Two-drug combination boosts survival in patients with metastatic, hormone-sensitive prostate cancer

Patients with newly diagnosed metastatic, hormone-sensitive prostate cancer gained a dramatic survival benefit with simultaneous initiation of two drugs, rather than delaying the second drug until the cancer began to worsen, according to results of a clinical trial recently published in The New England Journal of Medicine (2015; doi:10.1056/NEJMoa1503747).

Patients who underwent six cycles of treatment with docetaxel® (taxotere) along with a hormone blocker survived for a median of 57.6 months, more than 1 year longer than the median 44-month survival for men who received only the hormone-blocker. The immediate combination also prolonged the period before the cancer began to worsen, to a median of 20.2 months vs 11.7 months with the single agent.

The multicenter, phase III trial, involving 790 patients, “is the first to identify a strategy that prolongs survival in men [with] newly diagnosed with metastatic, hormone-sensitive prostate cancer,” said Christopher J. Sweeney, MBBS, of Dana-Farber’s Lank Center for Genitourinary Oncology in Boston, Massachusetts. He said the results of the multicenter phase III trial should change the way doctors have routinely treated such patients since the 1940s.

Sweeney had reported initial results of the trial in June 2014 at the annual meeting of the American Society of Clinical Oncology (ASCO), and they were so favorable that the new regimen has been adopted by some physicians. Since then, confirmatory data from the STAMPEDE trial were presented at the 2015 ASCO meeting, and those results, along with the new publication in the New England Journal of Medicine, are the final pieces “required for treatment guidelines to be updated around the globe,” Sweeney said.

The standard practice for decades has been to treat this group of prostate cancer patients with hormone blockers; chemotherapy is withheld until the hormone blockers become ineffective, which they do, on average, in approximately 3 years.

The new trial was designed and conducted by the ECOG-ACRIN Cancer Research Group to test Sweeney’s hypothesis that adding chemotherapy to hormone treatment from the start would impair the tumor cells’ ability to repair damage, delaying the development of resistance.

An Excellent Review of Current Imaging and Positron Emission Tomography (PET) Scanning and Their Use in Managing Recurrent and Advanced Disease

This website initially posted a review of positron emission tomography (PET) scanning on March 9th, 2015.

More recently, the Prostate Cancer Research Institute (PCRI) November Insights contained an updated and very informative review of the latest PET imaging techniques for managing recurrent and advanced prostate cancer. Their major utilities, advantages and their limitations are discussed clearly. The review was written by Dr. Fabio Almeida, Medical Director of Phoenix Molecular Imaging in Arizona. Rather than summarize the entire readable review, I will merely mention the various sections herein and provide the following link to the entire review.

In the November article, conventional types of imaging such as ultrasound, CT scans and prostate MRI and their uses are discussed initially. A section describing detection of bone metastases using Technetium-99 and sodium fluoride PET/CT scans follows. Carbon-11 acetate (available at Phoenix Molecular Imaging, Arizona) and C-11 choline (available at the Mayo Clinic, MN) are lipid metabolism PET agents both of which are useful for detecting recurrent disease and PSA relapse. In both cases, detection rates were dependent upon PSA values and doubling times.

Axumin (18F-FACBC) is a fluorine-18 radiolabeled synthetic leucine amino acid was has been recently approved by the FDA for detection of recurrent cancer in men with rising PSA after previous surgery or radiation. Amino acids are absorbed into cancer cells because of the increased metabolic demands of the growing cancer. In cited studies, optimal detection rates were seen when PSA levels were above 1.78. Direct comparison with C-11 choline scans indicated better performance for Axumin. For additional information on Axumin, see the website blog dated May 30, 2016.

The prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that occurs much more commonly in prostate cancer cells compared to benign prostate tissue. One of the PSMA agents under development is 68-gallium-PS-MA-11, which has demonstrated a higher diagnostic efficiency compared to C-11 choline.  Detection rates were dependent on PSA values. For example, a 93% detection rate was observed when the PSA was over 2.0 but only 50% when the PSA was 0.2-0.5. There are limitations to PSMA-targeting agents. Not all prostate cancers exhibit PSMA overexpression. In one study, about 8% of prostate cancer patients did not show PSMA overexpression. Benign lesions and several other types of cancers may also exhibit increased PSMA expression. False positive celiac lymph nodes have frequently been noted in the upper abdomen and detection of small locally-recurrent lesions and lymph nodes in the lower pelvis is challenging.

There is still no perfect imaging methodology with 100% accuracy. However, PSMA-targeted agents are becoming the major focus of future attention and development. “Despite some limitations, PSMA-targeted imaging appears to provide high sensitivity and specificity and is likely to become part of the routine evaluation and management of men with prostate cancer in the near future.”

For an initial review of PET imaging, see this website post dated October 9th, 2012. 

 

How to Find an Expert Prostate Surgeon

Radical prostatectomy can be a very difficult operation. The very best urological surgeons specialize in the prostate gland. They do a lot of these procedures annually. How do you find the right surgeon? The Prostate Cancer Foundation has published a checklist of things to consider before choosing the right surgeon.

1) First, locate a high-volume center that performs a lot of these procedures. Often this is an academic center. Not only are surgeons involved but supporting teams e.g. nursing, specialize in caring for prostatectomy patients. Websites that can help locate such high-volume centers include the National Cancer Institute’s website namely http://www.cancer.gov/research/nci-role/cancer-centers/.

The National Comprehensive Cancer Network (NCCN) also has a useful website for all types of cancer including prostate. See the following web address, https://www.nccn.org/patients.

2) Look for a place where different specialties work together in multi-disciplinary teams such as urology, radiation oncology, medical oncology and pathology. Since prostate cancer is not a “one size fits all” condition, one can get opinions from a team of experts who may recommend treatment modes other than surgery.

3) Ask the surgeon about his patient results. Does he keep results of his many patients regarding their outcomes, side effects such as incontinence and/or impotence, cancer recurrences, etc? Come prepared with a list of questions to ask as well as a detailed description of your specific condition and hopes.

4) Ask the surgeon to provide you with names of his patients who have agreed to speak to other patients about their experiences. If possible, contact some of them. This is helpful in demonstrating that the surgeon has many “happy” patients who comprise a support network to help prospective patients decide what’s best for them. Also check the prostate cancer support groups in your area and ask these men about their experiences and specific surgeons.

5) How many radical prostatectomies has the surgeon performed? The answer should be in the hundreds. If it’s something like “quite a few”, seek elsewhere.

6) Ask more than one doctor to recommend the best prostate surgeon in your area. Some doctors are in practice groups and therefore recommend the specialist in that group. That’s why it is good to ask different doctors in different practices.

7) Beware of the reviews or ads on the internet. The internet is full of false accusations or glamorization of surgeons, and specific hospitals and departments. One urologist said that online reviews are totally unreliable. This is not “Angie’s List of plumbers.” Medical groups or individual physicians may have ulterior motives or “good urology friends” who may or may not be the best choice for you.

8) Don’t worry about offending the doctor with questions or by getting a second opinion. Don’t be rude or disrespectful but don’t feel intimidated either. Do your homework. It’s your prostate and your recovery and your life. You don’t want to be one of those men who say afterward “I wish I had listened to good advice; my surgical experience was not as good as I had hoped.”

The Trap of Discouragement

St. Mark's Church, Petersville, MD Photo BJ Gabrielsen
St. Mark’s Church, Petersville, MD
Photo BJ Gabrielsen

Do you ever feel as if you are stuck in discouragement? Do you feel that you are facing a condition (such as prostate cancer) alone and that God Himself and family or friends truly do not understand your situation? If so, you are not alone. In the Old Testament biblical book of the prophet Habakkuk, the prophet writes “how long O Lord, will I call for help and You will not hear? I cry out to you….,  yet You do not save.” (Habakkuk 1:2).

