Saturday, July 25, 2015

Prostate Cancer News 07-24-2015


Prostate Cancer News 07-24-2015

Study Supports Surgery for High-Risk Prostate Cancer
- Renal and Urology News
Prostate cancer: treatment options | CPD article | Pharmaceutical Journal
Treatment of early stage prostate cancer and locally advanced disease can involve surveillance, radical treatment or androgen deprivation therapy; however, as the disease progresses, these options change. Although patients may require definitive therapy as their disease progresses, active surveillance is an important treatment option.
Radical prostatectomy or radical radiotherapy are recommended for men with intermediate- and high-risk localised prostate cancer, where there is a prospect of long-term disease control. However, both options are associated with complications, including impaired sexual function.
Androgen deprivation therapy has been the mainstay for advanced prostate cancer management; however, recently there has been a move towards initiating hormonal treatment in younger men with early disease or recurrent disease after definitive treatment. Advanced disease, or metastatic castrate resistant prostate cancer, usually occurs 12–18 months after diagnosis and androgen ablation, with a median survival of two to three years. Treatment usually involves chemotherapy with docetaxel, but a number of newer drugs, including cabazitaxel, abiraterone and enzalutamide, are available.

General

After years of overtreatment for patients with low-risk prostate cancer, rates of active surveillance/ watchful waiting increased sharply in 2010 through 2013, and high-risk disease was more often treated appropriately with potentially curative local treatment rather than androgen deprivation alone, according to a study in the July 7 issue of JAMA.  

Among men 75 years or older, the rate of surveillance was 54 percent from 1990 through 1994, declined to 22 percent from 2000 through 2004, and increased to 76 percent from 2010 through 2013. There was an increase in the use of surgery for men 75 years or older with low-risk cancer to 9.5 percent and intermediate-risk cancer to 15 percent; however, there was not an increase in use for those with high-risk cancer, among whom androgen deprivation still accounted for 67 percent of treatment.

Understanding the U.S. News Rankings for Prostate Cancer Care? - Cancer Answers
On Tuesday, U.S. News & World Report released its 2015–16 Best Hospitals rankings. The University of Texas MD Anderson Cancer Center in Houston regained the No. 1 ranking in cancer care. But does that mean it’s where prostate cancer patients should go?
As someone who lives with prostate cancer and heads a prostate cancer nonprofit, I believe the prostate cancer community would benefit from knowing about this top-ranked hospital’s prostate cancer care. But its No. 1 ranking doesn’t answer many questions.
 

What you can do

UnitedHealthcare steps to help prevent prostate cancer:
  • Eat Less Red Meat and Processed Meat. Red meat and processed meats like bacon have been linked to increased risk of prostate cancer.
  • Eat more fruits and vegetables.
  • Exercise more and maintain a healthy weight
This pilot randomized dose–comparison trial provides preliminary data to suggest that RT 3 days per week compared with 2 days per week may improve the strength and physical functioning in prostate cancer survivors, but may also blunt improvements in psychosocial functioning. Larger and more targeted phase II and III trials are needed to confirm the potentially complex effects of RT frequency in prostate cancer survivors.

The results of the study were encouraging. The researchers found that DNA damage decreased as adherence to the modified Mediterranean diet increased and there was an inverse association between olive oil intake and DNA damage. On the other hand, DNA damage was reported to increase with increased consumption of dairy products and red meat.
The authors also found that higher levels of whole blood monounsaturated fatty acids and oleic acid were associated with decreased DNA damage, while high levels of omega-6 polyunsaturated fatty acids were associated with increased DNA damage.
The benefits of the modified Mediterranean diet extended to include weight loss and a feeling of general well-being at the end of the three-month period by some subjects.
Overall results indicate that changing the Western dietary pattern to a modified Mediterranean dietary pattern that includes fish and olive oil can be beneficial in decreasing DNA damage in men with prostate cancer.

A review of research on the use of testosterone replacement therapy in men with a history of prostate cancer and in men with elevated prostate cancer risk found no evidence of statistically significant associations between such treatment and cancer progression.

