PSA Screening - Where are we now?

by Jan Manarite, VP of Advocacy & Education


Lonnie Silva’s story
(Click here) of having to ask for a PSA blood test for almost 10 years, just to get a baseline and screen for prostate cancer is frustrating to read.
  Even more frustrating is that his first PSA came in at 22.1 after being denied a PSA for so long.  Many of us know that even though Lonnie’s PSA screening struggle took place in the 90’s, the struggle is still real today for too many men. 

Part of the reason is that the US Preventive Services Task Force’s (USPSTF) ruling in 2012 was that PSA screening for men who don’t have symptoms, should be “discouraged” in clinical practiceIt was aD” recommendation (Table 1 below.)



Table 1- USPSTF Grading Definitions

Table 1- USPSTF Grading Definitions

 

So – where are we now, in summer of 2016?  The good news is that the USPSTF is in the process of developing a new ruling for PSA screening.  More good news is that in October 2015, at the very beginning of their process, they asked for input from the public and from medical professionals on how to compile their research.  Based on the very robust response they received from many people and many organizations, they changed the way they were approaching this current research process for developing a new PSA recommendation, and issued this response in April of 2016. 

 

Here is a look at the Task Force’s process, and where we are in the new recommendation development.

Figure 1.  See full graphic and text at
http://www.uspreventiveservicestaskforce.org/Page/Name/understanding-how-the-uspstf-works

 

The bad news is that this USPSTF process for a new PSA screening recommendation will take more time, and it is difficult to predict how long (Figure 1.).  A phone call to the media department of the USPSTF informed me that the entire process averages 2 ½ to 3 years from start to finish, although it could be shorter.  If the process started October 2015, then 2 ½ years later would put us at April 2018.  This is only the average expected time – hopefully it will be sooner than that.

 

So what can you do?

*If you are not diagnosed with prostate cancer, and are in the process of PSA screening, the decision is up to you.  If you need to advocate for yourself, the California Prostate Cancer Coalition has a Decision Aid you can print and bring in to your primary care physician.  This 2-sided document offers 1 side written for patients, and 1 side written for your primary care physician.  You can find it at http://prostatecalif.org/download/Patient10q052215English_2.pdf 

 

*If you would like to weigh in and comment on the Task Force’s upcoming draft recommendation for PSA screening, you can sign up for email alerts from the Task Force online at this link – http://www.uspreventiveservicestaskforce.org/Page/Name/email-updates .

Although we do not know when public comment will open, we know it will be open for 4 weeks.  PAACT recommends that you weigh in on the issue – post a public comment when it opens, and let your voice be heard.  Watch PAACT’s Facebook page for updates.  You can find us at www.PAACT.HELP, or call us at (844) PAACT 4U.




My Prostate Cancer Story: Avid Reader Becomes Advocate

By Lonnie Silva

Lonnie Silva Hayward, CA

Lonnie Silva
Hayward, CA

As I approached my mid-50s, I enjoyed reading well respected American publications. As an avid reader, I was never one for subscribing to rag sheets or the infamous tabloids. One subject on my reading list was prostate cancer. Through my research, I discovered a new blood test called prostate specific antigen, otherwise known as PSA. I asked my primary physician about the PSA test, but was told I didn’t need one. Unfortunately, I waited a few more years and asked again, but was handed the same confusing reply of “NO”. By this time I was approaching retirement, in fact I was retired…so I asked again and again, but heard the same “NO” and the same story.  As I look back now, it still makes me angry sometimes, but I choose to pay it forward and advocate for other men.

 

When I was 65, I looked up the some symptoms I was having and shared them with my primary physician. Finally, he ordered a PSA test, after a decade of “NO’s”.  Unfortunately for me my first PSA came back as 22.1, a number that brought great concern. Any time a doctor calls you at 9 o’clock on a Sunday morning you know you have reason to be worried.  My next procedure was a prostate biopsy, and to no surprise, it was positive for cancer.  My Gleason Score came back at seven, which is not exactly good news.  This was back in 1998 when Gleason Scores ranged from 1 to 10, so at that time, seven was a high score.  , Fortunately my digital rectal exam came back  negative and the doctor could feel nothing so my Clinical Staging was T1c, which is not too bad.

 

My wife and I had an appointment with a urologist, and this is one thing I will never forget as he walked into the room shouting, “Yes, you have prostate cancer and will cut it out and throw it in the bucket”.   Pardon my honesty here, but I think I’ve earned it…My first reaction was, “How about if I cut out your brain and throw that in the bucket”, as I walked out of the office and refused to have anything to do with him again. Also I had asked him about a second opinion, and he informed me that I would have to pay for it. This was not correct as California law states a patient has a right to a second opinion. We left the urology office and I came home to start my research on prostate cancer.  Immediately, I went on line with an old dial-up connection that began with researching the National Cancer Institute, Sloan-Kettering, and Mayo Clinic, and to my surprise I had all kinds of information, plus additional websites to review. I learned that in my own backyard I had the University of California at San Francisco and Stanford University, two very well respected institutions to seek out for help.

 

Immediately, I made appointments with a urologist, a medical oncologist, and a radiation oncologist, as I wanted to obtain as many opinions as I could get. The avid reader (me) had evolved into an avid researcher – and a good one at that.  I ran across one treatment called brachytherapy, which was relatively new at the time. I asked my health provider for an appointment to get their opinion. Once again, I was told no, which is a word I grew to dislike.  I immediately contacted the California State Board of Managed Care to file a complaint. I must say they were most helpful, and I quickly received an appointment for brachytherapy.  Unfortunately I was too far advanced for brachytherapy at that time which I was very sorry to hear.

By this time, I was thoroughly disgusted with my urologist and formed an opinion that most urologists should not be handling prostate cancer. Again, pardon my honesty, but you can see how I developed that viewpoint.  I made an appointment with a medical oncologist and finally was receiving some information more to my liking.  I waited for a total of eight months to make a decision because I didn’t like the choices in 1998 such as open surgery or 3-D conformal radiation.  Also, I asked the radiologist about the combination of brachytherapy 3-D conformal radiation, and I was informed that I would still have to go through 30 sessions of 3-D conformal and brachytherapy. Once again, I didn’t like the answer, and continued to follow my instincts which had served me well so far.

 

I finally came to the conclusion (reluctantly) that open surgery was the  best choice I had, but I chose my surgeon (urologist) carefully. Within 14 months of surgery, however my PSA had start rising, and at the time it would double every 90 days, which was again very alarming to me. Again I was advised that radiation therapy was the answer for a salvage treatment, and once again my instincts led me in a different direction.  After consulting a medical oncologist again I went on intermittent hormone therapy.  I was not fond of the hormone therapy, but I did look forward to the chance to come off the injections, and take a break. In 2001 there was a new form of treatment and using a vaccine that is an immunotherapy called Provenge. From everything I heard it was excellent, and with minimal side effects, but the FDA had not yet approved it. I had hoped that a hormone therapy would give me some breathing time until the FDA could give approval for Provenge. Unfortunately, it was nine more years before they approved it, and I had already been on intermittent hormone therapy twice.  That was a lesson in how long it takes to get a drug approved, and the good news is that I am now off hormone therapy.  I did choose salvage radiation with an expert in 2012, but the radiation choices and technology has improved greatly since 1998 when all I was offered was 3-D conformal radiation.

 

My long journey as a prostate cancer patient has included learning how to be my own researcher which helped me make the best treatment decisions, being proactive and an advocate for my own health, setting up and coordinating three prostate cancer support groups in Northern California, establishing a monthly newsletter on prostate cancer, sitting on panels and patient discussion boards as a representative for men with prostate cancer, staying abreast of the newest medical treatments for prostate cancer, attending as many prostate cancer conferences and workshops as I possibly could, mentoring other men who are facing the same prostate cancer battles I experienced, and advocate to men of all ages the importance of being proactive with their own health. Research and medical technologies for treating prostate cancer have come a long way since I was diagnosed in 1998, but the medical community has a while to go before prostate cancer is much more treatable with less-invasive techniques and no longer requiring surgery. It also has a long way to go in listening to a man when he wants to have his PSA tested, and be screened for prostate cancer.  It is unacceptable to tell a man “NO” when he is asking for a PSA, and it is unacceptable that my first PSA was 22.1 – after a decade of asking. However, I will continue my research and will continue to mentor other men to remain proactive with their own health and with prostate cancer. Remember, LEARN and LIVE. 

 

You can visit our prostate cancer support group in Hayward, CA on the 2nd Tuesday of every month at 6:30 pm – at St. Rose Hospital 27200 Calaroga Ave.  If I can help advocate for you, contact me at prostateworld@comcast.net, or (510) 783-5121.  You can also contact Josie E Nolasco phone number is (510) 264-4044.       

 




New PET Scan Approved for Prostate Cancer - for PSA Recurrence After Treatment

 

On May 27, 2016, the FDA approved a new PET Scan tracer (injection) for prostate cancer patients with suspected prostate cancer recurrence based on elevated prostate specific antigen (PSA) levels following prior treatment.” (1)  There are several names for this new PET imaging agent, but they are the same agent:

  • Axumin (brand name)
  • fluciclovine (generic name)
  • FACBC (previous clinical trial name)

A PET Scan is a type of medical imaging trying to locate your cancer -  especially outside the prostate.

A PET Scan is a type of medical imaging trying to locate your cancer –
especially outside the prostate.

 

It should probably be noted that this new PET Scan tracer was not studied in men on hormone therapy, but there are some studies that show its effectiveness in men with a rising PSA on hormone therapy, or “CRPC” (castrate resistant prostate cancer). (2)  As always, ask about insurance coverage and reimbursement.  But clearly this PET imaging could help fill a space where prostate cancer patients and their doctors are trying to make a treatment decision after surgery, and perhaps considering salvage radiation.  It may help some men make a decision on spot radiation or surgical removal of a lymph node in the setting of a rising PSA.  It may also help a patient make the decision to start hormone therapy, or other systemic treatments, instead of a more localized therapy.  These are all issues to research, and discuss with your doctors, but they are some of the possible scenarios where this PET Scan may be helpful. 

 

Two studies helped the Axumin PET Scan obtain its FDA approval.  In one study, results from the Axumin PET Scans were compared with biopsy pathology, and read by several radiologists independent of each other.(1)    

The second study compared the Axumin PET Scan to the C11 Choline PET Scan, which is currently available at the Mayo Clinic. (3)  Patients in this study had a median PSA of 1.44.  (Median is the middle number, not the average number.)  Again, several radiologists read the scans independently and reported their findings.  Based on these 2 studies, the FDA ruled that the Axumin PET Scan was both safe and effective.    

