A screening tool that lacks precision. Totally unnecessary treatment. Poor prognostic tools.
Men certainly draw the short straw when it comes to prostate cancer.
With 174,650 American men expected to receive a prostate cancer diagnosis in 2019, urgently needed are better methods of early detection, more reliable ways to predict an individual’s likely outcome, and improved treatments.
So, some good news: new developments are in the works, and some are already available. Details below. . .
The most important development in a century
Prostate cancer is not considered confirmed until the man has a biopsy, a procedure in which small samples of tissue are cut out and examined in a lab.
By all accounts it’s a nasty, uncomfortable procedure that can cause bleeding and pain in the days following. It also risks hospitalization due to infection. In addition to these downsides, three out of ten biopsies result in a false negative.
“False negative” means the test shows you’re cancer-free – when in fact you’re not.
Appalling, but even after submitting to this invasive, damaging procedure the diagnosis may be wrong.
What’s involved
In the standard transrectal ultrasonography-guided biopsy of the prostate, the doctor takes ten to twelve random samples (cores) from the organ. But this approach under-detects clinically significant cancers that need treatment, and over-detects low grade cancers that don't need to be treated.
So researchers are exploring a new method to see whether a biopsy is required at all, and if so, to take cores from suspicious tissue only. It's called multiparametric magnetic resonance imaging (MRI) -- cutting edge technology that can produce a detailed image of the prostate.
In a major study published in the New England Journal of Medicine last year, 500 men at 25 centers in 11 countries were randomized to receive either an MRI-targeted biopsy or a standard biopsy.
The former detected 46 percent more clinically significant, and 59 percent less clinically insignificant cancers than the latter, and it did so with far fewer biopsy cores, meaning less potential for harm.
71 of 252 men (28%) had MRI results that suggested there was no prostate cancer, so those patients didn't undergo a biopsy.1
Veeru Kasivisvanathan, the first author of the large research team, said, "This is the first trial in which men who have a negative MRI have had a chance to avoid biopsy altogether."
High hopes for the new approach
Another member of the team was consultant urologist Mark Emberton, Professor of Interventional Oncology at University College London. He has spent ten years investigating the new technology and is very enthusiastic about it:
"MRI for all men prior to biopsy of the prostate is the most important development in the management of men with early prostate cancer that we have had in the last 100 years."
Declan Murphy, director of genitourinary oncology at the Peter MacCallum Cancer Center in Melbourne, Australia, who was not involved with the study, was also upbeat about the findings. In his view, "This is an incredibly important, practice-changing study, and we need to fast-forward MRI to the diagnostic pathway prior to biopsy."
The UK's National Institute for Health and Care Excellence (NICE) was so impressed by the research, last December they recommended all men at risk of prostate cancer receive an MRI scan ahead of a biopsy. This will now be introduced across Britain's National Health Service.
Make an informed decision
Prostate cancer is usually diagnosed later in life, and in most cases progresses so slowly that, as doctors admit, more men die with prostate cancer than from it. But in a minority of cases – about one out of ten, from what I can learn -- prostate cancer can be aggressive and life-threatening.
Technology hasn’t advanced enough to make accurate predictions about which tumors will grow quickly and spread beyond the prostate, and which ones will develop slowly and remain confined.
This makes it difficult for the patient to know whether or not to opt for the conventional treatments – surgery, radiation and chemotherapy.
A study published in the New England Journal of Medicine in 2016 found those whose cancer was confined to the prostate and who were categorized as low or medium risk did not reap any benefit from surgery or radiotherapy over the following ten years compared to patients who refused these treatments and opted for “watchful waiting.” Men in both groups had equal chance of survival.2
And obviously, the untreated men avoided the horrible side effects of the conventional treatments.
New way to predict if prostate cancer is dangerous
To help both clinicians and patients decide whether to closely monitor tumors or to opt for treatment, an evidence-base web tool called PREDICT Prostate, created by researchers at Cambridge University, England, was launched in March.
Taking all diagnostic tests, age, and medical history into account, the tool provides an estimate for ten- to 15-year survival. It also takes the likelihood of treatment success and the risk of side effects into account, and provides a survival estimate based on each of the chosen options.
The tool was developed using a high-quality database of 10,000 UK men, and validated in 2,500 cancer patients in Singapore. The approach was 90% accurate at predicting the chances of dying.3,4
According to Vincent Gnanapragasam, a consultant urologist at the University of Cambridge, "When men are diagnosed with prostate cancer and are deciding what to do they are often given wishy-washy advice which hugely depends on who they have spoken to. Our work puts a number on it to help guide those decisions.
"I would say 30 percent or more of men diagnosed with prostate cancer may not benefit from treatment, based on our models. When men see their absolute risk of dying is quite low, they find it easier to decide to just monitor their cancer rather than choosing treatment."
Commenting on PREDICT Prostate, Dr. Iain Frame of Prostate Cancer UK said, "Too many men undergo radical treatments for prostate cancer -- and in some cases endure life-changing side effects -- for a cancer that may never cause them harm. A tool like this has tremendous potential."