At some point, everyone experiences dashed hopes. Perhaps a PSA test did not produce the result you had hoped for or as in my own case, a cancer detected early and removed surgically returned (a biochemical recurrence) dashing hopes for a quick cure. Disappointment – an emotional response to a failed expectation – is the normal initial reaction. But allowed to linger, it can turn into discouragement, which hovers like a dense cloud. When that’s the case, there is no sense of joy or contentment regardless of what you do.

The circumstances that trigger these emotions may be unavoidable, but how we as men respond to them is a choice. Either we can let sadness overwhelm our soul or we can face the situation with courage and bring it before the One who can help.

Living in discouragement will divide the mind, making it hard to focus on anything besides our pain, apprehension and dashed hopes. Then as anger becomes habitual and desired results do not happen, we may blame ourselves or God Himself.

Frustration and disappointment that isn’t handled well may develop into despair, which in turn can estrange us from those around us who do not enjoy the company of someone who is bitter and defeated. Finally, in the fog of discouragement and isolation, we can make poor decisions, attitudes and actions based on crushed emotions and expectations instead of truth. Obviously, this self-destructive path is NOT God’s best for us.

Though we all face disappointment from time to time in many areas not just those that are health-related, those whose faith is in God and His Son Jesus are not to wallow in it. Instead, God wants us to trust Him with everything – even unmet expectations and deep sadness. Remember to us as God’s children, there is a divine purpose for everything He allows to touch our lives. As Romans 8:28 states, “and we know that God causes all things to work together for good” (even if we don’t see it at the time), to those who love God who are called according to His purpose.” For everything that was written in the past was written to teach us, so that through the endurance taught in the Scriptures and the encouragement they provide we might have hope”. (Romans 15:4).

If you cannot relate to these admonitions, or if you are unsure that you have a personal relationship with God and therefore cannot trust Him, you can know Him intimately. See the following link.

(A portion of the text above was excerpted from the July 11th, 2016 In Touch devotional written by Dr. Charles Stanley.)

Alcohol May Raise the Risk of Prostate Cancer

An analysis by Canadian and Australian scientists of 27 previous studies led them to conclude that there is a significant association between alcohol use and prostate cancer risk. The more men drink, the greater the risk. Even low levels of drinking (up to two drinks a day) were associated with an 8 to 23 percent higher risk of prostate cancer when compared to no drinking, the researchers said. However, they did not prove that drinking caused the prostate cancer risk to increase. Alcohol is a known risk factor for breast cancer and at least seven types of digestive system cancers, and alcohol may also increase the risk of cancers of the skin and pancreas, the researchers said.

Additional details can be found on the following linked article published November 16th in the U.S. National Library of Medicine’s Medline Plus. See also the following item from Prostate Cancer News Today, Nov. 21.

 

The Four Stages of Prostate Cancer

When you’re diagnosed with prostate cancer, the doctor will determine how far the disease has progressed and tell you what stage the cancer is in. The staging shows how the tumor has grown and if the cancer has spread to other parts of the body. It’s important to know this information so that patients can start the correct course of treatment.

Here are the four recognized stages of prostate cancer:

Stage 1 refers to an early-stage diagnosis of prostate cancer and means that the tumor is in just one-half or less of one side of the prostate. At this stage, the tumor cannot be picked up on any imaging machines and cannot be felt in a digital rectum exam. The cancer is still confined to the prostate and hasn’t spread to any other parts of the body. Stage 1 prostate cancer will have a Gleason score below six and a PSA score below 10.

Stage 2 prostate cancer is split into stage 2A and 2B. In stage 2A, the cancer will still be confined to one-half of one side of the prostate and won’t have spread. The Gleason score will be 7 or under, and the PSA score will be 20 or under. At this stage, it still won’t be picked up via imaging or a digital rectum exam.

Stage 2B prostate cancer can be felt with a digital rectum exam and is now able to be picked up with imaging techniques. The cancer has now spread to the other side of the prostate, but not to the lymph nodes or other parts of the body. It will have a Gleason score of 8 or higher and a PSA score of 20 or higher.

