Category: Diagnostics, Genetics, Imaging

The Prostate Cancer Foundation (PCF) publishes a highly recommended e mail periodical entitled NewsPulse to which one can subscribe.  The October issue contained two articles which I will simply summarize and link.

The first article concluded that popular prostate supplements such as those containing saw palmetto do not benefit prostate cancer patients.  They do not decrease the risk of spread of localized disease, affect survival or lower the risk of side effects from radiation therapy.  The supplements offered no benefits related to prostate cancer outcomes.  However, it should be noted that the article did not address the issue of prostate cancer prevention.  The subjects in the study were all prostate cancer patients.  As an editorial note, I would not include pomegranate  extract in this group of supplements as some positive effects on prostate cancer and PSA doubling time have been observed with the extract (see April 4th, 2011 blog post).

The second article cited a study concerning the effects of the relaxed PSA testing guidelines issued in 2011 by the U.S. Preventative Services Task Force.  The current study results indicated that such relaxed screening may delay the diagnosis and treatment of aggressive prostate cancers.  Men who could have been eligible for treatment and perhaps cured of more advanced prostate disease may be diagnosed too late.  Since 2011, PSA screening has decreased by 28%.  The 2011 guidelines did have a positive effect in that diagnoses of new, low-risk cancers dropped by 38%.  However, researchers also found a drop of 28% in diagnoses of intermediate-risk cancer and a 23% drop in diagnoses of high-risk cancer one year after the guidelines were published.  These finding were consistent with what the researchers hoped would not happen.  They concluded that “men will develop more advanced prostate cancer before it is diagnosed and be less likely to be cured.”

The post below comes from a multi-year study at Johns Hopkins in Baltimore. It should be noted below that repeat biopsies performed on men undergoing active surveillance were performed using MRI-guided technology and pathologists checked biopsy tissue levels of proteins made by the PTEN gene, a biomarker for prostate cancer aggressiveness.

Men with relatively unaggressive prostate tumors and whose disease is carefully monitored by urologists are unlikely to develop metastatic prostate cancer or die of their cancers, according to results of a study by researchers at the Brady Urological Institute at Johns Hopkins, who analyzed survival statistics up to 15 years. Specifically, the researchers report, just two of 1,298 men enrolled over the past 20 years in a so-called active surveillance program at Johns Hopkins died of prostate cancer, and three developed metastatic disease.

“Our study should reassure men that carefully selected patients enrolled in active surveillance programs for their low-risk prostate cancers are not likely to be harmed by their disease,” says H. Ballentine Carter, M.D. , the Bernard L. Schwartz Distinguished Professor of Urologic Oncology and director of adult urology. Carter acknowledges that outcomes in the current study may be due to doctors’ careful selection of patients for active surveillance. “With longer follow-up, the data may change, but they’re unlikely to change dramatically, because men in this age group tend to die of other causes,” he says. Most of the men in the study were also Caucasian, and Carter cautions that these outcomes may not apply to African-American men, who tend to have more aggressive cancers.

For the study, described online Aug. 31 in the Journal of Clinical Oncology, men with prostate tumors classified as low or very low risk for aggressiveness opted to enroll in an active surveillance program at The Johns Hopkins Hospital. Their risk level was determined, in part, by Gleason scores, in which pathologists evaluate the aggressiveness of the cancer from prostate biopsy tissue.  When the study began in 1995, Carter says, urologists performed annual biopsies on the men in the program until they reached age 75. Now, doctors no longer require annual biopsies among the lowest risk groups, but when they do perform a biopsy, they use MRI-guided technology and will often ask pathologists to check biopsy tissue levels of proteins made by the PTEN gene, a biomarker for prostate cancer aggressiveness. Of the 1,298 men, 47 died of nonprostate cancer causes, mostly cardiovascular disease; nine of the 47 had received treatment for their prostate cancer. Two men died from prostate cancer, one after 16 years in the active surveillance program. In the second man’s case, Johns Hopkins doctors recommended surveillance, but the patient sought monitoring at another hospital and died 15 months after his diagnosis.  Three men in the program were diagnosed with metastatic prostate cancer.

