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Originally published as JCO Early Release 10.1200/JCO.2005.09.906 on November 30 2004 © 2005 American Society of Clinical Oncology.
Period Analysis of Prostate Cancer SurvivalComprehensive Cancer Center, University of Wisconsin, Madison, WI More than 220,000 men will be diagnosed with prostate cancer this year, representing about one third of all cancers diagnosed among men, and more than any other cancer.1 Once diagnosed, men and their families often face difficult treatment decisions, ranging from radical prostatectomy and radiation to watchful waiting. Unfortunately, for some men, the disease continues to progress, resistant to all forms of treatment. Many questions remain in our quest to understand better ways to prevent, diagnose, and treat prostate cancer. In the 1990s and early 2000s, we witnessed a marked initial increase in new diagnoses, followed by a plateau in the incidence of the disease, likely attributable to the increasing use of prostate-specific antigen (PSA). After a frightening increase to approximately 40,000 American prostate cancer deaths per year, we have experienced a decline in prostate cancer-related deaths to approximately 28,900 in 2003.1 Why did this reduction in the death rate occur? What can we do to sustain this rate of improvement in survival? How does a patient improve his chances of surviving his prostate cancer 5 or 10 years from now? And who should be implementing the changes in how we approach this disease? Brenner and Arndt,2 in this issue of the Journal of Clinical Oncology, do not provide definitive answers to any of these questions. But, they do provide helpful, up-to-date information about the survival experience among men diagnosed with prostate cancer. The bottom line is that most men diagnosed with the disease today can expect to live as long as, or longer than, men their age without the disease. Given the many uncertainties about this disease, this information alone will be helpful for clinicians and their patients when discussing treatment options and when considering what life will be like, living as a prostate cancer survivor. The authors of the study used a novel method to estimate long-term survival experiences of men diagnosed with the disease in an era of rapidly changing patterns of care of this disease. This is not a report on the value of PSA screening. PSA screening started to enter clinical practice in the late 1980s in the United States. By 2000, more than 50% of men aged 65 years or older had undergone a PSA test within the past year. Clearly, the 1990s represented a transition decade, when American men and their physicians were increasingly utilizing PSA screening. This resulted in an increase in diagnoses and in stage migration to more localized cancers, as well as an increase in the number of men undergoing therapy. In such a dynamic setting, standard cohort analyses for 5- and 10-year survival estimates would follow men diagnosed more than a decade ago; therefore, any impact of changes in patterns of care introduced recently might not be detected. The study by Brenner and Arndt2 used period analysis of more recent data; therefore, the impact of current treatment and diagnostic approaches is more likely reflected in the results.3 What is period analysis? In the context of this study, estimates of 5- and 10-year survival were generated using data on the survival experience of patients in the year 2000. To obtain survival estimates with this approach, the entire experience of cohorts of patients diagnosed in the previous 10 consecutive years (1990 to 1999) is used (not just those diagnosed a decade or more ago). The data from these more recent cohorts are then used to estimate 5- and 10-year absolute and relative survival rates. In contrast, more traditional cohort analysis would use data solely from men diagnosed in 1995 and 1990 to calculate the 5- and 10-year survival estimates. Importantly, this period analysis approach has been shown in other evaluations to provide more timely estimates of long-term survival rates than traditional survival analyses, as period analysis survival estimates for a particular year have closely reflected the survival eventually observed in patients diagnosed in that year.4-7 In the Brenner and Arndt study, Surveillance, Epidemiology, and End Results data on 180,605 men diagnosed in the United States between 1990 and 2000 were used to calculate both absolute and relative survival rates of prostate cancer patients compared with the general population. The results presented are very encouraging. Absolute survival rates 5 and 10 years after diagnosis were estimated to be 79% and 54%, respectively. Five- and 10-year period estimates of relative survival for the year 2000 were 98.9% and 94.8%, indicating that excess mortality due to prostate cancer 5 and 10 years after diagnosis could be as low as 1% and 5%, respectively. Comparison with traditional cohort survival analysis for patients diagnosed in 1990 showed 5- and 10-year relative survival of 90% and 82%. Evidence that period analysis of more contemporary data is reflective of current survival is provided in the 5-year cohort analysis of patients diagnosed in 1995, which showed a relative survival of 96%, very close to the 98.9% relative survival predicted by period analysis using 2000 data. If subsets of men are analyzed, period analysis of men diagnosed between the ages of 65 to 74 years—the age group representing the highest number of prostate cancer diagnoses—show little or no excess mortality associated with a diagnosis of prostate cancer. While white men continued to have a better survival than black