Stage 3 is when the cancer has spread from the prostate and could now be in the seminal vesicles, but the lymph nodes and other parts of the body remain unaffected. Both the Gleason score and the PSA score can be of any value at this point.

Stage 4 prostate cancer is where the cancer has spread into other tissues surrounding the prostate including the rectum, bladder, pelvic wall or the urethral sphincter. It may also have spread to the lymph nodes and other parts of the body. At this stage, the Gleason and PSA scores can be of any level.

The above was published online in the Nov. 17th Prostate Cancer News Today.

Two New DNA Cancer Vaccines in Phase 1 and Phase 2 Clinical Trials

Madison Vaccines Incorporated (MVI, see the linked news release), has begun a Phase 1 clinical trial for MVI-118 (pTVG-AR) in men with metastatic prostate cancer who are initiating androgen deprivation (hormonal) therapy (ADT). MVI-118 targets the human androgen receptor, the critical biological target responsible for driving prostate cancer progression and, in many cases, resistance to current therapies.  MVI-118 is intended to provide persistent activation of immune system CD8+ T-cells that target the androgen receptor, a key tumor cell protein that is frequently and highly overexpressed as resistance to ADT emerges. MVI-118 is being developed to prolong the duration of disease control gained from standard androgen deprivation therapies thus delaying resistance to ADT. The trial will be conducted at the University of Wisconsin – Madison Carbone Cancer Center and two additional Medical Centers including Rutgers Cancer Institute in New Jersey. For an overview see the link in the Nov. 7th Prostate Cancer News Today.

This is MVI’s second prostate cancer vaccine, along with MVI-816 (pTVG-HP), MVI’s lead vaccine that has demonstrated clinical evidence of safety, immune activation and biological signals (PSA changes) of activity. Both MVI-816 and MVI-118 are plasmid DNA vaccines that differ from other vaccines because they can be rapidly and inexpensively manufactured, can be administered by simple intradermal injection, and are relatively more stable in storage.

MVI’s lead vaccine, MVI-816, is in a Phase 2 clinical trials in patients with early biochemically recurrent prostate cancer intended to delay the onset of metastatic disease after primary therapy. MVI-816 is also in a second clinical trial in advanced metastatic, hormone-resistant cancer that began this past summer pairing it with an immunomodulatory PD-1 inhibitor which enhances the immune system’s activity against cancer cells but does not work alone in prostate cancer.  Final Phase 2 data on MVI-816, the lead vaccine, is expected in 2018. Both MVI-816 and MVI-118 are intended to address the anticipated surge in prostate cancers over the next two decades as “Baby Boomers” reach the age when men are most commonly diagnosed with the disease.

For MDI-118 clinical trial details concerning enrollment and other criteria, see the following link to the National Institutes of Health (NIH) ClinicalTrials.gov. Patients in the Phase 1 trial of MDI-118 must have metastatic prostate cancer (clinical stage D1 or D2 disease), with previously documented lymph node, soft tissue and/or bone metastases as evidenced by radiographic imaging (including CT (or MRI) of abdomen and pelvis and bone scans). Patients must have started androgen deprivation therapy at least one month (4 weeks) prior to enrollment and no more than six months (24 weeks) prior to enrollment. Patients must continue the androgen deprivation therapy throughout the study period, and patients are not permitted to change the type of androgen deprivation therapy  during the course of investigational therapy.

Hormonal (Testosterone Lowering) Therapy (ADT) Linked to Increased Dementia Risk for Prostate Cancer Patients.

It isn’t often that a research finding appears in 4-5 e mail or other  publications but such is the case herein.  Researchers at Stanford University School of Medicine published a study entitled “Association Between Androgen Deprivation Therapy and the Risk of Dementia” in the journal Journal of the American Medical Association Oncology. They reported that men treated with testosterone-lowering drugs for their prostate cancer are more than twice as likely to develop dementia as those not receiving such treatment, according to a study that reviewed the medical records of nearly 10,000 patients. But, the study only found an association between ADT and dementia risk, not cause and effect. The researchers advised however that men undergoing androgen therapy shouldn’t stop the treatment based on these findings because more studies are needed to verify this potential link.

