Lifetime economic burden of prostate cancer

According to the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database, prostate cancer (PCa) prevalence in 2008 was estimated at 2,555,936 [1]. Prostate cancer is the most common cancer affecting men in the United States (U.S.) [1]. This is a result of both advances in screening following introduction of the prostate specific antigen (PSA) test as well as increases in survival attributable to more effective therapies [2]. Although incidence has leveled off in recent years, the American Cancer Society estimates that approximately 186,000 men were diagnosed with PCa in 2008 [2]. Approximately 60% of incident prostate cancer cases are diagnosed at ≥ 65 years of age [3]. The initial treatment and subsequent monitoring of these large numbers of PCa cases places a burden on U.S. health care systems. Prevalence based treatment costs for 2006 alone have been estimated at $9.6 billion [4].

Two therapies including finasteride and dutasteride have recently been studied for the prevention of PCa [5, 6]. Economic burden of illness studies are important because they quantify the costs that could be avoided should these pharmacologic agents prove effective in reducing incident cancer cases. Common approaches to estimating disease-related costs often include the use of a healthcare claims database. However, databases often do not provide enough years of follow-up to estimate life-time costs. This is particularly problematic for PCa as five-year survival rates approach 100% and censored cost data become a concern [1]. Thus, there is a paucity of data concerning life-time PCa costs. This study provides estimates of total and disease-related per-patient lifetime costs using a phase-based model of cancer care among patients diagnosed with prostate cancer at ≥ 65 years of age.

Prostate cancer places a significant burden on the U.S. Medicare system with average per-patient life-time attributable costs of approximately $34,000 (discounted at 3%). PCa-related costs represented approximately one-third of total medical care costs. Our analyses indicate that the aggregate life-time disease-related burden attributable to incident PCa cases ≥ 65 years of age in 2008 approaches $4.0B (discounted at 3%). PCa-related life-time costs were variable by cancer stage and ranged from $26,078 (Stage III) to $39,182 (Stage I). Stage IV had the poorest prognosis as the mean survival time was only 44 months compared to 172, 180, and 196 months for Stages I, II, and III, respectively.

A study conducted by Riley and colleagues examined total life-time costs of several cancers including prostate in elderly Medicare-eligible patients using the SEER-Medicare database [14]. To the best of our knowledge this is the only study conducted to date that reports life-time estimates of treatment costs. Riley et al. estimated costs in PCa patients ≥ 65 years of age using data from 1984 to 1990, an era pre-dating widespread use of the PSA screening test [14]. Comparison of our dataset with Riley et al. allows us to examine trends in survival and costs occurring over time. We report estimates of total life-time costs that are higher (Stages I, II: $118,261, Stage III: $110,943, Stage IV: $73,587) relative to Riley (Local: $98,447; Regional: $99,542; Distant: $62,634, adjusted to 2004 US$). We also estimate longer periods of survival (13.2 vs. Riley: 7.0 years). This finding is largely the result of the fact that the majority of PCa patients diagnosed in the era of widespread PSA screening that has taken place since the early 1990s are now diagnosed at earlier stages and no longer have excess mortality compared to the general population [9]. Upon adjusting total costs by year of follow-up, our estimates were actually lower ($8,373) relative to Riley et al. ($13,028, adjusted to 2004 US$) [14]. This finding may suggest that PCa patients can now expect to have lower morbidity related to earlier diagnosis and therefore also accrue fewer costs. Patients diagnosed at earlier stages may also be more likely to receive watchful waiting which has the effect of lowering costs relative to patients diagnosed at higher stages.

An interesting finding of our study was that Stage III PCa patients were diagnosed approximately 3.4 years younger compared to Stages I/II (age at diagnosis: 67.8 vs. 71.2 years). Prior studies examining treatment and survival outcomes using SEER registry data and data from a tumor registry in Germany have also similarly reported that Stage III patients are diagnosed at younger ages versus Stages I/II [15, 16]. As part of our analysis, we assumed that survival among Stage I-III PCa patients would follow the U.S. general population based in part on 5-year relative survival statistics from SEER reporting that PCa patients diagnosed with local and regional disease is 100% [3]. Relative survival is a measure of net survival that is calculated by comparing overall survival with survival from similar individuals without cancer. We considered this to be a conservative assumption with respect to our estimation of costs since prior studies have reported relative survival for local/regional stage PCa in excess of 100% [9, 16]. This finding may be explained in part by the fact that many local/regional stage tumors are diagnosed as a result of PSA screening and men who undergo this preventive measure may in fact be healthier compared to men who do not participate in PSA testing [17]. Therefore, when we estimated predicted mean survival for Stage I-III patients based on U.S. life tables, longer survival for Stage III versus Stage I/II patients was a function of their earlier mean age at PCa diagnosis as well as the assumption that survival for these patients would follow the U.S. general population. Rather than report age-adjusted survival estimates, the authors considered it important to have the survival data reflect the finding that Stage III patients are diagnosed at earlier ages relative to Stages I/II.

