Anxiety-How to Win Our Biggest Battle.

Norwegian Stave church; A. Dalene photo.

I recently met with a well-known urologist whose research focuses on the use of our immune system to combat prostate cancer. In our conversation, I was able to share my own prostate cancer history and current status. He echoed the comment that had been stated by my oncologist and assured me that since there were so many current and future treatment options now available, I would more than likely outlive my own prostate cancer and die of another cause. The urologist went on to state that the biggest problem facing his prostate cancer patients is their own angst. I could certainly echo his sentiment.

In my own case, I had been diagnosed with prostate cancer in 1995. Shortly thereafter, I underwent a successful radical prostatectomy at Johns Hopkins. My cancer was completely localized, had not spread and my Gleason score was an average value of 3+3 or 6. I was an ideal candidate for a “cure”. But the cancer (PSA) returned 7-8 years later and was not completely eradicated by radiation therapy. My PSA doubling time had become 2-3 months, indicating an aggressive cancer. A former colleague of mine had published a paper in a peer-reviewed journal in which he concluded that patients like myself with such a short doubling time could expect an average 5-year survival period. The period of 1995-2004 was filled with lessons I had learned both medically and especially spiritually but it was interspersed with periods of high personal anxiety as recounted in this website (see My Story and Lessons Learned). I am currently asymptomatic and undergoing intermittent therapy. I have continued to pray that God would not allow this disease to take my life and He seems to be reinforcing His answer to me through His word and the predictions of two well-known oncology and urology physicians. God had allowed me to experience this cancer scenario for other reasons, such as that He would be glorified through my experiences and that other men might be encouraged.

I have learned that anxiety can become a bondage and is an individual choice. The apostle Paul states in Philippians 4:6-7 that Christians are to “be anxious for nothing, but in everything by prayer and supplication” (asking), “with thanksgiving, let (y)our requests be made known to God. And the peace of God which surpasses all understanding, will guard (y)our hearts and minds in Christ Jesus.” Worry indicates a lack of trust. I have often worried about the possibility of receiving negative results or news. When the actual results were known, they were never as bad as I had imagined and many times they were very positive. Negative results can serve as tests of our faith. God was showing me that I had a lack of trust and that my own anxiety was a faith battle which indicated that my own faith needed to be re-directed and strengthened. I am to release my anxiety to God and admit that I cannot handle the situation in my own strength. I simply need to trust that God will answer in His way and His time according to His purpose (see Jeremiah 29:11). This will also validate my own personal relationship with God and that it is not simply  intellectual knowledge and mis-placed faith. When we enter into a personal relationship with God, every promise in His Word (such as that above) becomes applicable to us.

Jesus Himself is our greatest example of how to handle anxiety. It is always encouraging to realize that He is both divine and human, and as such can associate with our own feelings. This is best exemplified by Christ’s experience in the Garden of Gethsemane prior to His crucifixion. He had been betrayed and denied by His own friends and disciples. Yet He cast His burden on His Father. First, like us, He prayed that His potential suffering be removed. In Matthew  26:39 He prays for deliverance, “O My Father, if it is possible, let this cup pass from Me.” I am sure any prostate cancer patient can relate to this statement. Then Jesus expresses acceptance stating “nevertheless, not as I will, but as You will.” In verse 42 He prays “O My Father, if this cup cannot pass away from Me unless I drink it, Your will be done.” The fact remains that we who have been diagnosed with prostate cancer must accept its medical reality. But there is better news. Jesus’ third prayer was a desire that God’s grace be seen in Him and that His Father would be glorified. In John 12:27-28, Jesus prays “But for this purpose, I came to this hour. Father, glorify Your name.” As a direct result of our personal relationship with God, we too can cast our burdens and anxiety on the Lord and help others to do so. For me, I often visualize packaging my anxiety in a container and laying it at Jesus’ feet or at the cross. May our deepest desire be that God’s grace and goodness would be seen in us and that He would be glorified in our individual scenarios and outcomes.

A Vitamin D – Prostate Cancer Connection and Other News.

