2013 Blog

Predicting Outcomes and Characterizing Prostate Tumors.

bjgabrielsen : February 28, 2013 2:37 am : 2013

Boca Pass toward Cayo Costa, Boca Grande, Florida. bjgabrielsen photo.

Boca Pass toward Cayo Costa, Boca Grande, Florida.
bjgabrielsen photo.

For a newly-diagnosed prostate cancer patient, the three most important initial parameters are the blood levels of prostate-specific antigen (PSA) and its rate of increase, the biopsy-based Gleason score that ranks a tumor’s aggressiveness, and the clinical stage of the tumor based on its physical appearance. In the early 1990’s, Dr. Alan Partin, currently director of Urology at the Johns Hopkins Hospital in Baltimore, MD, formulated the Partin Tables using data comprised of the three parameters above as a statistical modeling tool to predict the stage of cancer spread at the time of performing a radical prostatectomy and to assess the chance of a surgical cure. These tables were based primarily on data from men treated in the 1980’s who often were diagnosed with later-stage cancers. The tables have recently been updated with data from over 5,000 men treated at Johns Hopkins between 20o6-2011 and published in the British Journal of Urology International. The revised study found that men treated during this period were more likely to be diagnosed before their PSA had risen significantly and were more likely to have a Gleason score greater than six (6) at the time of biopsy. According to Dr. Partin and his colleagues, the updated Partin Tables show that “surgical cure may be possible for a greater percentage of men especially those whose Gleason scores (such as 8) put them at the high end of intermediate risk.” The updated tables also found that the majority of men who are diagnosed prior to surgery with intermediate Gleason scores of 6 or 7 had a very low (less than 2%) risk of having prostate cancer spread to surrounding lymph nodes. These terms are defined and discussed in more detail in an article published in the January 2013 issue of NewsPulse from the Prostate Cancer Foundation.

The Johns Hopkins Prostate Disorders Health Alerts recently published (Feb. 14th, 2013) a short article defining the terms used in the TNM (tumor, nodes, metastasis) staging system used to define a cancer’s clinical stage or how far it has spread. The TNM prostate cancer staging system is a predictor of the extent of the disease and is useful in choosing the best course of treatment.

A related study describing the effects of exercise on prostate cancer survival was recently published in the Journal of Clinical Oncology and summarized in the January 24th issue of the Johns Hopkins Prostate Disorders Health Alerts. Data was received from 2,705 men followed for a period of 18 years. The study concluded that any type of regular exercise improved overall prostate cancer survival regardless of the intensity of the exercise. However, men who took part in vigorous activity, defined as at least three hours of intensive exercise per week, had a significantly lower (61%) risk of dying from prostate cancer.


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Updates on Active Surveillance (AS) for Prostate Cancer.

bjgabrielsen : February 27, 2013 12:32 am : 2013

Active Surveillance (AS) is a monitoring program with possible application for patients diagnosed with low-risk prostate cancer. It is gaining popularity as a means to avoid overtreatment of indolent, slow-growing prostate cancers. The likelihood of harboring small bits of prostate cancer in a man is about equal to his age as a percentage. For example, in men age 50-70 (the key age group for diagnosing prostate cancer), around 60 percent of men will have small bits of prostate cancer. An example of a good candidate for AS would be a man with a mildly elevated PSA (less than 10) whose biopsy shows a relatively small amount of Gleason 6 prostate cancer. During active surveillance, prostate cancer is carefully monitored for signs of progression using a PSA blood test, a digital rectal exam (DRE) and a repeat biopsy of the prostate at one year and then at specific intervals thereafter. Subsequent treatment might be initiated if symptoms develop, or if tests indicate the cancer is growing. Recently, multiparametric magnetic resonance imaging (MRI) has also emerged as a tool in monitoring patients on AS. A new retrospective study published in the Journal of Urology (and summarized in the Jan. 23, 2013 issue of the Prostate Cancer Foundation NewsPulse) looked at a group of 262 men who were placed on a program of active surveillance in order to determine the rate of disease progression and time frames the men remained on active surveillance before moving to active treatments such as surgery, radiation or cryotherapy. During the follow-up period (a median of 29 months), 16 percent of the patients in the study ultimately received active treatment for their cancers. The authors found that the two-year probability of the men to remain on active surveillance was 91 percent; at 5 years, 75 percent. This study “provides short-term evidence that for highly-select patients, AS appears to be safe, durable and associated with low but finite risk of disease progression.” Larger and longer-term studies are needed and on-going. In an important comment, study author Dr. Peter Scardino strongly urged for a “mandatory” restaging, or repeat biopsy prior to men enrolling in an AS program. The researchers base this on their finding that a repeat biopsy prior to the initiation of active surveillance deceased the percentage of men deemed to be low-risk by approximately 30 percent.

