Tuesday, July 27, 2010

PSA Screening Halves Mortality From Prostate Cancer: Gothenburg Study

Lancet Oncol. Published online July 1, 2010.

News Author: Zosia Chustecka
CME Author: Désirée Lie, MD, MSEd

Clinical Context

PSA screening has been shown to reduce prostate cancer mortality rates at a screening period of 9 years, but the follow-up period may have been inadequate, and longer follow-up may demonstrate greater benefits.

This is a population-based, randomized study of a cohort of men who were invited to receive PSA screening every 2 years from inception to determine the effect of screening on prostate cancer diagnosis and mortality.

Study Highlights

* The study began in 1994 and involved a sample of men living in a city in Sweden. These men were identified by computer randomization and were then randomly assigned to either screening or no screening.
* 3 birth cohorts were included: those born in 1930 to 1934, 1935 to 1939, and 1940 to 1944.
* Men with existing prostate cancer and those who migrated or died before screening were excluded.
* Screening consisted of invitations every 2 years for PSA testing.
* The upper age of screening was predetermined as 69 years.
* The control group did not receive an invitation for screening.
* The incidence of prostate cancer was determined by linkage of the cohort with the West Swedish Regional Cancer Registry every third month. In 2009, all 6 regional cancer registries in Sweden were linked, and cancer data were obtained.
* The cause-of-death certificate was used to identify cases, and an independent committee adjudicated causes of death.
* There were 9952 evaluable men in each group.
* Median age was 56 years at baseline, and 20,000 men were randomly assigned.
* 76% of men in the screening group participated in at least 1 screening.
* 33% of men who received screening had an increased PSA level.
* Of those with an increased PSA level, 93% had a prostate biopsy at least once.
* The maximal follow-up period of 14 years was reached by 78% of the men in the screening group.
* Prostate cancer was diagnosed in 11.4% of men in the screening group and 7.2% in the control group.
* Of those with detected prostate cancer in the screening group, 78.7% were diagnosed directly as a result of screening.
* The cumulative incidence of prostate cancer at 14 years was 12.7% in the screening group vs 8.2% in the control group (hazard ratio, 1.64; P < .0001).
* The hazard ratio was 5.2 in the first year, decreasing to 3.7, 2.6, 2.1, then 1.2 by 8 years or more.
* Prostate cancers diagnosed in the screening group were more likely to be early stage, and the number of advanced cancers was lower in the screening group vs the control group.
* The difference in stage distribution was reflected in treatment, with the screening group more likely to be treated with surveillance or curative treatment.
* In men diagnosed with prostate cancer, the median follow-up after diagnosis was 6.7 years in the screening group vs 4.3 years in the control group.
* The RR of dying of prostate cancer was 0.56 (P = .002) in the screening group vs the control group.
* The absolute cumulative risk reduction was 0.5% (from 0.9% - 0.4% in the control group).
* In a secondary analysis, the RR of death from prostate cancer for those who attended screening vs the control group was 0.44 (P = .0002), whereas for those in the screening group who were invited for a screening but chose not to attend, the RR was 1.05
* Attendees who started screening when older than 60 years were at a higher risk of dying of prostate cancer vs men who were younger at study entry.
* The cumulative risk for deaths not related to prostate cancer was similar in the 2 groups.
* The NNS to prevent 1 prostate cancer–related death was 293, and the NNT was 12.
* When restricted to attendees of screening, the respective numbers were 234 and 15.
* The authors concluded that a PSA prostate cancer screening program was acceptable to men (response rate, 76%) and that screening was associated with an increased diagnosis of prostate cancer and a reduced mortality rate from the disease.
* However, they cautioned that benefits take a long time to achieve, are associated with risks for overdiagnosis and overtreatment, and may not be beneficial in older men.

Clinical Implications

* PSA screening every 2 years in men aged 50 to 69 years is associated with a 64% higher rate of diagnosis of prostate cancer vs no screening.
* PSA screening every 2 years in men aged 50 to 69 years is associated with lower mortality rates from prostate cancer.

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