Last year, the research team at  Stanford discovered that testosterone-lowering treatment was linked to a higher risk of developing Alzheimer’s disease. Since Alzheimer’s is commonly confused with vascular dementia, the team decided to explore if the association held true when including all types of dementia.

They identified medical records of 9,272 men with prostate cancer who had been treated between 1994 and 2003, of which 1,829 received testosterone-lowering treatment. To make sure results became as robust as possible, they first removed all patients who had dementia at prostate cancer diagnosis. Then, they matched treated and untreated patients with the same disease stages, to make sure the comparisons were valid.

The team discovered that within five years, 7.9 percent of those receiving testosterone-targeting treatment had developed dementia. Among patients not receiving such treatment, the number was 3.5 percent.

The risk is real and, depending on the prior dementia history of the patient alternative treatment treatment may be considered, particularly in light of a recent prospective study from the U.K., which showed that prostate cancer patients had the same chances of survival within a 10-year time frame, whether they received aggressive treatment or active monitoring. Only 1% of men died during the 10 years, suggesting that monitoring may be as good as treatment, without causing side effects.

According to an article in the Oct. 13th MedlinePlus published by the U.S. National Library of Medicine, one possible explanation is that androgens like testosterone are believed to be very important for neuron [brain cell] health. In the brain, the ability of neurons to repair themselves and not die off, those are at least partially regulated by androgens.  A very reasonable theory would be if you don’t have those androgens around to have that protective effect, you would be more susceptible to developing dementia.

Based on the findings, researchers argue it makes sense to identify those at risk for dementia before considering testosterone-lowering treatment. Researchers, however, underscored that the data are derived from medical records, and that prospective clinical trials ultimately are needed to remove any doubts that testosterone-lowering treatments may trigger cognitive decline.

The report above appeared in the October 18th Prostate Cancer News Today.

It was also cited in the following pdr.net article.

A slightly more extensive article for health professionals was published in the October 21st issue of Cancernetwork, home of the journal Oncology.

Monitoring, Not Treatment, May be Better for Very Low-Risk Prostate Cancer Patients

In a study published online on Oct. 20th in the Journal of the American Medical Association (JAMA) Oncology, more than 90 percent of men in Sweden who have very low-risk prostate cancer choose close monitoring rather than immediate treatment — and more American men should use that option, researchers say.

In a study of nearly 33,000 Swedish men with very low-risk (stage T1) prostate cancer diagnosed between 2009 and 2014, the number choosing what is called active surveillance increased from 57 percent to 91 percent during that time frame.

“For men who are diagnosed with low-risk prostate cancer, it is important to know that active surveillance is an accepted way to manage the cancer,” said lead researcher Dr. Stacy Loeb, an assistant professor in the departments of urology and population health at NYU Langone’s Perlmutter Cancer Center in New York City.

“There is no rush to get treatment — low-risk prostate cancer can be safely monitored,” she added. “Some men will eventually need treatment, but others will be able to preserve their quality of life for many years.”

In the United States, the majority of men with low-risk prostate cancer get treatment upfront, which can have side effects, such as urinary and erectile problems, Loeb said.

Active surveillance isn’t wait-and-see, she explained. It involves regular blood tests and regular biopsies to gauge the growth of the tumor. When the tumor grows to a point where treatment is needed, then it’s time for curative surgery or radiation.

A recent British trial showed that 10 years after diagnosis, the risk of dying from prostate cancer was the same whether men initially had surgery or radiation or opted for monitoring, Loeb added.

“We found that most men in Sweden with low-risk cancers are now opting for surveillance rather than upfront treatment,” Loeb said. “Hopefully, this study can increase awareness among patients in the U.S. and other countries that deferring treatment is an accepted option for low-risk prostate cancer.”

There is a lot of controversy about prostate cancer screening, Loeb noted. “Prostate cancer has no symptoms until it is advanced, so screening is actually very important to find life-threatening cancers in time for cure,” she said.

