Study Backs Active Surveillance for Prostate Ca : 'Among these untreated patients, zero have gone on to metastatic disease or prostate cancer death.'

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.