Another very interesting review article on AS has also been published in the Feb. 2013 issue of the Prostate Cancer Research Institute (PCRI) insights. One specific note from this article describes on-going research on the effects of capsaicin, the micro nutrient found in hot chili peppers. There is a specific receptor (TRPV-6) for capsaicin in prostate cancer cells which when activated results in inhibition of cell proliferation and invasion. Studies are on-going in mice and humans. The same review of active surveillance also describes a method of specifically killing prostate cancer cells in men using MRI-guided thermal ablation (targeted ultrasound waves which are converted to heat in the prostate tissue).

Finally, it should be noted that the terms “active surveillance” and “watchful waiting” differ as applied to prostate cancer. AS is a disease management strategy that delays curative treatment until it is warranted based on defined indicators of disease progression. In contrast, the strategy of “watchful waiting” foregoes curative treatment and initiates intervention only when symptoms arise.

 


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Weekly Consumption of Deep-Fried Foods Linked to Prostate Cancer.

bjgabrielsen : February 22, 2013 6:28 am : 2013

I don’t usually write about the implications of diet on prostate cancer. But a former scientific colleague recently sent me an article from Genetic Engineering and Biotechnology News which cited research findings from the well-respected Fred Hutchinson Cancer Research Center. Researchers there found that men who reported eating French fries, fried chicken, fried fish, and/or doughnuts at least once a week had an increased risk of prostate cancer that ranged from 30–37% as compared to men who said they ate such foods less than once a month. Weekly consumption of these foods was also associated with a slightly greater risk of more aggressive prostate cancer. The effect also appears to be slightly stronger with regard to more aggressive forms of the disease defined by elevated PSA levels or Gleason scores. “For the study, the investigators analyzed data from two prior population-based case-control studies involving a total of 1,549 men diagnosed with prostate cancer and 1,492 age-matched healthy controls. The men were Caucasian and African-American Seattle-area residents and ranged in age from 35 to 74 years.”  Further explanation is provided in the linked article. It may be that “we are what we eat.”


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“I Have Bad News”. Must it Always Be?

bjgabrielsen : January 15, 2013 4:03 am : 2013

I recently read a reprinted  “Sermon of the Week” from a local Florida newspaper. In the context of yesterday’s blog post, “Hope When Your World Falls Apart”, this “sermon” could be labeled as Part Two. The writer had been given bad news by a physician who used the phrase, “I have bad news, we found cancer.” Even while clinging to God’s peace, the emotions of shock, fear and uncertainty were very real to him. Full recovery was anticipated but the notorious words, “what if?” immediately came to mind. The “what ifs’ comprise an all-to-frequent condition in my own life at times. Some people believe that you should never question why circumstances and situations come your way, but just “trust and believe” and everything will be OK. Ideally, they may be correct but it is easier said than done. Thinking about it, spiritual giants of the Bible like David and Job questioned God and wondered “why?”. Even Jesus cried out while being crucified on the cross when He exclaimed “my God, my God, why have You forsaken me?”  While the perfecting of our faith is God’s ultimate goal for us, honest faith and feelings are often the case. Even the famous English pastor Charles Spurgeon once was quoted as saying “when you can’t hold onto God, He will always hold on to you.” Following his cancer surgery, the writer found himself resting on the words of Psalm 91 which state: “Those who live in the shelter of the Most High will find rest in the shadow of the Almighty…..He alone is my refuge, my place of safety; He is my God and I am trusting Him.” He also took comfort in the words written by the apostle Paul in Romans 8: “I am convinced that nothing can separate us from Christ’s love. Nothing in all creation will ever be able to separate us from the love of God that is revealed in Christ Jesus our Lord.” Neither death, nor life not even cancer! Our God is faithful and absolutely dependable. In the darkest hours and lowest valleys, He holds us in His nurturing arms of grace and we find rest in His protection. His love for us is unceasing, eternal and is for everyone. May we find peace, security and purpose in the love of this great God and His Son, Jesus, who never leaves us and walks with us always.


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Hope When Your World Falls Apart.

bjgabrielsen : January 13, 2013 11:46 pm : 2013

A pathway of bougainvilleas leading to a Gulf of Mexico beach at Boca Grande, Florida; BJ Gabrielsen photo.

