Hormone Blockade for Early-Stage Prostate Cancer

MARK SCHOLZ, MD

Being medical oncologists rather than surgeons—and being more impressed by the toxicity of surgery than by its effectiveness—my partners and I hypothesized back in the early 1990s that since testosterone inactivating pharmaceuticals (TIP) are powerful enough to reverse metastatic disease, they should be even more effective against early-stage disease.

Clinical Experience with TIP for Early Stage
In 2011, we published a scientific article in the Clinical Genitourinary Cancer detailing the twelve-year outcome for 73 men who embarked on TIP as primary therapy. In this group of men the average PSA was 9 and the average Gleason score was 7 (intermediate grade). Most of the men had tumors in their prostate large enough to be felt by digital rectal examination. Twenty-one of them maintained a low PSA indefinitely with a single course of TIP—they never needed a second cycle.

Another group of 24 men required periodic repeat cycles of TIP to keep their PSA less than five. In the remaining 28 men, after one or more cycles of TIP, the decision was made to undergo treatment with surgery, seeds or radiation.  However, the average time to treatment was 6.2 years after the first cycle of TIP. Only three of those 28 men ever relapsed after treatment. In summary, this study showed that initial remissions with TIP were universal and that even if the remission was not permanent, treatment with more radical therapy was delayed many years.

In 2012, we published another scientific study in The Prostate, in which we evaluated the effect of 12 months of TIP in 102 men. Twenty-two men were in the Low-Risk category, 30 were Intermediate-Risk and 50 were High-Risk. The median PSA was 7.8 and the median Gleason score was 3 + 4 = 7. The attainment of a clear biopsy after TIP followed by a sustained 7- year remission occurred in forty-five men. The likelihood of durable remission was dependent on the risk category: 82% of Low-Risk, 47% of Intermediate-Risk and 25% of men with High-Risk required no further treatment.

Monitoring TIP’s Effectiveness
One of the beauties of TIP is how easily its anti-cancer effects can be monitored with PSA. Although there is much debate about using PSA for cancer screening, PSA is an amazingly accurate tool for monitoring treatment response. In a study we published in Urology in 2007, we showed that more than 95% of men with newly-diagnosed disease drop their PSA to less than 0.05 within eight months of starting therapy. It’s a rare for cancers to continue producing PSAs above a threshold of 0.05 after six months of TIP therapy.  However, when these rare cancers occur, i.e. when an elevated PSA nadir occurs, it is a flashing sign that aggressive multi-modality therapy should be instituted.

What about Side Effects?
So what is the catch?  To this point TIP sounds like a very logical way to initiate treatment. Even if the disease is not arrested altogether, it delays progression for many years. And men who select TIP as initial therapy can always “jump ship” and undergo radiation or surgery. Delaying surgery or radiation with their potentially irreversible side effects makes sense considering the acclerating pace of medical progress. In this rapidly changing environment, postponing irreversible treatment for even five years is unquestionably an attractive proposition.

The catch is that while TIP side-effects are manageable, they are not trivial. Without attention to diet, notable weight gain occurs. Without regular resistance training and weight lifting, significant muscle weakness will ensue. While on treatment, the majority men lose their sex drive. A loss of sex drive is, however, different than impotence. With medications such as Viagra and Cialis most men on TIP can have erections sufficient for intercourse. Sex can be enjoyed, but it is not sought after with the usual male verve. There is also the potential for additional side effects such as breast enlargement, osteoporosis and hot flashes. As dire as these sound, they are preventable with common medications such as Femara, Prolia and progesterone. However, the side effects are cumulative and become more prominent the longer TIP treatment is continued.

Final Thoughts
Some men are concerned that their cancer will progress if “real treatment” like surgery or radiation is delayed. They forget that surgery and radiation only eradicate the “friendly types” of prostate cancer, the ones that remain contained in the gland. The real danger lies in the possibility of microscopic metastasis. Radiation and surgery have no effect whatsoever on cancer that has already spread. Only TIP circulates throughout the entire body attacking early-stage micro-metastasis in the lymph nodes or bones.