The finding supports the conclusion of several other recent studies that have attempted to evaluate replacement therapy in such populations and failed to find evidence of danger. - See more at: http://www.hcplive.com/medical-news/testosterone-replacement-therapy-and-prostate-cancer-risk#sthash.nr7HYohy.dpuf
A review of research on the use of testosterone replacement therapy in men with a history of prostate cancer and in men with elevated prostate cancer risk found no evidence of statistically significant associations between such treatment and cancer progression.

The finding supports the conclusion of several other recent studies that have attempted to evaluate replacement therapy in such populations and failed to find evidence of danger.

Screening; Diagnosis

Intermediate and high-risk prostate cancers have seen a major drop in U.S. diagnoses, according to a recent study led by Vanderbilt University Medical Center, published last month in The Journal of Urology. Don’t be deceived: This is anything but good news. This significant drop in the number of diagnoses of intermediate (28%) and high-risk (23%) prostate cancers is most likely an indication that many of these cancers are not being found.

John Julius Hungwe (68), a survivor of prostate cancer, said the condition severely impacts the family. Things were quite difficult in Zimbabwe as the cost of cancer treatment is quite costly there. Hungwe said he never wanted to die, as life is so much fun for him.
New research has shown how a smart sensor chip, able to pick up on subtle differences in glycoprotein molecules, can improve the accuracy and efficiency of prostate cancer diagnosis.

Read more at: http://phys.org/news/2015-07-sensor-technology-accuracy-prostate-cancer.html#jCp
New research has shown how a smart sensor chip, able to pick up on subtle differences in glycoprotein molecules, can improve the accuracy and efficiency of prostate cancer diagnosis.

 Initial

July 6, 2015
Rather than use the historical arbitrary cutoff of a 4.0 PSA reading to define abnormal, we now have tools to adjust our interpretation of readings for age (PSA levels normally rise with age); for race (this, too, affects what is considered normal); and for the size of a man’s prostate, which affects how much PSA he produces. We can test for how fast PSA levels rise over time. And we can analyze how PSA circulates in the bloodstream (free or bound to serum proteins), which can predict prostate cancer risk.
When we use these markers together, these varied interpretations of PSA levels give us a clearer picture of who does, or doesn’t, need further testing. And we keep refining our approach. Already, a urine test can find and measure the presence of genes associated with prostate cancer. M.R.I. images can help identify high-risk prostate lesions. And tests for the presence or activity, or both, of genes present in prostate tissue can help distinguish which patients can safely defer therapy from those who cannot.
what frustrates urologists most: Rather than using refined screening techniques to identify those who will benefit most from treatment, we’re just evaluating fewer men. So the task force needs to re-evaluate its recommendation based on the current state of medical knowledge.
But men should not wait for a government agency to tell them what’s best. My own strongest recommendation is that men insist on a baseline PSA test while in their 40s. From this baseline, a personalized screening regimen that considers risk factors and other indicators can be developed.
Men must understand that screening does not commit them to further testing or treatment, even if abnormalities are found. Screening, followed up with today’s sophisticated tools, simply provides information that helps them and their doctors make sound decisions — which could prolong their
lives, or leave them reassured that they have little to fear from an indolent tumor

So long as we go on re-fighting the PSA screening wars, we are not going to make any significant progress toward a better way to assess risk for prostate cancer. The PSA test is what it is — an indicator of the potential for any one of several types of prostate/urinary tract problem. And that is all it is. Getting an annual PSA test — and especially getting an annual PSA test while simultaneously refusing to have a digital rectal examination — is not a way to manage risk for prostate cancer.  On the other hand, not getting a PSA test when you need one (for all sort of possible reasons) is about as smart as not getting a vaccination against measles or tetanus or a whole bunch of other deadly disorders. You may well not need that vaccination. And you may well find you did not need the PSA test (just as you may never need certain types of vaccination) … but under the right conditions, any of these actions might help to save your life.
 
The National Cancer Institute (NCI) announced that it had removed all prostate specific antigen (PSA) data from the SEER (Surveillance, Epidemiology and End Results) and SEER-Medicare programmes. The PSA data were removed after quality control checks revealed that a substantial number of PSA values included in the programmes were incorrect.