A pathway of bougainvilleas leading to a Gulf of Mexico beach at Boca Grande, Florida; BJ Gabrielsen photo.

What was your first thought when you were initially informed that you had prostate cancer? Personally, mine was “can it be cured?” When reality and reason was restored, one of my predominant thoughts and prayers was (and remains) “God, please do not let me die of this disease.” More precisely, I don’t fear death itself but the process of dying can be very disturbing. Sadly, 24,000 American men succumb to prostate cancer annually. I personally have a prayer list of people I know who are battling various forms of cancer. I try to pray for each one on my list daily. My most important prayer is that they might all have a personal relationship with God through faith in Jesus Christ and thereby possess the gift of eternal life. Secondly, I pray that they may be healed of their cancer or that it could be treated as a chronic, non-life-threatening condition. I believe that God does miraculously heal cancer cases today and I know personally of several such cases but true accounts of such deliverances seem to be in the vast minority today.

My good friend and family physician reminded me that we all have to die of something. So given this fact, we should not obsess about the concept of death but instead focus on the wonder of knowing and trusting God and His attributes and promises and on living each day with no regrets. As a shining real-life example, I recently read about a minister named Ed Dobson who has been battling the fatal disease of ALS (amyotrophic lateral sclerosis, better known as Lou Gehrig’s disease) for eleven (11) years. His story was published electronically on November 21st, 2012 in a daily series of essays entitled “Breakpoint” which was founded by the late Charles Colson. Many of you might remember Mr. Colson as the Nixon administration White House lawyer who was convicted during the Watergate scandal and served time in prison. Through his humbling experience, he came to a personal faith in God through Christ and dedicated his remaining life to ministering to prisoners and their families. The daily Breakpoint series (to which one can subscribe electronically) describes how we as Christians should adopt a truly Biblical worldview while functioning in this secular and increasingly non-Christian society.

The November 21st, 2012 Breakpoint essay describes Ed Dobson as not a typical victim of Lou Gehrig’s disease. Dobson, a one-time mega-church pastor in Grand Rapids, Michigan “has lived with ALS for over 11 years—it kills most people within five. And during this difficult season in his life, Dobson has refused to hide himself away while awaiting his death. Instead, he has grappled with this disease and has written a brutally honest, often unsettling, account” entitled “Seeing Through the Fog: Hope When Your World Falls Apart.” His book describes how he has found hope in the midst of daily struggles and fears for the future. As could be the case for someone with advanced prostate cancer, Ed Dobson realizes that ALS is a “dowward  spiral, month after month. It is a fatal, terminal disease.” Like myself, he states that he has “never been afraid of dying, but was very concerned about the process of getting there.” 

Unfortunately today many people die slowly, and the experience often shakes their faith including the faith of sincere, believing Christians. Instead of transformation at the end of life and the process of faithfully dying, many people sincerely question the goodness, mercy and intentions of a loving God. As in the case of Ed Dobson, many well-intentioned people pray fervently for the healing of their friends and family members (see James 5:14-16). When God chooses not to answer their prayers in the manner they expect (and I have recently lost three friends to cancer for whom I had been praying), people are often left with few encouraging words to say. “Although he would still like to be cured, Ed Dobson says he isn’t obsessing about it. Instead, he’s focusing on the wonder of God and on living each day with no regrets.” For Dobson, that means asking forgiveness of people he has offended, learning to accept the help of others, and remembering that the significance of one’s life does not depend on one’s health.  Pastor Dobson states “I know that God and His grace are sufficient for the moment I find myself in. When I wake up tomorrow, whatever the challenges, I know God will be there and will provide His grace. This is my hope. This is my strength.” He is learning to trust God and give thanks in the midst of some supremely challenging circumstances. And that’s a lesson we will all have to learn some day whether we battle ALS or prostate cancer.

Itemized below are ten (10) lessons we can learn from Pastor Dobson’s on-going experiences whether we battle ALS, prostate cancer or another potentially life-threatening condition.

1.  Make absolutely sure that our sole hope and faith rests in a personal relationship with God, the forgiveness of our sins through Christ’s death and the accompanying gift of eternal life made possible by His resurrection. As Jesus Himself has said, our good works, exemplary as they may be, are not sufficient to merit God’s grace and eternal life. In His Sermon on the Mount, Jesus says in Matthew 7:21-23 “Not everyone who says to Me, ‘Lord, Lord,’ will enter the kingdom of heaven;…..Many will say to me on that day, ‘Lord, Lord, ……..did we not in Your name perform many miracles?’ And then I will declare to them, ‘I never knew you; depart from Me.'”