There has been much discussion concerning the role of blood vitamin D levels and its metabolism and their relationship to prostate cancer. A study examining this relationship published in the April 12th issue of the Journal of the National Cancer Institute found that men with the highest plasma levels of vitamin D “were 57% less likely to develop a lethal form of the disease.”  Plasma vitamin D levels and common variation among several vitamin D-related genes associated with its metabolism were associated with lethal prostate cancer risk, suggesting that vitamin D is relevant for lethal prostate cancer. However, vitamin D levels did not affect the chances of developing prostate cancer. It should be noted that vitamin D levels were determined by the 25-hydroxyvitamin D assay and not the 1,25-dihydroxy assay. One can attain sufficient vitamin D levels from foods, D3 supplements of varying strengths (units) as well as from calcium citrate or calcium carbonate supplements which also contain vitamin D. It is strongly recommended that the amount (units) of vitamin D required to maintain an optimal blood level should be determined in consultation with a physician as highly excessive amounts may be harmful. Optimal serum levels of vitamin D are 20-50 ng/mL in the USA according to some sources while others recommend 50-80 ng/mL. (International levels are 50-125 nMol/L.)  A summary of this research appeared in the April 27th, 2012 issue of the Prostate Cancer Foundation NewsPulse. In addition to this study, this issue of NewsPulse also contained articles dealing with High-Intensity Focused Ultrasound (HIFU) treatments and proton beam radiation therapy.

The April 3rd, 2012 issue of ZeroHour from the Project to End Prostate Cancer contained two articles of specific interest. One described a study concluding that oxygen levels measured in tumors might be used as a good predictor of prostate cancer recurrence. The other discussed a new zirconium radiotracer (89Zr-5A10)  designed specifically to target free PSA (a better biomarker of prostate cancer) as opposed to serum PSA. This radiotracer can be used in conjuction with positron emission tomography (PET) to identify metastatic bone lesions in a more specific manner than traditional bone scans.

The April 14th, 2012 issue of the Prostate Cancer Research Institute (PCRI) Weekly  contained information about availability and enrollment in Phase III clinical studies of alpharadin (radium-223 chloride) in hormone-refractory patients with symptomatic bone metastases. Alpharadin uses alpha-particle radiation from radium-223 to kill cancer cells by specifically targeting bone metastases by virtue of its property as a calcium mimic. It is being developed by a Norwegian company, Algeta ASA in collaboration with Bayer.

HisProstateCancer.com, a Website for Wives and Family Members of Men With Prostate Cancer.

Recently I was contacted by a woman whose husband had been diagnosed with prostate cancer at the age of 49.  He underwent a radical prostatectomy and subsequent radiation therapy. Their experience led to the generation of the website, HisProstateCancer.com with its specific focus to wives, partners and family members of prostate cancer patients. I recommend this site for your review.

A New Urine-Based PC Assay, Clinical Trials Providing Earlier Access to New Therapies and Other News from February-March, 2012.

Banyan tree overlooking inter-coastal waterway Boca Grande, Florida. – B.J. Gabrielsen photo.

It has been a month since I last updated this website and there have been significant news items which are summarized below.

1) FDA Approves a PCA3 Urine-Based Assay for Prostate Cancer that Could Reduce Unnecessary Prostate Biopsies.  On February 15th, 2012, the U.S. Food and Drug Administration (FDA) approved a urine-based molecular diagnostic test that aids clinical decision-making for repeat prostate biopsies in men who have had a previous negative biopsy. The test, developed by Gen-Probe, is called PROGENSA PCA3 (Prostate Cancer Antigen 3) assay. It tests for levels of PCA3 in the urine of men immediately after a digital rectal examination. PCA3 is produced by a gene that is normally expressed only in human prostate tissue and is highly expressed in 95% of all prostate cancer.  Thus the product of this gene is excreted in the urine of men with prostate abnormalities. The current prostate-specific antigen (PSA) screening test for prostate cancer is prostate-specific but not highly cancer-specific which is the case for PCA3 testing which has better positive and negative predictive values. Therefore, this test will aid faster and more efficient diagnosis of prostate cancer thereby minimizing additional repeat biopsies and their undesirable side effects including infections.  Additional details are available from Gen-Probe, in the March 20th, 2012 issue of the ZeroHour Newsletter and the February 27th, 2012 issue of the Prostate Cancer Foundation NewsPulse.

2) Patients Being Recruited for Clinical Trials Involving Provenge, Zytiga and/or Hormonal Therapy. During the last 1-2 years, several new therapeutic agents have been approved by the FDA for treatment of men with metastatic prostate cancer or who have had prior chemotherapy. The strategy now seems to be the application of these agents in men with earlier stage prostate cancer. To determine the effectiveness of such strategies, two clinical trials are described involving Sipuleucel-T (Provenge), abiraterone acetate (Zytiga) and androgen deprivation (hormonal) therapy (ADT). The first is entitled “Concurrent Versus Sequential Treatment with Sipuleucel-T (Provenge) and Abiraterone (Zytiga) in Men With Metastatic, Castration-Resistant Prostate Cancer (mCRPC).” This trial may provide earlier access to Zytiga for men who have not had chemotherapy. It is currently recruiting patients in the following locations: Denver, CO; Seattle, WA and Virginia Beach, VA.

The second trial entitled “Sequencing of Sipuleucel-T (Provenge) and ADT in Men with Non-Metastatic Prostate Cancer”, may provide earlier access to Provenge for men who have recurrent but non-metastatic prostate cancer. The trial is designed to determine whether ADT (hormonal therapy) started before or after sipuleucel-T leads to superior augmentation of immune response to sipuleucel-T. This trial is currently recruiting patients in the following states: Alabama, California, Colorado, Maryland (Johns Hopkins), New York, South Carolina, Texas and Washington. For details of both trials, see the Prostate Cancer Research Institute (PCRI) Weekly (Volume 2, Issue 2) of March 2nd and 8th, 2012.

3) Oligometastatic Prostate Cancer; an Intermediate Stage? The February 27th, 2012 issue of the Prostate Cancer Research Institute (PCRI) Insights contained several articles of interest including an update on brachytherapy and especially an article on an intermediate stage of prostate cancer termed oligometastatic prostate cancer. The authors, including Dr. Charles “Snuffy” Myers, outline the concept of this intermediate stage wherein cancer has spread outside the prostate gland but is not widespread. Pros and cons of various imaging techniques used to identify such metastatic sites are described. These sites are not always easily observed  by CT or MRI scans. The authors’ focus is not merely on bone metastases but lymph node metastases as well. Identified metastatic sites are then subjected to carefully focused radiation therapy such as provided by advanced versions of Intensity Modulated Radiation (IMRT) such as Image-Guide (IG) IMRT and  Dynamic Adaptive Radiotherapy (DART 4D) therapy.

4) Continued Development of OncoGenex’s OGX-427, a New Type of Anticancer Therapy. OGX-427 is a second-generation antisense drug designed to reduce the production of heat shock protein 27 (Hsp 27), a protein that regulates multiple cell mechanisms that cancers use to survive. Hsp 27 inhibits apoptosis (cell death), is found at high level in many human tumors especially hormone-resistant prostate cancer and is implicated in cancer progression and treatment resistance. Hsp 27 can also be induced by cell stress through chemotherapy, radiation or hormonal therapy.  When co-administered with prednisone, OGX-427 demonstrated promising results in a Phase II clinical trial versus prednisone alone. A new Phase II trial of OGX-427 in men with minimally symptomatic or asymptomatic advanced prostate cancer who have not yet received chemotherapy has recently been announced. This Phase II trial will measure disease progression at 12 weeks, PSA levels, time to progression by PSA or measurable disease, numbers of circulating tumor cells (CTCs) and other endpoints.  For additional details, see the Prostate Cancer Foundation NewsLetter, February 27th, 2012 and the OncoGenex website.

5) Custirsen (OGX-011) to be Further Evaluated in Phase III Trials. OncoGenex Pharmaceuticals and its partner Teva Pharmaceuticals plan to start a new Phase III trial for custirsen in combination with Sanofi’s approved taxane chemotherapy drug, Jevtana with the goal of improving survival in prostate cancer patients. A separate trial called Synergy, which aims to test custirsen in combination with chemotherapy in hormone-resistant prostate cancer patients, is boosting its patient enrollment. For further information see the March 20th, 2012 issue of the ZeroHour NewsLetter.

6) Alpharadin Update. The February 27th, 2012 issue of the Prostate Cancer Foundation NewsPulse had several articles of interest. One was an update on the therapeutic effects of the alpha-particle emitting Alpharadin (Radium-223) which is targeted to bone metastases and potent, localized, tumor cell-killing activity within a 10-cell radius. It’s half-life of 11.4 days seems to make it an ideal candidate for cancer therapy.