The U.S. Preventive Services Task Force (USPSTF) issued a grade D recommendation that discouraged PSA-based screening for prostate cancer in October 2011, according to study background.
“The results raise concern that if this trend continues, more men may be diagnosed at a point when their disease is advanced,” Barocas said. “Younger, healthier men with intermediate- or high-risk disease would normally be candidates for aggressive local therapy and they may not be receiving a timely diagnosis under this policy.”  

Researchers at Sanford-Burnham Medical Research Institute in Orlando are working to more accurately diagnose prostate cancer starting with a set of RNA molecules believed to regulate cell development.

Doctor Ranjan Perera, Associate Professor at Sanford-Burnham Medical Research Institute, said, "We were able to identify some of these RNAs being secreted in the urine of the prostate cancer patients." The team examined the urine and tissue samples of prostate cancer patients with those who did not have cancer and found the RNA levels were higher in those with cancer. Researchers say the RNAs are easily detected in urine.

"Our hope is that we can develop a urine test that would be a better biomarker for diagnosing prostate cancer," said Dr. Patel.

New screening that could be faster, more accurate, and end up saving even more lives. Professor Perera says the next step is to initiate a wide-scale clinical trial. He believes that the clinical study will be completed and a urine test will be developed and ready for use in three to five years. 

 Watching

'Genuine Change' in US Prostate Cancer Management
In the years 2010-2013, the use of active surveillance for low-risk disease "increased sharply" to 40% of all cases, say investigators. The rate had languished at only about 10% in the preceding 20 years.
At the same time, use of androgen deprivation as a monotherapy "decreased sharply," they note, down to only 3.8% of intermediate-risk and 24% of high-risk prostate cancer cases. These percentages represent drops of about one third and one half from earlier periods.
Both trends are desirable because they represent strategies to avoid overtreatment and undertreatment, respectively.
More men with prostate cancer are opting for surveillance | Reuters

There are several possible treatments for prostate cancer, including surgery and radiation. Some men - especially those who are older - may opt for active surveillance.
Men using active surveillance may undergo tests or biopsies to make sure the cancer isn't growing, the ACS says.
The approach helps avoid more aggressive treatments, which can carry the risk for complications such as incontinence and impotence.

Simply observing men with very low-and low-risk prostate cancer very effective and underused, UCLA researchers find - Medical News Today
"Ultimately, the decision-making process surrounding treatment for a man with localized prostate cancer must take an individualized approach. The risks and benefits of expectant management vis-a-vis active treatment should be reviewed with the patient in light of existing knowledge, potentially with the use of decision aids to help enable a truly shared decision-making process," the review states. "Active surveillance is a viable approach for most men with low-risk prostate cancer, and its broader adoption has the potential to stop the overtreatment of men with indolent lesions and redirect resources to men with more serious cancers." 
 

Biopsy/Pathology

Access : Improved detection of anterior fibromuscular stroma and transition zone prostate cancer using biparametric and multiparametric MRI with MRI-targeted biopsy and MRI-US fusion guidance : Prostate Cancer and Prostatic Diseases
MRI-targeted biopsies detected significantly more anteriorly located sPC compared with SBs in the repeat-biopsy setting. The more cost-efficient bpMRI was statistically not inferior to mpMRI in sPC detection in TZ/AFMS.

