Prostate Cancer And The Waiting Game - MedPage Today
When I was diagnosed with low-risk (Gleason 3+3) prostate cancer in December 2010, I had few choices.
The first was to treat the disease with a radical prostatectomy (recommended by my first urologist) or radiation. Nine years ago, maybe 94% of men like me opted for what was viewed as a "cure." Of course, what you often got in exchange were major lifestyle disruptions: incontinence and impotence, plus a risk of sepsis and even death.
The urologist saw it this way on a Tuesday that December: Bad news, you have cancer. Good news, I have an opening in the OR next Tuesday.
I didn't see it that way.
I went for a second-opinion the next day. The University of Chicago urologist said, "Surgery?" Bad idea. Instead, he proposed active surveillance (AS). Monitor the slow-growing disease and intervene if things became aggressive.
He said that I was the "poster child" for AS. He said I'd likely be in the same condition ten years hence. I drank the Kool-Aid on AS based on some Canadian research.
In the intervening years, it has been interesting to watch AS evolve.
I initially underwent PSA tests and digital rectal exams every three months and later every six months.
What is shocking is that in the beginning I underwent annual random biopsies. I felt like a pincushion. I had five biopsies in nine years. Three were clustered in the first year on AS.
Unlike many men, I don't find needle biopsies particularly painful. The doctor anesthetizes my prostate. Pain or no pain, I'd like to avoid these biopsies because they do carry risks.
Men today seem better informed than I was nearly a decade ago about the risks with AS. I find that many men today fear risks from biopsies, including infections, such as sepsis, and surgical misadventures, such as bowel damage.
MRIs? I used to think they were going to replace biopsies. And some urologists use them, along with PSA testing, to surveil prostate cancer and avoid biopsies. I've had only two MRIs: one in 2016 showed no lesions and the other from 2011 showed two, at least one of which I believe now was an artifact.
Fewer biopsies, for some
AS has evolved. Now there are fusion biopsies in which men on AS undergo MRIs to find suspicious lesions and then undergo targeted biopsies.
And the interval between biopsies has increased. I heard from a pioneer in the field that he now spaces out biopsies by 4-5 years. But there is no consensus on the interval between biopsies. Some get biopsies every two days.
It will soon be four years since my last MRI and biopsy. Several experts have advised me to stop biopsies altogether – though not my personal urologist.
Active surveillance, above all, is a waiting game.
For roughly one-third of the patients, it is more like "anxious surveillance"; they drop out of AS because they find they can't handle the uncertainties of living with cancer. Spouses and friends may be urging them to be "safe" and excise the cancer. One-third drop out because surveillance has shown they have more advanced cancers requiring intervention. The remaining third go on to live out their lives and die from something other than prostate cancer.
Active surveillance is a waiting game with a difference.
Men on active surveillance for low-risk or intermediate-risk (Gleason 3+4) disease aren't just waiting for their cancers to advance so they can undergo treatment. Patients may forget that AS can buy us time as new strategies and new technologies emerge.
These days 30%-50% of men newly diagnosed with low-risk prostate cancer opt for AS. That's way up from the 6% in 2010, but pales before the nearly 90% who do so in Sweden. Many Americans still buy into the idea that they need to remove prostate cancer no matter the cost, even if it is a slow-growing and non-threatening tumor, rather than learning to co-exist with this often benign cancer.
In the United States, more than 40,000 men a year are diagnosed with low-risk prostate cancer and go on AS. A similar number still opt for surgery or radiation rather than roll the dice with AS of a slow-growing disease.
New approaches
The latter group should be aware that postponing treatment may pay off for them, but they'll never know if they rush in to see the surgeon or radiation therapist.
There are a couple of new approaches to low-risk that have been in the news recently, which demonstrate the potential value of waiting.
This month, Steve Raman, MD, of UCLA, reported at the Radiological Society of North America meeting in Chicago on a promising new minimally invasive MRI-guided procedure that uses therapeutic ultrasound to treat low-risk prostate cancer.
The new research involves the MRI-guided transurethral ultrasound ablation (TULSA) system made by Toronto-based Profound Medical, which was tested on 115 men.
Raman reported that clinically significant cancer was eliminated in 80% of the men. Also, 65% had no evidence of any cancer at biopsy one-year after the treatment. These patients had low rates of impotence, and in most cases, they avoided urinary and fecal incontinence.