 

 

Positive Treatment Developments from Three Sources.

Too bad oranges have little effect on prostate cancer. BJ Gabrielsen photo.

 

At the Feb. 2nd-4th, 2012 meeting of the American Society of Clinical Oncology (ASCO), positive results were presented for two different prostate cancer treatments both currently under late stage Phase III clinical development. The positive results led to the studies being stopped earlier than anticipated.  These two drugs, radium-223 chloride (Alpharadin) and MDV3100 were both found to increase survival in metastatic, hormone-refractory prostate cancer patients and control the growth of bone metastases. Radium-223 chloride demonstrated improved survival and delayed cancer-related bone problems in men with advanced, spreading tumors. It delivers bursts of about four one thousandths of an inch of localized alpha radiation to the bone, thereby targeting the tumor. In addition, the average time to the first bone-break, fracture or need for radiation or surgery was significantly delayed among men treated with the new drug. The U.S. Food and Drug Administration (FDA) said it will fast track both Alpharadin and MDV3100 in its approval process for treatment in men with metastatic, hormone-resistant prostate cancer.

The second drug, MDV3100, increased survival by close to five months among men with advanced prostate cancer. This drug works by two routes. First it prevents testosterone from binding to receptors on cancer cells which require these male sex hormones in order to survive and grow. Secondly, MDV3100 prevents the production of proteins within the cell that induce tumor growth.

The next step for clinical researchers is to determine the best combination and sequence of administration of these two drugs in order to hopefully demonstrate their synergistic benefit which researchers believe is very plausible.

These positive reports were all recently independently published in: a) the ZeroHour Newsletter, Issue 26, Feb. 7th, 2012; b) the Feb. 7th, 2012 issue of the National Cancer Institute (NCI) Cancer Bulletin; and c) the February 9th on-line issue of the Prostate Cancer Research Institute (PCRI) Weekly (Volume 1, Issue 8).  Additional highlights of the 2012 Genitourinary Cancers Symposium held at the Feb. ASCO meeting are also presented in the PCRI Weekly.

The same issue of the Feb. 7th  NCI Cancer Bulletin also contained an analysis of the potential benefits and harms of three types of radiation therapy, a more recent proton therapy, brachytherapy and surgery for prostate cancer. Men considering any of these forms of therapy are urged to read this report and discuss it with their respective physicians.

PSA Screening Updates – Use of Nomograms.

 

Feeding on a fish in Venice, Florida; BJ Gabrielsen photo.

 

As you may have heard, in 2011, the U.S. Preventative Services Task Force (USPSTF) issued a controversial recommendation to no longer recommend prostate-specific antigen  (PSA) screening for healthy men under the age of 75.  The USPSTF’s recommendations often guide physicians in their decisions as well as impact what tests Medicare and private insurers will pay for. This recommendation evoked considerable response from the medical community.

The Johns Hopkins Hospital is consistently rated as the nation’s #1 urology department according to the annual survey published in U.S. News and World Report.  They published a response in the Jan. 3rd, 2012 issue of their Health Alerts entitled “Should You Have a PSA  Screening Test? Johns Hopkins Responds to Recent USPSTF Recommendations.” I encourage you to read the linked article. They concluded that targeted PSA screening focused on men with greater risk and active surveillance for those not requiring immediate treatment could shift the benefit / risk ratio toward greater benefit. Screening should not be discontinued but focused on reducing harm.

It is agreed that it would be desirable to limit the number of unnecessary prostate biopsies and their resulting side effects. To this end, the Johns Hopkins Health Alerts (December 22, 2011) discussed the use of nomograms to address problems with using specific PSA values to ascertain the need for a biopsy. A nomogram considers multiple weighted factors to calculate risk of having biopsy-detectable prostate cancer. These factors include race, age, PSA level, family history, digital rectal exams (DRE) and results of previous biopsies and whether one has previously taken finasteride (Proscar).

