Mark Scholz

Mark Scholz
Authors of the Invasion of the Prostate Snatchers, Ralph Blum and Mark Scholz, MD bring you a weekly Prostate Cancer Blog from Marina del Rey, CA and Los Angeles, CA.

BLOGGERS: MARK SCHOLZ, MD & RALPH H. BLUM

The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, July 22, 2014

Cannabis and Pain

BY RALPH BLUM

In the course of attending various workshops and meeting and corresponding with men in various stages of prostate cancer, those whose condition hurts my heart, are the men with chronic pain from advanced forms of the disease. For some of them, hope is already spent, and what remains is the pain. A number of them have turned to tetrahydrocannabinol, medicinal cannabis, as a palliative and effective way to cope with their suffering.
 
Proper name, delta-9-Tetrahydrocannabinol, THC is a psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer THC is considered the most active element, producing characteristic mood and perceptual changes associated with this compound. In recent years, the use of medical cannabis for the relief of pain has become an accepted practice, especially in those states where the possession of cannabis has been decriminalized.
 
In patients seeking pain relief, the compound is not employed for entertainment of adventure. If you can demonstrate a need, and with your doctor’s prescription, you can obtain THC for medicinal use, almost always specified as relief of chronic pain.
 
The stories I have heard from men who have benefitted from ingestion of THC are very encouraging. “I am pain free for the first time in two years,” one man told me. Another reported, “The constant nausea has subsided, I am able to get to sleep again.”
 
A number of these men are aware that they are dying. And prior to getting medical marijuana nothing else had helped. One must ask: Should these dying men be deprived of an effective palliative because it is known to be “habit forming” or might lead to the use of “stronger drugs?” Not one of those I have spoken with has sought relief or pleasure from “stronger drugs.” They do not have the time or the will to form habits.
 
Public support for medical marijuana has increased. As of this writing, more than 20 U.S. states plus the District of Columbia have legalized cannabis in some form, and recreational use of marijuana is legal in Colorado and Washington state. Medical conditions such as cancer, Parkinson’s disease and HIV are commonly treated with medicinal marijuana. And yet many physicians are still reluctant to recommend it, because federally cannabis remains illegal.
 
The situation is very different in the nation of Israel, where medical marijuana has been legal since the early 1990s. In the past decade, Israeli scientists have developed a strain of marijuana without THC. Apparently the Israeli government funds the research on medical marijuana, which today benefits some 18,000 or more Israeli patients and is grown on eight farms for a state-run medical cannabis distribution center.
 
The irony of the U.S. position on cannabis as a palliative was summed up in an e-mail I received from a man whose prostate cancer had advanced to his bones. “I’m dying and in constant pain,” he wrote “and they’re protecting me from addiction?” Perhaps in the future the controversial aspects of medical marijuana can be resolved by producing a “pleasure free” medical marijuana specifically for pain alleviation. In the meantime, the medical community needs be bolder in recommending such an effective agent that is now readily available to most.

Tuesday, July 15, 2014

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
 

Tuesday, July 8, 2014

Advances in Diagnosis: Magnetic Resonance Imaging

BY RALPH BLUM

Prostate tumors are often multifocal, which means they tend to occur in more than one place within the gland. The digital rectal exam performed by the urologist will often miss tumors. The PSA test, used to screen for prostate cancer, has a sensitivity of about 70% and will often yield unclear results. And the random prosate biopsy, which seeks to identify tumors, while performed systematically, is also done blindly, resulting in roughly one-third false negative results.



In recent years, Multi-parametric Magnetic Resonance Imaging (MP-MRI) has played an increasing role in prostate cancer detection. MP-MRI scans are now more effective in distinguishing cancer from normal prostate tissue.  And although MP-MRI is not yet considered the standard tool for diagnosis, it can uncover cancer that has been missed during biopsy. Moreover, MP-MRI plays a significant role in helping to determine whether active surveillance is a safe procedure, or whether a patient requires definite treatment.

