Xtandi and Zytiga, The Future is Now

MARK SCHOLZ, MD

There are two new kids on the block, Xtandi and Zytiga. Both medications are real game changers. They are special because they can induce cancer remissions in men whose prostate cancer has become resistant to Lupron.  These pills are so effective that protocols for managing hormone resistant prostate cancer have been completely revamped.  Previously, men with hormone resistance were first treated with Taxotere chemotherapy, typically with undesirable side effects and frequent doctor’s visits.  When men on Xtandi and Zytiga are responding well, since they no longer need an intravenous infusion of Taxotere every three weeks, they only have to come in for a doctor’s visit every three months.

While Xtandi and Zytiga are now FDA approved for hormone resistant prostate cancer, there is no reason to believe they won’t also show enhanced effectiveness against earlier-stage, hormone-sensitive disease as well.  This rationale is based on a long established fact about anticancer treatments in general: “Any treatment that is effective against advanced cancer generally proves to be more effective against earlier-stage cancer.”  This assumption is so logical one might wonder why the academic medical world insists on doing studies to prove it.  Honestly, the biggest barrier is probably cost.  Insurance companies that pay for these expensive medications demand ironclad proof of a beneficial effect before being willing to cover their expanded use.

Physicians, particularly urologists, who are unfamiliar with these potent new agents, are another barrier to the expanded use of Xtandi and Zytiga in earlier-stage prostate cancer.  Urologists, the surgeons who over the last 20 years have only slowly become familiar with how the standard medications Lupron and Casodex function, are often uncomfortable using new agents that can be associated with rare side effects such as high blood pressure, seizures, liver problems and potassium depletion.  To urologists, the doctors who are managing the men with early-stage prostate cancer, Xtandi and Zytiga are relative unknowns.

In spite of all these barriers, the logical place to consider using Xtandi and Zytiga is in earlier-stage, “high-risk” situations which have suboptimal cure rates with Lupron alone.  The situations where this might apply are listed below:

·         Newly-diagnosed men with a PSA over 20 and a Gleason score over 8

·         Newly-diagnosed men with seminal vesicle invasion or pelvic lymph node metastases

·         Relapsed men after surgery with a PSA doubling < 3 months having salvage radiation

·         Newly-diagnosed oligometastatic disease undergoing radiation to all sites of disease

In all these situations, Lupron is known to be beneficial.  In some cases, the addition of Casodex to Lupron further increases the anticancer effect over Lupron alone. This is an important observation because compared to Xtandi or Zytiga, Casodex is a very weak anticancer agent.  Substituting these far more potent agents for Casodex is very likely to result in substantial improvement of the anticancer benefit and is a logical consideration for men who want to optimize their cure rates.        

Prostate Cancer: Starting at the Very Beginning

BY MARK SCHOLZ, MD

Yesterday I sat down with a new patient, Sam, a charming man who, unfortunately, was just found to have a prostate nodule and a PSA of 50. When I asked Sam why he had not visited a doctor for over 10 years or undergone any PSA testing, he responded, “I have always enjoyed perfect health. Why see a doctor?” Sounds sort of like a stupid response, but judging by his healthy appearance, (looking more like a 70 year old than an 80 year old), one would have to say that until now his policy has been pretty successful.

However, if Sam was going to participate intelligently in further discussions about the selection of optimal treatment, his prostate cancer knowledge would need a major upgrade. Since my instruction had to begin at a very elementary level, I thought I would use this blog to share the main themes of our almost two-hour meeting together.  Focusing on the basic first steps seems an appropriate theme for this, my first blog of the New Year.

Not All Cancers Are the Same
Many patients introduced into the cancer world fail to understand that lung cancer, breast cancer, brain cancer and prostate cancer are each a distinct illness, each with more differences than similarities. These different cancers are as different as kidney stone disease is different from pneumonia. Therefore, preconceived notions coming from personal experiences with one type of cancer occurring in family members or friends are frequently misleading.

Prostate Cancers are a Mixed Bag
It’s fairly easy to see why dissimilar cancer types, such as bladder cancer and skin cancer for example, behave differently; it may be harder to understand that prostate cancer itself comes in many different and distinct subtypes. Part of this varied behavior can be explained by the disease stage: No one is surprised by the fact that cancer diagnosed at an early stage has a different outlook compared to cancer diagnosed after it has metastasized.

However, beyond the issue of variable stage, when comparing two different prostate cancers of exactly the same stage, what we call “prostate cancer” can be extremely variable. Consider the following: In 2014, 70,000 men were diagnosed with a type of prostate cancer considered to be so harmless that experts universally agree it is best managed with active surveillance only. However, at the other extreme, also in 2014, a very different type of prostate cancer led directly to 28,000 deaths.

