SAN DIEGO – Over the past 20 years, death rates from prostate cancer in the United States have declined by 39%, due largely to early detection and/or improved treatment, according to Dr. Peter R. Carroll.
"It’s important to realize that this accounts for 20% of the decrease in cancer-specific deaths in men," said Dr. Carroll, professor and chair of the department of urology at the University of California, San Francisco. "However, the Achilles’ heel of PSA [prostate-specific antigen] testing is that it does so at the risk of overdetection – detecting disease that would not have become clinically apparent over a patient’s lifetime if left untreated. In this country, detection and treatment are too tightly linked."
In addition, widespread use of serum PSA has resulted in a "dramatic stage and grade shift, with most cancers currently being detected of limited cancer grade and stage," he said. Data from his colleagues at UCSF found that between 1990 and 2012, age-adjusted death rates from prostate cancer decreased 3.96% in North America yet increased 41% worldwide. In the United States, men with nonpalpable PSA-driven cancer comprise the largest segment of prostate cancer patients. "We think that we’ve seen a leveling of overdetection, but I think we’ll see another round of overdetection, because of a lowering PSA threshold to prompt biopsy, aggressive rescreening, the use of PSA velocity at low PSA values to prompt biopsy, and the use of saturation biopsies," he said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.
Dr. Peter R. Carroll
In 2012 the U.S. Preventive Services Task Force came out against prostate cancer screening, classifying it as a grade D recommendation (Ann. Intern. Med. 2012;157[2]:120-34). The magnitude of overdetection varies with time period, age, comorbidities, region, definition, and screening practices and is thought to range between 2% and 67%, Dr. Carroll said. "I think a good number is somewhere between 35% and 40%." A recently published nomogram for predicting overdiagnosis found that depending on a man’s age, Gleason score, and PSA level, the likelihood that his tumor has been overdiagnosed ranges from 2.9% to 88.1% (J. Natl. Cancer Inst. 2014 [doi:10.1093/jnci.djt367]).
If prostate cancer screening is to be undertaken, "it should only be done recognizing that selective, rather than indiscriminate, treatment should follow," Dr. Carroll said. "Such an approach has been shown to reduce mortality while managing many with active surveillance in lieu of immediate treatment" (Lancet Oncol. 2010;11[8]:725-32). At UCSF, where more than 1,000 men are on active surveillance, the 5-year treatment-free survival is 65%, the 5-year overall survival is 97%, and the 5-year prostate cancer–specific survival is 100%. "The window of opportunity for treatment appears to be open for a long period of time," he said.
Potential solutions Dr. Carroll proposed to decrease the rates of overdetection include:
• Reducing the treatment of low-risk tumors.
• Identifying high-risk populations and targeting prevention and screening efforts to those populations.
• Developing new screening markers.
• Developing clinical and patient tools to support informed decision making about prevention, screening, biopsy, and treatment.
• Changing screening guidelines.
"The single biggest predictor of risk is a baseline PSA. It trumps ethnicity and family history," Dr. Carroll said. "I think there’s a strong rationale for a baseline screening between ages 45 and 55. If you screen beyond age 70, you increase the risk of overdetection. But if you stop screening you also increase the mortality. So beyond age 70 you want to individualize, consider screening only in those with a long life expectancy, and perhaps change the rationale for biopsy. Digital rectal examination in my mind is optional as a primary screening maneuver. Screening can be done at 1- to 2-year intervals. One thing we need to get away from is using PSA velocity at low PSA levels. That drives overdetection quite a bit."
Dr. Carroll disclosed that he has received honoraria, research support, and/or consulting fees from Genomic Health, Intuitive, Janssen, and Myriad.