It is important to note that there are different types of PET Scans – not all are the same.   The most commonly used PET Scan in cancer imaging overall is the FDG PET, which uses a glucose based tracer (injection).  The FDG PET has not proven very accurate in prostate cancer, although there are some exceptions in very aggressive or late stage disease.  Currently (summer 2016), there probably 3 other PET Scans in prostate cancer that are most commonly used (with several more still in clinical trials).  These include the F18 Sodium Fluoride PET Bone Scan, the C11 Choline PET at Mayo Clinic (for PC recurrence), and the C11 Acetate still in phase 2 trials.  All of this is subject to change, of course.

Better questions will get you better answers.  Always research a question before you ask  your doctor(s).

Better questions will get you better answers. Always research a question before you ask
your doctor(s).

It is also important to remember that no medical imaging is 100% perfect.  They all have degrees of accuracy based on what they are looking for, what part of the body they are imaging.  Always ask your physician(s) about the accuracy of a scan that you have received, whether it is PET, CT, bone scan or MRI, or anything else.  This will help with your overall understanding of your disease state and treatment decisions.  It is also important to note that Blue Earth has stated that “Axumin uptake may occur with other cancers”(3).  So for men with another type of cancer in addition to prostate cancer, this should be discussed with the radiologist and/or nuclear medicine physician interpreting the PET Scan.  A more detailed, developed understanding of the extent of accuracy (sensitivity and specificity) of Axumin PET is still being studied. 

 

As with all FDA approvals, a product can take a while to really be available on the market for patients.  Currently, I have been told by Blue Earth Diagnostics (the manufacturer) that the PET Scan should be available in a few places in the USA by mid to late summer.  To find current information about availability of the Axumin PET Scan, call 1-855-AXUMIN1 (1-855-298-6461).

 

However – this PET Scan is available in this clinical trial which is recruiting in Los Angeles, and planning on opening many more sites over the next year.

18F Fluciclovine (FACBC) PET/CT in Patients With Rising PSA After Initial Prostate Cancer Treatment (LOCATE) 
No placebo – all patients get PET Scan

Basic Eligibility Criteria:

  • Prior surgery, radiation, brachytherapy, or other local treatment for prostate cancer
  • For surgery patients – at least 1 year since surgery
  • For all other patients – at least 2 years since treatment
  • Rising PSA which includes the following:
    • For surgery patients, a PSA of 0.2 and rising
    • For patients who had radiation or other local treatment, a PSA that has risen 2.0 or more above PSA nadir
  • Off hormone therapy – for 3 months or longer
  • No known metastases (previous CT and/or bone scans negative)
    (For full eligibility criteria, check with contact below)

Location:  Los Angeles, CA
ContactTower Urology (310) 854-9898-0, ask for Research Dept

At the time this article is being written (summer 2016), Blue Earth Diagnostics has stated that they hope to roll out commercial availability in mid to late summer.  Although Blue Earth is the manufacturer, PETNET Solutions (a subsidiary of Siemens Medical Solutions USA) has commercial rights to manufacture, distribute, and sell Axumin in the U.S. (4)

 

At the time this article is being written, there is also no detailed information on Medicare or insurance coverage yet.  Stay tuned to PAACT’s Facebook page for updates, or call PAACT at (844) PAACT 4U.


References

  1. FDA approves new diagnostic imaging agent to detect recurrent prostate cancer. Press Release, FDA, May 27, 2016.
  2. Oni, et. al. [(14)C]Fluciclovine (alias anti-[(14)C]FACBC) uptake and ASCT2 expression in castration-resistant prostate cancer cells.  Nucl Med Biol. 2015 Nov;42(11):887-92
  3. Nanni et. al. 18F-Fluciclovine PET/CT for the Detection of Prostate Cancer Relapse; A Comparison to 11C-Choline PET/CT. Clin Nucl Med 2015 Aug;40(8):e386-91
  4. Blue Earth Diagnostics and Siemens’ PETNET Solutions Announce Commercial Availability of Axumin™ (Fluciclovine F 18) Injection for PET Imaging of Recurrent Prostate Cancer. Press Release, Blue Earth Diagnostics, June 7, 2016

 

 




Focal Therapy - Brief Overview and Focal Cryo Experience at PIOA

Duke K. Bahn, MD • Prostate Institute of America (www.PIOA.ORG) • Ventura, California (805) 585-3082  or  (888) 234-0004

 

DrBahn

 

INTRODUCTION: The progression of clinically localized prostate cancer is usually slower than other cancers, and has confounded the development of a national consensus regarding the optimal treatment for the disease. In addition, most of the observers believe that screening with PSA can result in the over-treatment of prostate cancer. However, the justification for PSA screening and treatment is still accepted by most experts due to the estimated 27,540 death from this disease last year in the United States. Although some prostate cancers are aggressive, the relatively slow growing nature of clinically localized prostate cancer has refuted the current established treatment options for the disease. This argument is supported by the fact that about one third men over 50 years of age will display incidental prostate cancer at autopsy, but only 10 – 16% will develop invasive prostate cancer during their life time, and only 2.5% will die from it.
Current treatment options for prostate cancer (PC) are either active surveillance or radical intervention treating the entire prostate (surgery, radiation, and others). Radical therapy may maximize the cancer control, but with a certain degree of sexual and urinary complications which may seriously affect quality of life. Active surveillance will not impact a patient’s sexual and urinary function, but it can carry the psychological burden of missing the window of opportunity for cure for some men.
This article reviews many forms of novel approaches that are called “focal therapy” or “subtotal therapy”. The goal of this approach is not only to achieve the same level of cancer control as seen in radical therapy, but also to maintain few or no complications in a selected group of men who have early stage organ- confined disease.  

 

DrBahn_CDUS

Dr Bahn has been targeting prostate cancer with color Doppler ultrasound for almost 2 decades.

DEFINITION OF FOCAL THERAPY:
Focal therapy is a generic term for destroying the tumors only by treating a portion of the prostate, and leaving the prostate gland intact. There is no consensus of opinion on the method of focal therapy. Some researchers treated only areas of known cancer while others have tried to treat the entire one half of the prostate that showed tumor involvement. There was also an attempt to treat the entire gland excluding the neurovascular bundles. Therefore, some advocate the term “subtotal therapy” instead of “focal therapy”. But “focal therapy” is the most common term, now spanning over a decade of research.

The advantages of focal therapy include:
1. It is a minimally invasive procedure using highly accurate imaging to target and destroy only the cancerous tissue within the prostate.
2. The side effects (mainly urinary and sexual dysfunctions) are far less frequent and severe than other conventional therapies.
3. If it fails, other currently available treatment options remain viable. In other words, it will not burn the bridge behind you.
4. It usually performed as an out-patient basis, if not an overnight hospital stay.
5. Recuperation from the procedure is mostly uneventful and quick.


The disadvantages of focal therapy include:
1. It is not widely available. The patient may need to travel to find an expert.
2. Parts of the procedure may not be covered by insurance for some men. The patient should ask about cost, insurance, etc.

 

TARGETED FOCAL (SUBTOTAL) CRYOABLATION
Focal (subtotal) cryotherapy is defined as the less than complete ablation of the prostate gland with freezing or ice.
A known tumor site (lobe) is aggressively treated, but the contralateral (opposite side) lobe of prostate tissue and surrounding structures are spared. This method offers targeted local cancer control, while preserving urinary continence and sexual potency for most. (See Table 1)
In the PSA era, many cancers are detected at an early organ contained stage, and may be confined in one lobe of the prostate. As many as 35% of clinically localized prostate cancers are unifocal and may be candidates for focal therapy. A tumor less than 0.5cc is used as a criterion for low-volume disease; this may not require any type of intervention. Others argue that even tumors smaller than 0.5 cc may be clinically aggressive and may require intervention. It is indeed a burden to identify the proper candidates for focal therapy.

 


PATIENT SELECTION FOR FOCAL CRYOABLATION:
Optimal patient selection criteria are not clearly defined nor agreed upon within the urology field. However, it is essential that the patient have unifocal (1 focus lesion) or unilateral (1 side of gland) prostate cancer. We perform a color Doppler transrectal ultrasound and staging biopsy (in addition to the initial extended blind biopsy that usually was already performed by the patient’s physician). Some centers advocate more invasive saturation biopsy to confirm the known tumor site but more importantly to reconfirm the absence of any additional tumor in the other lobe. If an unexpected clinically significant cancer is found in the other lobe by repeated biopsy, the patient is excluded as a candidate for focal therapy. In general, low-risk prostate cancers are preferred but moderate to high-risk cancers in men with medical co-morbidities can also be considered. Only unilaterality, not pre-operative PSA level or tumor differentiation (Gleason grade), are the defining issue. Men with extracapsular extension or seminal vesicle invasion can also have focal therapy.
Focal cryotherapy can also be offered as a salvage therapy (failure after any type of organ preserving treatment, such as radiation, cryotherapy, HIFU, and photodynamic therapy) as long as the recurrent disease is unilateral in location.

 


METHODS:
The cryoablation procedure uses extremely cold temperature (ice) to ablate the tissue. The third generation technology uses argon gas for cooling and helium for warming. It consists of two freeze and thaw cycles after the placement of a urethral warming device. Under general anesthesia or spinal block, cryoprobes are placed percutaneously under ultrasound guidance at strategic locations to be frozen. If seminal vesicle invasion is present, it would also be frozen by placing one of the probes in the lumen of the seminal vesicle. Usually 2-4 cryoprobes are used, depending on the size of the lesion and the size of the prostate. (See Figure 1) A single probe may be placed in the contralateral lobe close to the urethra and external sphincter in case heating is necessary to protect these organs (simultaneous heating and cooling). This can be a useful technique if the prostate gland volume is small. This combination of aggressive freezing at targeted locations within the prostate while maintaining the integrity of the urethra, external sphincter, and contralateral lobe, including the neurovascular bundle, is the premise of focal cryoablation.

 

Cryotherapy is an outpatient based procedure performed as same day surgery. However, if the patient visits from long distance he will have overnight observation in the hospital and discharged following day with a Foley catheter in place. The catheter is usually removed in 3-5 days. (See Figure 1)
As a follow up PSA levels should be checked once every three months for one year and every six months thereafter. Biopsy is encouraged at one year, two years, five years, and anytime there is a PSA elevating trend.