This study was subject to several limitations. Since PCa patients generally have a good prognosis following diagnosis and therefore long survival times, we did not have information on the date of death for the majority of patients in SEER. This was especially problematic for patients diagnosed at Stages I-III where it was assumed survival for these patients would follow the U.S. general population. This was a conservative assumption as a prior study reported relative survival rates for early stage PCa that were greater than 100% [9].

In partitioning the survival periods of patients into distinct phases of care, we used methodology similar to a study conducted by Brown and colleagues [7, 11]. It should be noted that these studies were conducted in populations of colorectal, breast and lung cancer patients. However, we believe that the application of their methodology to PCa is appropriate despite the fact that many early stage patients may receive watchful waiting. In a prior study, we found that ~45% of Stage I patients received active therapy [12]. It may be argued that, for Stage I-IIa patients where a watchful waiting approach is more common, separate initial and continuing care phases may not have been warranted. However, in defining treatment phases we also looked at diagnostic procedures for cancer staging as well as outpatient visits and hospitalizations and, in our exploratory analyses, we found that more early stage PCa patients used these service types in the first 6 months following cancer diagnosis. Therefore, we considered separate initial and continuing care phases appropriate for early stage PCa. Furthermore, our analyses of healthcare costs for each treatment phase among Stage I patients showed a U-shaped pattern characteristic of patients utilizing a higher degree of medical services both in the months shortly following PCa diagnosis and in the months leading up to death compared to the months defined as continuing care.

The economic analysis was conducted from a payer perspective and includes reimbursement payments made to physicians, facilities and other healthcare professionals for the medical services that were provided to PCa patients. Other components of the economic burden of PCa including out-of-pocket spending on direct medical care as well as the indirect costs associated with reduced productivity and lost work time for both caregivers and patients were not included in this study. These cost components have been shown to represent an important proportion of the total cost burden. A study by Chang and colleagues reported monthly costs of $373, $698, and $302 for absenteeism, short-term disability, and deductibles/copayments, respectively among newly diagnosed cancer (including brain, colorectal, lung, ovarian, pancreatic, prostate, and non-Hodgkin's lymphoma) patients during the first few years following cancer diagnosis [18]. Absenteeism and short-term disability data were not available in the data sources used for the current analysis. However, this may not have contributed greatly to costs related to PCa as the population was ≥ 65 years old and not likely to have still been working. It should also be noted that Medicare cost data from calendar years 1991 through 2004 were used for this current study. During this time, Medicare did not cover most prescription drugs. Hence, prescription drug costs were not included in our estimates of direct medical costs.

It is also important to note that our survival estimates for Stage IV patients do not account for the index year of PCa diagnosis in order to adjust for improvements in prognosis among patients diagnosed in more recent years. A recent study reports that during the early 1990s until 2001, the 5-year relative survival of Stage IV patients has increased from approximately 50%-60% [19]. Therefore, this will have the effect of underestimating slightly the economic burden of PCa for recently diagnosed Stage IV patients.

Finally, it should be noted that the estimation of life-time costs is an area of research that is highly speculative [20]. Our analyses are based on the treatment experience and cost profiles of a cohort of patients diagnosed during calendar years 1991 through 2005. It is unlikely that the resource trends and costs of patients diagnosed in 2008 and more recently will exactly mirror the experience of past cohorts. For example, laproscopic and robot-assisted surgical methods are now currently more widely used. Advances have also been made in the treatment of advanced stage PCa. In 2004, it was shown that docetaxel can prolong survival in men with advanced PCa no longer responding to hormone therapy and in 2010, cabazitaxel was approved for use in advanced PCa after failure with docetaxel. As a result of these treatment advances, the PCa cost estimates reported in this study will probably understate slightly the initial and life-time treatment costs for PCa patients diagnosed today.

Our analyses offer insight into the magnitude of total and disease-related lifetime costs for patients ≥ 65 years of age at PCa diagnosis in an era of improved screening and treatment (1991-2002). Long-term estimates are useful for understanding the upper limit of treatment costs that could be avoided should prevention strategies prove effective in reducing incident PCa cases. Study results indicate that the aggregate lifetime PCa-related burden for 2008 incident cases ≥ 65 years old is approximately $4.0 billion.