In my next blog, I will be discussing a new, more powerful type of TIP that has recently been approved by the FDA. The enhanced effectiveness of this new drug may enable a shorter course of treatment. And since testosterone levels in the blood remain normal throughout, the risk of lingering side effects should be eliminated.   

Value of a Single erection

BY RALPH BLUM

For many men who have trouble achieving potency— keeping an erection firm enough for sex—erection dysfunction (ED) medications--Viagra, Cialis, Levitra--work well and cause few side effects.

Sildenfil (Viagra), vardenfil (Levitra), and tadalafil (Cialis) are all medications that reverse ED by increasing nitric oxide, a chemical naturally produced by the body that opens and relaxes the blood vessels in the penis. While helping to get and keep an erection, these medications do not increase sex drive, and only cause erections if you are sexually stimulated.

In an article in My Generation magazine, Hal Ackerman wrote that after 12 months of hormone-deprivation therapy, his libido was totally gone, an empty balloon, with the result that women whose bodies in the past would have stimulated longing and desire, generated no more response than the sight of uncovered furniture. However Ackerman claims that “via the miracle of modern pharmacology” he was able to perform sex with his new girlfriend for her pleasure—though with little personal gratification.

Although they work in similar ways, each of the ED medications has a slightly different chemical make-up. These minor differences affect the way each medication works, such as how quickly it takes effect and wears off, as well as the potential side effects.

Viagra and Levitra can be taken without food, no more than once a day, about 30-50 minutes before sex, and are effective up to 5 hours. Cialis can be taken as a small daily dose, anytime, with or without food, and is effective anytime between doses. The 36 hour Cialis can be taken with or without food, no more than once a day, about 30 minutes before sex, and is effective for up to 36 hours.

Not all men can take these ED medications. They may not be safe if you have any kind of heart problems, high or low blood pressure that is not controlled, a history of stroke within the last six months, eye problems, severe liver disease, or kidney disease. Always check with your doctor, and be sure he knows any other drugs you are taking as ED medications can interact dangerously with a number of other drugs—including alpha blockers, antibiotics, anti-seizure drugs, blood thinners, and various heart medications. And a final caveat: as I wrote in a previous blog, if you have had a prostatectomy, ED medications only work if the nerves located close to the prostate have not been removed or damaged.

Most men who take Viagra, Levitra or Cialis are not bothered by side effects, but when they do occur they can include headache, flushing (Viagra and Levitra), indigestion, stuffy or runny nose, back pain and muscle aches (Cialis), temporary vision changes (Viagra and Levitra), and rarely, dizziness or fainting. Also rarely, priapism (an erection that doesn’t go away) can occur and requires medical treatment.

ED medications can be purchased over the Internet, but beware of scams. Check to see if an online pharmacy is legitimate—never order drugs if the pharmacy gives no phone number, if prices seem too good to be true, or if you are told no prescription is necessary. Make sure you get the exact dose and type prescribed by your doctor. And don’t be fooled into buying “herbal” or non-prescription equivalents. They are not as effective, and some can contain harmful substances. You may find yourself paying as much as $20 per dose. But then some of us would consider the restoration of potency a bargain at twice the price.

The Quest for the Prodigal Hard-On

BY RALPH BLUM

There is no doubt that all the main prostate cancer treatments—surgery, radiation or hormone therapy—are likely to affect erections. And although many men who are diagnosed with prostate cancer are older, and may therefore already be subject to the ordinary fatigue and malfunction of nature’s ultimate erector set, the degree to which sexual function returns—or fails to return—after treatment is still a matter of major concern for a number of us.

 

There is no set formula or predictable schedule for recovery of sexual function after prostate cancer treatment. If you choose surgery, your chance of recovering potency is partly dependent on the experience and skill of your surgeon. The minuscule nerves that control erections are located dangerously close to the prostate, and damage to or actual removal of those nerves during surgery causes permanent erectile dysfunction. Viagra or Cialis only works if the nerves can be spared. And even with successful nerve-sparing surgery it can take up to 12 months for the restoration of the natural ability to have an erection.

