Prostate cancer stage has declined more than Gleason score

The proportion of advanced prostate cancers has declined by more than sixfold over the last 2 decades; however, the proportion of high Gleason grade tumors has not followed suit.

The findings from a 22-year review of two large databases suggest that most low-grade prostate tumors do not progress over time. They further suggest that men can be successfully managed with active watchful waiting – repeated, close follow-up that could spare many from unnecessary and possibly harmful interventions, reported Kathryn Penney, Sc.D. The study was published in the Aug. 14 issue of Cancer Research (Cancer Res. 2013;73:5163-8).

"Men with low-grade disease are being encouraged more and more to do this sort of active surveillance, which isn’t just watching and waiting, but returning for regular visits, additional blood tests, or additional biopsies," Dr. Penney said in an interview. "This is an encouraging trend, because men who are candidates for this kind of follow-up may not end up being candidates for radiation or surgery, which can have long-term side effects."

Dr. Penney, an associate epidemiologist at Brigham and Women’s Hospital, Boston, examined prostate tumor characteristics among 1,207 men who were included in two longitudinal studies: 420 in the Physicians’ Health Study (PHS) and 787 in the ongoing Health Professionals Follow-Up Study (HPFS). All of the men had undergone radical prostatectomy. Dr. Penney and her colleagues analyzed tissue from each tumor and categorized the results from four epochs: 1982-1993, 1993-1996, 1996-2000, and 2000-2004.

Mean age at diagnosis was 66 years in both studies. Information about prostate specific antigen was not available for the PHS, since it was an earlier cohort examined from 1982 to 2004. For the HPFS data, PSA results were available from 1994 onward. In 1994, 42% of the entire study group had been tested in the previous 2 years; that increased to 81% by 2000.

From 1982 to 1993, the earliest epoch, 20% of tumors were stage T3 or higher. This proportion decreased over all four epochs, declining to 3% by the last period – an 85% drop. There were no T4 tumors in that epoch.

There was a 30% decrease in tumors with a Gleason score of 8 or more, dropping from 25% in the first epoch to 17.6% in the last.

"When restricting [the analysis] to men with stage T1/T2, the proportion of Gleason score 8-10 decreased even less across time periods, from 19.5% to 16%," the researchers wrote.

While there was a significant age/grade relationship, with older men having higher Gleason scores, it primarily occurred during the pre-PSA screening epochs. "This suggests that the change over time we observe for Gleason score is not due to a change in age at diagnosis and may represent an increase in screening of younger men detecting more indolent, lower grade tumors," they wrote. "Widespread PSA screening not only advanced the time of diagnosis of prostate cancer, but also has increased the prevalence of detected indolent tumors that would otherwise never have been diagnosed ... Although we cannot rule out the possibility that Gleason grade progresses within an individual, we conclude that it is not a major feature of prostate cancer."

The study speaks to the biology of prostate cancer as well, Dr. Penney and her coinvestigators noted. If Gleason score "seems set early in the disease," then later, potentially modifiable risk factors might be a trigger for progression in low-grade disease. "If we suppose that a Gleason score 3+3 will remain 3+3 for the entire course of the disease, active surveillance could be considered a definitive treatment for selected patients with [10 or fewer years life expectancy] and could significantly delay (potentially forever) the treatment of selected patients with [more than] 10 years life expectancy."

"Alternatively, earlier influences, such as genetics, may drive the development of a subtype of cancer that is more aggressive in a way that is not related to differentiation status," they said.

The study was funded by the Dana-Farber/Harvard Cancer Center, the National Cancer Institute, and the National Heart, Lung, and Blood Institute. Dr. Penney had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

The proportion of advanced prostate cancers has declined by more than sixfold over the last 2 decades; however, the proportion of high Gleason grade tumors has not followed suit.

The findings from a 22-year review of two large databases suggest that most low-grade prostate tumors do not progress over time. They further suggest that men can be successfully managed with active watchful waiting – repeated, close follow-up that could spare many from unnecessary and possibly harmful interventions, reported Kathryn Penney, Sc.D. The study was published in the Aug. 14 issue of Cancer Research (Cancer Res. 2013;73:5163-8).

"Men with low-grade disease are being encouraged more and more to do this sort of active surveillance, which isn’t just watching and waiting, but returning for regular visits, additional blood tests, or additional biopsies," Dr. Penney said in an interview. "This is an encouraging trend, because men who are candidates for this kind of follow-up may not end up being candidates for radiation or surgery, which can have long-term side effects."

Dr. Penney, an associate epidemiologist at Brigham and Women’s Hospital, Boston, examined prostate tumor characteristics among 1,207 men who were included in two longitudinal studies: 420 in the Physicians’ Health Study (PHS) and 787 in the ongoing Health Professionals Follow-Up Study (HPFS). All of the men had undergone radical prostatectomy. Dr. Penney and her colleagues analyzed tissue from each tumor and categorized the results from four epochs: 1982-1993, 1993-1996, 1996-2000, and 2000-2004.

Mean age at diagnosis was 66 years in both studies. Information about prostate specific antigen was not available for the PHS, since it was an earlier cohort examined from 1982 to 2004. For the HPFS data, PSA results were available from 1994 onward. In 1994, 42% of the entire study group had been tested in the previous 2 years; that increased to 81% by 2000.