 Genomics

Structural Organization of the Genome - Theory of Cancer Biology
British Journal of Cancer - The genomic evolution of human prostate cancer
Prostate cancers are highly prevalent in the developed world, with inheritable risk contributing appreciably to tumour development. Genomic heterogeneity within individual prostate glands and between patients derives predominantly from structural variants and copy-number aberrations. Subtypes of prostate cancers are being delineated through the increasing use of next-generation sequencing, but these subtypes are yet to be used to guide the prognosis or therapeutic strategy. Herein, we review our current knowledge of the mutational landscape of human prostate cancer, describing what is known of the common mutations underpinning its development. We evaluate recurrent prostate-specific mutations prior to discussing the mutational events that are shared both in prostate cancer and across multiple cancer types. From these data, we construct a putative overview of the genomic evolution of human prostate cancer.
Study Suggests 90% of Advanced Prostate Cancers May Have Anomaly that May Influence Treatment - Cancer Therapy Advisor
Tt may soon be easier to treat metastatic castration-resistant prostate cancer (mCRPC) based on genetic anomalies. A new international study suggested it may be possible to link specific aberrations to response or resistance to specific treatments in 90% of cases.
Researchers from eight institutions in the United States and in Europe collaborated and sequenced the DNA and RNA of tumor biopsy samples from 150 men with mCRPC. They found that patients with mCRPC harbor genomic alterations in PIK3CA/B, RSPO, RAF, APC, B-catenin, and ZBTB16 and 23% harbor DNA repair pathway aberrations.1
 New Study Published on Cover of Urology Finds that Decipher® Prostate Cancer... -- SAN DIEGO, July 14, 2015 /PRNewswire/ -- 
The Decipher test used in this study has been previously described in multiple blinded independent validation studies in men at high risk of recurrence at the time of prostatectomy. Researchers found that 60% of the clinically high-risk men would be reclassified as low risk based on the Decipher test and have only a 2.4% risk of metastasis at 5 years after surgery. In addition, the 19% of the patients with the highest risk based on Decipher had a nearly 10-fold higher risk of distant metastases by 5 years. The test provided a more accurate and precise estimate of a patient's risk of recurrence. Use of this test therefore has the potential to assist clinicians to better direct utilization of secondary therapy after surgery.
Researchers Find Potential Achilles’ Heel for Prostate Cancer and B Cell Lymphoma | Memorial Sloan Kettering Cancer Center
MicroRNAs are small molecules that regulate gene function. The laboratory of cancer biologist Andrea Ventura has found that one microRNA, miR-19, plays an important role in tumor cell growth in B cell lymphoma and prostate cancer. Blocking miR-19 seems to make cells resistant to these cancers while having no ill effects. The researchers also clarified the function of related microRNAs, which appear to play essential roles in embryonic development.
 
Access : Which, when and why|[quest]| Rational use of tissue-based molecular testing in localized prostate cancer : Prostate Cancer and Prostatic Diseases
An increased molecular understanding of localized prostate cancer and the improved ability for molecular testing of pathologic tissue has led to the development of multiple clinical assays. Here we review the relevant molecular biology of localized prostate cancer, currently available tissue-based tests and describe which is best supported for use in various clinical scenarios. Literature regarding testing of human prostate cancer tissue with Ki-67, PTEN (by immunohistochemistry (IHC) or fluroescence in situ hybridization (FISH)), ProMark, Prolaris, OncotypeDX Prostate and Decipher was reviewed to allow for generation of expert opinions. At diagnosis, evaluation of PTEN status, use of ProMark or OncotypeDX Prostate in men with Gleason 6 or 3+4=7 disease may help guide the use of active surveillance. For men with Gleason 7 or above disease considering watchful waiting, Ki-67 and Prolaris add independent prognostic information. For those men who have undergone prostatectomy and have adverse pathology, Decipher testing may aid in the decision to undergo adjuvant radiation. Newly available molecular tests bring opportunities to improve decision making for men with localized prostate cancer. A review of the currently available data suggests clinical scenarios for which each of these tests may have the greatest utility.

 Imaging

Dr. Aaron Ward is designing a road map - a computerized, 3D road map - to help better diagnose and treat prostate cancer. And it's getting national attention. A computerized road map uses artificial intelligence to help interpret the nuances in what's shown through an MRI.
Ward explains that the computer takes three different images of the prostate with different information, "and the idea is that this artificially intelligence system is going to automatically integrate and combine all of this information to produce a much simpler to read colour-coded road map for where the threatening areas of potential cancer are."