 

RESULTS:
Based on multiple publications in the literature (See Table 1.), the overall oncologic outcome of focal cryoablation therapy is encouraging. We recently published focal cryotherapy data for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow up of 3.7 years (1-8.5 years). Complete follow up was available in 70 patients. No patient died or developed metastasis. Pre-cryotherapy PSA was 5.9 ng/ml and Gleason score was 6 (n=30) and 7 (n=43). More patients had Gleason 7 (Intermediate risk) than Gleason 6 (Low risk) cancers. Post-cryotherapy mean PSA was 1.6 ng/ml (70% reduction). Of 48 patients undergoing post-cryotherapy biopsy, 36 (75%) had negative biopsies and 12 had positive biopsy for cancer. Reviewing the 12 cases with positive biopsies, 11 cancers were seen in untreated lobe and one in the treated lobe. Complete urinary continence and potency sufficient for intercourse were documented in 100% and 86% of patients, respectively. Matched-pair comparison of focal cryotherapy and robot assisted laparoscopic prostatectomy revealed similar oncologic outcome, defined as needing salvage treatment.
DISCUSSION:
Appropriate patient selection and standardized follow-up protocols remain controversial issues in focal therapy for prostate cancer. In our opinion, image visibility of prostate cancer is extremely important for proper patient selection, precise cancer mapping that allows accurate therapeutic targeting. We believe the encouraging oncologic outcomes (cancer responses) of our study were a result of accurate TRUS-based sextant and color Doppler targeted biopsy and mapping.
Follow-up biopsies in the treated side confirmed no evidence of cancer in 98% (47 of 48). Ohori et al reported that the index (primary) lesion typically accounts for 80% of the tumor bulk, with the remaining 20% comprising smaller secondary lesions. Removing or destroying the index tumor might eliminate the possibility of distant metastasis in the future and overall tumor burden by 90%.
Similarly, Villers et al. reported that 80% incidental cancers were <0.5 ml. In our series, the follow-up systemic biopsies from the untreated, contralateral, previously negative lobe revealed newly diagnosed cancers in 11 patients: most were small volume Gleason 6, but two were Gleason 7 = 3+4 and one was Gleason 7 = 4+3. However, 8 of 11 patients elected to undergo active surveillance for these newly diagnosed relatively low risk cancers. Consequently, only 4 (5.7%) of 70 patients underwent salvage treatment. Three patients chose focal cryotherapy and one had radiation therapy. In matched-pair radical prostatectomy series, 6 patients (8.8%) underwent salvage therapy.

Given the potential for cancer mutifocality (more than 1 tumor) and/or bilaterality (both sides of prostate), as well as potential under-diagnosis at the entry biopsy, follow-up biopsies for the untreated lobe are mandatory.
Following focal cryoablation, current PSA criteria have a limited role in predicting local recurrence in the treated lobe or progression in the untreated lobe. It is noteworthy that in our series, even patients with biopsy-proven recurrence had well controlled PSA levels (range: 0 – 1.5ng/ml). In other words, our mandatory post-cryotherapy biopsies revealed cancer before a significant PSA rise. Interestingly, percent decrease of PSA from pre to post-cryotherapy was
70%. Since untreated tissue remained in the contralateral lobe, this 70% PSA decrease after hemi-ablation seems a reasonable benchmark to indicate successful ablation of the index lesion, based on prior data that the index cancer accounts for 80% of entire cancer volume in a given patients.
A major limitation of our study includes the fact that 22 patients (33%) refused follow-up biopsy, mainly due to their negligible post-treatment PSA level (<1 ng/ml).

 

 

CONCLUSION:
Imaging visibility on scanning is necessary to achieve precise cancer mapping. Focal cryotherapy represents a modification of the whole gland approach and appears to offer acceptable oncologic effectiveness with reduced treatment related adverse events. The risk of incomplete eradication of cancer is likely to be small in appropriately selected men. It is precisely those types of patients who are presently confounded by the choice between active surveillance and a more complex whole-gland treatment. There are other competing technologies that can be applied to focal or subtotal therapy. Some of them are not ready for clinical use, but are intriguing. The most important component in any focal therapy is the precise imaging. Without clear identification of the tumor, its location and stage of the disease, focal therapy can be a blind approach with potential for suboptimal outcome.
Other Competing Focal Ablation Technologies
HIGH INTENSITY FOCUSED ULTRASOUND (HIFU)
In HIFU, ultrasound beam is focused at a small fixed point to create high power that produces heat ranging from 80 to 100 degrees C. It is proven to be lethal temperatures that will create tissue ablation. It has been applied towards organ-confined, localized prostate cancer treatment as a primary treatment or as salvage therapy (after failed any organ preserving therapy, such as radiation, cryoablation, etc). Recently the help of MRI scan is applied to enhance the targeting the cancer in addition to the ultrasound imaging. It is a quite popular procedure in Europe and Asia. This technology just received the FDA clearance, although patients should still ask about insurance coverage and costs.
HIFU is performed as an outpatient procedure, usually under spinal anesthesia. Real-time ultrasound imaging guidance and/or magnetic resonance guidance is used to position the probe and to monitor the procedure. Pulses of HIFU are directed at the targeted section of the prostate, inducing tumor necrosis.
A few published outcome data show fairly good cancer control and acceptable rates of complications. The study populations in the studies are all small and all had short follow up. One study reported the treatment failure (defined as any positive biopsy and/or need for salvage therapy prompted by rising PSA levels) was observed in 42%. Other studies reported the rates of positive biopsy at 12 months were in the range of 8-23%. The sexual and urinary dysfunction rates are fairly low (< 10%).

 


FOCAL BRACHYTHERAPY: LOW-DOSE RATE (LDR) AND HIGH-DOSE RATE (HDR)
LDR brachytherapy is typically used to treat the entire prostate by implanting permanent radioactive seeds that allow the delivery of high dose radiation to the prostate while limiting the collateral damages. The use of whole-gland brachytherapy for localized prostate cancer has been well established. Focal LDR brachytherapy is to target the cancerous area only in the prostate while sparing the rest of the prostate tissue. It will further reduce the radiation toxicity related complication. It usually performed under transrectal ultrasound guide.
HDR brachytherapy (temporary placement of radioactive material in the prostate) can be also used as a focal therapy modality. There is only limited information in the literature related to the clinical outcome of focal brachytherapy, either as LDR or HDR.

 

PHOTODYNAMIC THERAPY (PDT) OR VASCULAR-TARGETED PHOTODYNAMIC THERAPY (VPD)
This technique describes the destruction of a target tissue via the administration of an inactive, light sensitive agent (photosensitizer) and the local application of light in the presence of oxygen. The photosensitizer absorbs a laser light and transfers this energy to the tissues, creating cell destruction. One recently developed photosensitizer has a tendency of staying within the tumor vascular network. Due to this reason, when PDT is applied, extensive vascular damage is created that leads to tissue necrosis. It is referred to “Vascular-Targeted PDT.” One small study of 13 patients who had salvage VPD reported 8/13 biopsies negative at 6 months. Two patients experienced urethro-rectal fistulae. This therapy is not approved for prostate cancer in the US, but there are a few clinical trial sites.
NANOKNIFE
NanoKnife technology is known as an Irreversible Electroporation. Instead of using extreme heat or cold, the NanoKnife system uses electrical currents to treat the tumors. The device known as the NanoKnife passes an electrical current through the tumor. The expected electric injury is a creation of permanent nano-meter sized very small holes (pores) in the tumor cells, leading to the death of the cells. Ultrasound or other imaging techniques such as CT or MRI is used to focus the electric current precisely on the tumor. One study in the literature reported about 75% disease free survival at 10 years.

 

SUGGESTED READING
1. Bahn DK, et al: Focal prostate cryoablation: Initial results show cancer control and potency preservation. J of Endourology. Vol 20, No 9, p688-692, Sept. 2006
2. Onik G, et al: “Male lumpectomy”:focal therapy for prostate cancer using cryoablation. Urology. 2007 Dec;70 (suppl):16-21
3. Jones JS. Et al: Focal or subtotal therapy for early stage prostate cancer. Current treatment options in oncology. Springer, Boston. Vol 8, No 3, June 2007
4. Gillett MD et al: Tissue ablation technologies for localized prostate cancer. Mayo Clin Proc Dec 2004;79(12):1546-1555
5. Polascik TJ et al: Focal therapy for prostate cancer. Current opinion in urology 2008, 18:269-274
6. Lambert EH et al: Focal cryosurgery: Encouraging health outcomes for unifocal prostate cancer. Urology. 69(6), 1117-1120
7. Bahn DK et al: Focal cryoablation of prostate: A review. The ScientificWorld Journal (2008) 8, 486-491
8. Nguyen H, Bryan BS et al: Focal cryotherapy in the treatment of localized prostate cancer. Cancer Control 2013, Vol 20, No 3
9. Bahn DK, de Castro Abreu A, et. al: Focal cryotherapy for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow-up of 3.7 years. European Journal of Urology 2012:62 (1):55-63
10. Babaian RJ, Donnelly B, Bahn DK, et al.: Best practice statement on cryosurgery for the treatment of localized prostate cancer. J Urol. 2008;180(5):1993-2004
11. De Castro Abreu A, Bahn DK, et al: Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapy. BJUI 2013:112, 298-307
12. Tong W, G Cohen, et al: Focal low-dose rate brachytherapy for the treatment of prostate cancer. Dovepress, April 2013




Some Current Trials - In the Field of Biomarkers

Clinical trials are constantly changing. But to offer our readers some current options that might be worth researching, here is what I found for clinical trials using BRCA testing, or AR-V7 testing – both of which are mentioned in Dr Eshaghian’s article here.  

 

CURRENT TRIALS IN PROSTATE CANCER, USING BRCA 1 OR BRCA 2 TESTING
*Note – ask trial site how they are doing BRCA testing. Are they offering in trial? Or does it need to be done beforehand? Are they using the blood test or the pathology test?

1) A Phase II Study of the Chk1/2 Inhibitor (LY2606368) in BRCA1/2 Mutation Cancers, Including Metastatic Castrate-Resistant Prostate Cancer   Phase 2, NO Placebo

Basic Eligibility Criteria:
• Must be on hormone therapy, with cancer progressing
• Must have soft tissue mets that can be biopsied (lymph node, lung, bladder, etc)
• Must have had prior Xtandi OR Zytiga (for 1 month or more)
• No limit to the number of prior therapies
(For full eligibility criteria, check with contacts below)

Location: Bethesda, MD (NIH)
Contacts – Anna Couvillon, CRNP, (301) 443-6211, couvilla@mail.nih.gov  
or Cynthia Boyle, R.N, (301) 496-0932, helsabec@mail.nih.gov

 

2) Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and BRCA Mutations
Phase 1/2, NO Placebo

Basic Eligibility Criteria:
• Must be metastatic with at least 1 standard treatment for metastatic cancer
• Must be willing to undergo tumor biopsies
• At least 4 weeks since surgery, radiation, or chemo
(For full eligibility criteria, check with contact below)

Location: Bethesda, MD (NIH)
Contact: Melanie M. Herrin, (301) 402-5640, melanie.herrin@nih.gov

 

3) TOPARP: A Phase II Trial of Olaparib [Lynparza] in Patients With Advanced Castration Resistant Prostate Cancer (TOPARP)  Phase 2, NO Placebo

Basic Eligibility Criteria:
• On hormone therapy, or previous orchiectomy
• CTC blood test of 5 or more
• Previous Taxane chemotherapy – 1 or 2 cycles
• At least 4 weeks since chemotherapy
(For full eligibility criteria, check with contact below)

Location: United Kingdom – London and Sutton, Surrey Contact: TOPARP Trial Manager, 020 8722 4156,
toparp-icrctsu@icr.ac.uk

 

CURRENT TRIALS IN PROSTATE CANCER, USING AR-V7 BLOOD TESTING
*Note – AR-V7 blood testing is only available through Johns Hopkins, and for mCRPC patients. For more information about how to obtain AR-V7 testing through a local laboratory (your blood must be shipped to Johns Hopkins), please contact Katie Beierl, molecularpathresults@jhmi.edu. Or ask the trial site how they are doing their AR-V7 blood testing.

