On the surface, being on active surveillance (AS) for prostate cancer appears to be a care-free walk in the park as one avoids radical prostatectomy, radiation, and other therapies with serious side effects.
But in reality, AS patients, typically low-risk with Gleason 3+3 scores, find plenty to fuss over: Is AS safe? Will my cancer become more aggressive? Will I experience a serious infection or other problem from needle biopsies? What interval should I follow between biopsies?
And now a new risk is starting to worry men on AS: Deposits of the rare-earth metal gadolinium present in small quantities in the IV contrast used with magnetic resonance imaging to monitor prostate cancer, stage the disease, and serve as a beacon to guide biopsies. There are emerging concerns about whether gadolinium (Gd) is a risk for patients because the residues of the metal are known to deposit in the brain, bones, and vital organs.
Men on AS represent only a small portion of the many patients who undergo MRI with contrast, for other cancers, multiple sclerosis, etc. Just as multiparametric MRIs with contrast were seeming to find a strong role in targeted biopsies, questions are being raised about the safety of the contrast agents some radiologists feel are needed to enhance MRI images. Some patients worry that Gd deposits might cause Alzheimer's, though leading radiologists say there is no proof of that.
Emanuel Kanal, MD, a neuroradiologist and director of magnetic resonance services at the University of Pittsburgh, said there has been a special concern about the safety of gadolinium-based contrast agents (GBCAs) for MRI, especially for patients with kidney disease, since 2006 when a connection was first identified between the administration of at least some of the FDA-approved GBCA to patients with poor kidney function and the rare development in some of them of a serious disease, nephrogenic systemic fibrosis.
Questions about the safety of gadolinium are inevitably raised at a course he teaches several times a year on MRI safety, Kanal said, noting that radiologists, the pharmaceutical industry, hospital administrators, nurses, and technologists are well aware of the various safety concerns. A few physicians and some patients have been using the term gadolinium deposition disease (GDD) to describe possible side effects from GBCAs.
Risky or not?
Kanal maintained it is premature to use this term. "We have no reproducible, reliable, accepted definitions of symptoms for this disease that are not associated with other things. The subjective nature of what they're calling a disease is massive. This is not in the slightest something that has been accepted by everyone in medicine or radiology," he said.
Clare Tempany-Afdhal, MB, vice-chair of radiology research at Brigham and Women's Hospital in Boston and an expert on prostate imaging, pointed to "a lot of concerns going on in the news and less so in the scientific literature on the safety of gadolinium."
She said the issue centers mainly around some reports that demonstrated small amounts of Gd were detected in autopsies of the brains of patients who died from unrelated causes who had been given Gd contrast for MRI scans.
"The simple pragmatic approach to this has been that this gadolinium detection is actually not surprising, and it is probable that gadolinium leaks out of the blood into all the organs of our bodies after it's injected. In the majority of people, this seems to happen without untoward effects," she said. "We have not been able to demonstrate any evidence of brain disease or brain symptoms or cognitive disorders or other neurological disorders that relate directly to the presence of gadolinium deposition in the brain."
Still, the ears of product liability attorneys are always perked up for new opportunities. Some have latched onto GDD and have been advertising to locate candidates for class-action suits against the manufacturers.
Martial artist and actor Chuck Norris and his wife Gena put GDD on the map when they filed a $10-million suit in state court in San Francisco in November 2017 against several manufacturers of the agents. They alleged that Gena Norris had been poisoned by the contrast agents in several MRIs she underwent to evaluate her arthritis. She blamed GBCAs for "multiple, debilitating bouts of pain and burning."
A month after the suit was filed, the FDA issued a warning about GBCA but also offered some reassurance about the contrast agents.
The FDA said: "Gadolinium retention has not been directly linked to adverse health effects in patients with normal kidney function, and we have concluded that the benefit of all approved GBCAs continues to outweigh any potential risks."
"However, after additional review and consultation with the Medical Imaging Drugs Advisory Committee, we are requiring several actions to alert health care professionals and patients about gadolinium retention after an MRI using a GBCA, and actions that can help minimize problems. These include requiring a new patient Medication Guide, providing educational information that every patient will be asked to read before receiving a GBCA."
