Daniel Pendick

Prostate cancer lives as it is born: slow-growing and benign or fast-growing and dangerous

This year, more than 238,000 American men will be diagnosed with prostate cancer. In most cases, the cancer consists of small knots of abnormal cells growing slowly in the walnut-sized prostate gland. In many men, the cancer cells grow so slowly that they never break free of the gland, spread to distant sites, and pose a serious risk to health and longevity.

Evidence is growing that early treatment with surgery or radiation prevents relatively few men from ultimately dying from prostate cancer, while leaving many with urinary or erectile problems and other side effects. As a result, more men may be willing to consider a strategy called active surveillance, in which doctors monitor low-risk cancers closely and consider treatment only when the disease appears to make threatening moves toward growing and spreading.

This week, a study by Harvard researchers found that the aggressiveness of prostate cancer at diagnosis appears to remain stable over time for most men. If that’s true, then prompt treatment can be reserved for the cancers most likely to pose a threat, whereas men can reasonably choose to watch and wait in other cases.

“If you have chosen active surveillance, then this could possibly make you feel more confident in your decision,” says Kathryn L. Penney, Sc.D., instructor in medicine at Harvard Medical School and the lead author of a report published today in the journal Cancer Research.

Cancer lethality set early

The study looked for changes in cancer aggressiveness in men diagnosed with prostate cancer from 1982 to 2004. All of the men had their prostates removed after diagnosis, and biopsy samples were taken from the glands. The Harvard team reexamined the samples and graded them using a tool called the Gleason score, which assigns a number from 2 to 10 based on how abnormal the cells look under a microscope. High-scoring or “high-grade cancers” tend to be the most lethal.

Over the study period, fewer and fewer men were diagnosed with advanced, late-stage prostate cancers that had spread beyond the prostate gland. This reflected the growing use of prostate-specific antigen (PSA) testing to diagnose prostate cancers earlier and earlier. In contrast, the proportion of high-grade cancers, as measured by the Gleason score, remained relatively stable rather than gradually becoming more aggressive. Previous studies have seen a similar pattern.

“It’s a very interesting study that confirms what previous studies have found,” says Dr. Marc B. Garnick, a prostate cancer specialist at Harvard-affiliated Beth Israel Deaconess Medical Center who was not involved in the study. “There may be rare exceptions, but in the vast majority the cancer is born with a particular Gleason score.”

That means most prostate cancers that look to be slow growing at diagnosis could stay that way long enough that the man is likely to die from another cause before the cancer spreads beyond the prostate. “The ones that are low-grade and indolent are unlikely to cause problems in a man’s lifetime,” says Dr. Garnick, editor of the Annual Report on Prostate Diseases, from Harvard Medical School. On the other hand, he adds, most high-grade prostate cancers are also born that way and will behave aggressively.

Gleason grade is one of the best predictors of prostate cancer death. “Men with low-grade disease are much less likely to die from prostate cancer than men with high-grade cancers,” says Penney. She cautions, though, that the study looked at men as a group, and in this population the Gleason grade appeared to be fairly stable. “You might see progression in an individual, but we think that it’s uncommon,” she says. “We just can’t rule out this possibility in our study.”

How active surveillance works

The Gleason score is just one way that doctors monitor prostate cancer during active surveillance. They also do periodic follow-up biopsies and measure PSA levels, which may rise if cancer starts to spread in the prostate. Doctors may recommend treatment sooner if PSA begins to rise quickly or if a follow up biopsy reveals a higher Gleason score or more widespread  cancer within the prostate. It’s an inexact science that depends on a doctor’s skill and experience and a man’s willingness to wait for signs that a cancer poses a clear threat before opting for treatment and its potential for side effects.

Penney says she and her Harvard colleagues are among the many scientists now searching for better ways to predict which prostate cancers are likely to be lethal and which can be monitored and not treated. The answer may be found in genetic changes in prostate cancer cells that signal a higher threat. But finding a better way to predict which prostate cancers are likely to turn lethal is far from guaranteed.

“Some [researchers] believe it’s not possible,” Penney says. “After the cancer is diagnosed, so many things can change in unknown ways.” Diet, exercise, and other lifestyle factors, for example, could affect whether low-risk prostate cancers become more aggressive or threatening over time.