 

The radiation options—seed implants or IMRT—are associated with a significantly better chances for maintaining erectile dysfunction. But the reality is that radiation therapy still can cause erectile dysfunction because of the inflammation or scarring that occurs around the nerves.

 

Hormone therapy, another treatment alternative, causes total dissolution of sex drive, and you don’t even care that it’s gone! Fatigue, joint pain, depression and hot flashes are not exactly a turn-on either. And yet even without a libido, an erection can be achieved through the manipulation of modern pharmacology—that is if you can dredge up enough desire to give it a try for your partner’s sake—but even with a pharmacological assist, personal satisfaction is often seriously diminished.

 

There is, moreover, a “use it or lose it” caveat: many doctors who specialize in erectile dysfunction encourage sexual activity as soon as possible after treatment (or in the case of hormone therapy during treatment) on the grounds that the nerves and muscles that control erections can atrophy if they are not used for a long period of time.

 

If prostate cancer has already affected your ability to achieve erection, there are various options that might help—penile injections, a vacuum pump device, implantable pellets, or penile implants. I will present the pros and cons of these methods for inducing an erection in my next Blog. In the meantime, keep in mind that there are ways you can express your love for your partner and attain sexual gratification that don’t include penetration. Ways that include intimacy and tenderness, lest we forget.

Surgery vs. Seeds vs. IMRT

BY MARK SCHOLZ, MD

 

Many men with Intermediate-Risk prostate cancer consider treatment with radiation or surgery. Treatment selection is influenced by age and preexisting status, especially as regards baseline sexual and urinary function. These days “surgery” usually means robotic surgery rather than the older, “open” procedure. Brachytherapy (radioactive seeds), and intensity modulated radiation (IMRT) are the most widely used types of radiation.

 

Cure Rates

All treatment options result in similar cure rates assuming the best physicians and technology are used. If any single treatment can be considered to have a slight advantage, it is brachytherapy. Seed implants deliver a somewhat higher dose of radiation, possibly with slightly better accuracy. All types of radiation have a slight cure-rate advantage over surgery because radiation treats a small margin around the gland. Surgery, especially when extra-capsular disease is present, may leave cancer behind, an unfortuante situation called “a positive margin.”

 

Quality of Life

Since cure rates are equivalent, the main criteria for selecting treatment are side effects. Table 1 lists the risks faced by a 65-year-old with good erectile function and without preexisting prostate problems. Risks are adjusted up or down based on a man’s age and his sexual and urinary function prior to treatment.
 

Table 1 Long Term Side Effects

Impotence Incontinence Climacturia* Urethritis Stricture** Proctitis Surgery 50% 8% 15% - 5% - Seeds 30% 1% - 10% 2% 1% IMRT 30% 1% - 4% 2% 2% *Climacturia is the ejaculation of urine rather than sperm **Stricture is a urethral scar

Short Term Side Effects
Some of the long-term effects noted in Table 1 also occur short term. All men are impotent after surgery though 50% eventually recover some functionality. Urinary symptoms, termed “urethritis,” occur in two-thirds of men who undergo brachytherapy, usually lasting a couple months. Proctitis symptoms lasting one to two months occur in about half of the men who are treated with IMRT.

Treatment for Long Term Side Effects

Shrinkage and shortening of the penis due to surgery may be partially averted with early use of Viagra, Cialis or Levitra, and when necessary, the injection of prostaglandins. For treating impotence or incontinence, patient satisfaction is about 85% with a surgically implanted penile prosthesis and 60% with a surgically implanted artificial urinary sphincter. Chronic urethritis, a non-healing radiation burn of the urinary passage, manifests as pain, frequent urination, and a compelling urge to urinate right now. Proctitis side effects can be described similarly, but affecting the rectum. Palliative treatments for chronic urethritis and proctitis are only partially effective.