Prostate Cancer in the Bone is Not Bone Cancer
A common misconception that needs to be rectified is that cancer that originates in the bone, i.e bone cancer, is a totally different entity than prostate cancer that has spread to the bone. Primary bone cancer grows quickly, often spreads to the lungs and does not respond to hormones. Prostate cancer that spreads to the bone tends to grow much more slowly, only rarely spreads to the lung and usually regresses radically with hormone therapy. Prostate cancer in the bone and primary bone cancer are two separate and distinct illnesses that should not be confused with each other.

Doctors and Patients, the Human Factor
The human factor further complicates the selection of optimal treatment. Doctors who treat prostate cancer come from different schools of thought. Not only are urologists, who are surgeons, trained differently from radiation specialists, the true cancer specialists, the medical oncologists, are practically never involved with early-stage prostate cancer. Differences among patients—age, fitness, prostate size for example—can also radically influence treatment selection.

Sam’s Situation
With a PSA of 50, Sam is going to need a bone scan. He may have already developed metastases. His initial color Doppler ultrasound shows a rather vascular tumor (about an inch and a half long) with some early extra-capsular spread. A targeted biopsy, a single core of the tumor, is scheduled for next week and will let us know the Gleason score.

If the scans turn out to be clear, and if Sam was ten years younger, radiation and hormone therapy would give him the best chance for cure. But in an 80-year-old, the possible side effects that can result are more problematic. Also, we don’t know anything yet about the pace of his disease. Might it be feasible for Sam monitor to the situation for a while? Alternatively, radiation alone or mild hormonal therapy alone (with Casodex) could be considered. Sam and his wife left our meeting with a copy of Invasion of the Prostate Snatchers promising to read it in preparation for our next meeting.

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
 

INDIGO: Relapsed Prostate Cancer

MARK SCHOLZ, MD

Those dreaded words, “relapsed cancer,” shake you to the core. They mean that surgery or radiation has failed to “get it all.”  However, while with most cancers “relapse” is a fatal pronouncement.  However, prostate cancer has its own distinct reality. Most men who relapse don’t die from the disease.  The outlook is good because relapses are usually detected by a rising PSA when the cancer is still microscopic. Visible, scan-detected metastases may not appear for ten or more years after the PSA relapse occurs.

Multiple Treatment Options for a Rising PSA
The list of potential treatment options for INDIGO is extensive: observation, radiation, hormone therapy with Lupron and Casodex, salvage seed implant, salvage cryotherapy, Zytiga, Xtandi and Taxotere. However, combinations of these treatments are most commonly employed. Some of these combinations are listed below in order of increasing treatment intensity:  

1.     Observation

2.     Mild hormone therapy consisting of continuous or intermittent Casodex

3.     Monotherapy with fossa radiation, seed implant or cryotherapy for persistent local disease

4.     Combination hormone therapy with Lupron and Casodex given intermittently

5.     Same as #4 but with the addition of pelvic radiation and 4 months of hormone therapy

6.     Same as #5 but with hormone therapy extended for 18 months

7.     Same as #6 but with the addition of Taxotere or Zytiga or Xtandi

Defining Different Types of Relapses
Just as PSA, cancer grade, scan findings and stage were instrumental for assigning a SHADE in newly-diagnosed men; SHADES are important for putting a relapsed in perspective. Ultimately, how to treat INDIGO is guided by a combination of four factors— the SHADE before treatment, the PSA doubling time, individual patient factors such as age, sexual functionality and urinary control, and last, but not least, the cancer location.

The Original Shade before Treatment
In general, treatment should be more aggressive (combined therapy with Lupron and pelvic lymph node radiation) if the original SHADE was unfavorable (AZURE for example).  Treatment should lean toward a less aggressive approach—cryotherapy alone, seed implant alone or Casodex alone—if the original SHADE was SKY.

The PSA Doubling Time
Treatment is heavily influenced by the rate of PSA rise. For example, if the PSA is doubling in less than six months, aggressive combination treatment with Lupron and Casodex plus radiation (or cryosurgery in men previously treated with radiation) is probably required.  If the PSA doubling rate is between six and twelve months, a less aggressive treatment approach with radiation alone, cryosurgery alone or intermittent Lupron and Casodex is reasonable.  When more than a year is required for the PSA to double, observation without immediate treatment may be considered.

Patient Factors that Affect Treatment Selection
A patient’s age needs to be factored into the treatment decision-making process. Men who are more elderly can “step down” the intensity of their treatment by temporizing with milder hormone therapy such as Casodex with Avodart. Younger men, who, prior to relapse, were in the High-Risk (AZURE) category may want to consider upgrading the intensity of treatment by using prophylactic pelvic lymph node radiation plus a more intensive hormone therapy such as Zytiga or Xtandi and/or chemotherapy with Taxotere.

