Earlier chemotherapy may extend patient survival in multiple prostate cancer settings

Whether a prostate cancer patient is just presenting with localized high risk prostate cancer, presenting with metastatic prostate cancer, or experiencing a metastatic recurrence, earlier treatment with taxane chemotherapy may prolong survival.

June 19, 2015 — Chemotherapy with docetaxel® (taxotere) has traditionally been used to treat prostate cancer patients only after they have developed resistance to hormone therapy. However, two new studies presented at the 2015 American Society for Clinical Oncology (ASCO) Annual Meeting found that the addition of taxane chemotherapy extended survival in several groups of patients initiating hormone therapy: in patients with primary metastatic disease or relapse with metastases after definitive local treatment, and as a first-line therapy in previously untreated patients with localized high-risk prostate cancer.

Upfront Therapy with Docetaxel® Prolongs Overall Survival in Men with Hormone-Naïve Metastatic Prostate Cancer Commencing Hormone Therapy

Prostate cancer patients who present with primary metastatic disease or relapse with metastases after definitive local treatment with prostatectomy or radiotherapy (RT) typically receive androgen deprivation therapy (ADT) with or without RT as the standard of care. Taxane chemotherapy or 2nd generation anti-androgen medications are only prescribed following the onset of ADT resistance. However, it is hypothesized that earlier administration of these therapies may extend patient lives.

Dr. Nicholas James of the University of Warwick and Queen Elizabeth Hospital Birmingham presented the first survival results released from the STAMPEDE CLINICAL TRIAL, the largest randomized clinical trial ever conducted in prostate cancer patients. This study tested the outcome of adding various therapies to the standard of care—ADT with or without RT—in hormone-naïve patients either presenting with metastatic disease or relapsing after prostatectomy or RT. The addition of docetaxel + prednisolone to standard of care treatment extended the median failure-free survival time from 21 months to 37 months, and extended the median overall survival time from 67 months to 77 months.

These results support previous results from the CHAARTED trial, presented at the 2014 ASCO annual meeting, where the addition of docetaxel® to ADT improved median overall survival from 44 to 57.6 months in a cohort of hormone-sensitive metastatic prostate cancer patients.  Collectively, these results support a paradigm change in clinical practice. Docetaxel® in combination with ADT should now be considered much earlier in the treatment regimen for men with hormone-naïve metastatic prostate cancer. 

The 2015 ASCO Annual Meeting was held from May 29 – June 2, in Chicago, IL. The preceding article was adapted from the July 2, 2015 issue of the Prostate Cancer Foundation Publication, NewsPulse.

Men With Low-Risk Prostate Cancer In Active Surveillance Program Not Likely To Succomb To The Disease, Study Shows.

The post below comes from a multi-year study at Johns Hopkins in Baltimore. It should be noted below that repeat biopsies performed on men undergoing active surveillance were performed using MRI-guided technology and pathologists checked biopsy tissue levels of proteins made by the PTEN gene, a biomarker for prostate cancer aggressiveness.

Men with relatively unaggressive prostate tumors and whose disease is carefully monitored by urologists are unlikely to develop metastatic prostate cancer or die of their cancers, according to results of a study by researchers at the Brady Urological Institute at Johns Hopkins, who analyzed survival statistics up to 15 years. Specifically, the researchers report, just two of 1,298 men enrolled over the past 20 years in a so-called active surveillance program at Johns Hopkins died of prostate cancer, and three developed metastatic disease.

Our study should reassure men that carefully selected patients enrolled in active surveillance programs for their low-risk prostate cancers are not likely to be harmed by their disease,” says H. Ballentine Carter, M.D. , the Bernard L. Schwartz Distinguished Professor of Urologic Oncology and director of adult urology. Carter acknowledges that outcomes in the current study may be due to doctors’ careful selection of patients for active surveillance. “With longer follow-up, the data may change, but they’re unlikely to change dramatically, because men in this age group tend to die of other causes,” he says. Most of the men in the study were also Caucasian, and Carter cautions that these outcomes may not apply to African-American men, who tend to have more aggressive cancers.

