Despite compelling evidence regarding the effectiveness of same-day intravesical therapy, between 1997 and 2004, only 0.33% of eligible U.S. patients received this treatment. We demonstrated that in addition to reducing the rate of bladder cancer recurrences, same-day intravesical therapy could also save $538 to $689 of medical expenses per patient or over $15 to nearly $25 million a year nationally.
The rationale behind single immediate instillation intravesical chemotherapy is that by reducing the rate of implantation, the likelihood of disease recurrence will decrease, as will the need for repeat TURBs and for longer courses of intravesical therapy. reviews the results of randomized prospective trials of same-day intravesical instillation chemotherapy after TURB. This treatment has been shown to reduce recurrences by 17 to 44% compared with controls. A recent meta-analysis has confirmed that this treatment has decreased the risk of recurrence by 39% in patients with stage Ta and T1 bladder cancer(37
The purpose of the analysis was to provide a conservative estimate of the economic benefit associated with using intravesical chemotherapy after TURB in the US. Since differences between countries in terms of health care systems (e.g., financing and organization) could have a substantial impact on the types of services patients receive, it is necessary to focus on a specific health care system. We chose the US health care system, and specifically the health insurer’s perspective in order to notes the impact of this treatment on the overall cost of bladder cancer care. Similarly, we used Medicare reimbursement rates as a more conservative, lower bound estimate of the potential savings associated with the use of this intervention among both Medicare and privately insured patients. Another reason for using Medicare rates is that the average age of bladder cancer patients at the time of diagnosis is over 70 years(2
Several assumptions were made in order identify our sample population. The first was that the 3-year recurrence rate of newly resected NMI bladder cancer is 40%. This has been shown in a variety of follow-up studies of NMI bladder cancer as well as in placebo arms of randomized trials using BCG(20
). Thus in building our model we assumed that 40% of patients with newly diagnosed and completely resected low risk bladder cancer will have recurrence during the 3-year follow-up period. We also assumed that there was no stage progression to muscularis propria invading disease. This was an extremely conservative estimate since in published series, stage progression has been reported to occur in 1% to 20% of patients with low risk NMI cancer. The cost of managing invasive bladder cancer is far greater than for NMI disease, and so failure to consider stage progression biased our cost projections against immediate post-TURB instillation therapy. At the time this study was carried out, the AUA had not established immediate intravesical therapy as standard of care but does recommend it as a therapeutic option(38
), while the European Association of Urology had included it as standard of care for superficial bladder cancer(39
). The recently revised AUA guidelines have now included it as an “option” (the weakest grade of guideline with the greatest flexibility in application) for care, although not as a “standard” or “recommendation”(40
The next part of the model dealt with the treatment of patients with recurrences. Largely based on professional guidelines by the AUA and the results of randomized clinical trials(20
) such patients underwent 6 weekly instillations of BCG with 3 maintenance instillations of BCG every 6 months for 3-years (although other forms of intravesical therapy could be used). Again based on published reports(20
), we assumed that 25% of those receiving this course would recur and undergo further instillations with BCG and alpha interferon. Of those patients, we assumed that 60% would recur again(36
). While at this point, the decision would be influenced by the patient’s co-morbidities and wishes and non-standard treatment by the treating physician, to be very conservative, we projected that there would not be further recurrences, and that only frequent cystoscopic monitoring would take place. This again reduced costs compared with the more aggressive therapies that would often be selected (e.g. cystectomy). Similarly, we modeled the cost if for the first recurrence six intravesical instillations of mitomycin C was used with an assumption that 50% receiving this treatment would recur(24
). Subsequent recurrences were treated with BCG or BCG + alpha interferon. For both of these models we estimated and that were they to occur, all recurrences took place immediately after the index or subsequent TURB. While this is an oversimplification, the majority of recurrences take place within three to six months of the index TURB and over 70% within one year(40
). Because most published trials and series end at the time of the initial recurrence, little data are available about the times of second and third recurrences. With longer intervals between recurrences, expenses would have changed little, as long as recurrences were treated as they were in the models. Additionally, because recurrences took place at the first cystoscopic evaluation after TURB, it is likely that standard intravesical therapy would have been recommended (because of the frequent recurrences), rather than simply continuing observational management. Using the above assumptions, we formulated models for the treatment of a patient with newly diagnosed NMI bladder cancer.