Searching for the Location of the Cancer
Men with rising PSA should undergo standard imaging studies (listed below) in an attempt to determine the location of the cancer. Unfortunately, these scans are often unable detect recurrent cancer unless the PSA is over 20. However, improved PET scans that utilize C11 choline or acetate have the potential to detect recurrent disease with much lower PSA levels. Unfortunately, the PET scans are so new that insurance coverage is often limited.

Sometime even the best scans can’t detect where the cancer is. When this occurs after surgery, particularly when the PSA doubling time is slow, residual cancer in prostate fossa is often suspected and radiation to the prostate fosse is often administered. Cure rates are better when radiation is initiated at a lower level of PSA. 

Standard Imaging Studies for INDIGO

• Color Doppler Ultrasound or Multiparametric 3 Tesla MRI can be used to look for residual cancer in the surgical fossa or in the prostate gland in men previously treated with radiation. 
• Pelvic MRI or CT scans are used to check for spread to pelvic lymph nodes. (Carbon 11 acetate PET scan, however, is far more accurate than CT or MRI but some centers still consider them investigational/experimental)
• Technetium bone scans are standard. New F18 PET bone scans, however, are preferable because they can detect much smaller cancers than technetium bone scans.

Apparent Locally Recurrent Disease

Scans done in a man with a rising PSA after radiation that indicate a recurrence localized inside the prostate, may be curable with cryosurgery alone or possibly with a seed implant alone.  Similarly, an isolated local relapse in the prostate fossa after surgery may be curable with radiation alone. Even though scans show no metastases outside the prostate or the fossa, microscopic metastases in the pelvic nodes may be present, especially in men who have fast PSA doubling times or whose SHADE was originally AZURE.  In these higher risk situations, the addition of prophylactic pelvic lymph node radiation with intensity modulated radiation (IMRT) combined with hormone therapy may be advisable.

Regional Spread to Lymph Nodes

When cancerous nodes are detected in the pelvis, the idea of doing node-directed IMRT is even more compelling. Since overt cancer in the lymph nodes is an indication of potentially life threatening disease, an extended course of hormone therapy, possibly with the addition of second generation hormones such as Zytiga or Xtandi, can be contemplated. Taxotere chemotherapy is an additional consideration.

Hormone Therapy Alone

When the location of the relapse is unclear, or if the risks of side effects from radiation appear too high, relapsed disease can be effectively suppressed for many years with hormone therapy alone. The side effects of hormone therapy tend to increase with longer use so intermittent therapy is very popular. A typical intermittent protocol is to begin with an initial course of treatment for six to twelve month followed by treatment holiday. After hormone therapy is stopped, testosterone starts to recover and the PSA begins to rise. Treatment is restarted when the PSA rises back to the original PSA baseline, or up to five, whichever is lower.

Putting It All Together

Treatment selection for INDIGO can be complex. Constructing a cancer “profile” using the original SHADE, the PSA doubling time, and scan finding, is the first step. Unfortunately, the location of the recurrent cancer may remain uncertain, even after doing the best scans.  When this is the case the extent of disease may require a professional “guesstimate” based on the PSA doubling time and the original SHADE.  Despite all these difficulties and uncertainties, the good news is that a wide variety of treatment options are available and treatment is usually very effective. For the majority of men the disease can be controlled on a long-term basis, and some cases it can even cured. 

CALENDAR ALERT TO THOSE WHO LIVE AROUND LONG BEACH, CA Learn more about prostate cancer treatments as Mark Scholz, MD, discusses treating PSA relapsed disease at UsTOO Long Beach Prostate Cancer Support Group July 22, 2014 - 6:30 PM to 8:30 PM, at Long Beach Memorial Medical Center. For more information follow this link: http://goo.gl/HMojNV

 

Selecting Prostate Cancer Treatment

BY MARK SCHOLZ, MD

"You mean you have never heard of diffusion-weighted imaging” Exclaimed a recently-diagnosed prostate cancer patient to his doctor.  How could his doctor be unacquainted with this important aspect of modern prostate imaging? It’s shocking when a patient realizes he possesses more medical information than the “expert.” 

No One Can Be an Expert in Everything
Actually, in this modern era, this situation is being encountered more and more frequently. It’s not so surprising when considering the explosive growth rate of new medical information. It’s humanly impossible for anyone to stay abreast of every new medical development.  For example, even though urologists “specialize” in diseases of the urinary system, their area of responsibility demands expertise in a wide variety of unrelated but important areas such as urinary infections, prostate enlargement, prostate infections, sexual dysfunction and kidney stones. They also have to be expert at the surgical treatment of such problems as congenital defects, bladder cancer, testicular cancer and kidney cancer… just to name a few.

