Tuesday, March 26, 2013

Leading Experts Disagree On Evidence Behind Prostate Cancer Screening Recommendations

Do the results of recent randomized trials justify the recent U.S. recommendation against yearly measurement of prostate-specific antigen (PSA) as a screening test for prostate cancer? That's the topic of debate in a special "point/counterpoint" section in the April issue of Medical Care.

The recommendation against routine PSA measurement relies too heavily on randomized trial data, according to an article by Ruth Etzioni, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues. They argue that modeling studies provide a truer picture of the long-term benefits of PSA screening. But Dr Joy Melnikow of University of California, Davis, and colleagues disagree, asserting that randomized trials provide a sufficient level of certainty to recommend against PSA screening.

Point: Short-Term Trials Don't Reflect Long-Term Risk Last year, the U.S. Preventive Services Task Force recommended against routine PSA measurement to screen for prostate cancer. The recommendation was mainly based on two recent studies -- one conducted in Europe and one in the United States -- in which men were randomly assigned to annual PSA screening or no screening. Both studies concluded that annual screening did not reduce the risk of death from prostate cancer.

But randomized trials have important limitations as a basis for screening policies, according to Dr Etzioni and colleagues. They note that screening trials generally provide short-term results, in contrast to the long-term results generated by population-wide screening programs. They argue that taking the randomized trial data at face value "misrepresents the likely long-term population impact of PSA screening (relative to no screening) in the United States."

Dr Etzioni and coauthors discuss the results of modeling studies that give a different picture of the benefits of PSA screening. Based on those models, screening may explain 45 percent of recent declines in U.S. deaths from prostate cancer, while changes in treatment account for 33 percent. When the randomized trial data are extrapolated to the U.S. population over the long term, the absolute reduction in deaths attributed to screening appears at least five times greater than in the original trial reports.

Modeling studies also suggest a lower rate of overdiagnosis -- screening detection of slow-growing prostate cancers that otherwise would have caused no harm -- than reported in the trials. Dr Etzioni and colleagues conclude, "With a disease whose hallmark is a lengthy natural history, the harms of developing cancer screening policies based primarily on limited-duration screening trials may well outweigh the benefits."

Counterpoint: Trials Are Best Evidence on Screening Effects But in their "Counterpoint" essay, by Dr Melnikow and colleagues notes that the U.S. and European trials provided 11 to 13 years' follow-up in more than 250,000 individuals. They also point out that the U.S. trial was highly representative of the population and showed no reduction in death resulting from annual PSA testing. (Dr Melnikow and colleagues were members of the U.S. Preventive Services Task Force when the recommendation was made.)

They add that, because of "competing causes of death," it becomes even less likely that a large reduction in deaths from prostate cancer will appear over long-term follow-up. The chances of overdiagnosis and potential harms from screening are also likely to increase with continued aging. Dr Melnikow and coauthors conclude, "Projections from models are subject to mistaken assumptions and investigator biases, and should not be accorded the same weight as evidence from randomized controlled trials."

In an editorial response, Dr Etzioni's group points out that modeling plays an essential role in addressing questions about the harms and benefits of screening. "While we acknowledge the centrality of screening trials in the policy process," they write, "we maintain that modeling constitutes a powerful tool for screening trial interpretation and screening policy development."

The debate is "no mere academic exercise," according to an editorial by Ronnie D. Horner, PhD, of University of Cincinnati Medical Center. With the increased emphasis on disease prevention under health care reform, it is essential to offer those services most likely to represent value -- including cancer screenings. While there's no easy answer, Dr Horner writes, "I am hopeful that this Point-Counterpoint exchange will initiate a discussion among healthcare scientists that will yield greater guidance for determining whether a health care service is, indeed, value health care."

Monday, March 18, 2013

Surgery Is Superior to Radiotherapy in Men With Localized Prostate Cancer

Surgery offers better survival benefit for men with localised prostate cancer, according to a large observational study, conducted by a group of researchers in Sweden and the Netherlands.

"The current gold standard management of localised prostate cancer is radical therapy, either as surgery or radiation therapy. This study suggests that surgery is likely superior to radiation for the majority of men who have localized prostate cancer, especially the younger age group and those with no or few comorbidities," said Dr. Prasanna Sooriakumaran, lead study author, of the Karolinska University Hospital in Stockholm.

In their study, Sooriakumaran and colleagues compared the oncologic effectiveness of radical prostatectomy and radiotherapy in prostate cancer, and analysed the mortality outcomes in 34,515 patients treated with up to 15 years follow-up.

Data from Sweden's National Prostate Cancer Registry showed that the men were treated for prostate cancer throughout Sweden with either surgery (n=21,533) or radiotherapy (n=12,982) as their first treatment option and form the study cohort. Patients were categorised by risk group (localised- low risk, localised- intermediate risk, localised- high risk, and non-localized- any T3-4, N+, M+, PSA>50), age (<65, 65-74, ≥75), and Charlson co-morbidity index or CCI (0, 1, ≥2).

In their results, the researchers said radiotherapy patients generally had higher Gleason sums and clinical stages, were older, and had higher PSA than patients that underwent surgery (p<0.0001 for all comparisons). Prostate-cancer-mortality (PCM) became a larger proportion of overall mortality as risk group increased for both the surgery and radiotherapy cohorts. The study also showed that for localised prostate cancer patients (risk groups 1-3) survival outcomes favored surgery, and for locally advanced/metastatic patients treatment results were similar.

"This study may herald an increasing use of surgery over radiation in this group. Also, our study concluded that for men with advanced prostate cancer, both modalities appear equivalent and thus the conventional view that surgery is not indicated in this group may be incorrect," explained Sooriakumaran. He added that with their results majority of men with low risk prostate cancer do not die of the disease.

"A very long follow up period is needed to make any comments regarding comparative oncologic outcomes between treatments. Hence, the use of active surveillance may be appropriate in men with low risk disease," Sooriakumaran pointed out.

However, men with intermediate and high-risk disease are at relatively high probability to die from prostate cancer. "Especially when we look at the absolute numbers involved," he said, adding that radical treatment, preferably in the form of surgery, is warranted if possible.

The study won the second prize for best abstract in oncology at the 28th Annual EAU Congress which will opened in Milan on March 15.