men, both groups showed improvement in relative survival, indicating that factors contributing to these improved survival data were impacting both populations. Stage and grade of tumor were the strongest prognostic factors. The overall conclusion of the investigators is that period analysis of survival in prostate cancer shows that most patients diagnosed with prostate cancer in the United States no longer have excess mortality compared with the general population. This information will be welcome news to patients at the time of diagnosis. The methods used in this study accurately report the actual survival experience of men diagnosed during the past decade. However, there are important methodologic reasons that may account for these results. PSA screening, newer treatments, earlier therapy, and increased awareness and knowledge of prostate cancer have likely all contributed to this improvement in survival. The authors have provided a balanced discussion, cautioning the readers not to overinterpret these results. First, there is undoubtedly an element of lead-time bias for some patients, and there are likely patients who are diagnosed and treated who might never have become clinically relevant.8 In addition, screening certainly contributed to a significant shift towards earlier-stage disease at diagnosis.9 This would be significant if these men are then more likely to be cured by current primary therapy; otherwise mortality would still likely occur, but outside the boundaries of the 5- and 10-year benchmarks. Likewise, improvement in local therapy and the implementation of early hormone therapy in patients at risk of developing metastatic disease after primary therapy might also be contributing to improved survival.10 Although the recent decline in the death rate from prostate cancer is encouraging, and suggests real improvements in survival, other explanations exist. For example, the increase in death rates observed before 1990 may have been an artifact of screening, with more diagnoses of prostate cancer simply being listed on the death certificate, rather than actually being the underlying cause of death.11-12 Prostate cancer continues to be a major health problem and a leading cause of death in men. While advances have been made in understanding the biology, diagnosis, public awareness, and treatment of local and advanced disease, there is still a lot of work to be done. Observational studies such as this one cannot answer important questions about the efficacy of screening or therapeutic interventions. These questions must be answered in carefully designed clinical trials. Nevertheless, Brenner and Arndt present us with a new tool to provide information to patients and their families about what they can expect following the diagnosis of prostate cancer. Two thirds of patients diagnosed today with prostate cancer have a relative survival equal to the general population. This is welcome news. For some men, the diagnosis of prostate cancer will not affect their survival. Since we do not know what exactly has caused this improvement in survival, we should certainly continue to apply our current standards of care in treating patients with prostate cancer. We still have a long way to go to prevent the 28,900 deaths of American men annually from prostate cancer and to prevent prostate cancer itself. Many of these issues will only be answered through large trials. Continued progress, with the aid of tools such as period analysis, is dependent on the devoted participation in clinical trials of men with prostate cancer and their caregivers. Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES 1. American Cancer Society: Cancer Facts & Figures, 2003. http://www.cancer.org
2. Brenner H, Arndt V: Long-term survival rates of patients with prostate cancer in the PSA screening era: Population-based estimates for the year 2000 by period analysis. J Clin Oncol 23:441-447, 2005 3. Brenner H, Gefeller O, Hakulinen T: Period analysis for up-to-date cancer survival data: Theory, empirical evaluation, computational realization and applications. Eur J Cancer 40:326-335, 2004 4. Cutler SJ, Ederer F: Maximum utilization of the life table method in analyzing survival. J Chronic Dis 8:699-712, 1958[CrossRef][Medline] 5. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 58:457-481, 1958[CrossRef]
6. Brenner H, Hakulinen T: Up-to-date long-term survival estimates of patients with cancer by period analysis. J Clin Oncol 20:826-832, 2002
7. Brenner H, Hakulinen T: Advanced detection of time trends in long-term cancer patient survival: Experience from 50 years of cancer registration in Finland. Am J Epidemiol 156:566-577, 2002
8. Draisma G, Boer R, Otto SJ, et al: Lead times and overdetection due to prostate specific antigen screening: Estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst 95:868-878, 2003
9. Harris R, Lohr KN: Screening for prostate cancer: An update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 137:917-929, 2002
10. Messing EM, Manola J, Sarosdy M, et al: Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 341:1781-1788, 1999
11. Hankey BF, Feuer EJ, Clegg LX, et al: Cancer surveillance series: Interpreting trends in prostate cancer Part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates. J Natl Cancer Inst 91:1017-1024, 1999
12. Feuer EJ, Merrill RM, Hankey BF: Cancer surveillance series: Interpreting trends in prostate cancer Part II: Cause of death misclassification and the recent rise and fall in prostate cancer mortality. J Natl Cancer Inst 91:1025-1032, 1999 Related Article
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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