The tool is available at https://prostate.predict.nhs.uk
A liquid biopsy
Another option now available is a simple, non-invasive urine test for men over 50 who have a PSA reading between 2–10 ng/ml. It's called ExoDx Prostate(IntelliScore) or EPI.
The test measures three important genomic RNA bio-markers that are only expressed in high-grade prostate cancer.
It provides a score which corresponds to the Gleason Score, another and more common test for gauging the seriousness of a prostate cancer. EPI grades the aggressiveness of cancer in biopsied tissue, and helps both the doctor and patient decide whether a biopsy is needed.
It's been clinically validated in over a thousand patients in two large trials involving leading experts.
The authors of the most recent study, published in December 2018, wrote that EPI "improves identification of patients with higher grade disease and would reduce the total number of unnecessary biopsies."5
All the patient needs is an order from his physician and a urine collection device. Further information is available at https://epi.exosomedx.com
Reducing side effects
One of the most common prostate cancer treatments involves directing high-energy X-ray beams at the prostate from outside the body. In a series of treatments it kills cancer cells or slows their growth, but it's hard to prevent damage to the prostate’s healthy tissues.
The result is unpleasant side effects -- and the potential to grow secondary tumors in the bladder or bowel.
But a new procedure greatly reduces the risks. It's a firm but pliable hydrogel made from a type of flexible plastic called polyethylene glycol. The product is named Space OAR (space for organs at risk).
It's injected as a liquid into the perineum - the gap between the anus and scrotum - until it reaches the small space between the prostate and the rectum.
Here it spreads over a distance of about an inch, and quickly solidifies into a soft gel to magnify the width tenfold to four-tenths of an inch. This creates a protective barrier between the prostate and the rectum.
The procedure takes place about a month before radiotherapy is scheduled. After six months the gel breaks down into tiny molecules and passes out of the body.
Clinical trials have shown it to be safe and effective, lowering the radiation dose to the rectum by nearly three-quarters (73.5 percent), and thereby reducing rectal and urinary complications. After 3 years, retained sexual function was 78 percent more likely to occur in Space OAR patients compared to controls.6
In the control group, a clinically significant decline of these three quality of life factors (bowel, urinary, sexual) was eight times higher than among the Space OAR group.
The procedure was cleared by the FDA several years ago and is currently being used in many leading cancer centers throughout the United States.
Victor Tomlinson, MD, radiation oncologist at AnMed Health Medical Center in Anderson, South Carolina said the new procedure has "really changed the game in prostate cancer care. We've had great success with this product and it's worked every time we've used it."
Douglas Brown, MD, radiation oncologist at Cowell Family Cancer Center in Traverse City, Michigan, was equally positive, saying "the results are phenomenal. This is a real game-changer for patients. It essentially eliminates one of the most feared toxicities of radiation, and that's injury to the rectum."
Targeted treatment
X-rays targeted at the prostate from outside the body damage healthy tissue because they release energy both before and after they hit their target.
Proton beams however, release the bulk of their energy only when they hit the prostate gland. The protons themselves are subatomic, positively-charged particles. Five trillion of them are fired every second after being 'accelerated' to two-thirds the speed of light.
A small dose is delivered along the way to the prostate but virtually none beyond it. This allows more radiation to be delivered with little damage to normal tissues.
It has even more advantages.
It can be delivered with laser-like precision. Intensity of radiation can be varied at any point within the tumor, and involves little or no recovery time or impact on energy levels. Patients are able to work, exercise and remain sexually active both during and after treatment.
In spite of all these benefits, researchers from Harvard in a recently published review found clinical trials to date do not point to any clear advantages for proton beam therapy over conventional photon-based radiotherapy.7
However, as they also pointed out, this is fast moving technology and we need to await the results of trials currently in progress before we can make a final judgment.
Yet many doctors who carry out the procedure are already convinced it's a step forward over conventional radiotherapy. One of these is radiation oncologist Edward Soffen, MD from Princeton Radiation Oncology, New Jersey.
He calls proton therapy "one of the most advanced, sophisticated ways of treating patients with radiation. The patients who go through this form of treatment have significantly fewer side effects and they also demonstrate fewer long term issues."
There are currently only 26 operational treatment centers in the US. They can be found at https://www.proton-therapy.org/map
Best regards,
Lee Euler,
Publisher
References:
- https://www.nejm.org/doi/full/10.1056/NEJMoa1801993
- https://www.nejm.org/doi/full/10.1056/NEJMoa1606220
- https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002758
- https://www.cam.ac.uk/research/news/evidence-based-web-tool-aims-to-better-inform-and-refine-need-for-treatment-in-early-prostate-cancer
- https://www.europeanurology.com/article/S0302-2838(18)30604-3/fulltext
- https://www.spaceoar.com
- https://www.ncbi.nlm.nih.gov/pubmed/30967625