Overall, the researchers calculated that men in the program were 24 times more likely to die from a cause other than prostate cancer over a 15-year span.  After 10 and 15 years of follow-up, survival free of prostate cancer death was 99.9 percent, and survival without metastasis was 99.4 percent in the group.  Some 467 men in the group (36 percent) had prostate cancers that were reclassified to a more aggressive level within a median time of two years from enrollment in the active surveillance program. For men with very low-risk cancers, the cumulative risk of a grade reclassification to a level that would have generally precluded enrollment in the program over five, 10 and 15 years was 13 percent, 21 percent and 22 percent, respectively. For men with low-risk cancers, this risk increased to 19 percent, 28 percent and 31 percent. Over the same time frames, the cumulative risk of a grade reclassification to a level that would be considered potentially lethal in most cases but still curable was no more than 5.9 percent for both very low and low-risk prostate cancers, Carter says.  Also among the group, 109 men opted for surgical or radiation treatment despite the absence of significant change in their prostate cancer status. In those whose cancers were reclassified, 361 opted for treatment.  “The natural progression of prostate cancer occurs over a long period of time, some 20 years, and most men with low-risk prostate cancer will die of another cause,” says Carter, a member of the Johns Hopkins Kimmel Cancer Center. “There is a careful balance, which is sometimes difficult to find, between doing no harm without treatment and overtreating men, but our data should help.”  Carter estimates that 30 to 40 percent of U.S. men with eligible prostate cancers opt for active surveillance, compared with Scandinavian countries, where use of the option is as high as 80 percent. The reasons for less use in the U.S., he says, could stem from fear of losing the opportunity for a cure.

Carter says one of the benefits of active surveillance is reduction in the rates of complications and costs of prostate cancer treatments. In a recent report, 20 percent of men undergoing a prostate cancer treatment – radiation or surgery – were readmitted to the hospital within five years of treatment for a complication related to the original treatment.  “Our goal is to avoid treating men who don’t need surgery or radiation. The ability to identify men with the most indolent cancers for whom surveillance is safe is likely to improve with better imaging techniques and biomarkers,” says Carter.  Active surveillance is included in best practice guidelines for doctors developed by the National Comprehensive Cancer Network, a group of the nation’s top cancer centers. Carter recommends that men see urology specialists to be monitored in an active surveillance program.

 

The following article dated August 6th came from a site entitled Prostatesnatchers authored by a noted prostate oncologist, Dr. Mark Scholz. He suggests that a commercial OPKO-4Kscore blood test and a high-resolution color Doppler ultrasound or a 3-Tesla multi-parametric MRI can help identify aggressive cancers and minimize the use of standard 12-core prostate biopsies and their potential side effects. The OPKO-4Kscore blood test is comprised of measurements of total and free PSA coupled with proprietary tests for intact PSA and a panel of four kallikrein (a specific group of enzymes) blood markers.  My own prostate oncologist commented favorably on this test. “It won’t be the last word, but it is a productive departure from single-lab-value (PSA) technology, which is over 30 years old.”  Remember the contents of this website are not intended as personal recommendations but the potential use of this information should be discussed with your personal physician. You should also check on the cost and insurance coverage of the tests described below.

“You PSA is elevated. Now your doctor recommends a needle biopsy, 12 cores through the rectum to check for cancer in the prostate.  Sounds icky, but also logical; after all who wants to miss cancer? But come on, do you really have to do 12 stabs via the rectum?

Each year over a million men submit their prostates for a biopsy.  At an average cost of around four thousand dollars, the prostate biopsy business is a 4-billion-dollar-a-year enterprise.  But it’s not merely the cost that gives pause.  Three percent of men end up hospitalized with life-threatening infections.  Around a 100,000 men every year get a confounding diagnosis of Grade 6 prostate cancer, a truly harmless entity, unless you get suckered into an unnecessary radical prostatectomy.

Obviously, prostate biopsy is an unpleasant proposition with notable risks.  However, ignoring a high PSA incurs the risk of missing a diagnosis of a higher grade prostate cancer. As things stand now, of the million biopsies being done annually, over a hundred thousand men with Grade 7 or higher cancers are being detected. For these men, their early diagnosis is beneficial, leading to early, curative treatment in a timely fashion.

How can we detect the 100,000 men with higher-grade cancers that need to be detected without doing 900,000 “unnecessary” biopsies?   The answer to this question continues to evolve as technology marches forward. Our latest thinking at Prostate Oncology (assuming the PSA is not wildly elevated, say over 20) is a three step process:

1.    Simply repeat the PSA to confirm it is indeed abnormally elevated.  All sorts of things can cause temporary elevations of PSA ranging from nonspecific inflammation of the prostate, to recent sexual activity, to simple laboratory errors. 

