April 21, 2011 — Active surveillance for "carefully selected" older men with prostate cancer "appears to be a safe alternative" to immediate treatment, according to researchers from the Brady Urological Institute at Johns Hopkins University in Baltimore, Maryland.
There have been no known prostate-cancer-specific deaths among the 769 men who have been enrolling in the program continuously since 1995. The average age of the participants is 66 years and most are white (90.4%).
About one third of the men have undergone treatment at some point, either because of biopsy-proven disease progression or anxiety/psychological discomfort with active surveillance.
These and other results from the prospective study were published online April 4 in the Journal of Clinical Oncology.
"This study offers the most conclusive evidence to date that active surveillance may be the preferred option for the vast majority of older men diagnosed with a very low-grade or small-volume form of prostate cancer," said study senior author H. Ballentine Carter, MD, in a press statement. "These are men with a favorable risk disease profile to begin with."
Most of the men (78.4%) in the Johns Hopkins cohort met all the criteria for very-low-risk prostate cancer, defined by the National Comprehensive Cancer Network: clinical stage T1c disease, prostate-specific antigen density below 0.15 ng/mL, Gleason score of 6 or lower, 2 or fewer cores with cancer, and 50% or less cancer involvement of any core.
Notably, these men were 30% less likely to be reclassified to a high-risk category during surveillance and to need subsequent surgery or radiation than men who did not meet 1 or more of the study criteria.
"Limiting surveillance to patients with the lowest-risk category of disease may reduce the incidence of adverse outcomes," say Dr. Carter and his coauthors.
The authors, who report that men in the current study have an average follow-up of only 2.7 years, offer a very important caveat about active surveillance at this point in time: "even 10 years [of follow-up] is not an adequate time frame for the evaluation of prostate-cancer-specific survival." In other words, only more time will tell just how safe active surveillance is for men in this cohort.
Until more is known about the risks of delaying treatment, active surveillance hinges on a bet, said one of the investigators of the Surveillance Therapy Against Radical Treatment (START) trial, the first-ever North American phase 3 trial comparing active surveillance and treatment (radiotherapy or prostatectomy).
"The bet is that we can detect disease progression before it causes the patient harm," Adam Kibel, MD, from the Washington University School of Medicine in St. Louis, Missouri, told Medscape Medical News last year.
Accordingly, the authors from Johns Hopkins remind clinicians that active surveillance is not without risk: "patients considering surveillance should be counseled on the possibility that delayed intervention may compromise the opportunity for cure in some cases."
Intervention Based on Biopsy, Not PSA
The surveillance cohort at Johns Hopkins is 1 of a number of major cohorts in North America and Europe. All of the studies are based on the idea that surveillance might reduce the overtreatment of prostate cancer, which has been estimated to affect as many as 1 million men in the United States since the inception of widespread prostate-specific antigen (PSA) testing in the mid-1980s.
The Johns Hopkins study is different in 2 major ways from the other studies, the authors say.
"Our approach to surveillance differs somewhat from other programs in both the selection of candidates and the criteria for intervention," they write.
The Hopkins study consists mainly of men with very-low-risk disease, as opposed to low- and intermediate-risk disease, and it uses surveillance biopsy findings, which are taken annually, as the trigger for intervention, as opposed to biochemical recurrence (PSA kinetics).
The rate of curative intervention in all of the studies has been about 30%, observe the authors, but the reasons for the intervention differ by study, they explain.
"Although 73.4% of men in our program underwent intervention because of biopsy reclassification, other programs cite PSA kinetics as a common trigger for intervention," the team writes. PSA kinetics have proven to be an unreliable measure in their study, as reported earlier by Medscape Medical News.
The study has a lower proportion of men who have had biochemical recurrence than studies in Europe and Canada. "This may be the case because of previously described differences in entry criteria specific to each program and may further support our belief that active surveillance is safest for those with very-low-risk disease," say Dr. Carter and colleagues.
Further Details
The primary outcome of the study was survival free of intervention. The median for this measure among the participants was 6.5 years (range, 0 to 15 years) after diagnosis, report the authors.
The proportions of men remaining free of intervention after 2, 5, and 10 years of follow-up were 81%, 59%, and 41%, respectively.
Overall, 255 men (33.2%) underwent intervention. The median time of the intervention was 2.2 years (range, 0.6 to 10.2 years). Of these men, 188 men (73.7%) underwent intervention on the basis of disease reclassification after biopsy.
As noted above, the proportions of men who underwent curative intervention (P = .026) or had biopsy reclassification (P < .001) were significantly lower in men who met the enrollment criteria than in those who did not.
Funding support for the study was provided by the Patrick C. Walsh Prostate Cancer Research Fund. The author have disclosed no relevant financial relationships.