 

1) Biomarker-Driven Therapy with Nivolumab [Opdivo] and Ipilimumab [Yervoy] Treating Patients with Metastatic Hormone-Resistant Prostate Cancer Expressing AR-V7 (STARVE-PC) Phase 2 – NO placebo

Basic Eligibility Criteria:
• On hormone therapy, with progressing disease
• Two or more bone metastases
• At least 4 weeks since radiation or major surgery
• At least 4 weeks since use of antiandrogens
(For full eligibility criteria, check with contact below)
Location: Baltimore, MD
Contact: Rana Harb, MS, (443) 287-6662, Rharb1@jhmi.edu

 

2) Niclosamide and Enzalutamide [Xtandi] in Treating Patients With AR Splice Variant [7]-Positive, Castration-Resistant, Metastatic Prostate Cancer  Phase 1 – NO placebo

Basic Eligibility Criteria:
• On hormone therapy, with progressing disease
• Must be metastatic
• Must have taken, and failed abiraterone (Zytiga)
(For full eligibility criteria, check with contact below)

Location: Seattle, WA
Contact: Michael Schweizer, (206) 288-6252, schweize@uw.edu

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TIPS FOR PATIENTS & CAREGIVERS – CLINICAL TRIALS:

Think of a clinical trial as another treatment choice. Therefore, weigh the Risks and Benefits with your doctors and nurses, just like any other treatment.

Here are some things to consider & ask:
• How long is the enrollment paperwork & process for this trial? (it’s usually 3-4 weeks) How does that affect your current cancer situation? What is your PSA Doubling Time (PSADT), for example?

 

• Can you do anything (as a patient or caregiver) to speed up the paperwork and enrollment process? Ask to speak directly to the clinical trial nurse, who is usually a different nurse than your regular nurses. Develop a relationship with them, and hand them any medical records they may not have.

• How much testing is involved? Is the patient willing to do the testing?

• Is there any travel or cost involved? Is the patient willing to travel? (There is usually no cost for a trial, but ask – there are always a few exceptions.)

Remember, clinical trials are voluntary and you can pull out of a clinical trial any time you want.




On the Horizon-Individualized Biomarker Driven Therapy for CRPC

By Shahrooz Eshaghian, MD FACP • Compassionate Oncology Medical Group Clinical Instructor UCLA School
of Medicine • Attending Physician, Division of Hematology & Oncology at Cedars Sinai Medical Center
eshaghian@compassionateoncology.org

 


The past decade has brought many advances for the treatment of CRPC, or MCRPC (metastatic CRPC). This includes the remarkable approval of at least 5 novel treatment options for these patients, who are on hormone therapy, with progressing disease. In previous years, we have called them hormone refractory (or androgen independent) prostate cancer patients:

• Novel anti-androgens: Abiraterone acetate (Zytiga) & Enzalutamide (Xtandi)
• Second line chemotherapy: Cabazitaxel (Jevtana)
• Immunotherapy: Sipuleucel-T (Provenge)
• Radiopharmaceutical therapy: Radium-223 (Xofigo)

 

Although these agents have improved the progression free survival & overall survival in CRPC patients, the disease unfortunately still remains incurable. So, what does the future hold for patients that have progressed past these novel lines of therapies?

————————————————————————————————————
‘Novel’ – a term in medicine used to describe something “new, different, or unusual.”

————————————————————————————————————
Attending conferences & meetings and exploring various clinical journals & NCCN guidelines, the one common answer usually is – enrollment in a clinical trial. Although, we fully support enrollment in clinical trials, as a medical oncologist for almost a decade, I have seen that such a route is not always an option or desire for patients. Understandable information on trials is also difficult for patients to find. (However, please see PAACT’s corresponding article on current clinical trials using biomarkers here )   Still, if a trial isn’t a reasonable option, what else is left for an oncologist and patient to do? One answer that I have found in our clinic is individualized biomarker driven oncology treatment based on novel molecular tests that may help guide a personalized decision. Below, I will briefly discuss and review a few such options that can be offered to patients.

One option would include, assessing for alterations in the expression of the androgen receptor (AR). It has been demonstrated that splice variant AR-V7 predicts a likely low response rate to androgen pathway therapies (REF). Additionally, such a finding might even imply the transition to a distinct new more aggressive histology, which is now termed: intermediate atypical carcinoma (IAC). Prior to this new classification, tumors were traditionally classified as adenocarcinoma or small cell cancer. Although no standard therapy has yet to be established for the treatment of IAC tumors, it would not be unreasonable to consider treatment with chemotherapy (possibly a platinum based chemotherapy regimen) – instead of pursuing additional anti-androgen treatment options.

Additionally, an image guided biopsy (usually bone or lymph node) can be pursued with the help of a skilled radiologist. The tissue sample can then be tested for a possible novel targeted pathway. For many patients, this would also be their first biopsy since being diagnosed with prostate cancer – sometimes many decades ago and the pathology of a patient’s tumor now can certainly be different than it was at the time of their original diagnosis.
An example of testing for a novel pathway would be assessing for BRCA1 and/or BRCA2 mutations that tend to predict a more aggressive phenotype of disease; but, one that might demonstrate response to novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors. Although these mutations are rare (estimate <5% of MCRPC patients will harbor a BRCA1 or 2 mutation), such a finding can lead to a novel approach of therapy with a possible prolong response to treatment.
There are various labs that can offer such personalized genomic analysis. A reputable lab we have come to rely on in our clinic (COMG) to analyze a comprehensive genomic profile for our patients is: FoundationOne (www.foundationone.com). Please visit their website for more information and details about their various testing options. This test is normally covered by most insurance carriers and has a turnaround time of 2 weeks.

Finally, more and more serum liquid biopsies are becoming commercially available in the clinic and might one day replace the need for invasive biopsies. These liquid biopsies can possibly also identify a potentially novel targeted signal pathway, which can lead to the utilization of an individualized treatment plan. Again there are various labs that offer such services and one that we have become most familiar with has been the Guardant360 (www.guardanthealth.com). Again, please visit their website for additional information and testing options. This test is also usually covered by most insurance plans and has a turnaround time of approximately 1 week.
As most readers like to end with a real life case example, I will briefly review a recent case example at Compassionate Oncology Medical Group (COMG) utilizing such methods:

Case Report – JM: 66-year-old male with no significant medical problems.
• 2001: Diagnosed at age 50 with Gleason 3+4 prostate adenocarcinoma, PSA 2.9. He underwent radical prostatectomy. PSA was zero post-operatively and surgical margins were free of cancer.
• 2004: Biochemical (PSA) recurrence and underwent salvage radiation therapy followed by androgen deprivation therapy (hormone therapy).
• 2006: Castrate resistant & established care at COMG with Dr. Bob Leibowitz. By 2009 had progressive bone metastasis & was treated with Dr. Bob’s three-prong therapy including: Taxotere/Emcyt /Carboplatin (TEC) x5-cycles + Triple Hormone Blockade x9-months.
• 2011-15: Zytiga (2011-12), Xtandi (2012-13), Jevtana x21-cycles (2013-15). Briefly treated with Cometriq and then did not qualify for any clinical trials. He deferred Xofigo given rapidly rising PSA (194) & CTC (158) with progressing & symptomatic (painful) bone metastasis.
• 2015: Bone biopsy done & sent to FoundationOne that demonstrated BRCA -2 positivity. Some extensive paperwork granted compassionate approval through FDA (read more below) of Lynparza (olaparib) and he has been on oral Lynparza daily since October 2015. Since then, bone pain has resolved and PSA (94) & CTC (1) are decreasing, and follow up is continuing. He continues to work daily and lives an active lifestyle.

————————————————————————————————————————————
Lynparza (olaparib) is not currently available commercially for prostate cancer in the U.S. There is presently one clinical trial in Europe – See article, Some Current Trials – In the Field of Biomarkers .  

*Trial info is constantly changing. Check www.ClinicalTrials.gov for latest info.
————————————————————————————————————————————————–

In conclusion, the future continues to hopefully look more promising for patients with MCRPC and more personalized therapies are likely in the landscape for a select group of patients.

This article is not meant to be an endorsement for any one test or lab and is meant to serve as a review for the reader, which will hopefully start a conversation with their own personal oncologist &/or physician about what individualized biomarker driven therapies might be available for them, like the AR-V7 blood test, and BRCA 1 or 2 – if ever needed. If I can be of any assistance, please feel free to contact me via phone (310)229-3555 or email (eshaghian@compassionateoncology.org).




Adding Prednisone to Zytiga - More Side Effects?

Zytiga (abiraterone acetate)

I have heard a few prostate cancer patients comment that they are worried about taking Zytiga (abiraterone) because they are concerned about the side effects of the 5 mg prednisone ( 2 x day) which is prescribed with the Zytiga.  People who have been on prednisone for other reasons (gout, arthritis, etc) may have had prednisone side effects which might make them hesitate to try Zytiga – just for this reason.

However, when prednisone is given with Zytiga, it’s given for a different reason.  One of the purposes is to actually LESSEN side effects from the Zytiga treatment.  Simply put, Zytiga (abiraterone) can actually lower blood levels of cortisol in many patients, so the prednisone is considered cortisol “replacement”, which can help reduce side effects from Zytiga treatment.  This is a much different situation than giving prednisone alone for other reasons such as gout or arthritis.   

An article in December 2014 of  The Oncologist says it this way, “…glucocorticoid compensates for abiraterone-induced reductions in serum cortisol and blocks the compensatory increase in adrenocorticotropic hormone seen with abiraterone.  Consequently, 5 mg prednisone twice daily serves as a glucocorticoid replacement therapy when coadministered with abiraterone acetate…”

Dr Leonard Gomella also discusses the issue in this online video, “I think you can safely say that low dose of prednisone does not cause any specific corticosteroid toxocity…”

Since prednisone administration is clearly different than prednisone prescribed for other reasons, talk to your pharmacist if you have any concerns.  Zytiga is usually administered through a Specialty Pharmacy, not a retail or neighborhood pharmacy.  Talk to a pharmacist at one of these locations if you have any questions.  Make sure the information you are working from is correct as you make your ongoing treatment decisions for your prostate cancer.  