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  3. vihra

    My husband ,76y,in moderate general health,diagnosed -Prostate cancer(30.7 1013)-Gleason 3+4=7a in/12/6 samples /25%/moderate differentiated acinares carcinoma
    Kindly suggest the best choice of therapy.
    Thanks

  4. Don I

    Between 59 and 63 – my PSA slowly climbed from 3.5 to 4
    URO Doc said DRE normal for my age. My physical at age
    64 showed PSA doubled to 8. Biopsy disclosed cancer
    mostly on right side with Gleason total at 8. After
    consultations with a surgeon and radiation specialist,
    and MRI, CT scans, bone scans etc. etc. – I went for what
    I was TOLD had the lowest chance of side effects – EBRT.
    First 8 weeks was fine – then with less than 4 days left
    for treatment, the side effects started with a nasty
    infection, but treatment continued, up to the point
    I wound up in the ER with urinary retention and a catheter
    was used to drain out over 2 liters!! The day I got the
    Gleason results – I was also started on HORMONe / ADT .
    I now have to self catheter 3 times and day, can not sleep
    and completely impotent. I wish I knew home many years
    I would have had if left alone. LIFE WAS GOOD. SEX WAS
    GREAT! And I could PEE standing up !!

  5. Jason

    I was told by a doctor that most man at the age of 40 will have prostate problem of some sort. That is why we need to be taking care at very early age. Is that true? Anyway, its a very interesting article.

  6. MsGael

    I agree with Roger Magyar:
    “This paragraph is incomprehensible:
    ‘Over the study period, fewer and fewer men were diagnosed with advanced, late-stage prostate cancers that had spread beyond the prostate gland. This reflected the growing use of prostate-specific antigen (PSA) testing to diagnose prostate cancers earlier and earlier. In contrast, the proportion of high-grade cancers, as measured by the Gleason score, remained relatively stable rather than gradually becoming more aggressive.'”

    I read it several times trying to figure out what the writer meant. Please clarify.

    I have a personal interest in this because my father-in-law died of prostate cancer, and I’m anxious that my husband doesn’t get it. He has had the PSA test several times, but I wonder if it’s very useful.

    • Bill M

      The quoted statement seems to say that advanced cancers are not bering found as much because PSA testing has identified them earlier, but aggressive cancers are being found at the same rate. The aggressive cancers are being found early (i.e., when they are “born”), rather than transforming into aggressive cancers over time.

  7. Roger Magyar

    This paragraph is incomprehensible:
    “Over the study period, fewer and fewer men were diagnosed with advanced, late-stage prostate cancers that had spread beyond the prostate gland. This reflected the growing use of prostate-specific antigen (PSA) testing to diagnose prostate cancers earlier and earlier. In contrast, the proportion of high-grade cancers, as measured by the Gleason score, remained relatively stable rather than gradually becoming more aggressive.”

    Aren’t advanced, late-stage cancers that spread the high-grade, aggressive cancers that kill people? Does the word “aggressive” in the last sentence of the paragraph mean a growing proportion or a growing cancer?

    If fewer men have advanced, late-stage prostate cancer because of PSA testing, then fewer men are dying. But two large studies, one in the U.S., the other in Europe, revealed that is not the case. That is why the U.S. Preventive Services Task Force recommended in May of 2011 that PSA testing not be used for anyone as a screening device.

    What is the paragraph I quote attempting to say? If it means that the enormous amount of expensive, unnecessary, and harmful treatment of prostate cancer provided by the American medical industry has attacked prostates with high-grade or low-grade cancers in roughly the proportion nature has produced those cancers, it is not surprising that the proportion of high-grade cancers has remained stable. Unfortunately, that stable proportion has come at a very high cost for patients who did not have high-grade cancers but receive treatment anyway.

    If the paragraph is attempting to say something else, I would like to know what it is.

    Thank you.

  8. Bruce Rocheleau

    I am a 68-year old healthy male who has been getting PSA Tests since 1999 when I was 54 years old. Over these years, I have been tested 20 times (sometimes twice a year) and the overall mean is for all tests .998. with a standard deviation of .654. Note that I have been taking propecia during these years that I know cuts the score about in half.

    I twice reached my highest score of 2.4 in 2005 and 2007. A second follow-up test in 2007 came in as .7. Since then, my psa scores have been as follows: .3 (2008), .3 (2009), .39 (2010), .6 (2011), 1.08 and .87 (2012), and 1.62 (2013).

    During 2005, I had a one-time discharge of some blood and my urologist performed a prostate biopsy which was negative. I also had surgery to remove a growth in bladder and my urologist took a biopsy on my prostate then and both growth and prostate biopsies were negative—I think this was in 2007.

    I should mention also that during all of these years, I also had digital rectal exams and they were fine.

    My urologist wanted to do a third psa test in 2012 after I had scores of 1.08 and .87 but I did not return to have these done.

    It seems apparent to me that my psa score has a high degree of variability over many years and I don’t understand why I should get psa’s done for such scores or even with my current score of 1.62.

    Assuming a digital rectal exam is normal, how high would my psa score have to be before any biopsy would be called for? Indeed, given my previous negative results from biopsies, I am not sure what value the simple psa test has for me? What about the urine test for PCA3 or T2-ERG or a free-PSA test?