 

Further Aspects of Surgery and Radiation

 

Surgery: The surgical skill of urologists varies and is measured by how frequently cancer is left behind after the surgery, termed a positive margin. The best surgeons average a 10% rate. Studies show that many urologists, even at reputable centers, leave cancer behind up to 50% of the time. Prostate removal gives information about the size and grade of the cancer, helping to improve the accuracy of projections about future relapse. Surgery also simplifies PSA monitoring, since unlike radiation, there is no residual prostate gland producing PSA.

Seeds: Brachytherapy with permanent seeds is an outpatient procedure. Temporary, high-dose-rate (HDR) brachytherapy requires an overnight stay in the hospital. Men with preexisting urinary problems or glands over 60cc are more prone to develop urethritis from brachytherapy. A benign PSA rise after the implant, termed a “PSA Bump,” occurs in 30% of men and can engender considerable anxiety.

IMRT treatment requires two months to deliver. Radiation beaming through surrounding organs may increase the risk of bladder and rectal tumors, though the risk is clearly less than one percent. The biggest risk besides impotence is proctitis. In the future, the injection of hydrogel between the prostate and the rectal wall may eliminate this risk (Hydrogel is pending FDA approval).

Cyberknife and Proton Therapy: Cyberknife is like IMRT but treatment is over one to two weeks rather than two months. Proton therapy is also similar to IMRT except it fires heavier subatomic particles (proton vs. photon). Proctitis rates are reported to be slightly higher with either of these two modalities.

Combination Radiation with Seeds and IMRT: Men with High-Risk disease and even some with Intermediate-Risk are treated with a combination of Seeds and IMRT. The side effects of Seed/IMRT combinations are similar to those of seeds alone.

The Outdated Sequencing Argument
As stated at the outset, cure rates are high with both radiation and surgery. Arguments touting surgery as the “Gold Standard” were true ten years ago when suboptimal radiation resulted in lower cure rates. Regrettably, to this day, many surgeons are still claiming that sequencing surgery before radiation is advantageous. This outdated thinking prioritizes planning for relapse, forgetting about the need to focus on quality of life. The goal is to be cured with the first treatment and be spared the side effects of additional rounds of therapy.

Taking Time to Decide
Prostate cancer is slow moving condition. There is no need rush to a decision. Radiation or surgery cures men with Intermediate-Riskprostate cancer 70-90% of the time. Even if a relapse occurs, salvage therapy usually gives a normal life expectancy. Additional options, besides surgery and radiation, can also be considered for men in the Intermediate-Risk category including active surveillance, focal therapy and intermittent hormone blockade. However, these treatments are outside the medical mainstream and beyond the scope of this short blog.

 

Sexuality and Intimacy after Prostate Cancer Treatment

BY MARK SCHOLZ, MD

My life is turning into an evangelistic crusade to raise awareness about the risks of prostate cancer treatment.  Tens of thousands of men are undergoing unnecessary radical prostate cancer therapy with dire sexual consequences. These inappropriate and often fatefully wrong treatment choices are made because men are often completely unaware of the irreversible effects of the treatment itself.

Thankfully, I am not alone in this battle to inform men about the harm associated with prostate surgery. Another prostate oncologist, Dr. Celestia Higano from the University of Washington, recently published a scientific review on this very topic in the Journal of Clinical Oncology (JCO). For those of you who haven’t heard of the JCO, I consider it to be the most prestigious scientific cancer journal in the world.

Today’s blog will offer quote seven selected sections from Dr. Higano’s important article. To add some gravitas to the eye opening statements you are about to read, please realize that every one of her comments was referenced to a specific scientific report.  In other words, these statements have nothing to do with opinions. They are genuine outcomes from published scientific studies.

So without further ado let’s start with the first quote from the article:

Quote #1: “Unfortunately, many couples believe that even if they have problems with erectile dysfunction (ED) … they will be able to resume their normal sexual practices through the advances of modern technology.4 They are not informed that sexual function will never be the same after any form of therapy and they are often unprepared for the changes in their sexual and intimate relationship.” (Italics mine)

Quote #2: “PDE5 inhibitors (Viagra, Cialis) and other erectile aids are not successful for all patients with ED and, even when effective, half the patients stop using them within one year.11 Why couples stop using ED therapies has not been adequately investigated , but disappointment that sex life is not the same … likely contributes to this outcome.”