Also, if you would like to receive a copy of one of our new brochures called “Ask Your Pharmacist (too…)”, please email PAACT at paact@paact.help with your request and mailing address.

 

(The brochure is completely free,
but donations are always appreciated if possible.)Brochure




AR-V7 Blood Test now Available – for mCRPC Patients

The AR-V7 blood test may help patients and doctors make decisions on treatment choices when prostate cancer patients are metastatic, and castrate resistant, or mCRPC.  The term AR-V7 stands for androgen-receptor splice variant 7.  This blood test recently became available to the public through Johns Hopkins’ Molecular Diagnostics Lab.  

No blood test is perfect, but having a negative AR-V7 test has shown the following in a study of 62 men, published in New England Journal of Medicine Sept 2014:

  • Better PSA response to Zytiga (abiraterone) and/or Xtandi (enzalutamide)
  • Better progression-free survival and overall survival when taking Zytiga (abiraterone) and/or Xtandi

 

In another small study (37 men) published in JAMA Oncology June 2015, having a positive AR-V7 test did not hinder men from responding to chemotherapy, specifically Taxotere (docetexel) and/or Jevtana (cabazitaxel).  In addition, it was noted that “certain patients with detectable AR-V7 at baseline converted to AR-V7 negative status during the course of taxane therapy [chemo].”  There are no promises that a man’s AR-V7 test can be improved (from positive to negative) after doing Taxotere or Jevtana, but at a dinner presentation at ASCO 2016, Dr Antonarakis stated that so far, they have seen this in “about 50% of patients.”  

 

Dr Dan Petrylak also discusses AR-V7 in this short (2016) video.

 

*IMPORTANT – The AR-V7 blood test may or may not be covered by your insurance.  If it is NOT covered by insurance, the cost is approximately $1,000 right now.  It is advised that you call your insurance company and ask about insurance coverage.  It is essential to give your doctor the right CPT code to write on the order – See Step 7 below.

As a patient or caregiver, you will need to do the following to obtain an AR-V7 test:

  1. Verify that your prostate cancer is metastatic, castrate-resistant.”
  2. Print this requisition form from Johns Hopkins lab, and show to your doctor.  Ask your doctor if he will write the order/script for the test.  (The doctor who writes the script for the AR-V7 test CANNOT be in FL or NY.)
  3. Find a local lab who is willing to draw the blood for you, according to detailed instructions on AR-V7 requisition form.  (tip – Medical oncologists usually have their own lab for blood draw, in their clinic.)
  4. There are special FedEx refrigerated shipping instructions you have to follow.  The FedEx package must also arrive at Johns Hopkins lab before 10:00 am the next day (not in the afternoon).   If the lab who draws your blood cannot do this shipping procedure, you may have to do it and pay for it yourself.  For further questions on this shipping to JH lab, you can contact them at molecularpathresults@jhmi.edu or (410) 955-1438.  Hours are 8:30 am – 5:30 pm EST, M-F.
  5. Since the blood needs to be received by Johns Hopkins the next morning, you cannot draw your blood at your local lab on a Friday.  Make sure your AR-V7 blood test is drawn Mon – Thu.
  6. The turnaround time can vary, but test results are usually released to your doctor in 1 – 2 weeks.  Ask for your own copy.
  7. For information on the ordering code (CPT code), call the JH lab at (410) 955-1438.


*For more information on this article, call Jan Manarite of PAACT at her home office – (239) 208-4400, or email her at JManarite@paact.help 




Dr Fred Lee, 1930 - 2016

DrFredLee

PAACT mourns the loss of Dr Fred Lee, the Father of color Doppler ultrasound for prostate, and a pioneer in cryotherapy in the USA.  He was a true advocate at heart, and helped hundreds of patients in his clinic in Rochester, Michigan.

 

Dr Lee often joked that his close friend Dr Duke Bahn was his student, but also became his teacher.  Duke Bahn remembers Fred Lee with the same fondness, stating that  “Dr. Fred Lee was a true humanist with virtue. His remarkable contribution to prostate cancer diagnosis and treatment can’t be properly described in a short sentence.

 

He had been a close friend and a contributor to PAACT since its inception. He touched many lives with love and compassion. His incredibly wonderful spirit will be in their hearts and minds forever.

 

I have been extremely blessed to know Fred as a mentor, colleague, and more importantly a good friend. We lost a big star in prostate community. I will miss him dearly.”

 

PAACT President Rick Profit also remembers Dr Lee – “I first met Dr Lee shortly after I began working at PAACT in October of 2000, a meeting which blossomed into a friendship, personal and professional. Often I would personally take patients to Dr. Lee’s office to have him perform his magic with the color Doppler ultrasound to determine if there was evidence of prostate cancer, which would usually result in a targeted biopsy. Dr. Lee was always a patient’s doctor, his patients always came first regardless of cost or the ability to pay. To the best of my knowledge, every man I ever took to Dr. Lee for CD-TRUS benefited greatly from the care, attention, and expertise of his diagnostic skills – and his generosity to see these men at NO CHARGE. As a bonus of seeing me, he would never let me leave without a complimentary look at my prostate as well. Dr. Lee was a great friend and will truly be missed, not only by me, but by so many more as well.  You will be missed, but never forgotten, my dear friend.”

 

A Memorial Service honoring Dr Lee’s life will be held at 3:00 PM on Saturday, February 20th at the
First Unitarian Universalist Church of Ann Arbor ((4001 Ann Arbor Saline Road, Ann Arbor, MI 48103).   
Any questions can be directed to the church

(734) 666-6158.  The service is open to the public.

 

If you would like to leave comments for his family, you can sign Dr Lee’s memorial guestbook here.

 

RIP, wonderful Dr Lee.




Winter 2015, Article 71

What the Heck Has Been Going on in My World?
By Mark A. Moyad, MD, MPH, University of Michigan

article #71 – Winter 2015

Note: A total of 71 (YES THAT IS 71…that’s a lot…even higher than the number of times my kids said “I am sorry and I will not do that again” and then they did that again!) times in a row (and for 16+ years!) I have written and volunteered for this newsletter. I have yet to receive any personal financial compensation or personalized classic timeless gifts such as PAACT complimentary lifelong mental health therapy for Dr. Moyad after Michigan lost to Michigan State in football on the last play of the game when we were all set to beat those evil guys and their “I am always serious and in a cranky mood” coach (although the guy is really a genius and needs to go coach another team far away, for example some team at the North Pole or Russia, because he is making me crazy) so I can quit seeing him finally semi-smile when he beats Michigan!!! At least it took a miracle to beat Michigan this year and that will be true in the future. Also, by the time you read this newsletter the Mighty Michigan versus the Overrated Ohio State Football game will be over and if we don’t beat those dudes, I’m going to need twice as much mental health therapy so PAACT should get ready to pay for my medical needs ASAP! However, if Michigan can beat Ohio State this year, then I’m going to be in a VERY HAPPY PLACE!!! In fact, if Michigan beats/upsets Ohio State this year, please send me beer and money, because I will have deserved it and if they lose please send me beer and money because I will deserve it and need it!

I WANT TO THANK YOU AGAIN FOR CONTINUING TO MAKE “THE SUPPLEMENT HANDBOOK” – my semi-new book a best seller. YEAH!! THANK YOU!!! Second, if you have not picked up a copy please get one on Amazon.com (the very cheapest place to procure a copy) to support my “Just for Men” fund because my hair is turning even more gray and thin with every issue of PAACT (because I’m getting older, not because I’m experiencing more stress – except when Rick Profit from PAACT sends me an email every 2.5 months stating “your column is due this Friday.” Then I experience stress and I place a small picture of him on my office wall and throw darts at it – especially trying

to hit his mid-section, but then after I turn the column in I feel bad that I did this and take his picture down, but I never tell him that I have this nefarious regular habit and I am sure there is no way he will ever find out that I temporarily throw darts at his picture – I mean how could he find out that I do this on a quarterly basis???)! And, for about 19 bucks (the cost of only 10 two dollar candy bars or a few boxes of Girl Scout cookies – I like the mint ones by the way) you get 512 pages of material on over 100 medical conditions and when not using this amazingly big book it also functions as a football or a Discus.

BREAKING NEWS!!!

325) HILLARY CLINTON EMAILS & President Bill Clinton and Monica Lewinsky! (Actually have nothing to do with this article I just wanted to get your attention).

MY TRIP TO ITALY AND WHAT IT MEANS FOR YOU = COFFEE HAS ANTI-CANCER EFFECTS (Maybe) AND POMEGRANATE DOES NOT???! HEY, THIS IS 3 ARTICLES IN ONE! A TRIFECTA! WHAT A DEAL!!!

(Reference: Moyad and Delta Airlines; Guercio BJ, et al. J Clin Oncol 2015, released early on-line; Liu H et al. Nutr Cancer 2015;67:392-400. & Discacciati A, et al. Ann Oncol 2014;25:584-591).

BOTTOM LINE

Italians drink a lot of coffee and now caffeinated, low or no calorie coffee has some preliminary evidence that it could

Cups of coffee with smoke and coffee beans on old wooden background

reduce the risk of colon and prostate cancer returning after treatment OR this positive evidence only exists because some men that drink a lot of coffee harbor a lot of other healthy behaviors. Regardless this is pretty cool stuff! And, pomegranate juice/extract? Let’s just say it’s not been a good year for pomegranate and prostate cancer evidence, especially when compared to placebo.  OUCH!!!

WHAT ELSE DO I NEED TO KNOW?

I just returned from a brief working trip that took me throughout Southern Italy – I know…life is really tough at times, but someone has to be Mark Moyad. Now I am semi- or actually fully addicted to coffee because in Italy it is ubiquitous, you can’t escape from it, which is kind of like those lawyer ads on TV that promise you big money if you just take someone to court, and they/lawyers do not get paid unless you get paid (wow!). That’s so kind! Expresso, cappuccino, café Americano …yummy for my tummy. I learned about all of them by trying them over and over again! Man, I had more energy than a 16-year old kid getting his driver’s license and a new car on the same day! However, wha t was really incredible is that I saw no one – not a single person in Italy use a “to go” cup or simply walk down the street drinking coffee – not a single person in any of the many cities I visited?! What the heck is going on? These well-dressed Italians (Man they look good even in the early morning…I mean who looks that good in the United States so early in the morning…apart from my wife of course – BOOM! Man, I am as smooth as a baby’s bottom) stand or sit in a café and drink and talk and then move on with big smiles on their faces.