J Clin Oncol. Published online April 4, 2011. Abstract
There have been no known prostate-cancer-specific deaths among the 769 men who have been enrolling in the program continuously since 1995. The average age of the participants is 66 years and most are white (90.4%).
About one third of the men have undergone treatment at some point, either because of biopsy-proven disease progression or anxiety/psychological discomfort with active surveillance.
These and other results from the prospective study were published online April 4 in the Journal of Clinical Oncology.
"This study offers the most conclusive evidence to date that active surveillance may be the preferred option for the vast majority of older men diagnosed with a very low-grade or small-volume form of prostate cancer," said study senior author H. Ballentine Carter, MD, in a press statement. "These are men with a favorable risk disease profile to begin with."
Most of the men (78.4%) in the Johns Hopkins cohort met all the criteria for very-low-risk prostate cancer, defined by the National Comprehensive Cancer Network: clinical stage T1c disease, prostate-specific antigen density below 0.15 ng/mL, Gleason score of 6 or lower, 2 or fewer cores with cancer, and 50% or less cancer involvement of any core.
Notably, these men were 30% less likely to be reclassified to a high-risk category during surveillance and to need subsequent surgery or radiation than men who did not meet 1 or more of the study criteria.
"Limiting surveillance to patients with the lowest-risk category of disease may reduce the incidence of adverse outcomes," say Dr. Carter and his coauthors.
The authors, who report that men in the current study have an average follow-up of only 2.7 years, offer a very important caveat about active surveillance at this point in time: "even 10 years [of follow-up] is not an adequate time frame for the evaluation of prostate-cancer-specific survival." In other words, only more time will tell just how safe active surveillance is for men in this cohort.
Until more is known about the risks of delaying treatment, active surveillance hinges on a bet, said one of the investigators of the Surveillance Therapy Against Radical Treatment (START) trial, the first-ever North American phase 3 trial comparing active surveillance and treatment (radiotherapy or prostatectomy).
"The bet is that we can detect disease progression before it causes the patient harm," Adam Kibel, MD, from the Washington University School of Medicine in St. Louis, Missouri, told Medscape Medical News last year.
Accordingly, the authors from Johns Hopkins remind clinicians that active surveillance is not without risk: "patients considering surveillance should be counseled on the possibility that delayed intervention may compromise the opportunity for cure in some cases."
Intervention Based on Biopsy, Not PSA
The surveillance cohort at Johns Hopkins is 1 of a number of major cohorts in North America and Europe. All of the studies are based on the idea that surveillance might reduce the overtreatment of prostate cancer, which has been estimated to affect as many as 1 million men in the United States since the inception of widespread prostate-specific antigen (PSA) testing in the mid-1980s.
The Johns Hopkins study is different in 2 major ways from the other studies, the authors say.
"Our approach to surveillance differs somewhat from other programs in both the selection of candidates and the criteria for intervention," they write.
The Hopkins study consists mainly of men with very-low-risk disease, as opposed to low- and intermediate-risk disease, and it uses surveillance biopsy findings, which are taken annually, as the trigger for intervention, as opposed to biochemical recurrence (PSA kinetics).
The rate of curative intervention in all of the studies has been about 30%, observe the authors, but the reasons for the intervention differ by study, they explain.
"Although 73.4% of men in our program underwent intervention because of biopsy reclassification, other programs cite PSA kinetics as a common trigger for intervention," the team writes. PSA kinetics have proven to be an unreliable measure in their study, as reported earlier by Medscape Medical News.
The study has a lower proportion of men who have had biochemical recurrence than studies in Europe and Canada. "This may be the case because of previously described differences in entry criteria specific to each program and may further support our belief that active surveillance is safest for those with very-low-risk disease," say Dr. Carter and colleagues.
Further Details
The primary outcome of the study was survival free of intervention. The median for this measure among the participants was 6.5 years (range, 0 to 15 years) after diagnosis, report the authors.
The proportions of men remaining free of intervention after 2, 5, and 10 years of follow-up were 81%, 59%, and 41%, respectively.
Overall, 255 men (33.2%) underwent intervention. The median time of the intervention was 2.2 years (range, 0.6 to 10.2 years). Of these men, 188 men (73.7%) underwent intervention on the basis of disease reclassification after biopsy.
As noted above, the proportions of men who underwent curative intervention (P = .026) or had biopsy reclassification (P < .001) were significantly lower in men who met the enrollment criteria than in those who did not.
Funding support for the study was provided by the Patrick C. Walsh Prostate Cancer Research Fund. The author have disclosed no relevant financial relationships.
J Clin Oncol. Published online April 4, 2011. Abstract
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