Another important factor which could be used to identify candidates for biopsies is PSA density (PSAD). In a recent article published Dec. 12, 2011 in Medical News Today (a recommended source of prostate cancer information), Dr. Martin Sanda of Harvard Medical School wrote that PSA screening could be improved to identify only aggressive cancer requiring treatment by adjusting various factors like prostate size (volume, density, PSAD), obesity and family history. In my own case in 1995, my PSA values at the time of cancer detection averaged around 4 ng/ml.  I had undergone a routine biopsy in 1994 which revealed no cancer but concluded that my prostate gland itself was not enlarged. I therefore reasoned that my smaller prostate gland seemed to be producing a more significant amount of PSA (4.0) than it might under normal conditions. Following up with a second biopsy in October, 1995, the presence of cancer was revealed. Therefore I was using the concept of “PSA density” (PSAD) without knowing about it medically.  In his article, Dr. Sanda also recommended nomograms to predict aggressive cancers and identify candidates for biopsies. The use of two specific urine genetic biomarkers, TMPRSS2:ERG and PCA3, (see Sept.21, 2011 post) was also mentioned in the article entitled “PSA Testing Combined with Other Relevant Patient Data Can Reduce Unnecessary Prostate Biopsies.” The article was also cited in the January 10th, 2012 issue of the ZeroHour Newsletter (from Zero-The Project to End Prostate Cancer).

Lastly, WebMD is an illustrated internet resource that covers many medical issues. One can however choose those areas of specific interest such as prostate cancer. On Jan. 24th, 2012, the WebMD-Cancer published an illustrated introductory primer dealing with prostate cancer. WebMD-prostate cancer should be added to the list of medical resources.

 

 

Robotic-Assisted Prostatectomy May Not Reduce Surgical Side Effects.

Currently, four out of five prostatectomies are performed laparoscopically using robotic technology. It was hoped that such surgical techniques would demonstrate clear benefits such as fewer side effects when compared to the traditional open radical prostatectomy. A recent article appearing in the January 10th, 2012 issue of the National Cancer Institute (NCI) Cancer Bulletin concluded that older men who chose to remove their prostate glands to treat cancer have a high risk of developing incontinence or sexual dysfunction regardless of whether the surgery was performed laparoscopically using robotics or by traditional open surgery. The article cites a study involving 685 men performed by researchers at Massachusetts General Hospital and published in the January 3rd issue of the Journal of Clinical Oncology. The researchers noted however that future studies involving younger men should be carried out to more fully assess the risks, benefits and cost effectiveness of the two types of  surgeries. The skills and experience of the surgeons and their hospital system must also be considered when choosing one type of surgery over another.

How to Handle Anxiety.

A western Norway fjord; Provided by Arnold Dalene.

I try to read a devotional from the Bible daily. Yesterday I read a portion which could apply to anyone with prostate cancer or any other stress-inducing condition. The Old Testament book of Jeremiah 17 :verses 7-8 state as follows. “Blessed is the man who trusts in the Lord and whose trust IS the Lord. For he will be like a tree planted by the water, that extends its roots by a stream and will not fear when the heat comes; but its leaves will be green, and it will not be anxious in a year of drought nor cease to yield fruit.” One can interpret Biblical passages several ways. Some people read them as a personal preference asking “what do these words mean to me?” But a better approach would be to evaluate the words in terms of “what is God actually saying?” Having prostate cancer can often be likened to “turning up the heat on our lives” or experiencing a time of personal drought and anxiety. We need to remember however that God can use everything in our lives including cancer to point people to Him, to glorify Himself, to provide fulfillment and purpose to our own lives and in short, “to bear fruit”. So what is God actually promising in the verses above? We will all experience some form of “heat” and “drought” in our lives. But first our trust should be IN the Lord, His Word, His nature, His character and His plans. Secondly, our needs will be met (green leaves and watered roots) if we are so grounded. Next we need not be anxious about any of these situations. Finally, our life circumstances will not be wasted but instead be bearing wonderful and lasting fruit in our relationship with the Lord and with those around us.

Cardiovascular Issues and Hormonal Therapy.

In November, 2011, I had my six-month appointment with my oncologist at Moffitt Cancer Center, University of South Florida, Tampa.  My prostate cancer is in remission and I  currently receive no hormonal (androgen deprivation, ADT) therapy with Lupron until my PSA begins to rise. When my micro metastases are not under hormonal control, my PSA doubles in three months hence doctors label my cancer as “aggressive”. But for now, my PSA remains ‘undetectable’ for which I am grateful to God and I am on intermittent therapy to minimize the potential side effects of ADT. I expressed to my oncologist that it was my most sincere prayer that I not die of prostate cancer to which he confidently responded that it was much more likely that I would die of cardiovascular causes instead of cancerous ones. He also specified that I was “too good for participation in clinical trials of new therapies”. I do try to maintain good cardiac health with diet, medication and exercise under the care of a cardiologist.

