Objective
To evaluate the current prostate cancer screening and treatment paradigm in light of recently published long‐term results of major screening and treatment trials.
Methods
Historical review ...of the evolution of the diagnosis and treatment of prostate cancer followed by a detailed summary of the findings and differences among the three major screening trials and the three major treatment trials.
Results
Prostate‐specific antigen (PSA) testing can identify clinically significant prostate cancer and has produced a significant stage shift and is the likely explanation for the decline in prostate cancer mortality. Unfortunately, PSA testing predominantly identifies low‐grade disease that is unlikely to progress during a patient’s lifetime leading to substantial diagnosis of indolent disease. Treatment with radical prostatectomy (RP) appears to benefit primarily younger men (aged <65 years) with intermediate‐grade disease. Too few men with low‐grade disease benefit from RP to justify intervening in all. Unfortunately, high‐grade prostate cancer often progresses despite surgery and radiation.
Conclusion
The primary PSA testing paradigm is wrong. Rather than attempting to identify all prostate cancers as early as possible, testing objectives should shift towards identifying men likely to harbour clinically significant disease. These are the men who appear to benefit from early diagnosis and intervention, including the earlier use of antiandrogen therapy prior to widespread metastases.
Background Although there is uncertainty about the effect of prostate-specific antigen (PSA) screening on the rate of prostate cancer death, there is little uncertainty about its effect on the rate ...of prostate cancer diagnosis. Systematic estimates of the number of men affected, however, to our knowledge, do not exist. Methods We obtained data on age-specific incidence and initial course of therapy from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. We then used age-specific male population estimates from the US Census to determine the excess (or deficit) in the number of men diagnosed and treated in each year after 1986—the year before PSA screening was introduced. Results Overall incidence of prostate cancer rose rapidly after 1986, peaked in 1992, and then declined, albeit to levels considerably higher than those in 1986. Overall incidence, however, obscured distinct age-specific patterns: The relative incidence rate (2005 relative to 1986) was 0.56 in men aged 80 years and older, 1.09 in men aged 70–79 years, 1.91 in men aged 60–69 years, 3.64 in men aged 50–59 years, and 7.23 in men younger than 50 years. Since 1986, an estimated additional 1 305 600 men were diagnosed with prostate cancer, 1 004 800 of whom were definitively treated for the disease. Using the most optimistic assumption about the benefit of screening—that the entire decline in prostate cancer mortality observed during this period is attributable to this additional diagnosis—we estimated that, for each man who experienced the presumed benefit, more than 20 had to be diagnosed with prostate cancer. Conclusions The introduction of PSA screening has resulted in more than 1 million additional men being diagnosed and treated for prostate cancer in the United States. The growth is particularly dramatic for younger men. Given the considerable time that has passed since PSA screening began, most of this excess incidence must represent overdiagnosis.
Any effective screening program must satisfy 2 criteria: 1) the test must identify clinically significant disease earlier than its clinical presentation, and 2) a treatment must be available that ...will alter the natural history of the disease. The controversy surrounding PSA testing that has raged since 1991 centers on these 2 points. Screening and treatment trials published during the past 3 decades have provided critical insights into our understanding of the natural history of PSA identified cancers and the impact of treatment. This in turn raises questions concerning the mechanism of prostate cancer mortality reduction. This essay reflects on the mechanisms of disease progression and the implications for future screening and treatment efforts.
The appropriate therapy for men with clinically localized prostate cancer is uncertain. A recent study suggested an increasing prostate cancer mortality rate for men who are alive more than 15 years ...following diagnosis.
To estimate 20-year survival based on a competing risk analysis of men who were diagnosed with clinically localized prostate cancer and treated with observation or androgen withdrawal therapy alone, stratified by age at diagnosis and histological findings.
A retrospective population-based cohort study using Connecticut Tumor Registry data supplemented by hospital record and histology review of 767 men aged 55 to 74 years with clinically localized prostate cancer diagnosed between January 1, 1971, and December 31, 1984. Patients were treated with either observation or immediate or delayed androgen withdrawal therapy, with a median observation of 24 years.
Probability of mortality from prostate cancer or other competing medical conditions, given a patient's age at diagnosis and tumor grade.
The prostate cancer mortality rate was 33 per 1000 person-years during the first 15 years of follow-up (95% confidence interval CI, 28-38) and 18 per 1000 person-years after 15 years of follow-up (95% CI, 10-29). The mortality rates for these 2 follow-up periods were not statistically different, after adjusting for differences in tumor histology (rate ratio, 1.1; 95% CI, 0.6-1.9). Men with low-grade prostate cancers have a minimal risk of dying from prostate cancer during 20 years of follow-up (Gleason score of 2-4, 6 deaths per 1000 person-years; 95% CI, 2-11). Men with high-grade prostate cancers have a high probability of dying from prostate cancer within 10 years of diagnosis (Gleason score of 8-10, 121 deaths per 1000 person-years; 95% CI, 90-156). Men with Gleason score of 5 or 6 tumors have an intermediate risk of prostate cancer death.
The annual mortality rate from prostate cancer appears to remain stable after 15 years from diagnosis, which does not support aggressive treatment for localized low-grade prostate cancer.
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