From 1982 to 1993, the earliest epoch, 20% of tumors were stage T3 or higher. This proportion decreased over all four epochs, declining to 3% by the last period – an 85% drop. There were no T4 tumors in that epoch.

There was a 30% decrease in tumors with a Gleason score of 8 or more, dropping from 25% in the first epoch to 17.6% in the last.

"When restricting [the analysis] to men with stage T1/T2, the proportion of Gleason score 8-10 decreased even less across time periods, from 19.5% to 16%," the researchers wrote.

While there was a significant age/grade relationship, with older men having higher Gleason scores, it primarily occurred during the pre-PSA screening epochs. "This suggests that the change over time we observe for Gleason score is not due to a change in age at diagnosis and may represent an increase in screening of younger men detecting more indolent, lower grade tumors," they wrote. "Widespread PSA screening not only advanced the time of diagnosis of prostate cancer, but also has increased the prevalence of detected indolent tumors that would otherwise never have been diagnosed ... Although we cannot rule out the possibility that Gleason grade progresses within an individual, we conclude that it is not a major feature of prostate cancer."

The study speaks to the biology of prostate cancer as well, Dr. Penney and her coinvestigators noted. If Gleason score "seems set early in the disease," then later, potentially modifiable risk factors might be a trigger for progression in low-grade disease. "If we suppose that a Gleason score 3+3 will remain 3+3 for the entire course of the disease, active surveillance could be considered a definitive treatment for selected patients with [10 or fewer years life expectancy] and could significantly delay (potentially forever) the treatment of selected patients with [more than] 10 years life expectancy."

"Alternatively, earlier influences, such as genetics, may drive the development of a subtype of cancer that is more aggressive in a way that is not related to differentiation status," they said.

The study was funded by the Dana-Farber/Harvard Cancer Center, the National Cancer Institute, and the National Heart, Lung, and Blood Institute. Dr. Penney had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

The proportion of advanced prostate cancers has declined by more than sixfold over the last 2 decades; however, the proportion of high Gleason grade tumors has not followed suit.

The findings from a 22-year review of two large databases suggest that most low-grade prostate tumors do not progress over time. They further suggest that men can be successfully managed with active watchful waiting – repeated, close follow-up that could spare many from unnecessary and possibly harmful interventions, reported Kathryn Penney, Sc.D. The study was published in the Aug. 14 issue of Cancer Research (Cancer Res. 2013;73:5163-8).

"Men with low-grade disease are being encouraged more and more to do this sort of active surveillance, which isn’t just watching and waiting, but returning for regular visits, additional blood tests, or additional biopsies," Dr. Penney said in an interview. "This is an encouraging trend, because men who are candidates for this kind of follow-up may not end up being candidates for radiation or surgery, which can have long-term side effects."

Dr. Penney, an associate epidemiologist at Brigham and Women’s Hospital, Boston, examined prostate tumor characteristics among 1,207 men who were included in two longitudinal studies: 420 in the Physicians’ Health Study (PHS) and 787 in the ongoing Health Professionals Follow-Up Study (HPFS). All of the men had undergone radical prostatectomy. Dr. Penney and her colleagues analyzed tissue from each tumor and categorized the results from four epochs: 1982-1993, 1993-1996, 1996-2000, and 2000-2004.

Mean age at diagnosis was 66 years in both studies. Information about prostate specific antigen was not available for the PHS, since it was an earlier cohort examined from 1982 to 2004. For the HPFS data, PSA results were available from 1994 onward. In 1994, 42% of the entire study group had been tested in the previous 2 years; that increased to 81% by 2000.

From 1982 to 1993, the earliest epoch, 20% of tumors were stage T3 or higher. This proportion decreased over all four epochs, declining to 3% by the last period – an 85% drop. There were no T4 tumors in that epoch.

There was a 30% decrease in tumors with a Gleason score of 8 or more, dropping from 25% in the first epoch to 17.6% in the last.

"When restricting [the analysis] to men with stage T1/T2, the proportion of Gleason score 8-10 decreased even less across time periods, from 19.5% to 16%," the researchers wrote.

While there was a significant age/grade relationship, with older men having higher Gleason scores, it primarily occurred during the pre-PSA screening epochs. "This suggests that the change over time we observe for Gleason score is not due to a change in age at diagnosis and may represent an increase in screening of younger men detecting more indolent, lower grade tumors," they wrote. "Widespread PSA screening not only advanced the time of diagnosis of prostate cancer, but also has increased the prevalence of detected indolent tumors that would otherwise never have been diagnosed ... Although we cannot rule out the possibility that Gleason grade progresses within an individual, we conclude that it is not a major feature of prostate cancer."

The study speaks to the biology of prostate cancer as well, Dr. Penney and her coinvestigators noted. If Gleason score "seems set early in the disease," then later, potentially modifiable risk factors might be a trigger for progression in low-grade disease. "If we suppose that a Gleason score 3+3 will remain 3+3 for the entire course of the disease, active surveillance could be considered a definitive treatment for selected patients with [10 or fewer years life expectancy] and could significantly delay (potentially forever) the treatment of selected patients with [more than] 10 years life expectancy."

"Alternatively, earlier influences, such as genetics, may drive the development of a subtype of cancer that is more aggressive in a way that is not related to differentiation status," they said.

The study was funded by the Dana-Farber/Harvard Cancer Center, the National Cancer Institute, and the National Heart, Lung, and Blood Institute. Dr. Penney had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal