) is often better. One theory is that men with bigger prostate glands get biopsied more frequently and at a younger age because their PSA levels run higher. Therefore the cancer is being caught at an earlier stage and monitored.

Another theory is that bigger prostate glands result from hormonal changes within the gland and that these hormonal changes somehow have an inhibitory effect on cancer growth. The particulars of these purported hormonal changes are never specifically elucidated.

Regardless of the cause, men with smaller glands—say with prostate volumes less than 40 grams should be aware that, all other things being equal, their risk of harboring a higher Gleason score or a type of cancer that invades through the capsule is somewhat greater than it is for the men who have larger glands.

Prostate size is an additional factor besides Gleason score, PSA and the percentage of core biopsies involved with cancer that needs to be considered when going through the treatment selection process.   

Two “Positive Side Effects” of Prostate Cancer

BY RALPH BLUM

There is an aspect of being diagnosed with prostate cancer that has proved to be, for many men, quite literally, a life-saver, and that is being compelled to undergo a physical. For example, men who had always avoided getting regular physical exams learned that they had dangerously clogged arteries, making that checkup, literally, a life saving event. So that although prostate cancer is no day at the beach, and every treatment comes with a stiff price, there can be unexpected benefits. What I think of as “positive side effects.” Getting a check-up is one such.

The second positive side effect concerns the loss of sexual drive. Aka the loss of libdo. So is there life without libido? Wrong question. Better ask, “After a life lived entirely with sex as your objective, what happens when your libido is gone?”

I spent 24 months with no libido. When I was diagnosed with prostate cancer, given my aversion to being sliced open, fried by radiation, or poisoned by chemotherapy, my choice of treatment was hormone blockade. At the same time, I was far from enthusiastic about becoming a chemical eunuch. So instead of the suggested three drug protocol—Proscar, Casodex, and Lupron—with the approval of my oncologist, Mark Scholz, I decided on “monotherapy,” a single drug treatment with Lupron. In less than four weeks my PSA had dropped from 18 o 5.3, so I knew that the Lupron was working. With no testosterone, however, my libido was zip. Nada.

A fate worse than death, right? Wrong. To my surprise, I didn’t feel defeated or “less of a man.” I realized it was not the end of the world. In fact, if not getting my libido back is my fate, well and good. Been there, done that. And then I got another big surprise: Being in this unfamiliar, hormonally uncharged space, permits a freedom I had not experienced during over half a century of full-blown libido. And a much richer emotional life with my partner. A new kind of intimacy.

In his play, Testosterone: How Prostate Cancer Made a Man out of Me, Hal Ackerman confessed that when he was on hormone blockade he found women’s bodies about as exciting as covered furniture. But through the wonders of Big Pharma, Ackerman discovered that having sex, love-making without libido, was a completely different and very rewarding experience: During their love-making, he focused totally on his partner’s pleasure instead of on his own.

When I was doing research for Invasion of the Prostate Snatchers, I interviewed a number of men who expressed their own surprise as the result of having no libido. As one man put it, “Remove the ‘slam-bam-thank-you, Ma’am’ routine and what’s left? I guess you could call it taking pleasure in giving pleasure.”

Now there’s a positive side effect if there ever was one.

Avodart & Proscar for Men on Active Surveillance

BY MARK SCHOLZ

More and more men are embarking on active surveillance—close monitoring of their prostate cancer—rather than implementing immediate radical therapy. Of course, only individuals with carefully selected low-grade prostate cancer are eligible for this approach. During the extended observation period many men enquire if there are nontoxic interventions to improve their odds that the cancer will stay dormant. The important issue of diet often arises though that is not the subject of today’s topic. Hormonal treatment, on the other hand, is a treatment that calls for further discussion.

Targeted Hormone Blockade

Blocking testosterone production with testosterone inactivating pharmaceuticals (TIP) is an amazingly effective anticancer maneuver unique to prostate cancer. However, TIP is generally reserved for treating the more aggressive types of prostate cancer since it has potentially unpleasant side effects like impotence, weight gain and reduced muscle strength.  However, there is a way that hormonal therapy can be targeted to specifically block testosterone activity inside the prostate while sparing the rest of the body from negative side effects. Proscar and Avodart—both FDA-approved medications to shrink the prostate gland function by this very mechanism. They block a special form of testosterone called dihydrotestosterone (DHT) that only occurs inside the gland.  The general public is familiar with these medications due to their ability to reduce the size of the prostate gland and ameliorate a common problem familiar to aging men:  the need to get up frequently at night to urinate.  Yet thanks to their lowering effect on DHT, these drugs also have anti-cancer effects.   

The Benefits of Proscar and Avodart for Fighting Prostate Cancer

The effect of Proscar and Avodart against cancer have been evaluated in several double blind placebo controlled trials.  In one trial 18,000 men¹ were treated with Proscar or placebo for seven years. Ten thousand of these men then underwent a prostate biopsy. The Proscar treated men were 25% less likely to be diagnosed with prostate cancer, compared to the men treated with placebo. In two other double blind placebo controlled trials, Avodart was also shown to reduce the risk of a prostate cancer diagnosis by about 22%.^2,3

More recently, in a study reported in abstract form at the American Society of Clinical Oncology in March this year, 302 men on active surveillance were given either Avodart or placebo for 3 years. As is typically the case with men on active surveillance, repeat prostate biopsies were performed 18 and 36 months after the initial diagnosis to determine if the cancer was progressing.  Men who received Avodart had a progression rate that was 38% less than the men on placebo.

Another study published in European Urology retrospectively evaluated 288 men on active surveillance who received Avodart or Proscar that were compared to men who received neither.  After three years of observation, the biopsy progression rate was 50% lower—18% for the men on treatment vs. 36% for the men on no treatment.⁴

Is There a Downside Risk?

Given that Avodart and Proscar lower PSA by about 50%, the question becomes: “Are they masking the capacity of PSA to detect cancer progression?”  The answer is no.  PSA still rises in men with progressive disease.  In fact, studies show that Avodart and Proscar improve the accuracy of the PSA monitoring process, enhancing the likelihood of detecting High-Risk cancer.⁵  The standard approach in our practice is to offer Avodart or Proscar to all our patients on active surveillance. 

When taking these pills, about one out of five men will notice a modest reduction in their sex drive.  This reduction in libido may fade away after a few months with continued treatment.  Even so, if a reduction in libido occurs, we often simply advise stopping the medication since these medications are not essential to the active surveillance approach but rather an optional enhancement.

References

1. Ian Thompson, The influence of finasteride on the development of prostate cancer. The New England Journal of Medicine, July 2003.
2. Gerald Andriole, Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia. UROLOGY, 2004.
3. Gerald Andriole, Further analysis from the REDUCE prostate cancer risk reduction trial. The Journal of Urology, April 2009.
4. Antonio Finelli, Impact of 5-Alpha-Reductace inhibitors on men followed by active surveillance for prostate cancer.  European Urology, Vol. 59; 509.
5. Ian Thompson, Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. Journal of the National Cancer Institute, August 2006.