Push comes to shove
I know from talking with other men on AS for prostate cancer that many are anxious about gadolinium-based contrast agents. Some are addressing the subject with their urologists and oncologists. One urologist told me that his patients need to undergo the tests with contrast and biopsies to be surveilled properly, so these are necessary risks. Meanwhile, an underground of prostate cancer patients on AS has been growing.
Some patients have described the pushback they are getting from physicians who do not take the potential Gd threat seriously.
Mark Lichty, 70, an entrepreneur from Pennsylvania's Pocono Mountains who has been on AS since 2005, said his urologist "fired" him when he kept asking questions about the gadolinium contrast agents after a multiparametric MRI was recommended to him for a kidney problem. He said his health network told him it was its policy to use Gd contrast. Lichty fought back.
"It was a struggle to be listened to," said Lichty, co-founder and chairman of Active Surveillance Patients International and co-host of a new online virtual support group sponsored by his organization along with Answer Cancer Foundation and Us TOO.
Lichty said he prefers to follow the precautionary principle which guided him to refuse a radical prostatectomy 15 years ago, and to stop undergoing biopsies 13 yrs ago. "Going against the medical consensus has been extremely difficult but has served me well," he said.
Martin Gewirtz, 63, a New York City-based business consultant, went on AS in 2018. He heard about the gadolinium issue from a closed Facebook support group. He broached the issue recently with his urologist at a New York area hospital, saying he didn't want Gd. He got attitude in return.
"He basically dismissed what's been negatively said about gadolinium and added that it will ultimately affect my reading," Gewirtz said.
The urologist told him that without contrast the radiologist may not be able to detect areas that required further testing.
An administrator of at least one closed support group suggests that men can avoid gadolinium by claiming they have allergies.
When to say no
But there is another way to get an MRI without an agent. The answer may be simple for many men like us with low-risk Gleason 6 prostate disease and is just to say no.
Tempany-Afdhal noted in a phone interview that MRIs with contrast are not very good at finding Gleason 6 disease and their sweet spot is finding riskier Gleason 3+4.
Her take is that all these AS patients should have an MRI with contrast for a baseline. If a follow-up MRI is suggested for a patient with Gleason 6, she said: "Gadolinium could be avoided if the patient is concerned and the doctor and the patient talk about it. They should proceed with the MRI scan, but leave out the gadolinium part."
"If someone's coming in with the biopsy-proven prostate cancer Gleason 3+4, they're coming in for disease characterization and staging. They do need an MRI with gadolinium, in my opinion."
Along the same lines, Hedvig Hricak, MD, chair of radiology and an expert on genitourinary imaging at Memorial Sloan Kettering Cancer Center in New York, told me in an email that her program since 2015 stopped using gadolinium for prostate cancer detection/diagnosis or diagnosis unless the MR image is degraded by artifacts caused by adjacent metal, such as hip prostheses. "There is ample evidence that for an experienced reader, contrast very rarely helps and does not justify the patient discomfort, potential side effects and costs," she said.
There are some new options to make prostate images sans Gd. There is a high-rez ultrasound device researchers originally used to image prostate glands in mice. I plan to write more on this technology in an upcoming column.
And Tempany-Afdhal added that the so-called bi-parametric approach, an MRI-guided biopsy, which she uses, is another option to avoid gadolinium exposure.
Personally, as an active surveillance patient, diagnosed with a Gleason 3+3 in 2010, who has undergone too many (five) biopsies and two MRIs with GBCAs, I plan to avoid, if possible, gadolinium-based contrast, MRIs, and needle biopsies unless there is a drastic change in my prostate-specific antigen scores. Less is more.
Gewirtz went through a thorough process of weighing his options before finally deciding he will look for a new urologist at MSKCC or elsewhere to order scans from a radiologist who tries to avoid gadolinium and is confident he or she can get a good reading without contrast.
For his part, Lichty finally persuaded his medical group at Lehigh Valley Health Network to perform a gadolinium-free multiparametric MRI. The radiologist obtained good prostate images without Gd.
And, Lichty said, "the urologist rehired me as a patient."
Howard Wolinsky is a medical journalist based in the Chicago area. He has been blogging for 51˶ about his experiences with active surveillance since February 2016. Read more of his posts here.