2.  As personal Christians, focus on God’s nature, character, His creation and His eternal plans and promises for us. In the words of an old song, “This World is Not My Home, I’m Just a-Passin’ Through”.

3.  Live each day with no regrets. Live it as if Jesus were to return that very day (which is certainly possible). If at all possible, live at peace with all people.

4.  Write a personal legacy letter to each family member, close friends and colleagues. Thank them for their roles in your life and share with them the specific aspects of your life which you consider most important. If you had only 5 minutes of their undivided attention, what would you communicate to them? Don’t wait until circumstances would prohibit you from sharing these most important thoughts.

5.  Ask forgiveness from anyone whom you might have ever offended.

6.  Learn to accept the help of others. Be as transparent as possible, allowing God and Jesus to be openly seen through your life and conditions.

7.  Remember that your life’s significance does not depend upon the state of your health.

8.  Trust solely in God’s grace and provisions which can be provided in many ways including through excellent health professionals.

9.  Give thanks for all circumstances even though they may be challenging.

10. Life is comprised of anticipating specific events from our earliest childhood to our retirement years. Therefore, as members of God’s family through Jesus, always look ahead to our ultimate destination of a new heaven and a new earth containing all God’s natural creation to be experienced in a new eternal, pain-free, perfectly-functioning body; all of this to be experienced forever, with no end. This concept and promise is so fantastic our finite minds can only grasp a small portion of our true “inheritance” through Christ.

 


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Galeterone and Tasquinimod, Two New Drugs in Late-stage Clinical Development.

bjgabrielsen : January 6, 2013 6:57 pm : 2013

Florida bobcat; photo, BJ Gabrielsen.

Florida bobcat; photo, BJ Gabrielsen.

New information has recently been published updating early clinical trials results for two new promising prostate cancer drugs, galeterone (TOK-011 from Tokai Pharmaceuticals) and tasquinimod (TASQ, from Active Biotech and Ispen).  Both drugs have been described in the December 20th, 2012 issue of the Prostate Cancer Foundation NewsPulse.

Galeterone: Resistance to therapy is a growing concern in treating cancer as cancer cells mutate to avoid the effects of a given therapy. This is a major problem in androgen-deprivation (ADT) prostate cancer treatment (hormone therapy) when men become resistant (refractory) and testosterone levels rise thus fueling the proliferation of cancer cells. Galeterone, an oral drug also known as TOK-011, is unique in that it is the first and only single-agent therapeutic that combines three distinct approaches to attack prostate cancer and which thereby may help to prevent resistance to ADT. Galeterone’s development and review has received a “fast-track designation” by the U.S. Food and Drug Administration.  Androgen is mainly produced in the testicles (90%) and to a lesser degree by the adrenal glands and even the prostate tumor itself. The male androgen testosterone fuels prostate cancer and triple-action galeterone thwarts prostate cancer cell proliferation by targeting the primary driver of treatment-resistance disease—androgen receptor signaling—in various ways. Galeterone works by blocking testosterone synthesis (specifically by blocking the enzyme CYP17 lyase), blocking testosterone’s ability to bind to its androgen receptor (the prostate cell molecule that responds to the androgen) and finally, by limiting overall androgen receptor levels in the body. A Phase I dose-finding study in 49 chemotherapy-naïve patients produced PSA reductions of greater than 50 percent (50%) in 11 patients (or 22%). Another 26 percent of patients had PSA declines ranging between 30 to 50 percent. Galeterone is now entering a Phase II trial in which Tokai plans to enroll 196 patients, the first of whom has already begun treatment. This trial will use a slightly reformulated version of galeterone that has improvements in its uptake and absorption in the body. In addition, the Phase II trial will not only include men who are chemotherapy-naïve, but also men whose disease has progressed while taking Zytiga (abiraterone acetate), another androgen-inhibiting drug. All patients will be evaluated to determine galeterone’s effects upon PSA levels and their overall safety profiles.  An interesting article about how galeterone was co-developed was published in the Baltimore Sun in September, 2014.