For the study, described online Aug. 31 in the Journal of Clinical Oncology, men with prostate tumors classified as low or very low risk for aggressiveness opted to enroll in an active surveillance program at The Johns Hopkins Hospital. Their risk level was determined, in part, by Gleason scores, in which pathologists evaluate the aggressiveness of the cancer from prostate biopsy tissue.  When the study began in 1995, Carter says, urologists performed annual biopsies on the men in the program until they reached age 75. Now, doctors no longer require annual biopsies among the lowest risk groups, but when they do perform a biopsy, they use MRI-guided technology and will often ask pathologists to check biopsy tissue levels of proteins made by the PTEN gene, a biomarker for prostate cancer aggressiveness. Of the 1,298 men, 47 died of nonprostate cancer causes, mostly cardiovascular disease; nine of the 47 had received treatment for their prostate cancer. Two men died from prostate cancer, one after 16 years in the active surveillance program. In the second man’s case, Johns Hopkins doctors recommended surveillance, but the patient sought monitoring at another hospital and died 15 months after his diagnosis.  Three men in the program were diagnosed with metastatic prostate cancer.

Overall, the researchers calculated that men in the program were 24 times more likely to die from a cause other than prostate cancer over a 15-year span.  After 10 and 15 years of follow-up, survival free of prostate cancer death was 99.9 percent, and survival without metastasis was 99.4 percent in the group.  Some 467 men in the group (36 percent) had prostate cancers that were reclassified to a more aggressive level within a median time of two years from enrollment in the active surveillance program. For men with very low-risk cancers, the cumulative risk of a grade reclassification to a level that would have generally precluded enrollment in the program over five, 10 and 15 years was 13 percent, 21 percent and 22 percent, respectively. For men with low-risk cancers, this risk increased to 19 percent, 28 percent and 31 percent. Over the same time frames, the cumulative risk of a grade reclassification to a level that would be considered potentially lethal in most cases but still curable was no more than 5.9 percent for both very low and low-risk prostate cancers, Carter says.  Also among the group, 109 men opted for surgical or radiation treatment despite the absence of significant change in their prostate cancer status. In those whose cancers were reclassified, 361 opted for treatment.  “The natural progression of prostate cancer occurs over a long period of time, some 20 years, and most men with low-risk prostate cancer will die of another cause,” says Carter, a member of the Johns Hopkins Kimmel Cancer Center. “There is a careful balance, which is sometimes difficult to find, between doing no harm without treatment and overtreating men, but our data should help.”  Carter estimates that 30 to 40 percent of U.S. men with eligible prostate cancers opt for active surveillance, compared with Scandinavian countries, where use of the option is as high as 80 percent. The reasons for less use in the U.S., he says, could stem from fear of losing the opportunity for a cure.

Carter says one of the benefits of active surveillance is reduction in the rates of complications and costs of prostate cancer treatments. In a recent report, 20 percent of men undergoing a prostate cancer treatment – radiation or surgery – were readmitted to the hospital within five years of treatment for a complication related to the original treatment.  Our goal is to avoid treating men who don’t need surgery or radiation. The ability to identify men with the most indolent cancers for whom surveillance is safe is likely to improve with better imaging techniques and biomarkers,” says Carter.  Active surveillance is included in best practice guidelines for doctors developed by the National Comprehensive Cancer Network, a group of the nation’s top cancer centers. Carter recommends that men see urology specialists to be monitored in an active surveillance program.


More Evidence for the Positive Effect of Statins and Metformin in High-Risk Prostate Cancer.

A total of 22,110 high-risk prostate cancer patients were evaluated of which 1,365 died of prostate cancer.  The study authors concluded that the use of a statin medication in combination with metformin was associated with a 43% reduction in prostate cancer mortality.  The benefit was present in all men but was present to a larger degree in men with obesity.

The preceding abstract was presented at the 2015 meeting of the American Society of Clinical Oncology (ASCO) by Dr. Grace L. Lu-Yao of the University of Medicine and Dentistry of New Jersey.