Now it appears that coffee is healthy for you? Perhaps it’s not the coffee but the underlying comprehensive healthy behavior of the coffee drinker in some of these countries. They appear to regularly socialize, relax, remain strong spiritually, walk constantly, and eat very healthy diets, but only in small to moderate portions. For example, I ordered a crab-stuffed ravioli in Rome, a pizza in Naples, Caprese salad in Sorrento, and anchovies in Amalfi that I swear in every case were considered a main course, but were so small that in America they would not even qualify as an appetizer! In other words, the portion sizes were so tiny! I mean even their soda drinks were tiny! This must be the secret of the Mediterranean diet or perhaps it’s the fact that I dumped gallons of olive oil on everything because right now the oil is so fresh and yummy with bread and veggies and meat and fish and _______ (insert your favorite food)! You could almost drink the olive oil straight because it was so fresh in Italy! And, olives themselves were so fresh that I ate a plate of them at every meal! Just call me “Mayor of Olive City” because I LOVE to EAT OLIVES (get it…olive is like saying “I love” – in fact it you mouth the words “olive juice” from a distance to a friend or relative they actually think you are saying “I love you.” Try it sometime, it’s funny!).

Back to my story! Multiple new human (not mouse or rat) studies are also suggesting that coffee (especially the low or no calorie caffeinated type) itself has some anti-cancer/anti-inflammatory properties and could reduce insulin over-exposure, which means not only as a preventive, but also as a way to reduce cancer recurrence. Wow! Is this possible? I mean coffee actually does have some interesting compounds like “chlorogenic acid” that could be healthy! And, in a recent American colon cancer study of patients that had been treated for colon cancer the results were pretty good and got my attention (even though I never drank coffee before except one time in high school before I had to stay up all night for an exam that I think I ended up failing – thanks a lot coffee). In a recent study a total of 953 patients with stage III colon cancer during and 6 months after adjuvant chemotherapy who were prospectively followed over time and the dietary intake of a variety of foods and beverages were self-reported and recorded. Patients ingesting 4 cups/day or more of caffeinated coffee experienced a significant (p=0.002) 52% reduction of colon cancer recurrence or mortality (HR=0.48) versus never drinkers. Non-herbal tea and decaffeinated coffee were not associated with a clinical benefit. Greater coffee intake could be correlated with a significant reduction in colon cancer recurrence and mortality in patients with stage III colon cancer. I wanted to ignore past data that had been primarily retrospective and observational through the years but the accumulating data in cancer has become difficult to ignore.

Yet, is it really the coffee or the average healthy behavior of the coffee drinker that is the secret? It doesn’t even matter because the message of eating a healthy diet but in small portions and moving more and staying skinny is just part of the theme of the coffee drinker. If many Italians would just quit smoking they would live even better and longer, this is what they can learn from us in America (not smoking). Although, many Italians would then start struggling with massive weight gain, which has begun to occur. My trip to Italy was a beautiful educational experience that reinforced some of the similar cultural secrets to a better and/or longer life that I have witnessed from traveling throughout the world from Singapore to South Africa to South America over the past 30 years. However, the smoking part is devastating because although smoking DEFINITELY helps you stay skinnier it also increases the chances of making your life worse while you are living it and ending your life earlier and exposing all those arounds you to this carcinogen. DISGUSTING! In fact, a few times my wife and I walked into a store and were going to spend an obscene amount of money (aka 20-30 dollars) and the store employee or store itself smelled so much like tobacco we had to turn around and leave the store!

Interestingly, at the time I was writing this column, suffering from massive acid reflux and sleepless in Ann Arbor, moments from drinking coffee, there was another research study from the National Cancer Institute (aka NCI) that was published (Loftfield E, et al. Cancer Epidemiol Biomarkers Prev 2015;24:1052-1060.), which suggested that coffee is potentially associated with lower death rates from colon, endometrium, liver and prostate cancer and that improving insulin sensitivity and decreasing inflammation may be the reasons for this potential benefit. So, NCI researchers decided to measure blood levels of 77 immune system and inflammatory markers in over 1700 individuals. Coffee drinkers appeared to have lower blood levels of several inflammatory blood tests! Man, this is getting weird and awesome (kind of like watching your parents trying to operate an I-phone)! And now the bad news that has to do with another highly touted anti-cancer beverage (please read the next paragraph)!

Despite over 10+ years of excitement in the area of pomegranate extract or juice there were few long-term placebo comparative trials and this is what always worried me. It was also worrisome that when someone ingested pomegranate supplements (juice, pills…) there were no significant beneficial changes in weight/waist size, blood sugar, blood pressure, or LDL or “bad” cholesterol. HEART HEALTHY = PROSTATE HEALTHY = Moyad circa 1999 and beyond. It was for these and other reasons I have for years commented that pomegranate could be getting WAY, WAY too much hype and might not do well overall in more rigorous clinical trials and I predicted in my SUPPLEMENT HANDBOOK (available now on Amazon.com = shameless plug #345) that it would fail to work in bigger and better studies. Many people/experts that will remain nameless (until I see them and remind them that they were wrong), pushed the pomegranate agenda aggressively and I do not believe this was helpful. Regardless, here are the issues – after 3 high quality trials it seems that pomegranate is not working much better than a placebo for most individuals. One study was for advanced prostate cancer patients (Stenner-Liewen F, et al. Journal of Cancer 2013;4:597-605.), another was for patients having surgery for prostate cancer (Freedland SJ, et al. Cancer Prev Res 2013;6:1120-1127.), and the third and more recent major trial was for men with rising PSA after primary therapy (Pantuck AJ, et al. Prostate Caner and Prostatic Disease 2015;18:242-248). This is not good news for pomegranate juice or other products derived from the pomegranate, but I have always believed that eating a real and NATURAL (can I use that dirty word) POMEGRANATE will always be healthier than drinking the juice or taking the supplements. Now, that’s a clinical trial I would like to see….pomegranate juice versus supplements versus a pomegranate itself in a CAGE MATCH for a FIGHT WHERE WINNER TAKES ALL!!! My money is on the ignored low cost pomegranate fruit to win in a knockout in the second round!! Regardless, let me remind you what a “natural” pomegranate gives you and why it’s always a healthier choice (in my opinion) versus the pills or juice. It’s because there is approximately 3.5 GRAMS OF FIBER in a serving of pomegranate seeds, which is very high compared to many fruits and helps control the amount of sugar absorbed from the juice. And, if you remove the fiber and just keep the juice then what do you have apart from a lot of liquid sugar? I’m not sure what you have, this is why I put a question mark at the end of the last sentence.

Now, let me ask you 5 questions that are more important than any pomegranate or supplement product or almost any product on the market. PLEASE INSERT YOUR NUMBERS BELOW AND THEN BRING THEM TO ME WHEN YOU SEE ME AT A LECTURE, MEETING, BAR, OR A MCDONALD’S NEAR YOU!

1. Do you know exactly your weight/waist size?

2. Do you know exactly your last LDL cholesterol (aka “bad cholesterol”) value?

3. Do you know your blood sugar value?

4. Do you know your blood pressure numbers?

5. Do you know why Coach Jim Harbaugh at Michigan will win the national title in college football in 2017 and 2018 (rhetorical question…of course the answer is “because he is Jim Harbaugh the most brilliant coach in the history of college football” and because he went to grade school with another fabulous person named Mark Moyad…no kidding “St Francis of Assisi” in the 1970s, I think…it was while ago)?

Anyhow, let’s conclude this section on coffee by reminding you that the next time you go to Starbucks just order a tall medium or light coffee with no extras and that’s only 5 CALORIES!! If you don’t like coffee just order their OATMEAL (only 160 calories and 4 grams of fiber and virtually no sugar and 5 grams of protein) with a dash of milk and no extras – you will like it and your colon and prostate and heart and your sexual organs (I was going to use that “p” word for example, but PAACT is a family newsletter so using the word “penis” would have been inappropriate, so whenever you see the letter “p” by itself it means “penis” or it could also mean “PAACT” I guess…you decide) will say thank you very much for consuming such a healthy product!

326) What I ordered at McDonald’s the other day!

(Reference: McDonalds in Ann Arbor, MI or Detroit Airport or Denver, Colorado or coming to a McDonalds near you)

BOTTOM LINE

Fast food restaurants get a lot of criticism, as they should, because many items are as unhealthy as a swift kick in the groin area that just keeps on hurting, but once in a while they come up with a delicious low calorie option that should be given credit! So, let’s give them credit for inventing the EGG WHITE DELIGHT McMUFFIN! Hip, Hip, Hooray, it may actually be good for your waist and hip bones!

WHAT ELSE DO I NEED TO KNOW?

What tastes amazing, costs very little money, and only has 250 calories but also has 18 grams of PROTEIN (that’s a lot) and 7 grams of fat, zero trans-fat, only 30 milligrams of cholesterol, 1 gram of dietary fiber, 3 grams of sugar and 230 milligrams of calcium (that’s a lot) and again did I mention it tastes VERY YUMMY AND AMAZING AND IT MAKES ME FEEL FULL!!! IT IS THE EGG WHITE DELIGHT McMUFFIN!!! HIP, HIP, HOORAY!!! HIP, HIP, HOORAY!!! HIP, HIP, AND IT’S GOOD FOR YOUR HIP(s)!

Wait, Dr Moyad you are actually pushing fast food and McDonalds, which has arguably kept most cardiologists in business over the past few decades?! So, what’s the catch with this newer food or breakfast item besides the fact that McDonalds invented it? There is a catch – it contains 760 mg or 31% of your daily intake of SODIUM – YIKES!!! So, of course there’s a catch, but if this is all that you eat for breakfast and you regularly watch your sodium intake or in reality increase your potassium intake then WHO THE HECK CARES!!! I LOVE THIS NEW BREAKFAST ITEM!!! TRY IT AND AFTER YOU LOVE IT SEND ME A GIFT CERTIFICATE TO MCDONALD’S FOR CHRISTMAS or HANUKKAH or whatever you celebrate! Anytime is a good time to buy Mark Moyad a gift!!!

327) Why calcium supplements are not needed anymore for most people (exceptions include those on osteoporosis prescription drugs and steroids long-term like prednisone and those that rarely consume foods and beverages with calcium, which is hard to do by the way…did you see the amount of calcium in the McDonalds item from the previous news story Moyad discussed?)!   (Reference: Moyad MA. The Supplement Handbook-best book in world)

BOTTOM LINE

Calcium supplements (with or without vitamin D) have many risks including: increasing the risk of kidney stones, constipation (Hey, wait slow things down – get the joke…constipation? Really?), inflammation of the throat, swallowing problems, and even heart disease (controversial, but concerning). Additionally, there’s so much calcium in food and beverages today that people are being over exposed to it. The goal is to normalize your intake of calcium and vitamin D to prevent falls but there’s no reason to get excess amounts of calcium and vitamin D. I have written about this many times but there’s new information on the subject so let’s discuss it.

