Comparison of Health-Related Quality of Life Between Japanese and American Patients with Bladder Cancer as Measured by a Newly Developed Japanese Version of the Bladder Cancer Index

INTRODUCTION

Recently, there has been a great deal of progress in the treatment of bladder cancer, including the introduction of new surgical techniques. Many patients who undergo bladder cancer surgery will experience urinary symptoms, bowel symptoms, and sexual dysfunction. Evaluating health related quality of life (HRQOL) is an important key to understanding the degree to which patients’ daily lives are impaired by post-operative side effects. Although several clinical studies have assessed the HRQOL of postoperative patients using a Japanese version of FACT-BL (which is the only Japanese disease specific HRQOL questionnaire designed for bladder cancer patients), this instrument is limited in application because it incorporates few items that measure urinary, bowel, and sexual symptoms. However, the bladder cancer index (BCI) questionnaire was developed and validated to assess the HRQOL of bladder cancer patients [1, 2]. The BCI was designed to be a gender- and diversion-neutral instrument for patients treated with radiation, transurethral resection with or without intravesical therapy, and cystectomy. It consists of 34 items in 3 primary domains (urinary, bowel, and sexual health), with 2 subdomains (function and bother) for each primary domain. It has been translated and validated into Arabic, Dutch, French, Hungarian, Japanese, and Spanish [3–8].

The present study was performed to assess Japa-nese patients with bladder cancer, who had been treated with various surgeries, using the newly developed Japanese version of the BCI (BCI-Japanese). This data was then used to assess and compare function and bother scores for the urinary, bowel, and sexual health domains among bladder cancer patients in Japan and the United States. Although there is a big difference (e.g., health insurance, health care system) between the two countries, [9] we also to analyze how race affects the profiles of the HRQOL after controlling for age and gender between the two countries.

MATERIALS AND METHODS

This study consisted of two parts. The first was a characterization of bladder cancer HRQOL in Japanese patients, and the second was a comparison of HRQOL between Japanese and American patients.

RESULTS

Table 1 shows the clinical characteristics of the cohort of 371 patients. The median age was 72 years (IQR 65–77), and most of the patients (75.7%) were male. The median disease duration was 31 months (IQR 12–67). Noninvasive tumors (76.5%) were more common than muscle invasive disease (21.3%), and about half of cases (54.4%) consisted of high-grade cancer. Approximately 59.6% of patients enrolled in this study were treated endoscopically, including transurethral tumor resection and intravesical therapy. Of the remaining approximately 40.4% of patients who were treated with cystectomy, 101 underwent continent diversion (67.3% of those with cystectomy, and 27.2% of the overall cohort), and 49 underwent ileal conduit diversion (32.7% and 13.2%, respectively).

Table 2 shows a comparison of the six BCI subdomain scores among the four treatment groups. The BCI subdomain scores for urinary, bowel, and sexual health were significantly different among the four treatment groups, except for the sexual bother subdomain score (p = 0.14). Although the difference of FACT-G score across the four treatment groups was not significant, the bladder cancer specific FACT-BL score was significantly different among the four treatment groups. Regarding BCI subdomain scores, the urinary function and bowel function scores were significantly lower among the cystectomy with neobladder group compared to the cystectomy with ileal conduit group (Fig. 1). In addition, the urinary bother and bowel bother scores were significantly lower among the cystectomy group compared to the native bladder group. Regarding the sexual health domain, the sexual function subdomain score was significantly lower among the cystectomy group compared to the native bladder group, although the sexual bother subdomain score was not significantly different among the four groups. The FACT-BL scores of the ileal neobladder group were significantly lower than that of the native bladder with or without intravesical therapy group.

Fig. 1

Mean BCI subdomain scores and standard error by treatment group, adjusted for age and sex (n = 371, Japanese cohort). Higher scores indicate better health status. (^** indicates p < 0.01, and ^* indicates p < 0.05).

A comparison of the clinical characteristics of Japanese patients (n = 371) and American patients (n = 315) is shown in Supplementary Table 1. The male to female ratio was similar between the two groups. However, there were a number of differences in baseline characteristics between the two groups, as the Japanese cohort tended to be older and had a higher disease stage, while the American cohort had more recorded high-grade disease and was more likely to have been treated with cystectomy, compared to the Japanese cohort (59.7% vs. 40.4%). Figure 2 and Table 3 show the six BCI subdomain scores stratified by the four treatment groups. Even after adjusting for age and gender, Japanese patients were more likely than American patients to report poor sexual function (p < 0.01), except in the native bladder with intravesical therapy group. However, Japanese patients were less likely than American patients to be bothered by poor sexual function (p < 0.01) in all four treatment groups. Tables 4 and 5 present the proportions of patients in each cohort who reported ‘poor’ for sexual function and ‘no problem’ for sexual bother, according to each question. The Japanese cohort reported significantly worse sexual function subdomain scores for four of the seven questions. However, both the Japanese and American cohorts similarly reported that they were able to be sexually aroused, to have intercourse, and to function sexually. However, the Japanese patients were more likely to report ‘no problem’ regarding sexual bother. There were no significant differences in scores for the urinary and bowel domains between Japanese and American patients.

Fig. 2

Mean BCI subdomain scores and standard error by treatment group, adjusted for age and sex. The four groups are: A, native bladder without intravesical therapy; B, native bladder with intravesical therapy; C, cystectomy and ileal conduit urinary diversion; and D, cystectomy and ileal neobladder urinary diversion. Shaded areas show the mean scores across BCI domains within a treatment group. Higher scores indicate better health status. (^* indicates p < 0.05).

DISCUSSION

We translated the BCI into Japanese, providing for cultural adaptation while maintaining the intent of the original BCI. The Japanese version of the BCI comprehensively covered the symptoms of patients with bladder cancer with high reliability and good construct validity, as well as the original BCI did [8]. In addition, we found substantially different cultural profiles of sexual function between Japanese and American patients with bladder cancer. To the best of our knowledge, this is the first study to report a cross-cultural comparison between Japanese and American bladder cancer patients. These findings are important as they provide evidence that HRQOL results reported in Western countries may not be directly generalized to Japanese patients. A cross-cultural comparative study using an internationally approved and well validated HRQOL questionnaire would certainly be beneficial to the global improvement of patient reported outcome evaluation and would support the importance of assessing HRQOL for each group.

As reported elsewhere, we found that urinary function in the Japanese cohort was significantly lower in the cystectomy with neobladder group compared to the cystectomy with ileal conduit group [2, 12]. This result indicates that improvement in urinary incontinence after radical cystectomy with neobladder would be beneficial for patients and improve their HRQOL. This low score in the urinary function domain was thought to be due to more frequent incontinence and lack of urinary control in the cystectomy with neobladder group [2]. Despite this significant difference, the urinary bother subdomain scores did not significantly differ between the cystectomy with neobladder group and the cystectomy with ileal conduit group. In the Japanese cohort, the FACT-BL scores significantly differed among the four treatment groups, and the scores for the neobladder group were lower than in the other three treatment groups. FACT-BL scores measure HRQOL related to urinary, bowel, sexual function, body image, appetite, and ostomy care (for patients with ostomy), and it also covers patients with a wide range of bladder cancer treatments [13]. However, it cannot identify the reasons for the difference. In other words, FACT-BL lacks the ability to discriminate which symptoms are most disturbing to the patient. In contrast, the BCI can help identify the reason for the difference of HRQOL, because it includes more question items and separately calculates subdomain scores for urinary, bowel, and sexual HRQOL.

Interestingly, Japanese patients reported lower sexual function compared with American patients in three of the four treatment groups, even after adjusting for age and gender. This finding is consistent with findings for other urologic cancers. For example, assessment of sexual function among patients with localized prostate cancer also showed that Japanese men tended to report lower sexual functioning than American men [14]. Although the baseline differences in sexual health between the two cohorts was unknown due to the design of this cross-sectional study, it is possible that the baseline sexual function of the Japanese cohort may have been lower, as seen in men with prostate cancer [15]. Additionally, in one study of a multiethnic sample, Japanese women appeared to have less desire and less arousal than the white women in the study [16]. Although American patients have been reported to greatly focus on their sexual function and feel bothered by sexual dysfunction,[17, 18] Japanese patients did not perceive this dysfunction as a bother and might more readily accept this as normal. This might be clarified by an earlier report, in which a satisfactory sexual life for Japanese women was not necessarily accomplished by more frequent intercourse, but that foreplay and orgasm were essential [19]. On the other hand, American patients tend to perceive sexual impairment as a serious medical problem, especially when they are married or living with a partner.

As we reported previously, there were substantial differences between Japan and the US in perioperative management (e.g., length of hospital stay, type of postoperative complications) and health care system (e.g., hospital volume, medical cost) [9]. Regarding hospital volume, the median number of the radical cystectomy case per year in Japanese institutions and the US institution was 4 and 119, respectively [9]. The apparent differences such as more elderly patients and higher stage in Japanese patients were also observed here between the Japanese population and the American population in this study. Despite this difference, the BCI scores for each subdomain were largely comparable, other than the significant difference in the sexual subdomain scores between Japanese and American patients. For example, patients diagnosed at initial stages of bladder cancer and cystectomy treated endoscopically showed good urinary function in both cohorts. Furthermore, urinary function in the / neobladder group was lower compared with cystectomy/ ileal conduit group in both cohorts.

This study has several potential limitations. First, it lacks longitudinal assessment, which would have allowed us to adjust for baseline assessment (e.g., baseline sexual function) and evaluate the HRQOL scores in different phases. Second, our study included a relatively small number of female patients. However, women less commonly have bladder cancer, and our Japanese cohort had approximately the same proportion of women as the American cohort did [1]. Third, the operative procedures used (such as robotic surgery and nerve-sparing technique), were not recorded for each case, due to our study’s retrospective design; variation in surgical techniques might add other potential factors that could influence the postoperative sexual function between the two cohorts. Finally, the cohorts of these two countries were not a random sample, so selection bias may have been present. Moreover, the two cohorts were not well balanced in several baseline characteristics. Given the relatively short overlap between the two cohorts, this might introduce time dependent biases. These issues remain to be resolved by future cross-cultural study. Nevertheless, we believe that the current Japanese version of the BCI will contribute to the assessment of HRQOL in Japanese patients with bladder cancer and will provide useful information for comparison of different health services on both national and international levels.

An effective assessment of bladder cancer HRQOL among Japanese patients can be performed using the BCI-Japan questionnaire. Japanese patients with bladder cancer reported worse sexual function, but less sexual bother from the worse function, when compared with American patients. The Japanese version of the BCI can be used to evaluate the HRQOL of patients who undergo new treatment options for bladder cancer.