Stereotactic Body Radiation (SBRT) and CyberKnife in the Treatment of Prostate Cancer

Stereotactic Body Radiation (SBRT) accurately delivers very high doses of external radiation beams to the whole prostate gland thereby treating the tumor within while minimizing extra-prostactic radiation exposure to the adjacent normal tissues.  Because SBRT delivers a much higher dose of radiation during each treatment visit, the overall treatment time is sharply reduced. Generally a full course of therapy can be completed in 4-5 sessions over the course of 1-2 weeks.  Other radiation treatments for prostate cancer often require approximately 35-45 sessions over 6-9 weeks.  SBRT for low and intermediate-risk prostate cancer is covered by Medicare in all 50 states and the District of Columbia.  In addition, most private insurance payers and health exchange insurers cover SBRT treatment for prostate cancer.  A full report on SBRT was published in the January 22nd, 2015 issue of Frontiers of Oncology.  The full article can be viewed at http://journal.frontiersin.org/article/10.3389/fonc.2014.00369/abstract.

The prostate gland can move unpredictably throughout the course of treatment making the ability to track, detect and correct for motion during treatment critically important.  CyberKnife is one of several SBRT systems available but it is the only system that is entirely robotic.  In fact. the prostate has been documented to move as much as 5 millimeters in less than 30 seconds because of normal patient bodily functions such as filling the bladder, gas in the bowel or even slight patient movement during the procedure.  Unlike other radiation treatments, the CyberKnife system continually tracks and automatically corrects the radiation beam to adjust for movement of the prostate in real-time throughout the entire treatment session.  This capability enhances the doctor’s ability to accurately deliver high doses of radiation to the intended target while still preserving the surrounding healthy tissue to minimize potential side effects.  For contact information for centers specifically offering the CyberKnife System for prostate cancer, visit http://www.cyberknife.com.

Radiation Cystitis – An Undesirable Potential Side Effect of Radiation Therapy

I was recently made aware of an unexpected, undesirable side effect of prostate cancer radiation therapy called radiation cystitis which first occurred more than ten years after radiation treatment.  This can be caused by the incidental irradiation of the bladder during radiation therapy for prostate cancer.  Radiation cystitis is  characterized by blood in the urine (hematuria) and can manifest itself from 2 months to greater than ten years after treatment.  A teaspoon of blood can easily color the urine but more significant amounts of blood can be a sign of more serious conditions including bladder cancer.  Radiation treatment of the pelvic area can cause inflammatory changes in bladder tissue and its vasculature.  This particular patient suddenly encountered heavy bleeding for several hours during urination.  Eventually he could not urinate at all due to blood clot blockage which was accompanied by severe abdominal pain.  He had to undergo catherization and his bladder was irrigated to flush out any clots.  A subsequent CT scan and cystoscopy revealed bladder vascular changes but showed no pathological evidence of bladder cancer.  There are a number of possible treatments for radiation cystitis including hyperbaric (greater than atmospheric pressure) oxygen therapy consisting of significant number of daily treatments.  Useful links providing additional information include: a) an overall review of radiation cystitis;  b)  a series of testimonials from actual patients; c) a urology textbook review of radiation cystitis.  Unfortunately, I could not find any reviews suitable for the layman.  In summary, any unusual bleeding upon urination after radiation therapy should be discussed with your health care provider to differentiate mild causes from more serious ones.

