In this study, we have observed a consistently increasing trend in both genders of cumulative incidence rates of RCC (Fig. 1), which are associated with a heavy loss of LE and large lifetime financial burdens during the last two decades (Table 1). The accuracy of our estimations can be supported as follows. First, because all patients diagnosed with cancer have been eligible for a copayment waiver from the NHI since 1995, every cancer diagnosis must be validated by at least two specialists to prevent abuse 17. To qualify for a copayment waiver, the cancer diagnosis must be substantiated by pathological proof, ensuring the accuracy of estimated incidence rates. Second, because the index cohorts have been followed for up to 19 years, which is longer than the typical LE of patients diagnosed with RCC who are older than 50 years of age, relatively few years required extrapolation (Tables 1 & 2 and Fig. 3). Our extrapolation method is performed through repeatedly constructing spline models based on the logit of the survival ratio between the index cohort and age-, sex-, and calendar year-matched referents simulated from general population mortality rates, which were corroborated by recent statistical reviews 18–20. Third, because all patients diagnosed with RCC were waived from copayment, our estimation of lifetime costs reimbursed by NHI is comprehensive. Fourth, although the effectiveness of healthcare services is directly compared for survival rates in randomized control trials, the adoption of real-world data must adjust for differences in the age, sex, and medical technology in the calendar year of diagnosis. The comparison of loss of LE, or, difference-in-differences would be less confounded by these issues than LE. Thus, we tentatively conclude that our estimations are relatively accurate and would be useful in consideration and comparison of cost-effectiveness across different technology and diseases.
Although most studies related to long-term outcomes in RCC typically quantify the 5- or 10-year survival rates, these numbers may not be easily comprehensible by laypeople. In this study, we adopted a novel method for estimating LE and the loss of LE to compare across various RCC subcohorts. Table 1 shows that women with RCC generally presented with longer LE than men, especially those diagnosed in the younger age group, which appear to corroborate previous reports 21–23. However, the loss of LE was similar between men and women, suggesting that the health impacts of RCC are similar between sexes after adjusting for age, sex, and differences in available medical technology at the time of diagnosis. The Taiwan Cancer Registry began collecting detailed data regarding pathological subtypes in 2005, and the follow-up time for clear cell RCC is approximately 10 years. Our initial analysis revealed a larger loss of LE among women diagnosed with clear cell RCC relative to men (Table 2), which deserves attention and future studies.
Most previous studies have generally reported cost per year or lifetime costs associated with specific medications used to treat metastatic RCC and have been based on Markov models with underlying assumptions, supplemented by sensitivity analyses for the potential adoption of health policy decisions 5,13. In contrast, our team has taken the advantage of 19 years of follow-up data 24 and developed a novel method for extrapolating the survival function over the patient’s lifetime. We have successfully estimated lifetime medical costs based on real-world data 25,26, which could be considered a validation of Markov model predictions. We found that the lifetime costs of RCC are similar between men and women, but women diagnosed with RCC tend to consume a lower average cost per life-year than men after stratification by age (Table 1). As the patient’s age increased, the costs of caring for RCC also tended to increase 14, which was corroborated by the present study.
Target therapy for RCC in Taiwan included sorafenib, sunitinib and everolimus, which have been reimbursed by NHI since October 1, 2009, January 1, 2010, and April 1, 2010, respectively. We compared costs of patients who received surgical treatment only versus those ever received target therapy. Patients who received surgical treatment only are those at early cancer stages and usually associated with better prognosis, or, longer survival and smaller costs. In general, the longer the life expectancy, the higher the reimbursed lifetime costs in patients with RCC treated without target therapy. Table 2 indicates that clear cell RCC showed generally higher proportions of patients received surgical treatment only. Unfortunately, male patients with clear cell RCC showed a comparative lower rates of receiving surgical treatment only at age 50–64, which may be associated with the highest lifetime costs in this group. Namely, increased target therapy of clear cell RCC in this group make them the highest lifetime and monthly costs.
Limitations
This study has the following limitations that must be acknowledged: First, because the staging and detailed treatment information were not available from Taiwan’s NHI databases, LE, loss of LE, and other parameters were unable to be further classified according to differences in disease stage or treatment methods. Early diagnosis and treatment could reduce LE loss, and further studies are warranted to explore potential screening methods to decrease the burdens associated with RCC. Second, the lifetime costs associated with an RCC diagnosis in our study were calculated according to reimbursement data obtained from Taiwan’s NHI database, which does not include patients’ out-of-pocket expenses. As we have included all reimbursement data after diagnosis, our estimation of lifetime costs is also likely to include reimbursement costs related to other comorbidities and likely overestimates the total costs that can be directly attributed to RCC, especially among patients with longer survival. Third, because this study did not consider patients’ quality of life, we were unable to estimate the quality-adjusted life expectancy or cost per quality-adjusted life-year). Future studies are warranted to incorporate this information to provide a more comprehensive estimation of the cost-effectiveness of RCC treatment.
In summary, the incidence rates and economic burdens associated with RCC have increased over the past two decades in Taiwan. The results of our study may help patients, clinicians, and health authorities better understand the epidemiological and pharmacoeconomics landscape associated with RCC treatment in Taiwan. Early diagnosis of clear cell RCC may be the first strategy we shall take to control this dreadful disease, especially for those at young and/or middle ages. Future studies must consider both quality of life and other societal impacts associated with an increasing burden of RCC, such as productivity loss and demands for long-term care 11. Especially, we had better evaluate cost-per-QALY (quality-adjusted life year) for different target therapies.