Active Surveillance for Men with Intermediate Risk Prostate Cancer

BY MARK SCHOLZ, MD

People are starting to become familiar with the modern way of conceptualizing prostate cancer.  When men are newly diagnosed, 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.

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-Risk factor.  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 Abstract #82 from the 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.

 

 

 

Dying for a Biopsy?

MARK SCHOLZ, MD

Screening for prostate cancer is big business. The PSA blood test, first implemented in the late 1980s, resulted in a doubling in the number of new cases, from 100,000 a year to more than 200,000 annually. The cost of simply diagnosing prostate cancer—after adding up doctor, lab and pathology charges—easily surpasses a billion dollars annually.

Cancer is diagnosed by a specially-trained doctor, a pathologist, who examines the prostate tissue under a microscope. Tissue is extracted by needle biopsy, a procedure that is performed in a doctor’s office. The patient lies on his side and an ultrasound probe is inserted into the rectum. Then after Novocain is injected, 12 to 14 tissue samples are removed using a spring-loaded needle gun that is fired in a grid pattern over the surface of the prostate . The tissue samples are then transported to the pathologist who determines whether or not cancer is present.

Over a million men undergo a prostate biopsy each year. Immediate biopsy at the first sign of PSA elevation has been the standard approach for more than 30 years. However, this policy needs to be reconsidered. Last year the US Preventative Services Task Force reconfirmed their strong warning against PSA screening, pointing out that it leads directly to an egregious degree of overtreatment in men with microscopic amounts of harmless low-grade prostate cancer.  The problem is that surgery and radiation induce shockingly high rates of permanent sexual dysfunction and loss of urinary control. These are distressingly serious problems when considering that treatment is frequently unnecessary in the first place.

Until recently, the needle biopsy procedure itself was perceived as being reasonably safe. However, two just-released studies indicate that it is nowhere near as innocuous as most physicians had assumed.  For example, at the American Urology Association meeting in May, doctors from Memorial Sloan Kettering reported that infectious complications requiring hospitalization occur 2.8% of the time.* In a separate study at the American Society of Clinical Oncology meeting, Dr. Boniol from the International Prevention Research Institute reported that 1.3 deaths occurred for every 1,000 men who undergo biopsy. To put this latter finding in perspective, Dr. Boniol commented, “This prostatic biopsy mortality would occur earlier than any benefit from a screening program and could reverse any potential gain from screening…”

Fortunately, there is an alternative to immediate biopsy.  MRI scanners can guide a biopsy needle directly to the area of the prostate gland where the disease is located, thus allowing a reduction in the number needle biopsies by 90%.  While there are drawbacks to this new technology—it requires special training and the equipment is expensive—the risk of serious infections should be much lower.

Change is often resisted by the status quo, especially when it involves a major shift in reimbursement patterns.  Doctors who do random prostate needle biopsies will likely view these technological advancements with suspicion. Even so, the 30-year old methodology of puncturing the prostate with multiple random needle sticks is overdue for replacement. Noninvasive MRI imaging technology to detect prostate cancer is a far more sensible way to evaluate men with rising PSA levels. 

*Abstract 1244 -The Impact of Repeat Biopsies on Infectious Complications in Men with Prostate Cancer on Active Surveillance: a Prospective Study

Urologist and Radiation Therapist Attitudes toward Active Surveillance

BY MARK SCHOLZ, MD

In May of every year over 10,000 medical oncologists from around the world attend a 5-day meeting sponsored by the American Society of Clinical Oncology (ASCO) where preliminary results of the latest cancer research are presented.  Thousands of research projects are summarized and published in short 300-word abstracts.  What follows is a long quote of almost the entire abstract published in 2012 by Dr. Simon Kim from the Mayo Clinic:

“While active surveillance is well recognized as an acceptable treatment strategy for low-risk prostate cancer, the extent to which radiation oncologists and urologists perceive active surveillance as effective and routinely recommend it to patients is unknown. Therefore, we sought to assess the attitudes and treatment recommendations for low-risk prostate cancer from a national survey of prostate cancer specialists.

Methods: A mail survey was sent to a population-based sample of 1,439 physicians in the U.S. from late 2011 and early 2012. Physicians were queried about their attitudes regarding active surveillance and treatment recommendations for patients diagnosed with low-risk prostate cancer (PSA<10 ng/dl; Stage = T1c; Gleason 6 in one of twelve cores).

Results: Overall, 321 radiation oncologists and 322 urologists completed the survey for a 45% response rate. Most physicians reported that active surveillance is effective for low-risk prostate cancer (71%) and stated that they were comfortable routinely recommending active surveillance (67%). Urologists were more likely to agree that active surveillance is effective (77% vs. 67%; p=0.005) and were comfortable recommending active surveillance (74% vs. 61%; p=0.001) compared with radiation oncologists. Most physicians recommended radical prostatectomy (47%) or radiation therapy (32%), but fewer endorsed active surveillance (21%) for low-risk disease. After adjusting for physician covariates, radiation oncologists were more than eleven-times more likely to recommend radiation therapy, while urologists were 4.7-times more likely to recommend surgery and 2.1 times more likely to recommend active surveillance for low-risk prostate cancer.

Conclusions: Although active surveillance is widely viewed as effective by radiation oncologists and urologists, most urologists continue to recommend surgery, while most radiation oncologists recommend radiation therapy. Our results may explain in part the relatively low contemporary use of active surveillance in the U.S.”

My Comment: This study clearly documents that urologists and radiation therapists, while acknowledging that active surveillance is acceptable, overwhelmingly recommend surgery and radiation. Not surprisingly, the urologists recommend surgery and the radiation therapists recommend radiation. The study findings are remarkable because they were not generated by a third party. This report depicts urologist and radiation therapist behavior though a self-description survey. Clearly, broader acceptance of active surveillance will be impeded until the day when urologists and radiation therapist physicians are willing to act on what they know to be true about active surveillance rather than simply giving it lip service.