Western Diet is Harmful for Prostate Cancer Patients

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According to a new study published in Cancer Prevention Research (June 8th, 2015), prostate cancer survivors who consume a typical Western diet consisting of red meat, refined grains, processed foods and high-fat dairy products may be at an increased risk of death from recurrent prostate cancer as well as other causes.  Researchers at Harvard T.H. Chan School of Public Health studied 926 men aged 40 to 84 who were diagnosed with prostate cancer that had not spread.  Subjects answered questions about their diets five years after receiving a prostate cancer diagnosis and were monitored for approximately 10 years.  The men diagnosed with non-metastatic prostate cancer who ate a diet that was more Westernized were 2.5 times more likely to die of prostate cancer than those who ate the healthiest diet and 1.5 times more likely to die of any cause.  The healthiest diet was a Mediterranean-style diet rich in fruits, vegetables, and fiber with fewer dairy products and less red meat.  The researchers concluded that their “results suggest that the same dietary recommendations that are made to the general population primarily for the prevention of cardiovascular disease may also decrease the risk of dying from prostate cancer among men initially diagnosed with non-metastatic disease.”


An Alternative to Immediate Prostate Biopsy

The following article dated August 6th came from a site entitled Prostatesnatchers authored by a noted prostate oncologist, Dr. Mark Scholz. He suggests that a commercial OPKO-4Kscore blood test and a high-resolution color Doppler ultrasound or a 3-Tesla multi-parametric MRI can help identify aggressive cancers and minimize the use of standard 12-core prostate biopsies and their potential side effects. The OPKO-4Kscore blood test is comprised of measurements of total and free PSA coupled with proprietary tests for intact PSA and a panel of four kallikrein (a specific group of enzymes) blood markers.  My own prostate oncologist commented favorably on this test. “It won’t be the last word, but it is a productive departure from single-lab-value (PSA) technology, which is over 30 years old.”  Remember the contents of this website are not intended as personal recommendations but the potential use of this information should be discussed with your personal physician. You should also check on the cost and insurance coverage of the tests described below.

“You PSA is elevated. Now your doctor recommends a needle biopsy, 12 cores through the rectum to check for cancer in the prostate.  Sounds icky, but also logical; after all who wants to miss cancer? But come on, do you really have to do 12 stabs via the rectum?

Each year over a million men submit their prostates for a biopsy.  At an average cost of around four thousand dollars, the prostate biopsy business is a 4-billion-dollar-a-year enterprise.  But it’s not merely the cost that gives pause.  Three percent of men end up hospitalized with life-threatening infections.  Around a 100,000 men every year get a confounding diagnosis of Grade 6 prostate cancer, a truly harmless entity, unless you get suckered into an unnecessary radical prostatectomy.

Obviously, prostate biopsy is an unpleasant proposition with notable risks.  However, ignoring a high PSA incurs the risk of missing a diagnosis of a higher grade prostate cancer. As things stand now, of the million biopsies being done annually, over a hundred thousand men with Grade 7 or higher cancers are being detected. For these men, their early diagnosis is beneficial, leading to early, curative treatment in a timely fashion.

How can we detect the 100,000 men with higher-grade cancers that need to be detected without doing 900,000 “unnecessary” biopsies?   The answer to this question continues to evolve as technology marches forward. Our latest thinking at Prostate Oncology (assuming the PSA is not wildly elevated, say over 20) is a three step process:

1.    Simply repeat the PSA to confirm it is indeed abnormally elevated.  All sorts of things can cause temporary elevations of PSA ranging from nonspecific inflammation of the prostate, to recent sexual activity, to simple laboratory errors. 

2.    If the PSA remains elevated with repeat testing the next step to consider is an OPKO-4Kscore blood test. The OPKO test reports a percentage estimate of the likelihood of higher grade cancer being present.  The test is not perfect, but it performs pretty well.  For example, if a specific patient receives an OPKO report with an estimated risk of high grade disease of less than 15%, a standard random biopsy (if he elected to do one) will confirm the absence of high grade disease 92% of the time. Not bad.

3.    Our next step at Prostate Oncology in the cases where a patient has an OPKO test indicating that the risk of high grade disease is over 15%, is to obtain a prostate scan with high-resolution color Doppler ultrasound or with a 3-Tesla multiparametric MRI. With scanning, the location of the high-grade disease can be determined over 90% of the time so that a targeted biopsy with 2 or 3 cores can be substituted for the traditional 12-core biopsy.       