 The typical biopsy that doctors perform to check a man for prostate cancer is far from a precise procedure, says the trial’s principle investigator Clare Tempany, a radiologist and director of the National Center for Image Guided Therapy at Brigham. Typically a physician targets the prostate, which is the size of “a small peach or plum,” she says, by placing a grid guide between the patient’s legs. Then the doctor inserts needles through the skin and into each quadrant to get tissue samples. “This is somewhat disparagingly called ‘the blind biopsy,’ ” says Tempany. “There’s no lesion targeted, it’s just: ‘Let’s push a bunch of needles in and see what we get.’ ”
These biopsies are sometimes aided by ultrasound imaging, which requires inserting a ultrasound wand into the patient’s rectum. Because ultrasound doesn’t provide clear enough images, doctors aren’t able to make precision strikes with their needles, says Tempany. They often end up taking 10 to 50 core samples, she says, and each needle stick carries the risk of infection.
This clinical trial literally shows a better way. Looking at real-time MRI images, the doctor can identify parts of the prostate that look suspicious, and direct the robotic tool to those spots. “In our procedure, a small little robot places the needle on the skin’s surface and says, ‘This is the spot where you need to push, and in five or six centimeters you’ll hit your target,’ ” Tempany explains. In the current trial the doctor takes the actual step of inserting the needle, and typically takes samples in just four locations. “It’s a smarter biopsy,” she says.

Treatment

Case Studies Offer Window Into Evolving Prostate Cancer Paradigm
In the ever-evolving treatment landscape in metastatic prostate cancer, healthcare providers have more options that ever before. Although guideline organizations have now incorporated the results of major clinical trials into treatment paradigms, much controversy remains over how best to sequence therapies, according to experts who participated in a recent OncLive Peer Exchange.

In recognition of this complexity, moderator Raoul S. Concepcion, MD, FACS, and colleagues took a case-based approach to explore the ways in which oncologists and urologists can employ newly acquired evidence to manage patients whom they encounter in their practices. The Peer Exchange session, entitled “Integrating Prostate Cancer Trial Findings Into Practice: A Case-Based Discussion,” incorporated four cases, two of which are presented here.
- See more at: http://www.onclive.com/publications/Oncology-live/2015/July-2015/case-studies-offer-window-into-evolving-prostate-cancer-paradigm#sthash.FozlFACb.dpuf
In the ever-evolving treatment landscape in metastatic prostate cancer, healthcare providers have more options that ever before. Although guideline organizations have now incorporated the results of major clinical trials into treatment paradigms, much controversy remains over how best to sequence therapies, according to experts who participated in a recent OncLive Peer Exchange.
In recognition of this complexity, moderator Raoul S. Concepcion, MD, FACS, and colleagues took a case-based approach to explore the ways in which oncologists and urologists can employ newly acquired evidence to manage patients whom they encounter in their practices. The Peer Exchange session, entitled “Integrating Prostate Cancer Trial Findings Into Practice: A Case-Based Discussion,” incorporated four cases, two of which are presented here.
- See more at: http://www.onclive.com/publications/Oncology-live/2015/July-2015/case-studies-offer-window-into-evolving-prostate-cancer-paradigm#sthash.FozlFACb.dpuf

Radiation

Pioneering treatment for prostate cancer sufferers (From The Northern Echo)
Specialists at Middlesbrough's James Cook University Hospital will be able to use radioactive radium 223 to treat prostate cancer patients for the first time.
The radium is used to treat prostate cancer which has spread to the bones and specifically targets tumours with less pain and fewer side effects.
Radiation therapy may improve survival even when PSA ≥ 75 ml/ml | THE "NEW" PROSTATE CANCER INFOLINK
Sometimes, when patients originally present with very high PSA levels, a negative bone scan, and a negative CT scan, they are put on permanent androgen deprivation  therapy (ADT) because the doctor just assumes it is micrometastatic. A closer look at the data demonstrates that an attempt at curative radiation may improve outcomes.
 
Access : Primary radiotherapy vs conservative management for localized prostate cancer|[mdash]|a population-based study : Prostate Cancer and Prostatic Diseases
Among men >65 years of age, the benefit of primary radiotherapy for localized disease is largely confined to patients with high-risk prostate cancer (Gleason scores 7–10).
 