While cystectomy is sometimes performed for patients who recur after BCG treatments, this is almost exclusively reserved for patients with high grade disease. It is likely that very few (if any) patients would undergo it within the first three years of being diagnosed with low grade, NMI bladder cancer(28
). Furthermore, we are unaware of any data addressing the circumstance (the proportion of patients with low risk newly diagnosed bladder cancer who are treated with BCG, recur after that treatment and who immediately go on to cystectomy) to guide our model. Both because such a circumstance is very rare and generally would occur beyond the time horizon of this study, it is not included in our model. Moreover, to be conservative, we assumed no grade (to high grade) or stage progression (to stage T2) would occur. These occur rarely in the population being considered(28
). If either occurred, cystectomy would be more likely. The huge cost associated with this procedure, which would be far more likely to occur in the observed arm, would further bias the results of the study in favor of immediate post TURB intravesical therapy. Lastly, we took a conservative estimate of 25% for the reduction in recurrence rate after immediate post-TURB intravesical instillation(37
As with all studies using health-care databases, several factors should be considered when interpreting our findings. First, while the sample was drawn from more than 7 million lives, it may not be representative of the general population. There are regional biases in medical and urologic care(37
), and it is possible that the geographic imbalance in our data may misrepresent what is occurring in the U.S. as a whole. However, given the only modest imbalance in geographic distribution, and the verified utilization of this database for other medical and oncologic conditions, this likely provides a relatively small bias, not explaining our results. Furthermore, although the databases allowed for the analysis of a large sample of patients across the U.S., only patients with commercial health coverage or private Medicare supplemental coverage were analyzed. Finally, these findings are based on retrospective analyses of claims data, and reliance on this data has limitations. For example, patients may receive treatment that is not submitted to their health plan for reimbursement, and thus is not included in claims data, and a small proportion of claims may be subject to coding errors. However, we believe our methodology to determine how often immediate post-TURB instillation therapy is used is reliable because it is administered by qualified medical personnel (and thus has a CPT code). Moreover because errors in billing that lead to problems in payments rarely go uncorrected, billing data are usually highly reliable(19
Since we used Medicare reimbursement rates (which are usually lower than the rates reimbursed by private health plans) to estimate the cost of interventions, our estimates represent the lower bound of possible savings. However, the effectiveness of the same-day intravesical instillation chemotherapy may also vary depending on patient risk factors and medical histories. We demonstrated that as long as the intervention is at least 7% to 10% more effective than the TURB alone, post-TURB single intravesical instillation chemotherapy provides economic savings.
Why is the treatment performed so rarely? One reason is that while it is considered safe and well tolerated(5
), there obviously are some patients with suspected bladder perforation or post TURB hematuria who should not receive it. Another reason is a technical matter involving dispensing and administering chemotherapy. Many American centers require chemotherapy nurses and ancillary staff to handle and instill these agents, preventing most operating or recovery room nurses from administering them. Currently, some urologists resort to instilling and overseeing the dispension and handling themselves. The inconvenience of ordering, instilling, and waiting for the chemotherapy to dwell for 1–2 hours is, for a busy practitioner, clearly a deterrent to its use. Another barrier to its acceptance is the economic burden placed on the hospital. Currently, the additional expense of using intravesical chemotherapy in a hospital-based setting (e.g. operating room), are borne by the hospital without reimbursement for longer recovery room time, increased monitoring by specially trained nursing staff, and the expenses of disposing of the chemotherapeutic agent.
Another possible reason for not performing this treatment may be the way new scientific data are transmitted to, and incorporated into practice by physicians. Although, numerous clinical trials have shown its effectiveness, these data have not been widely accepted by U.S. urologists. Whether this is because they are unaware of the published data or because these trials have largely been performed outside the U.S. without the participation of American centers is unclear. American urologists may be resistant to embracing this approach without validation by a large American study. The recent revision of AUA guidelines may have an influence on altering this practice, but this will not be ascertainable for several years.