Patients with high-risk cancer do need treatment right away, and that treatment can be lifesaving, Loeb said. “However, many other men are diagnosed with low-risk cancers that have a very good prognosis without any treatment, and deferring upfront treatment can allow them to preserve their quality of life longer,” she said.

About 181,000 American men will be diagnosed with prostate cancer in 2016, and most of those will be in the earliest stages, according to the U.S. National Cancer Institute (NCI). Approximately 26,000 men will die from prostate cancer in 2016, the NCI estimates. The five-year survival rate for prostate cancer is nearly 99 percent, the NCI says.

“This [study] is more evidence of active surveillance becoming a standard of care,” said Dr. Matthew Cooperberg, an associate professor of urology, epidemiology and biostatistics at the University of California, San Francisco and author of an accompanying journal editorial.

Sweden has been far ahead of the United States in terms of active surveillance, but it is becoming more accepted here, Cooperberg said. About 40 percent to 50 percent of men with low-risk prostate cancer are choosing surveillance, “so we still have some catching up to do,” he said.

Adoption of active surveillance has been slow in the United States for several reasons, Cooperberg added. Among these are the financial and legal incentives to treat patients.

“In addition, culturally Americans have been uncomfortable with the idea of not treating cancer, because of the psychology that comes with the ‘C’ word,” he said. “But things are changing; it’s not such a foreign concept.”

Cooperberg said the future of active surveillance is refining it based on an individual’s cancer, so that tests and biopsies aren’t done on an arbitrary schedule, but on a schedule based on the characteristics of the patient’s tumor.

“Prostate cancer decision-making — from PSA testing on through treatment — really needs to be personalized,” he said.

As always, if this information pertains to your specific diagnosis, it should be discussed with your personal health care provider before taking any action. This report appeared in the October 20th issue of MedlinePlus, published online  by the National Institutes of Health U.S. National Library of Medicine. This information also was posted on-line by Prostate Cancer News Today on October 31st (see link).

Radiation Therapy Improves Survival Over Hormone Therapy (ADT) Alone in Metastatic Prostate Cancer

A large database analysis showed that the addition of external beam radiotherapy (RT) to androgen deprivation therapy (ADT) significantly improves overall survival (OS) in men with metastatic prostate cancer.

“As advances in systemic therapy for metastatic prostate cancer have improved OS and the control of metastatic disease, a greater interest has emerged in therapies to promote local control of the primary prostatic tumor,” wrote study authors led by Chad G. Rusthoven, MD, of the University of Colorado School of Medicine in Aurora. There is relatively limited data so far, though, on the use of external beam RT in these patients.

The study analyzed outcomes from 6,382 men diagnosed between 2004 and 2012 included in the National Cancer Data Base (NCDB), all of whom received ADT. Of these men, 538 (8.4%) also received prostate RT. The results of the analysis were published in the Journal of Clinical Oncology and linked herein.

Those who received RT were younger, had better comorbidity scores, lower prostate-specific antigen levels, and higher T stage, and were more likely to have n0 disease, to be treated at a community facility, and to have private insurance.

After a median follow-up of 5.1 years, the addition of RT was associated with a longer median OS of 53 months, compared with 29 months without RT. The 3-year OS rates were 62% with RT and 43% without RT; at 5 years, these rates were 49% and 25%, respectively, and at 8 years, the rates were 33% and 13% A subgroup analysis showed that the biggest benefit of RT was gained in patients with Gleason scores of 8 or below, and for T1–3 tumors compared with T4 tumors. Higher RT dose was also associated with better OS compared with lower doses.

The analysis has limitations inherent to retrospective cohort studies, including the possibility of selection biases and imbalances. The authors noted that performance status and extent of metastatic disease burden could not be controlled for, and the sites of metastatic spread were unavailable.

Still, they concluded, “In this large contemporary analysis, men receiving prostate RT plus ADT lived substantially longer than men treated with ADT alone. Randomized trials to evaluate the impact of local therapy for men with metastatic prostate cancer appear warranted and several trials are ongoing.”