Quote #3: “In a Memorial Sloan-Kettering series of 475 men … 20% of men who had radical prostatectomy (RP) had climacturia at one year, and climactauria as associated with both painful orgasm and penile shortening.13” (Climacturia means that orgasm results in the ejaculation of urine instead of semen).

Quote #4: “At the Karolinska Institute, 1,288 patients had either open or robotic-assisted laparoscopic RP, and of the 691 men who were sexually active, 38% reported climacturia at least sometime during sexual activity. Of the men who reported climacturia, 72% had climacturia less than half the time, 17% more than half the time, and 11% all the time.14”

Quote #5: “In a review of 1,459 men who had RP at New York University, climacturia was found to decrease from 44% at 3 months to 22% at 24 months after surgery. Climacturia is a common complication of RP but is often overshadowed by concerns about ED and overt urinary incontinence.14-16”

Quote #6: “In a study of VED (vacuum erectile device) use after RP, the length and circumference of the penis decreased in 63% of patients who did not use a VED after RP compared with only 23% who did.18-20”

Quote #7: “Surgery can also result in Peyronie’s disease (also called, “crooked penis”) in up to 16% of patients.23"

When patient are informed of the dire consequences of surgery they are often mystified as to why urologists, who must be aware of the damage surgery causes, continue vigorously to recommend it. I have heard many patients voice the opinion that urologists are driven by a selfish desire for financial gain.   

The financial motive, however, fails to ring true. As medical procedures go, prostate surgery is poorly reimbursed. Also, when urologists are diagnosed with prostate cancer they themselves often proceed with a radical prostatectomy. So money is not the primary issue. Rather, consider that performing surgery is part of the very fabric of a surgeons’ persona. From a surgeon’s point of view, if you are not operating, you are not a surgeon.

Men considering surgery for prostate cancer need to be aware of its substantial risks. And when getting advice about which treatment to select, patients also need to realize that surgeons usually can’t provide balanced advice. They are too close to the trees to see the forest.   

Erection? Who said “Erection?”

BY RALPH BLUM

Although most men, when they are diagnosed with prostate cancer, are primarily concerned with staying alive, there is a surprisingly large constituency who, as my psychiatrist friend put it “vote with their dicks.” For these men, not being able to have an erection is literally a fate more awful than death. But for almost all of us, the degree to which sexual function returns—or fails to return—is a matter of serious concern.

The three basic questions doctors hear when discussing treatment options are:

Will it cure me?

Will I have to wear diapers?
And the big one:  Will I be able to get an erection?

No doctor can answer any of these questions with an unequivocal “Yes.” The reality is that there are no guarantees. It’s a tough call whether to go for a cure, or for quality of life—which for many of us means being able to get an erection.

“I gotta tell you, Betsy is so much younger than I am. She’s right at the peak of her sexuality,” my friend Calvin pointed out. “My ability to perform still matters a lot to her. And there are plenty of folks like us—the May and September couples. Far as I’m concerned, quality of life isn’t an option. It’s the name of the game."

 

Compared to other treatment options such as active surveillance or hormone therapy, surgery and radiation have one clear advantage: closure. But surgery is also the chief culprit when it comes to ruining your sex life. The nerve bundles that control erections are located perilously close to the prostate gland, so you’re cutting past a lot of delicate apparatus, and even with nerve-sparing surgery performed by an experienced and talented surgeon, it’s very easy for things to go wrong. Once those nerve bundles are cut, it’s goodbye to erections.

However, the two modern radiation options—permanently implanted radioactive seeds (Brachytherapy) and intensity modulated radiation therapy (IMRT)—are at least as effective as surgery at curing the disease. And more importantly, the precise targeting means less risk of “collateral damage.” In other words, Calvin has a better chance of keeping Betsy happy—especially with a little help from the wonders of modern pharmacology.  Calvin and Viagra are now wedded at the hip!