While I was thankful for the opinions expressed by my oncologist, I recently read several on-line articles dealing with potential cardiovascular and metabolic syndrome side effects related with hormonal therapy. The December 20th, 2011 issue of the Prostate Cancer Foundation Newsletter contained an article which stated that “hormone drugs might not raise heart-related deaths in prostate patients” but for those with a history of heart disease, stroke may pose a higher risk. To further substantiate this conclusion, the December 13th, 2011 issue of the National Cancer Institute (NCI) Bulletin  contained an article entitled “Prostate Cancer Trials Show No Link Between Androgen-Deprivation Therapy and Cardiac Deaths.” A new analysis of eight clinical trial results showed no evidence that ADT increased the risk of cardiovascular deaths in the case of patients with non-metastatic, high-risk prostate cancer. The original article had been published in the Journal of the American Medical Association (JAMA) by researchers from the Dana-Farber Cancer Institute who cited an additional benefit that men who had been treated with ADT had a lower risk of dying from prostate cancer and other causes than men who did not. Their conclusions however could not be extrapolated to men with a history of cardiovascular disease who could potentially be harmed by ADT.

Hormonal prostate cancer therapy has recently been associated with blood clots. An article by Amy Norton published December 1, 2011 by Reuters Health, stated that hormonal therapy for  prostate cancer “may raise the risk of potentially-dangerous blood clots” according to a U.S. study led by Dr. Behfar Ehdaie of the Memorial-Sloan Kettering Cancer Center in New York and published in the journal Cancer. Dr. Ehdaie cautions that for men weighing their options for prostate cancer treatment, the risk of blood clots and other side effects needs to be balanced against potential  benefits. It is not proven that hormonal therapy itself is the direct cause of the blood clots but men on ADT had a 56% greater chance of developing a blood clot. The clot risk also increased the longer a man was on the treatment. It is possible that hormone therapy’s negative effects on metabolism might increase a man’s fat mass. Men are urged to discuss the risks and benefits of hormonal therapy and other treatments with their physician.

 

Prostate Cancer Research Institute (PCRI) Insights – must reading.

The Prostate Cancer Research Institute (PCRI) publishes a newsletter called “PCRI Insights” to which I strongly suggest an on-line subscription. The last issue I received was the November issue. The general website for the PCRI is http://prostate-cancer.org/pcricms. It is also listed in the Medical Resources section of this website. The November issue (Vol. 14, No. 4) included a feature article on Provenge (Sipuleucel-T), the immunotherapy from Dendreon approved by the Food and Drug Administration for treatment of metastatic, hormone-refractory, asymptomatic prostate cancer patients. The article described in detail how Provenge works as well as its availability, eligibility and cost.

Also included was an article entitled “What’s Your Shade?” citing a method formulated by Harvard’s Dr. Anthony D’Amico by which the stage of one’s prostate cancer can be described by compiling five factors: PSA, Gleason score, percentage of biopsy cores, and results of rectal and pelvic MRI scans. The goal of identifying one’s “shade” is to ascertain potential risk of relapse (low, intermediate or high) after local therapy and subsequent treatment options if needed.  The Johns Hopkins Prostate Cancer Health Alerts issue of January 12th, 2012 contained a very informative discussion of the TNM (tumor, nodes, metastasis) staging system as used to describe a cancer’s clinical stage or how far it has spread.

The PCRI Insights also contain short highlights and abstracts from recent prostate cancer conferences. The November issue contained updated information on several therapies under development including Ipilimumab (Yervoy), MDV3100, ARN-509 (Prostvac VF) and XL-184 (cabozatinib). In a section on conference summaries, it was noted that C-11 radio-labeled acetate PET scanning was a better method of detecting cancer metastases than the current FDA and Medicare-approved ProstaScint methodology. While information in the PCRI Insights may not be applicable to everyone’s specific medical condition, it provides an excellent overview of the current status of diagnostics and treatments.