Advances in MP-MRI technology include specific targeting known as MRI-guided biopsy. Since cancers that occur in the anterior or front part of the prostate are often not being sampled because they are out of the reach of standard biopsy techniques, they often contain undetected areas of cancer.  An optimal magnetic resonance imaging study employs a powerful magnet to create detailed images that are then displayed on a computer screen. According to K.J. Macura, MD, at Johns Hopkins:

Based on the scans, radiologists assign scores of 1 to 5 for the presence of prostate tumor on MRI, with 1 being deifinitely benign, 3 either benign or not (i.e. we can't tell), 4 being probably malignant, and 5 definitely malignant.

This greater specificity is valuable since a lower score indicates that a follow up biopsy may not be necessary, while high scores indicate that a confirmatory biopsy may be advisable, and that the disease may require up-grading.

There are various types of MRI equipment available. When my MRI was performed, the MRI unit was operating at “3T”, T standing for Tesla and 3 the current state of the art technology, a unit of magnetic strength that provides hundreds of images and a detailed anatomy of the prostate.  However as of 2014, most of the men I have spoken with have undergone MRI testing with the older, less comprehensive 1.5 Tesla unit.

And while the number  of the MRI centers that use the latest technology is increasing, progress has been slow. So if you are scheduled to undergo an MP-MRI-guided biopsy using transrectal ultrasound and MRI guidance, make sure your MRI guidance is performed with the 3-Tesla machine. The results may make the difference between your being subjected to unnecessary, invasive treatment versus continued on active surveillance.
 
If necessary, make a fuss. It's your prostate cancer and your life.

FIND OUT MORE ABOUT RALPH'S STORY IN THE BOOK Invasion of the Prostate Snatchers


 

Tuesday, July 1, 2014

Combidex the Detective: Where has the Cancer Spread?

MARK SCHOLZ, MD

In our book, Invasion of the Prostate Snatchers, Ralph Blum and I devoted a chapter to the heartbreaking story of how Combidex, a revolutionary way to detect cancerous lymph nodes, was shot down by the FDA.  Detecting cancer in the lymph nodes is the Holy Grail of cancer scanning because the lymph nodes are the first place prostate cancer usually spreads if it leaves the prostate.  Standard CT scans fail to detect cancer until the tumorous nodes are bulging with cancer.



The early detection of lymph node metastases has become a much higher priority now that lymph nodes can be safely targeted with modern radiation.  In the past, with older radiation, side effects were excessive due to collateral damage to the intestines.
 
At Prostate Oncology Specialists we have had reasonably good results imaging lymph nodes with C11 acetate PET scans performed by Dr. Fabio Almeida in Phoenix.  Also, Choline PET scans have been used with success at the Mayo Clinic. However, even with PET scans there needs to be minimum amount of tracer present in the lymph node before it reaches the threshold of detectability. Therefore, PET scans may be unable to detect metastatic nodes until the cancerous nodules are more than 6 mm in diameter.  Studies evaluating intravenous Combidex in conjunction with MRI scanning indicate that normal lymph nodes can be distinguished from metastatic nodes even when the metastases are as small as 3 mm. In one study comparing Combidex with Choline PET scans, Combidex was more accurate at detecting metastatic nodes.
 
I am raising the matter of Combidex in this blog because now, for the first time in years, Combidex has become commercially available again in Europe.  Dr. Jelle Barentsz from the University in Nijmegen has been able to purchase all rights to Combidex along with all the documents and files from the original manufacturer. Unfortunately, as yet there are no sites in the United States that offer Combidex.
 
More than 50,000 men annually develop a cancer relapse after surgery or radiation.  A relapse is indicated by the presence of a rising PSA level in the blood. The rising PSA signals that cancer is present, but offers no indication about the location of the cancer in the body. New scans such as C11 PET and Combidex-enhanced MRI have opened up a whole new realm of treatment possibilities. After all, if the cancer can be located, it creates a possibly for cure by targeting it with radiation.
 
We welcome the renewed availability of Combidex, thanks to the concerted efforts of Dr. Barentsz.

READ MORE ON COMBIDEX

Past Blogs by Ralph Blum
http://prostatesnatchers.blogspot.com/2012/11/life-after-combidex-part-1.html
http://prostatesnatchers.blogspot.com/2012/11/life-after-combidex-part-2.html
http://prostatesnatchers.blogspot.com/2012/12/blog-post.html

Latest PCRI Insights written by Jelle Barentsz, MD
http://prostate-cancer.org/detecting-lymph-node-metastases-combidex/