 

According to the TV commercials, part of the cure for erectile dysfunction appears to be lounging with your sweetie in adjacent bathtubs while holding hands and watching the sunset. Providing, of course, you have taken the pill that does increase blood flow to your penis.

 

Bottom line: While the use of Viagra and Cialis to prevent ED after treatment is still not totally proven, and despite the fact that these pills can be very expensive, most of us guys, when we find out that using them will probably contribute to sustaining our long term sexual function and keeping the physical side of our relationships sweet and nourishing, we feel that using these pills regularly is a must. Like an insurance policy for intimacy.

A Question of Blood Flow?

BY RALPH BLUM

Have you been watching the TV commercials for drugs that combat erectile dysfunction?  I don’t know about you but I’ve been conditioned PR wise—only in the wrong direction. I mean, I’ve become like one of Pavlov’s dogs gone bonkers - every time the bell rings, instead of salivating, I tend to piss on the bell-ringer’s leg. It’s gotten to the point where I grab the mute button whenever I hear any one of the brand names, or see a shot of a couple lying in his-and-hers bathtubs on a cliff overlooking the Promised Land. “A question of blood flow,” my keester! Still, in case you’re still in the “Help me get it up” market, let’s review a few of the offerings.

In addition to Viagra, Cialis, and Levitra, I found 12 other erectile dysfunction drugs listed; drugs with names like Staxyn, Yohimbe, Erex and Testomar . . . Compared with the big three, the others received very few, if any, reviews. However, ED commercials are ubiquitous on the Internet. When I last looked, I found over 300 “male enhancement” products on the market, each of them promising “bigger and better erections.” But what if you’re just not interested? What if one’s desire for sex is totally absent?

We know certain things for sure about prostate cancer and one of them is that it is, to various degrees, testosterone driven. Unfortunately, so is sexual desire. So what controls the cancer—a radically diminished testosterone level in the blood, aka TIP, as Mark has christened, it is a part of the formula for staying alive.

Attending Support Groups over the past two decades, I’ve heard a lot of discussion about erections and the absence of same. I’d bet that 96% of the complaints concerning the ED resulting from hormone therapy (and the resulting suspension of intercourse) do not come from our partners. It’s a guy thing. As one woman summed it up at a Support Group at the PCRI Conference last year, “If it’s a choice, believe me, we would rather have you alive than have sex.” So we’re talking ego versus reality.   

Yet all is not lost. Some couples, like my old Ojai friends, J and L, have replaced coitus with massage and cuddling and exploring touch, only to find that they actually have greater intimacy. As they have told one another, “I can’t see you too well, and I can’t hear you . . . But it feels really good.”

With all the horror stories, stories of fear and shame, of loss and self doubt, I find it heartening to see the lighter side. So when it comes to a catalogue of all the possible unpleasant side effects of erectile dysfunction drugs—ranging from dizziness and stuffy nose to seizure or sudden decrease or loss of hearing or vision—my favorite warning concerns priapism: “To avoid long term injury, seek immediate medical help for an erection lasting more than four hours.” By all means, call your doctor. In fact, you could make two calls, one toThe Guinness Book of Records!

In Chapter 16 of Invasion of the Prostate Snatchers, Mark talks about the effects of testosterone reduction and how to minimize its negative impact. While Viagra would permit most men to attain a workable erection, the problem proved to be more basic. When he was conducting a study, Mark found that many men simply “forgot” to take their Viagra. He wrote:  “To complete the study I had to resort to phoning them at home to remind them to take their pill.” While helping to preserve their lives, TIP had actually sapped all their interest in sex.

I have ridden the edge for what is now approaching a quarter of a century.  I have undergone no invasive treatment. Only hormone blockade.  There are no guarantees. Things may change, making treatment advisable at some point in my future. But so far so good.  For me my low libido has been a small price to pay to keep my show on the road.  

In Praise of Life in the Libido Free Zone

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