Diagnostics & Imaging Week Contributing Writer

CHICAGO — The annual meeting of the American Urological Association (AUA; Linthicum, Maryland) the largest worldwide meeting for this specialty, is taking place here. Although a broad variety of topics are traditionally covered at this meeting, prostate cancer remains a crucial focus at every AUA meeting. And well it should, as it is the most common cancer in men with about one in six American men predicted to get prostate cancer during his lifetime.

According to the most recent data from the American Cancer Society (ACS; Atlanta), about 186,000 new cases of prostate cancer were diagnosed in the U.S. in 2008. This cancer will cause an estimated 29,000 deaths in the U.S. this year, making it the second-leading cause of cancer death in men, exceeded only by lung cancer.

The screening and treatment for prostate cancer have long been and continues to be mired in heavy controversy. There are several reasons for this situation, a critical one being that prostate cancer typically is a very slow growing, making "watchful waiting" a viable treatment option. On the screening side of the ledger, there has never been an appropriate analysis of the risks and benefits of the prostate specific antigen (PSA) test, which over the past two decades has been widely adopted as a screening tool in the U.S. and other countries.

Further confusion has arisen because of divergent screening recommendations from key organizations. For example, the AUA and the ACS both recommend offering annual PSA testing and digital rectal examination beginning at the age of 50 years for men with a normal risk of prostate cancer and beginning at an earlier age for men who are at higher risk.

The National Comprehensive Cancer Network (Fort Washington, Pennsylvania) recommends a risk-based screening algorithm, including family history, race, and age. The U.S. Preventive Services Task Force (USPSTF), an independent panel organized by the Agency for Healthcare Research and Quality, recently concluded that there was insufficient evidence in men under the age of 75 years to assess the balance between benefits and side effects associated with screening, and the panel recommended against screening men over the age of 75 years.

The raging controversy was further stoked recently, with the release of data from two landmark trials in the March 26, 2009 issue of the New England Journal of Medicine. These studies, called Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC) were discussed here on Sunday at a packed "Late Breaking Clinical Trials" plenary session.

The two trials, which enrolled a huge number of patients over many years, shared a virtually identical goal, i.e., to evaluate the effect of PSA screening on the death rate from prostate cancer.

The PLCO trial concluded that "... prostate-cancer screening provided no reduction in death rates at 7 years," thereby supporting the recent recommendations of the USPSTF. Conversely, the ERSPC study demonstrated a statistically significant 20% relative reduction in prostate cancer mortality associated with PSA screening, but the authors cautioned that "the ratio of benefits to risks that is achievable with more frequent screening or a lower PSA threshold than we used remains unknown."

The ERSPC authors, as might be expected from a study generated in healthcare cost conscious Europe, also stated that "... screening must take into account ... over-diagnosis, over-treatment, quality of life, cost, and cost-effectiveness."

The lead author of the ERSPC, Fritz Schroeder, MD, a urologist from the Erasmus Medical Center (Rotterdam, the Netherlands) told the AUA plenary session audience that "the message of prostate cancer screening has changed."

"We have clearly shown that early detection can significantly reduce the death rate but this comes at a very high cost. In my opinion, it is unethically unacceptable to screen 1,410 men and treat an additional 48 men to prevent one death."

David Crawford, MD, professor of surgery, University of Colorado Health Sciences Center (Denver) and one of the lead authors of the PLCO trial, said that "PSA is not the best test ... far from it. We need a better test and better markers of disease progression."

Echoing the frustrations of the diagnosis and treatment of prostate cancer, Crawford concluded that despite the fact that routine screening did not reduce the death rate in the PLCO trial, "we cannot ignore the fact that 28,000 men died from prostate cancer in the last year."

Meanwhile, prostate cancer therapeutic options continue to increase and improve. At an AUA sponsored "Industry Clinical Update," one of the newest modalities, the CyberKnife (CK) robotic radiosurgery system, was discussed.

The CK system, which was pioneered and commercialized by Accuray (Sunnyvale, California), has been widely and successfully used for a variety of cancers for many years. Its use in prostate cancer began in early 2004 and recently the company reported that more than 3,000 prostate cancer patients have been treated worldwide. The pace of its use is clearly accelerating, as evidenced by the fact that in the recently completed third quarter of Accuray's 2009 fiscal year, about 400 prostate cancer patients were treated.

The clinical credibility of this modality was recently boosted by an article in the March 15, 2009 issue of the venerable International Journal of Radiation Oncology/Biology/Physics – more widely known as the Red Journal.

The study, lead by Christopher King, MD, at the Stanford University School of Medicine (Stanford, California) treated 41 low-risk prostate cancer patients and showed that at a median follow-up of 33 months, no patient experienced a PSA recurrence and early side effects were no worse than other prostate cancer therapies.

The authors noted that these results are "highly encouraging," but cautioned that longer follow-up is required "to confirm durable biochemical control rates and low late toxicity profiles."

Speaking at the AUA meeting, Lee Ponsky, MD, assistant professor of urology at Case Western Reserve University School of Medicine (Cleveland) said that the CyberKnife is "one of the most exciting innovations in urology."

Ponsky, who described himself as a "serious skeptic" about new technology, has treated 28 patients to date and reported similar results to the Red Journal, i.e., that for early stage prostate cancer patients, the technology is effective and has tolerable side effects.

Another urologist, David Spellberg, MD, from Naples Urology Associates (Naples, Florida), voiced similar positive sentiments, saying "we are seeing very good clinical results ... this technology is clearly another good option for our prostate cancer patients."

His hospital has been by the far the most active center in the U.S., treating about 400 patients in recent years. Spellberg noted that word of mouth has been a very strong factor in the robust growth of procedures, as patients are drawn by the very short five-day treatment regimen. This compares very favorably to a 40-day course of therapy for traditional external radiation.

Accuray is now in the midst of conducting two large trials, both of which will eventually report five-year follow-up data. The first trial is treating early stage organ confined cancers and compares the CyberKnife to HDR (high dose rate) temporary brachytherapy. The second trial compares the CyberKnife to a homogeneous dose distribution in early-stage organ confined cancers.

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