2.    If the PSA remains elevated with repeat testing the next step to consider is an OPKO-4Kscore blood test. The OPKO test reports a percentage estimate of the likelihood of higher grade cancer being present.  The test is not perfect, but it performs pretty well.  For example, if a specific patient receives an OPKO report with an estimated risk of high grade disease of less than 15%, a standard random biopsy (if he elected to do one) will confirm the absence of high grade disease 92% of the time. Not bad.

3.    Our next step at Prostate Oncology in the cases where a patient has an OPKO test indicating that the risk of high grade disease is over 15%, is to obtain a prostate scan with high-resolution color Doppler ultrasound or with a 3-Tesla multiparametric MRI. With scanning, the location of the high-grade disease can be determined over 90% of the time so that a targeted biopsy with 2 or 3 cores can be substituted for the traditional 12-core biopsy.       

The business of prostate biopsy has become so out of control the US Preventative Services Task Force advocates against PSA testing altogether.  The Task Force’s scientifically-based arguments that PSA testing is causing more harm than good are really quite convincing.  However, back in 2011 when they published their recommendations, the OPKO test and 3-Tesla multiparametric prostate MRI were unavailable. With the advent of these new technologies, PSA screening to detect higher grade prostate cancers at an early stage when they are still curable makes perfect sense.“

When men are newly diagnosed with prostate cancer, they are split into three broad categories: Low-Risk, Intermediate-Risk and High-Risk. This system, which was invented by Dr. Anthony D’Amico, is helpful for the proper selection of optimal treatment; men with more favorable types of prostate cancer can receive milder therapy and still maintain normal survival rates. In a recent e mail message from prostatesnatchers, below) these categories are defined and appropriate therapeutic options given.  A major conclusion cited is that “the cancer of men with the favorable type of Intermediate-Risk prostate cancer behaves the same as Low-Risk.  Analysis provides further clinical evidence that men with the favorable type of Intermediate-Risk prostate cancer can forego immediate radical therapy and embark on active surveillance.”

As far as treatment selection is concerned, as a general rule of thumb, men with Low-Risk disease are encouraged to simply monitor the disease, withholding therapy altogether unless tumor growth is detected on subsequent testing.  At the other extreme, men with High-Risk disease typically undergo combination treatment with three forms of therapy: seed radiation, IMRT and hormone therapy, which is continued for a year and a half.

Treatment recommendations for men with Intermediate-Risk range widely from surgery, to the many types of radiation—IMRT, seed implants, SBRT and Proton therapy to focal therapy, as well as the alternative of simply giving hormone therapy by itself. This wide variety of treatment options is not merely a result of physician bias.  It turns out that the types of cancer that occur in the Intermediate-Risk category also vary widely.  At the “good” end of the spectrum, men with the favorable type of Intermediate-Risk disease have a condition that behaves more like Low-Risk while cancers men at the unfavorable end of the Intermediate-Risk spectrum have a condition that behaves more like High-Risk.

The indicators that define an unfavorable type of Intermediate-Risk disease are multiple intermediate characteristics rather than having a single Intermediate-Riskfactor.  For example, it is considered unfavorable when the PSA is over ten and the Gleason is 4 + 3 (instead of 3 + 4) and there are more than 50% of the biopsy cores containing cancer.  At the other extreme are men with the favorable type of Intermediate-Risk disease. These men are characterized by having all the Low-Risk factors in combination with only a single Intermediate-Risk factor.

Making a proper distinction between the favorable and unfavorable types of intermediate risk disease can be monumentally important as it relates to treatment selection. Studies show that men with favorable Intermediate-Risk disease are potential candidates for active surveillance.  A recently published report at this year’s Genitourinary ASCO meeting bears directly on this issue:

In an  abstract from the ASCO meeting authored by Ann Caroline Raldow from Harvard, 6500 newly-diagnosed men treated with radiation and hormone therapy at the Chicago Prostate Cancer Center between 1997 and 2013 were evaluated.  Dr. Raldow calculated their survival rate after treatment based on their risk category: low, favorable-intermediate, unfavorable-intermediate, and high. Eight years after treatment 820 men had died, 72 of them from prostate cancer. Men in the favorable Intermediate-Risk category had the same survival rates as men in the Low-Risk category.  Men in either the High-Risk category or in the unfavorable Intermediate-Risk category demonstrated an increased mortality rate from prostate cancer.

Bottom line, the cancer of men with the favorable type of Intermediate-Risk prostate cancer behaves the same as Low-Risk.  Dr. Raldow’s analysis provides further clinical evidence that men with the favorable type of Intermediate-Risk prostate cancer can forgo immediate radical therapy and embark on active surveillance.