 Prostate cancer: Radiotherapy is effective in old men with high-risk cancer : Nature Reviews Urology : Nature Publishing Group
In a population-based study of 57,749 patients with prostate cancer, the effectiveness of primary radiotherapy versus conservative management was investigated by comparing patient outcomes in geographical areas with high, versus low radiotherapy use. In older patients (>65 years of age), those in high radiotherapy use areas had small, but significant…
 
Low utilization of immediate and delayed postoperative radiation for prostate cancer with adverse pathologic features - Beyond the Abstract
immediate radiotherapy is still being underutilized after prostatectomy, and this underutilization does not appear to be explained entirely by the use of delayed radiotherapy, which is also low. Urologists should discuss the risks, benefits, and evidence behind immediate vs. delayed radiotherapy with their patients. For those patients who are considering postoperative radiotherapy, referral to a radiation oncologist may be beneficial.
 
Increased radiation offers no survival benefit for patients with low-risk prostate cancer
Increased radiation dose is associated with higher survival rates in men with medium- and high-risk prostate cancer, but not men with low-risk prostate cancer, according to a new study from Penn Medicine published this week in JAMA Oncology. Already-high survival rates for men with low-risk prostate cancer were unaffected by higher radiation dosages compared to lower radiation dosages. 

 Hormone Therapy

Statin Therapy May Help Delay Prostate Cancer Progression in Men Receiving ADT - Cancer Therapy Advisor
Taking a statin while undergoing androgen deprivation therapy (ADT) for prostate cancer appears to pay off when it comes to delaying disease progression, according to researchers at the Dana-Farber Cancer Institute. They analyzed data on 926 men with prostate cancer receiving ADT and found that time to progression (TTP) was significantly delayed if the men were taking a statin.
Androgen deprivation of prostate cancer: Leading to a therapeutic dead end.
In this review, we describe molecular alterations in tumor cells during ADT, which lead to deregulation of different signaling pathways and castration-resistance, and how they might interfere with the clinical outcome of different second-line therapeutics. A recent breakthrough finding that early chemotherapy is associated with a significant survival benefit in metastatic hormone-sensitive disease highlights the fact that there is time for a fundamental paradigm shift in the treatment of advanced prostate cancer. Therapeutic intervention seems to be indicated before a castration-resistant stage is reached to improve therapeutic outcome and to reduce undesirable side effects.

Chemo

Predicting response to chemotherapy for prostate cancer and other stories . . . | The BMJ
A new study shows that the measurement of androgen receptor splice variant 7 (AR-V7) in circulating tumour cells can predict which men with castration resistant prostate cancer are most likely to respond to treatment with chemotherapy rather than enzalutamide or abiraterone (JAMA Oncology 2015, doi:10.1001/jamaoncol.2015.1341).

Detection of AR-V7 in CTCs from men with metastatic CRPC is not associated with primary resistance to taxane chemotherapy. In AR-V7–positive men, taxanes appear to be more efficacious than enzalutamide or abiraterone therapy, whereas in AR-V7–negative men, taxanes and enzalutamide or abiraterone may have comparable efficacy. Circulating tumor cell–based AR-V7 detection may serve as a treatment selection biomarker in CRPC.

Advanced - Recurrent

 A bird's eye view of advanced prostate cancer
An estimated 220,000 American men are diagnosed with prostate cancer each year, with 30,000 expected to die of it this year. While androgen deprivation therapy (ADT) is initially effective against metastatic disease, most men develop tumors that ultimately become resistant to ADT, including the most recent ADT regimen (abiraterone acetate and enzalutamide). This condition is known as metastatic castration-resistant prostate cancer (mCRPC). While many studies have cataloged somatic alterations in primary prostate cancers, genomic studies of mCRPC have been limited to either autopsy samples or preclinical models. To address the gap in our understanding of mCRPC, an international and multi-institutional consortium that included Fred Hutch investigators and benefitted from key contributions from Dr. Pete Nelson’s Laboratory (Human Biology, Clinical Research and Public Health Sciences Divisions), sequenced the DNA and RNA from biopsies of bone or soft tissue metastases prospectively from 150 mCRPC affected individuals. This work was recently published in the journal Cell.
 
Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial
Current studies on salvage radiotherapy (sRT) investigate timing, dose-escalation and anti-hormonal treatment (ADT) for recurrent prostate cancer. These approaches could either be limited by radiation-related susceptibility of the anastomosis or by suspected side-effects of long-term ADT.

A phase II protocol was developed to investigate the benefit and tolerability of regional hyperthermia with moderately dose-escalated radiotherapy.
 

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