Findings on finasteride

SWOG, PHS lead study to determine prostate-cancer prevention drug's impact on survival for men age 55 and older
Joseph Unger (left) and Dr. Michael LeBlanc
Joseph Unger (left), a statistician in the Southwest Onocology Group (SWOG), and Dr. Michael LeBlanc, PHS, developed statistical methods to weigh the risks and the benefits of the drug finasteride. Their results suggest that administering finasteride to men above age 55 could save more than a quarter of a million years of life over a ten-year period. Photo by Todd McNaught

A drug that has been shown to prevent prostate cancer in clinical trials could have a dramatic impact on survival if widely prescribed for older men, according to a new study led by Southwest Oncology Group (SWOG) researchers in the Public Health Sciences Division. The results suggest that administering finasteride, a medication already prescribed to reduce the size of the prostate gland, to men above age 55 could save more than a quarter of a million years of life over the course of a decade.

The predictions are part of a follow-up analysis of SWOG's Prostate Cancer Prevention Trial (PCPT), which in 2003 reported a nearly 25 percent reduction in prostate cancer among men who took finasteride. That study also found a potential increase in the rate of high-grade prostate cancers among men who took the drug compared to those who received a placebo, leading to debate about whether older men should take the drug.

In the new study, which is based on a statistical model to determine finasteride's potential impact on survival in the general population, researchers found that the benefits of the drug would far outweigh the possible risks.

Extending lives

The analysis is published in the Feb. 28 online version of the journal Cancer and will appear in the print edition of the journal in April. Joseph Unger, a statistician in the SWOG Statistical Center — which is jointly housed within the PHS Division and Cancer Research and Biostatistics, a Seattle nonprofit organization — led the study.

The researchers measured the potential impact of finasteride on survival by calculating the number of "person-years" that would be saved among men ages 55 and older assuming a 25 percent reduction in the occurrence of prostate cancer. One person-year is equal to the extension of a single individual's life by one year.

"If you apply our method of calculation and assume that there is no increase in the rate of high-grade cancers due to finasteride, you would save 316,000 person-years," Unger said. "That is very substantial. If you assume the same absolute percentage increase in high-grade tumors that was observed in PCPT, more than 260,000 person-years would be saved. That is still a substantial survival benefit."

To conduct their analysis, Unger and PHS colleague Dr. Michael LeBlanc developed statistical methods that allowed them to compare the drug's risks and benefits.

"The question is how you do this, and it depends on how you weight the risks and benefits," Unger said. "They aren't equivalent. Our idea was to weight by survival because it's clearly an important outcome to the patient. It's easy to measure and we can obtain good survival data in the general population from the national cancer registries."

Gleason-grading system

The primary PCPT study found that among 4,368 participants who received finasteride, 803 (18.4 percent) developed prostate cancer, compared to 1,147 (24.4 percent) prostate-cancer cases among 4,692 men who took a placebo. The difference equals a 24.8 percent reduction in prostate-cancer cases during the seven-year study period.

Tumors were evaluated to determine their Gleason score, an indicator of a tumor's grade. High-grade tumors, which have higher Gleason scores, have a poorer prognosis than low-grade cancers. Of the tumors detected at the end of the study, most were determined to be of low or intermediate grade. However, the researchers found that a higher proportion (11.9 percent) of tumors in men who developed cancer in the finasteride group were of a high grade compared to tumors that occurred in the placebo group (5 percent).

Breakthrough analysis

To estimate the impact of the clinical-trial results on survival in the general population, Unger and colleagues drew upon data from PCPT and from national cancer registries, which maintain information on cancer occurrence and survival in the United States. To match the number of cancer cases and age range in the PCPT study with that of the general population, the researchers focused on prostate-cancer cases in the registry among men age 55 and older from 1993 to 1997. In contrast to the small percentage of high-grade cancers in the placebo group of PCPT, more than 19 percent of cancers reported to the registry had high Gleason scores.

Using several different scenarios for the proportion of cases that were high grade, the scientists calculated the predicted number of person-years saved that would occur if finasteride were prescribed to this population group. Only when they applied their model to a scenario in which 60 percent of cancers were high-grade — a situation Unger described as "extremely unlikely" — did the risks outweigh the benefits.

"We consider this to be a real breakthrough in analysis," said Dr. Charles A. Coltman Jr., chairman of SWOG and an author on the study. "Clearly, finasteride would benefit older men by preventing prostate cancer."

Ongoing efforts

SWOG investigators do not yet understand why men taking finasteride in the PCPT study had higher rates of high-grade cancer, nor have they determined whether these cancers would have negatively impacted the survival of those men. Finasteride has been thought to alter the appearance of cancers, which would make the Gleason-grading system unreliable to use when analyzing tumors from men taking the drug.

"While we feel this analysis clearly shows the benefit of taking finasteride to prevent prostate cancer, we are continuing to study why some of the men who took finasteride while on the study developed high-grade cancers," said Dr. Ian Thompson, lead study coordinator for PCPT and chairman of the Department of Urology at The University of Texas Health Science Center at San Antonio. "A major ongoing series of efforts are helping us to better understand if this phenomenon is occurring, and if so, why."

Other co-authors included Dr. John Crowley, principal investigator of the SWOG Statistical Center and chief executive officer of Cancer Research and Biostatistics; Phyllis Goodman, PHS; Dr. Leslie Ford of the National Cancer Institute; and Dr. Charles Coltman, SWOG Operations Office in San Antonio.

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