Tasquinimod: Tasquinimod, or TASQ (ABR-215050), is an oral experimental treatment for men with metastatic, treatment-resistant prostate cancer. Chemically, TASQ is a quinoline-3-carboxamide with three-pronged immunomodulatory (activates the body’s immune system to fight cancer), anti-angiogenic (prevents the formation of new blood vessels to feed tumor cells) and anti-metastatic (inhibiting tumor growth) activity. Specifically, TASQ modulates the expression of thrombospondin-1 in human prostate tumors.  After completing Phase I and II clinical trials, Active Biotech and Ispen, the drug’s developers, announced successful enrollment of 1,200 patients in 250 clinics for a global, randomized, double-blind, placebo-controlled Phase III clinical trial evaluating TASQ in men with metastatic, hormone-refractory prostate cancer. The end points of the Phase III study will be progression-free (PFS) and overall survival. Dr. Andrew Armstrong, principal investigator from the Duke University Medical Center, describes the Phase II results as published in the Journal of Clinical Oncology in September, 2011. They showed a median overall survival benefit of three months (33.4 vs. 30.4 months) in favor of TASQ versus placebo. In patients with bone metastases, median overall survival was 34.2 versus 27.1 months. Six month progression-free proportion of patients for TASQ and placebo treatment groups were 69% and 37%, respectively with a median progression-free survival of 7.6 vs. 3.3 months. TASQ treatment also had an effect on biomarkers relevant for prostate cancer progression and was generally well tolerated. In the Phase III clinical trial, researchers will further investigate the drugs overall efficacy, with an ultimate goal of receiving approval from the Food and Drug Administration for the treatment of men with metastatic castrate-resistant disease (CRPC). Phase I and II data show that tasquinimod’s long term safety is acceptable according to Dr. Armstrong. “Tasquinimod may therefore be a suitable therapy to evaluate at an early stage in management of CRPC, either as monotherapy or in combination with other effective agents for prostate cancer, as it does not jeopardize the patient’s chances to receive additional treatment.” For additional information on TASQ and its clinical trials, see the Drugs.com and Active Biotech websites.  The web addresses are: http://www.drugs.com/clinical_trials/active-biotech-ipsen-report-tasquinimod-tasq-phase-ii-long-term-safety-data-27th-european-13084.html; and http://www.activebiotech.com/press-releases?pressurl=http://cws.huginonline.com/A/1002/PR/201212/1663501.xml.

 


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Prostate Cancer Information from Johns Hopkins Urology.

bjgabrielsen : January 2, 2013 3:27 am : 2013

There are numerous excellent medical research institutions and hospitals which specialize in the diagnosis and treatment of prostate cancer. I can speak first-hand about one of them, namely Johns Hopkins in Baltimore, MD. Each year, the U.S. News and World Report magazine ranks medical institutions according to their specialty and for the past fifteen years at least, Johns Hopkins Urology has been ranked #1. I can also personally attest to their expertise, care and knowledge since I have had successful surgeries at Hopkins as far back as the 1990’s. Hopkins publishes their Johns Hopkins Health Alerts covering a multitude of disciplines including urology and prostate cancer. To any man who has questions about prostate health and cancer, I would recommend their reference entitled “Choosing the Right Treatment for your Prostate Cancer.” I can personally recommend the knowledge and expertise of the chief author, Dr. Jacek Mostwin as well as his colleagues, among them Dr. H. Ballentine Carter.

In addition to commercial materials as described above, Johns Hopkins also publishes their Prostate Disorders Health Alerts to which one can subscribe electronically. Their recent December 19th, 2012 issue described four (4) categories of prostate cancer risk as defined by the National Comprehensive Cancer Network. These categories range from very low risk, to low, intermediate and high risk. The categories are based upon the stage of the cancer, prostate-specific antigen (PSA) and PSA density values, Gleason scores and the percentage of cancerous prostate cores as detected by biopsies. Guidelines for possible management scenarios are also provided for the four classification categories. The December 13th, 2012 issue of the Hopkins Prostate Disorders Health Alert describes four (4) common misconceptions about prostate cancer. These misconceptions are related to “normal” PSA values and the presence or absence of prostate cancer and potential negative side effects of prostate biopsies including the spread of the cancer and erectile dysfunction.

Androgen-deprivation (hormone therapy) for advanced prostate cancer is accompanied by several risks, among them osteoporosis and loss of bone mineral density which may result in fractures. For such men, Johns Hopkins (in their January 3rd, 2013 Health Alert) recommends annual bone-density scanning with dual-energy X-ray absorptiometry (DEXA scanning). If osteoporosis is indicated, treatment with bisphosphonates (such as Fosamax or Reclast) or a new drug that blocks the formation of a protein that causes bone to break down (Prolia) may be prescribed.


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