WHAT ELSE DO I NEED TO KNOW?

If you want to learn about the highest sources of calcium in foods and beverages go ahead and GOOGLE IT (or in reality I say “MICHIGAN IT” because one of the founders of google went to the University of Michigan and he loved it as much as Tom Brady loved it, because it’s the greatest school in the world.

I’m not biased at all….oh and did I mention it’s the greatest school in the world and Tom Brady went there and loves it!).

Calcium is so replete in multivitamins (heck I saw one the other day with 500 mg of it per multivitamin pill), food and fortified beverages today it has become easier than ever before to attain the recommended 1000-1200 mg per day (1000 mg in 19-50 year old males and females, 1000 mg in 51-70 year old males, 1200 mg in females 51 years and older and males 71+ years). The table on this page is a representation of how much easier it is to reach the RDA goal of calcium without having to take separate calcium supplements.

In fact, in the largest dietary supplement trial ever conducted on calcium supplements (WHI) the baseline intake of calcium from foods, beverages and supplements was already approximately 1150 mg/day of calcium before randomization to the calcium or placebo groups! In other words, many of us are already getting too much calcium or enough calcium.

The Women’s Health Initiative (WHI) was a double-blind, placebo-controlled clinical trial and the largest U.S. clinical trial to address the issue of calcium and vitamin D supplementation. This trial included 36,282 postmenopausal U.S. women who were to ingest 1000 mg elemental calcium carbonate plus 400 IU of vitamin D3 (OsCal® brand of calcium supplements, GSK Company) or placebo for 7 years. The average BMI was 29 (almost obese) and there were a greater number of obese versus overweight women in the trial, which interestingly appears to reflect the current U.S. population. The primary endpoint was the reduction in hip fractures, and secondarily total fractures and colorectal cancer. Calcium and vitamin D supplementation significantly increased hip and total bone mineral density (BMD) versus placebo (p<0.01), but there was no overall evidence to suggest a reduction in hip or total fracture risk. There was an increase in kidney stone risk and there were no impacts on cardiovascular events or colorectal cancer risk. This study, the largest of its kind, continues to suggest that normalization or increased calcium and vitamin D supplementation could improve bone mineral density and may have an impact on hip fracture risk but arguably only in those individuals that are not getting enough calcium and vitamin D. But, keep reading because you might be surprised as to how calcium and/or vitamin D might be reducing the risk of bone fractures, if they do at all.

A recent extensive analysis of the calcium and vitamin D supplementation data from the U.S. Preventive Services Task Force or USPSTF (the same group that now discourages PSA screening…love them or hate them) found treatment of vitamin D deficiency in some asymptomatic person might prevent falls (not fractures). They concluded their findings the following way: “Treatment with vitamin D, with or without calcium, may be associated with decreased risk for mortality and falls in older or institutionalized adults. Vitamin D treatment did not reduce fracture risk…” This is a critical initial finding from the research, which in my opinion also suggests cancer patients should normalize their calcium and vitamin D intakes to maximize the benefits of bone loss prevention and especially FALLS, which could lead to an increased risk of fractures. And, there is enough evidence from these past reviews of the data that calcium and vitamin D are also important for muscle health and coordination.

Additionally, most major trials of drug interventions to prevent bone loss and fractures in cancer patients, including denosumab (Xgeva®) and zoledronic acid (Zometa®), utilized some form of calcium (1000 mg per day) and vitamin D supplementation (400 or more IU per day) or normalization of intake to ensure adequate responses to these bone medications.

Thus, when these drugs received FDA approval in breast and prostate cancer it was due to phase-3 trial evidence of the drug with the use of calcium and vitamin D in combination (not by itself) to normalize daily intakes. So, how much vitamin D is enough? Well, the Institute of Medicine (IOM) has done a good job of simplifying the requirements. Age 18 to 70=600 IU of vitamin D a day and from the age of 71+ then 800 IU per day! That’s it!!!

Now, without going through all the side effects of taking calcium dietary supplements, which I have covered adequately in past PAACT issues (along with which calcium supplements are better or worse or pose less of a risk of kidney stones…) there is now a new issue “PILL ESOPHAGITIS” (inflammation of your food pipe). Pills come with unique side effects and although life-saving in many cases another reason not to ingest a pill unless needed is due to “pill esophagitis.” This is well-known in the pharmaceutical industry, for example, and often it is due to patients not drinking enough water or standing up when ingesting a pill (for example this is why all osteoporosis pills come with these instructions and warnings). The symptoms of pill esophagitis include difficulty swallowing, pain on swallowing and retrosternal pain. Yet, dietary supplements can also cause pill esophagitis and esophageal ulcers, so the concern or at least recognition over this side effect in the supplement industry should immediately match that of the pharmaceutical industry. Increasing awareness of dietary supplement side effects allows for the identification of pill side effects unique to the industry itself, especially when compounds such as “silicon dioxide” (aka “sand”) are utilized in some products to a large extent. Recently, recognition of an increased risk of 100% silicate based kidney stones can occur in products that contain ample amounts of this compound. And, this is just one of many compounds uniquely utilized in pills, especially supplements that were believed to be inert in humans.

However, back to the famous/infamous calcium supplements for a second because some are as large as the front door of your house (THAT IS A BIG FRONT DOOR Dr. Moyad). Recently there was a report that suggested over 23,000 emergency room visits occur PER YEAR because of dietary supplements (Geller AJ, et al. N Engl J Med 2015;373:1531-1540)! YIKES!!!! I actually think this number is a lot higher for many reasons that would be boring to you and would just take up a lot more space and I am getting tired typing (I have fingeritis, I wonder if I should call one of those lawyers on TV and hold PAACT responsible for this clear cut disease caused by PAACT)! Anyway what got missed in the publicity around this paper that mostly focused on weight loss supplements or energy products was the finding that “AMONG ADULTS 65 YEARS OF AGE OR OLDER, CHOKING OR PILL-INDUCED DYSPHAGIA” (problems with swallowing) was responsible for 38% of all those emergency department visits in this age group!!! And, more than half of the swallowing problems (54%) with pills from this study from emergency room departments around the U.S. were due to “CALCIUM PRODUCTS/SUPPLEMENTS!!!” This is another big problem with calcium supplements today because like multivitamins they are becoming too big or are too big! In the pharmaceutical world the FDA recommends that a pill should not be greater than 22 millimeters, but with supplements there is no recommendation or rule! GEESH!!

328) Fiber Primer and why getting more dietary (not supplemental fiber) is one of the keys to internal anti-aging! So, it’s a form of BOTOX®? YES!!! But, wait you have talked about this before in the PAACT newsletter and readers are sick of hearing about it! Nope! There is breaking news and new information on it and it has to do with PSA screening?! And, how about some of my favorite BOTOX jokes you have never heard and why exercise keeps things flowing and lets you sleep at night if your prostate is large and in charge?

(Reference: Moyad MA, 2015)

BOTTOM LINE

Consume more (soluble and insoluble) dietary fiber (20-30 grams/day or 14 grams per 1000 calories consumed), especially from food sources. “Fiber is nature’s internal Botox for the human body” (Moyad Circa 2014) and both soluble and insoluble fiber have unique and synergistic benefits when found together (as in most healthy dietary sources). OH BOY HERE GOES MOYAD AGAIN TALKING ABOUT FIBER!!! That’s correct! I have mentioned much of these benefits before, but let’s review again and add some new information! So, let’s get things moving (get it?) and talk fiber!

WHAT ELSE DO I NEED TO KNOW?

General and numerous health benefits are derived from consuming dietary fiber that have been well documented and include reductions in the following:

• Coronary heart disease (CHD) risk

• Stroke

• High blood pressure

• Diabetes

• Obesity

• All-cause mortality=death from all•causes (which is a good thing)

For example, a pooled analysis of past cohort studies of dietary fiber for the reduction of CHD (coronary heart disease) included research from 10 international studies and included the U.S. Over a period of 6-10 years of follow-up, and after multivariate adjustment it was revealed that each 10 gram/day increase of calorie-adjusted total dietary fiber was correlated with a 14% reduction in the risk of total coronary events and a 27% reduction in risk of coronary death. These findings were similar for both genders, and the inverse associations occurred for both soluble (also known as “viscous”) and insoluble fiber (both are found in most healthy food sources of fiber compared to commercial pills and powders that normally just or primarily contain “soluble” fiber).

Past studies have not observed a consistent benefit with one class of fiber over the other (soluble or insoluble). Recent large U.S. and other international studies have even found more striking overall potential benefits for consuming more dietary fiber. For example, the NIH-AARP U.S. prospective cohort found not only a lower risk of dying from cardiovascular, respiratory and infectious disease with greater intakes of fiber but a significantly lower risk of dying younger (“total death”) in men and women. This study may represent a major shift into the research behind fiber intake because now the potential health impact may be so much larger than first realized since reductions in the death rates of some of the largest causes of mortality may occur with greater fiber intakes.

Even minor additions of some commercial fiber sources (to your overall large dietary fiber intake) can positively impact medication dosages. A total of 15 grams of psyllium (Metamucil for example) husk supplementation daily with a 10 mg statin (simvastatin) was demonstrated to be as effective as 20 mg of this statin by itself in reducing cholesterol in a preliminary placebo-controlled study of 68 patients over 12-weeks. Although adding soluble fiber from commercial products appears to be safe and synergistic with cholesterol lowering medications, the first choice of increasing fiber intake should be FOOD SOURCES based on cost-effectiveness and simplicity. I’m not a big fan of Metamucil in large amounts, but if you need a little help getting to your daily fiber total, then Metamucil is an option.

More benefits should be emphasized so let’s do this – a meta-analysis of 24 randomized placebo-controlled trials of fiber supplementation found a consistent impact on blood pressure reduction. Supplementation with a mean dose of only 11.5 g/d of fiber reduced systolic blood pressure by –1.13 mm Hg and diastolic pressure by –1.26 mm Hg. The reductions were actually greater in older and more hypertensive individuals compared to younger and normotensive participants. Recent international studies continue to support the modest reduction or control in blood pressure with greater intakes of dietary fiber.

How much fiber should patients be consuming daily? Daily intakes of total fiber in the U.S. and many other Western countries is approximately 10-15 g/d, which is approximately only half or even less than half of the total amount consistently recommended by the American Heart Association (AHA) and American Dietetic Association (20-30 g/d) for adequate overall health. Another perspective on recommended fiber intake for children and adults is that for every 1000 calories of food and beverage consumed there should be at least 14 grams of fiber consumed.