The business of prostate biopsy has become so out of control the US Preventative Services Task Force advocates against PSA testing altogether.  The Task Force’s scientifically-based arguments that PSA testing is causing more harm than good are really quite convincing.  However, back in 2011 when they published their recommendations, the OPKO test and 3-Tesla multiparametric prostate MRI were unavailable. With the advent of these new technologies, PSA screening to detect higher grade prostate cancers at an early stage when they are still curable makes perfect sense.

Combination Therapies in Clinical Trials for Advanced Prostate Cancer

In a recent interview, Dr. Mario Eisenberger, Professor of Urology and oncology at Johns Hopkins, summarized a group of on-going clinical trials for patients with metastatic, hormone-resistant prostate cancer.  Trials are ongoing combining agents targeting the androgen receptor such as abiraterone (Zytiga®) with chemotherapies such as docetacel® (taxotere) or cabazitaxel (Jevtana®). Other trials such as the Alliance trial, combines abiraterone with enzalutamide (Xtandi®).  An on-going phase III trial combines abiraterone with radium -223 (alpha-radin, Xofigo®) in men with metastaic disease who have not received chemotherapy.  Dr. Eisenberger states that there are a number of trials combining approved drugs with chemotherapy and hormonal therapy and radiopharmaceuticals such as radium-223.  There are also trials using combinations of PARP inhibitors (s0 far un-approved for prostate cancer) with standard, second line hormonal therapies. Also there are antitumor PI3K  and AKT inhibitors some of which inhibit more than one pathway which are over-expressed in prostate cancer patients who progress on androgen receptor-targeted compounds such as abiraterone or enzalutamide.  The question is whether PI3K or AKT inhibitors will enhance the effects of abiraterone or enzalutamide.  Dr. Eisenberger also discusses trials involving approved agents for metastatic disease as well as unapproved agents like TAK-700 (Ortoronel®) and ARN509 being tested in men with metastatic, hormone-naive cancer.  In addition, chemotherapy trials such as CHAARTED and STAMPEDE are discussed.  This post is primarily aimed at physicians.  If you are a patient with metastatic disease, I suggest you discuss these trials with your physician to see if any one would apply to your specific situation.

Don’t Waste Your Adversities

Gulf of Mexico at Boca Grande, SW Florida; BJ Gabrielsen photo,
Gulf of Mexico at Boca Grande, SW Florida; BJ Gabrielsen photo,

The book of James 1-24 state: “2 Consider it all joy, my brethren, when you encounter various trials, 3 knowing that the testing of your faith produces endurance. 4 And let endurance have its perfect result, so that you may be perfect and complete, lacking in nothing.”

Prostate issues such as cancer are indeed troublesome trials. Are you wasting your troubles? Any time God allows trials to enter your life, He has a purpose for them. He wants you to squeeze out every ounce of spiritual growth instead of letting difficulties force you into despair and discouragement. If you’ll just respond in the right manner, the trial that looks as if it could destroy you becomes an instrument of blessing.

The most natural response to adversity is to groan and plead with the Lord to remove it. If that doesn’t work, we might get angry and say “why me?”  But in truth, ultimately God allowed it. No matter where affliction originates by the time it reaches you, it’s been dipped in the Father’s love and shaped to accomplish His good purpose. The question is, will you cooperate with Him, or will you resist?

Perhaps the key word is found in verse 4 of the verses above.  God wants to use our trial to develop spiritual maturity, but unless you let it do its work, that opportunity will be lost. If we could foresee every benefit the Lord designed our trials to accomplish, maybe we’d be more cooperative.

Although we can’t see all the specifics of God’s plan, we know that His goal is to use our adversity to supply something we lack so we can be mature and complete. Even though the experience is painful, rest in the Father’s comforting arms, and let Him do His perfect work in you.

If you are not sure how these scriptural truths can apply to you, or if you are not sure whether or not you have a personal relationship with God through His Son, Jesus Christ, please see the following linked website section.

The above message was excerpted and adapted from the In Touch devotional by Dr. Charles Stanley, August 17th, 2015.