26 May 2016

Prostate Cancer: Over 50% Of Men Choosing To Wait On Treatment

Beyond skin cancer, prostate cancer is the most common malignancy diagnosed in men, with more than 180,000 new cases every year. It also happens to have one of the most hopeful prognoses. In fact, there’s even a form of the disease, “clinically insignificant prostate cancer,” defined by the fact that it will not affect a patient’s health during their lifetime.

In increasing numbers, men have been deciding on a treatment option that doesn’t include surgery, radiation or chemotherapy. It’s called “active surveillance,” and many cancer specialists believe it’s the right choice for some patients. Other researchers have called active surveillance a potentially “tragic mistake,” especially for the younger men who may dread the side effects of treatment, like impotence, more than anyone else.

What Is The Prostate?

Prostate DiagramThe prostate is a gland, about the size of a walnut, found only in males. It’s right below the bladder, and directly in front of the rectum. Running through the center of the prostate is the urethra, a tube that leads from the bladder, past the seminal vesicles, which produce most of the fluid contained in sperm, and out through the penis.

Almost every man will eventually develop benign prostatic hyperplasia, an enlarged prostate gland. While the condition can be uncomfortable, squeezing down on the urethra, and make urination difficult, it does not lead to prostate cancer.

The prostate gland itself produces a milky white fluid that, during ejaculation, is secreted into the urethra. Prostatic fluid is alkaline, with a high PH level, unlike the walls of the vagina. Once surrounded by this alkaline fluid, sperm are better able to survive the acidic vaginal environment.

Nearly every prostate cancer begins here, in the organ’s glandular cells, the ones that actually produce prostatic fluid. As such, physicians classify most prostate cancers as adenocarcinomas, a broad category of cancers that begin in glands.

Delaying Treatment Might Be The Right Option – Or Not

Most prostate cancers grow slowly, the American Cancer Society reports.

In fact, prostate cancers are so slow to develop that many never metastasize, or spread to other organs, at all. Autopsy studies have found that a fairly high percentage of men, ones who died from completely unrelated conditions, also had prostate cancer, but the disease was never noticed because it never caused them any problems. That’s why many patients, after a prostate cancer diagnosis, choose “active surveillance,” rather than undergoing immediate treatments.

For some men, treatment is actually the worst idea. Daniel Pendick, former executive editor at Harvard Men’s Health Watch, says that recent medical evidence has shown that more-aggressive treatment plans for prostate cancer likely do more harm than good.

While it may be counter-intuitive, remember that many men live long, apparently disease-free lives, with prostate cancer. It’s one of the only malignancies with a 5-year survival rate of 100%. Longer-term survival rates are nearly just as optimistic. Only 5% of men diagnosed with prostate cancer will die after 15 years. Prostate cancer treatments, on the other hand, can leave men with urinary and erectile problems.

Grading On A Curve

Of course, not every prostate malignancy will be slow-growing. But it turns out that physicians can determine how aggressive a cancer is likely to be shortly after an initial diagnosis. In a 2013 paper, researchers at Harvard reviewed the Gleason grades of 1,207 prostate cancer patients diagnosed between 1982 to 2004.

Physicians routinely grade prostate cancer cells, after a biopsy or removal of the gland, using a diagnostic technique called the Gleason score. Basically, it’s a measure of how abnormal the cancer cells look, and researchers have long known that more abnormal cancer cells pose a higher likelihood of developing aggressively and becoming lethal. But what they didn’t know is whether or not prostate cancer cells could become more or less aggressive over time.

The Harvard team found that Gleason scores, for the vast majority of patients, remain stable. Prostate cancers don’t suddenly, or progressively, become aggressive. In the words of study co-author Marc B. Garnick, MD, prostate “cancer is born with a particular Gleason score.” That means men with low Gleason scores should feel more confident in their choice of “watchful waiting,” since there’s a very low possibility of the cancer becoming lethal. Cancers with high Gleason scores, Garnick says, “are also born that way and will behave aggressively.”

Active Surveillance Can Be A “Tragic Mistake”

Around half of all the men diagnosed with prostate cancers have low-risk tumors, with Gleason scores of 6 or below. With or without treatment, their chances of survival remain the same, at around 99% over the course of ten years.