New options for AS patients would seem to be welcome. But Bert Vorstman, MD, a urologist from Coral Springs, Florida, and a long-time critic of the "prostate cancer industry," is skeptical.
"There is no prostate cancer treatment, radical or focal, that has objective evidence for safety and benefits," he said, "because none has been undertaken with men stratified according to validated Gleason grade/score and tumor volume or taken out for enough years, such as 25-30 years."
Could Provenge be part of AS?
In late October, Dendreon Pharmaceuticals announced research had just begun on a radically new approach for men with low-risk disease -- the immunotherapy sipuleucel-T (Provenge) currently approved for advanced prostate cancer. This is a personalized treatment that works by programming the patient's immune system to seek out cancer and attack it as if it were foreign cells.
More than 30,000 men have been prescribed Provenge since the FDA approved it in 2010. It has been shown to extend the lives of certain patients with advanced prostate cancer.
But what about those of us on AS?
Dendreon is about to find out with its new ProVent study, which is evaluating whether sipuleucel-T reduces disease progression in newly diagnosed patients with low-risk disease who are placed on an AS protocol with transrectal biopsies. The study finished enrollment in October with more than 450 patients. Two-thirds will get three infusions of sipuleucel-T. The remaining men receive placebo. Participants will be followed for three years.
Bruce Brown, MD, chief medical officer at Dendreon, told me he's optimistic about the possibility that sipuleucel-T could provide a potential alternative to choosing a treatment that can negatively impact quality of life.
"As is typical in oncology drug development, we started with the most advanced stage because that's where the need is, and that's where the patients have the most to gain," he said.
However, data from two earlier studies in non-metastatic disease provide a strong rationale for evaluating the use of sipuleucel-T in men on AS. So the AS patients are the new research target.
Brown said, "If fewer of those men progress on their biopsy, we can keep them on active surveillance longer, maybe even keep them on active surveillance long-term. And the benefit of that would be they avoid having radiation or surgery, which has profound side effects.
"If we can maintain men on active surveillance longer by treating them with sipuleucel-T, I think that will be a big win. And our drug is generally well tolerated, and doesn't cause the types of side effects one may experience with radiation or surgery."
Like many new immunotherapies, Provenge has a steep cost, $130,000 for three infusions, Provenge will be scrutinized carefully before it will be unleashed commercially.
Laurence Klotz, MD, the University of Toronto urologist who pioneered AS in 1997, thinks cost may hold back Provenge. "Doesn't make sense given the economics. Cost per life year saved would be millions, possibly billions," said Klotz, who is not involved in the study. He noted that Provenge has not been approved for advanced prostate cancer in Canada.
A Dendreon spokeswoman responded, "When [Klotz] says it doesn't make sense given the economics, is he comparing it to a) an AS patient that would otherwise receive no treatment? or b) to a patient undergoing treatment? In the second instance, Provenge is actually less expensive than an oral like enzalutamide."
My friends on AS are divided on Provenge. One, another medical writer who covered the drug industry, and who is newly diagnosed with Gleason 6, feels immunotherapy has a safe profile and could be a great option for him. Side effects generally are mild: chills, fatigue, fever, back pain, nausea, joint ache, body aches, and headache. Things are more complicated for men who have undergone transplants.
But Martin Gerwitz, who has been an AS patient for the past year and a half, relies on a plant-based diet to stave off progression and is skeptical of any drugs because of potential side effects. "Provenge is overkill for AS. Everyone wants to pop a magic pill instead of leading a healthy lifestyle -- food, exercise, getting rid of toxic products," he said.
Prostate cancer is a risk for all men: 60% of men aged 60 have prostate cancer cells, 70% have it at age 70, etc.
Could all men benefit from immunotherapy? Potentially. Will all men be allowed to get the treatment without waiting for signs of prostate cancer progressing? That's me, not the manufacturer, asking.
I think there is a clear target if Provenge is safe and effective for AS -- the one-third plagued with anxiety and unwilling to wait any longer. They potentially could avoid radical prostatectomies and radiation.
In any case, the outlook for men on active surveillance for low-risk and intermediate-risk prostate cancer is looking up from where they were in 2010 when I was diagnosed. The waiting game is paying off for many of us; maybe more will benefit in the short-term.
Howard Wolinsky is a medical journalist based in the Chicago area. He has been blogging for MedPage Today about his experiences with active surveillance for low-risk prostate cancer since February 2016. Read more of his posts here.
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