Dietary fiber from food is easily achieved by low cost sources of soluble and insoluble fiber. For example, I often tell patients to consume a third of a cup of a bran cereal such as All-Bran Buds several times a week, which is approximately only the size of 1-2 liquor shot glasses, with flaxseed and some fruit, and before they leave the door in the morning approximately 20 grams of fiber will have already been ingested toward the 25-30 gram goal! Low cost fiber sources such as flaxseed can provide potentially numerous heart healthy and overall health benefits. Perhaps the low-cost and non-commercialization of this product on a large-scale has led to the lack of adequate education that I’ve observed on this product. Flaxseed is one of the highest plant sources of heart healthy omega-3 fatty acids, and chia seed is arguably the largest plant source of fiber and omega-3, and both of these additions to the overall diet would be ideal. Also, the
original Fiber One® cereal contains 14 GRAMS of fiber in just a half a cup! WHAMMMO! This definitely keeps the train moving!

Interestingly, the preliminary clinical trial data on ground flaxseed (average of 30 grams or 3 rounded tablespoons per day) in other hormone mediated cancers such as breast cancer has been as or more impressive (reduced proliferation rates or Ki-67, which is a marker of potential cell or abnormal cell growth). Thus, it shouldn’t be a surprise that preliminary data of flaxseed in prostate cancer is also impressive and similar to some of the breast cancer observations. Flaxseed oil also has preliminary data against cancer, but this and other oils are a large source of calories (120-130 calories/tablespoon) and contain no fiber so rarely have I recommended them over low cost flaxseed powder (similar to the real whole non-processed fruit versus the fruit juice debate mentioned earlier).

Overall dietary fiber intake (again not pills or powders) continues to garner evidence as a method of cancer prevention. Multiple mechanisms are potentially involved with this fiber benefit including:

• reduction in by-products of male and female hormones that could stimulate cancer growth

• reduction in insulin and growth factors/mitogens,

• reduction in inflammatory compounds potentially via production of short-chain fatty acids when fibers are fermented in the colon by flora and products of fermentation such as butyrate and propionate enter the circulation.

• plethora of heart healthy changes altering cancer risk/recurrence (lower weight/waist, reduced cholesterol and blood sugar…)

Still, fiber itself appears to have become overtly commercialized, and in my experience some patients are turning primarily toward powders and pills to solve their fiber deficit, and this is not only costly, but also provides primarily small amounts of soluble fiber that make it difficult to reach total fiber goals utilizing only these sources. For example, I often ask audiences and students how many fiber capsules/pills are needed to be consumed daily to obtain just 20-30 grams of fiber, and the answer always seems to provide adequate shock value (the answer is 30-50 pills a day or more depending on the commercial source)! A bolus of only soluble fiber without insoluble fiber can also create excessive bloating and other gastrointestinal issues because soluble fiber is utilized by gut bacteria and then subsequently converted to gaseous compounds (aka “passing gas”).

Processed soluble fibers abound today in protein bars and cookies and these items need to be avoided not only for a lack of evidence but again gastrointestinal discomfort with moderate to high intakes. Research continues to support the overall and heart healthy health benefits of fiber, especially when it’s primarily derived from food sources, because these sources also provide a unique and optimal balance of soluble and insoluble fiber. Another comprehensive list of dietary fiber benefits are found in the table on this page (see table) and this is why I often tell patients that “nature’s greatest internal Botox” has to be dietary fiber! The plethora of internal anti-aging effects it provides is noteworthy, from preventing cholesterol and glucose changes to preventing hemorrhoids, and it’s easy to forget that humans don’t just age externally but internally with time. Botox for cosmetic anti-aging is attention grabbing but why isn’t fiber just as notable for preventing internal aging?

I find it interesting that most fruits, veggies, beans, bran, oatmeal and other dietary sources of fiber are primarily an equal mix of soluble and insoluble fiber or insoluble fiber actually predominates over soluble in these products, while again most commercial products are basically almost all soluble fiber. They are both needed to improve overall health (Yin and Yang). The reason one can consume 2 medium apples (about 10 grams of fiber total) without experiencing significant bloating, gas or discomfort is the majority of the fiber is insoluble (about 30% soluble). Again, the reason one cannot consume a large bolus of processed or commercialized fiber supplements or powders is that the vast majority is soluble fiber.

Now, you think all of this information would be enough to make you run out and start gobbling (Is that even a word???)

It is on Halloween….bad joke…like most of my jokes) up a ton of fiber! Still, there is another reason to do this and this is the most surprising of all! You may remember the U.S. study called “PLCO” that demonstrated no benefit to general PSA screening and the USPSTF used this information to no longer recommend PSA screening. After that point all heck broke loose and people started arguing back and forth on whether or not PSA screening should be recommended or not. It was kind of like Republicans and Democrats arguing back and forth and not getting anywhere, which is what happens only 365 days a year (they get things done on the other days of the year). Yet, the USA PSA screening study known as “PLCO” was a well done study not just in terms of asking the screening question, but perhaps more importantly answering other important questions on diet and exercise and this is what gets missed or no one knows about! So, what other findings occurred in this famous study that hardly received any media attention. Here is one conclusion of a finding that was also uncovered in the PLCO study and I quote: “This large, prospective study within a population-based screening trial suggests that individuals consuming the highest intakes of dietary fiber have reduced risks of incident colorectal adenoma and distal colon cancer and this effect of dietary fiber, particularly from cereal and fruit, may begin early in colorectal carcinogenesis.” (Reference is Kunzmann AT, et al. Am J Clin Nutr 2015;102:881-890). THAT IS INCREDIBLE!!! So, while all these folks run around and argue whether or not an otherwise healthy man should be screened for prostate cancer, the same study that helped generate this controversy found that DIETARY FIBER (not fiber from pills) found a potential large reduction in colon cancer or precursors to colon cancer-premalignant lesions with fiber! Amazing! Okay, tell me more Dr. Moyad! Tell me more! Okay I will and quit yelling at me with exclamation marks!

In the same PLCO clinical study that generated so much controversy with PSA screening and found a potential great benefit with fiber, also found another potentially incredible benefit with physical activity or exercise that few people know about and again why these researchers did such an incredible job! Here is what they found: “we did find strong and significant associations between physically active lifestyle and nocturia….Combined with other management strategies, physical activity may provide a strategy for the management of BPH-related outcomes, particularly nocturia.” (Reference is Wolin KY, et al. Med Sci Sports Exerc 2015;47:581-592). SEE IF YOU UNDERSTAND THIS INCREDIBLE FINDING! The same study that generated the PSA controversy and found that dietary fiber could be colon healthy also found that exercise could reduce the risk of getting up at night to urinate (NOCTURIA) when a man has prostate enlargement or BPH! This is amazing!!!

In the meantime, it you are not convinced that you should be more physically active and consume more fiber you could instead pay a ton of money for the real BOTOX. Ahhh, yes the real BOTOX, which is really expensive and comes with many jokes such as:

• “People tell me that Botox is way too expensive but I just met 10 people who paid for the treatment and they didn’t look surprised!”

• “There was some major recent controversy over Botox injections but these stories never seem to make the headlines!”

Okay, that’s it! I actually don’t have any good Botox jokes, but I don’t know how to use an iron so I did inject my favorite shirt with Botox before my last talk so that there would be no wrinkles in it – Ouch! That was bad!

329) Over the next 2 years there is a good chance there will be a new Shingles vaccine and it could be one of the best preventive vaccines ever invented! Keep asking your doctor about it!

(Reference: Himal L, et al. N Engl J Med 2015;372;2087-2096)

BOTTOM LINE

The company GSK has a new shingles vaccine and you should ask your doctor about it over the next year or two. Cross your fingers! If this gets approved it could be incredible because it would be over 97% effective for all age groups from 50 and older! The current shingles vaccine is not that great especially as you get older it gets weaker and weaker. However, this is not the case with the GSK vaccine!

WHAT ELSE DO I NEED TO KNOW?

The current shingle vaccine (Zostavax®) isn’t that great as you get older, but it’s all we have right now! For example, it’s 64% effective for those in their 60s but when you are age 70 and older it’s only 38% effective compared to 70% effective for those ages 50-59 years! So, we can do better and better may be right around the corner! A new vaccine that may hit the market in 2017 is currently MORE THAN 97% EFFECTIVE REGARDLESS OF AGE!!! THAT WOULD BE INCREDIBLE! Notice how I like the word “incredible” because it is incredible. GSK completed a study in 2015 with more than 15,000 patients age 50 and older (some 80 years and older). Currently only about 1 out of 4 individuals age 60 and older get the currently available Zostavax vaccine, but if this new one becomes available, I hope we get close to 100% of the people that need it get vaccinated. What’s the catch with the new GSK vaccine if it becomes available? Well, the study was over about 3 years, so long-term, researchers are not sure if the results will continue to be this amazing. Also, you will need 2 shots separated by 2 months when or if you get it. Still, if these results stand then I wouldn’t hesitate to get this vaccine when it comes out, also because side effects are not greatly different compared to a placebo vaccine.

And, now another new study from Sweden or as I like to say “Svvvvvveeeden” (because it sounds so much cooler) continues to demonstrate an increased risk for stroke and other unpublicized problems when getting Shingles! So, yes I do think the Shingles vaccine will eventually demonstrate that it can prevent cardiovascular disease including shingles! The risk of stroke and sepsis (serious infections) were significantly higher in the 12 months after getting shingles from this population study of over 13,000 cases of shingles! Yikes! Some researchers theorize that the shingles virus can actually infect arteries in the brain and others suggest that it creates a full body long-term inflammatory response that increases the risk of a number of cardiovascular problems. It’s interesting that in this recent study it was found that even younger individuals had a much larger risk of stroke if they had shingles. This is scary stuff and another reason why I am a BIG, BIG FAN of the current and future shingles vaccines. Finally, I think the potential for another benefit could occur with shingles and that is a reduction in the risk of COLD SORES! What? Moyad has lost it (but he never had “it”) and thinks the future shingles vaccine could prevent cold sores?! Yes, because cold sores are in the herpes virus family, which is a large family of viruses that also includes shingles. In fact, there are several studies now showing that there is an increased risk of being infected or bothered by one condition if you already have the other and vice versa. HOW MUCH FUN IS THIS STUFF (not shingles or cold sores but just this information is fun right?)!!!

I just love to talk about cold sores and shingles especially at the family dinner right after the family begins to take their first bite! It’s really great watching everyone get sick or look horrified at the table (reminds me of the holidays). You should try this some time, it will definitely get the attention of everyone and it’s also educational!

THAT’S ALL FOLKS…. See you in the SPRING, when I will write about many other serious issues and give timeless advice in the next newsletter, such as: why it’s never good to carry a heavy, hard to manage chainsaw in a crowded male nudist camp, it’s never good to talk about shingles and cold sores at the dinner table, it’s never a good thing to hear a surgeon say “I can’t find my glasses” right before you receive anesthesia as a patient, it’s never a good thing to take a laxative, a sleeping pill and a Viagra at the same time, and why it’s never good to tell someone you love them and then burp loudly.