Active surveillance is becoming an increasingly common choice among men diagnosed with early-stage prostate cancers. Just five years ago, according to the New York Times, nearly all of these patients would have opted for treatment, either surgery or radiation therapy. But today, between 40% and 50% of prostate cancer patients with early-stage forms of the disease are choosing to hold off. New data collected by the American Urological Association suggests that even more men are deciding on active surveillance in 2016.

Instead of undergoing surgery or radiation, these patients work closely with their doctors to monitor the onset of symptoms, receiving blood tests and rectal exams around twice a year. Biopsies are often performed annually, although an even less “active” form of monitoring, termed “watchful waiting,” cuts down on testing and relies primarily on the observation of symptoms.

This trend has some researchers worried. Active surveillance, Dr. William Catalona says, might be the right option for men who are diagnosed at an advanced age, especially those who can expect to live only another 10 or 15 years. But for younger patients, taking a course of watchfulness, rather than chemotherapy, may be “a tragic mistake.” Prostate cancers can become more aggressive, even though the progression seems to be rare, and Catalona fears that some young men may learn only too late that their tumors have begun to spread. But it’s these very patients who may fear the side effects of prostate cancer treatments, like incontinence and impotence, the most. It’s a Catch-22, with significant risks on both sides of the equation.

Do Doctors Really Misdiagnose Prostate Cancer 50% Of The Time?

In the case of prostate cancer, misdiagnosis isn’t usually a problem of overlooking the disease entirely, or diagnosing patients with a condition that causes similar symptoms. Instead, the majority of misdiagnoses appear to be issues that crop up during the grading of a tumor’s severity.

In the world of prostate cancer diagnosis, it’s all about Gleason scores. Recent studies suggest that many pathologists get this scoring wrong.

In their 2008 study, tellingly titled “Identification of pathologically insignificant prostate cancer is not accurate in unscreened men,” researchers at the University of Cambridge tried out a deceptively-simple experiment. First, they used a traditional method of biopsy to extract a portion of prostate tumor for grading. Then, after 415 of the men involved had opted to undergo a radical prostatectomy, the doctors reevaluated their cancer cells on the Gleason scale.

Prostate Adenocarcinoma

Prostate adenocarcinoma. Copyright © 2010 Michael Bonert. Permission is granted to copy, distribute and/or modify this image under the terms of the GNU Free Documentation License Version 1.2 or any later version published by the Free Software Foundation.

Over 50% of the initial diagnoses were found to be incorrect. Invariably, the patients who had been incorrectly scored the first time around were told that their tumors were less aggressive than the second grading indicated. In almost one-third of those patients, the cancer had spread beyond the prostate gland. After highlighting these glaring inaccuracies, lead author Greg Shaw told the BBC that around 30% of men who opted for active surveillance would eventually require “radical treatment” within five years.

Diagnosing Prostate Cancer: The Pathologist’s Hardest Challenge

Since 2008, doctors have made some progress in their diagnostic methods. The researchers at Cambridge made their initial diagnoses based on needle biopsies, using ultrasound images to guide the needle. It’s a technique that’s been compared to “educated guessing.” Today, patients usually undergo an MRI before a biopsy is conducted, so pathologists can more accurately locate a tumor, and urologists can more accurately position their needle.

But diagnosing prostate cancer, even in the estimation of the world’s best urologic pathologists, is still ludicrously difficult. That’s what Jonathan Epstein, a pathologist at Johns Hopkins and likely the world’s foremost researcher on prostate cancer, thinks.

Consider first the size of the prostate gland. We compared it to a walnut earlier. Epstein uses a large strawberry as an example, but you get the point. It’s small. The average cancerous prostate is studded by around 7 different tumors, but these patches of cells are about the size of a strawberry’s seed. Obviously, finding one of these tumors in the first place is hard. Accurately piercing one with a needle is even harder.

Once the cells are on the slide, Epstein says, the pathologist’s work becomes even more difficult. Prostate cancer cells are “often maddeningly ambiguous,” a problem for many hospital pathologists who usually don’t have a special expertise in working with the disease. One biopsy sample is likely to present “a jumble of cells,” Epstein told an editor at the James Buchanan Brady Urological Institute, “run[ning] the gamut from the almost ordinary-looking to cells that are so poorly differentiated and obviously diseased that they could never be considered normal.” Even worse, some prostate cancer cells mimic benign prostate conditions, even under the microscope. Epstein says he’s found that pathologists are “just as likely” to diagnose cancer in samples where the disease is not present, as they are to miss a case of cancer sitting right in front of them.

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