Prostate Cancer by Itself is Quite Complex
Prostate cancer alone is intricate enough to keep a specialist occupied full time. For example, simply staging prostate cancer is complicated. Prostate cancer staging uses a multimodality profiling system that estimates the likelihood of microscopic metastases outside the prostate using PSA, Gleason grade, and a percentage of cancer-containing biopsy cores.  Now, new imaging techniques are providing further information about the size and location of the cancer within the prostate gland. And even more recently molecular profiling has become commercially available.  Staging prostate cancer properly has become a continually developing art form.

Seeking Advice—Delivered from a Level Playing Field
Equally important is the need to seek out unbiased treatment advice. Unfortunately, the process of rendering advice about treatment options is usually very slanted. Urologists (who are surgeons) usually recommend surgery.  Radiation therapists usually recommend radiation. This is not to imply that these physicians have less than the best intentions.  Over time they just become convinced that what they do is the best option for their patients who are consulting them.

What You Don’t Know Can Hurt You
The number of treatments available for men with newly-diagnosed disease is rapidly expanding.  For example, what was previously known simply as “radiation” now includes IMRT, Proton therapy, Cyberknife, two types of Brachytherapy as well as various combinations of these different radiation modalities.  Hormone therapy options have now expanded beyond traditional Casodex and Lupron to include Zytiga and Xtandi. The management of the potential side effects of hormone therapy requires special training in diet physical fitness, bone integrity and sexual health to limit the risk of lingering damage after treatment is completed. These days, relapsed or advanced prostate cancer requires physicians who are conversant in genetic typing, modern PET scans, immunotherapy and injectable radiation.

Every Journey Begins with a Single Step
So newly diagnosed prostate cancer patients are faced with daunting situation. Clearly there is no simple answer to this tangle of complicated issues. However, the newly diagnosed cancer patient is far from helpless. He has two overriding responsibilities. First, he must learn as many facts as possible by getting thoroughly educated about the different treatments for his specific type of prostate cancer. Second, he must use discernment in the selection of which physicians to consult.

There is Time to Learn
With prostate cancer there is rarely a need to rush into making a treatment decision because it is usually slow growing.  There is plenty of time for the shock of diagnosis to wear off, giving you enough time to get educated about the scientific facts.  Published studies comparing outcomes are available. The PCRI in particular publishes articles that translate scientific information into a patient-friendly format.  Ultimately, all claims about treatment should be supported by references published in the scientific literature.  Selecting treatment for prostate cancer is a high stakes proposition, potentially risking sexual function, urinary function, even life itself.  I want to encourage patients to take a leadership role in the treatment-selection process.

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. 

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.

Adjuvant Hormone Blockade (HB) after Surgery for Men with Aggressive Disease

BY MARK SCHOLZ

The term "adjuvant" means treatment “added to” the primary or initial treatment. When the primary treatment is surgery, even when all detectable disease is removed, there remains a statistical risk that the cancer will return due to microscopic cancer cells left behind. Men with high-risk features such as extra-prostatic extension or high Gleason score face a higher risk of recurrence.

We need to understand the rationale for considering hormone blockade (HB) in treating aggressive prostate cancer. However, the scientific studies supporting this approach are still preliminary. Patients who have aggressive prostate cancer now are forced to make the best treatment decision possible with the data currently available.

In May 2011 the Journal of Clinical Oncology, Dr. Tanya Dorff and others reported on 351 men, average age 60, who were treated with two years of Casodex & Zoladex initiated immediately following surgery. The average PSA prior to surgery for men in the study was 7.8. PSA had to be less than 0.2 after surgery to be eligible for participating in the study. After completing two-years of hormone blockade half the men recovered normal testosterone within a year. By 18 months, 89% had recovered. After five years, relapse free survival rates of over 90% are impressive for these high risk patients where “high risk” is determined by historical relapse rates that approach 50%.

Almost all previous studies evaluating the benefit of adding HB to surgery showed no benefit. The resultant lack of benefit was probably due to the very short duration of HB—usually for only three months. There is one study by Dr. Martin Gleave at Vancouver General Hospital, comparing three months with eight months of HB after surgery, and showing a slightly better outcome for men with aggressive disease when HB was continued eight months.

The most compelling previously published study of adjuvant HB, authored by Edward Messing was performed in 98 men with proven node metastasis, half of whom received immediate HB.  In the case of men who did not get adjuvant HB, the relapse rate was quadrupled.

Adding HB to radiation for men with bad prognostic factors is standard because several large randomized prospective trials show that HB reduces relapse rates and prolongs survival. Given these indisputable benefits, it is surprising that a similar study to evaluate the benefit of longer duration HB after surgery has never been undertaken.

Long-term HB after surgery results in a much lower incidence of PSA progression compared to historical PSA relapse rates that have been reported in multiple studies. However, actual proof that long-term hormone blockade after surgery will enable men to live longer will require a randomized prospective trial.  The table below lists the projected five year outcome in the study by Dorff et al. depending on the different stages of the men participating in the study.

CLICK TABLE FOR LARGER VIEW