Abstract
PURPOSE
To examine the effect of non-muscle-invasive bladder cancer (NMIBC) diagnosis and treatment on survivors’ quality of life (QOL).
PATIENTS AND METHODS
Of the 5,979 NMIBC population diagnosed between 2010–2014 in North Carolina, 2,000 patients were randomly selected to be invited into this cross-sectional study. Data were collected by postal mail survey. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core (EORTC QLQ-C30) and NMIBC-specific module (QLQ-NMIBC24) were included to measure QOL. Descriptive statistics, t-tests, ANOVA, and Pearson’s correlation were utilized to describe demographics and to assess how QOL varied by sex, cancer stage, time since diagnosis, and treatment.
RESULTS
A total of 398 survivors returned questionnaires (response rate: 23.6%). The mean QOL scores for QLQ-C30 (range 0 – 100, higher = better QOL in all domains but symptoms) were: global health status 73.6, function domains ranged 83.9 – 86.5, and top five symptoms (insomnia, fatigue, dyspnea, pain, and financial difficulties) ranged 14.1 – 24.3. The lowest NMIBC-specific QOL domain was sexual issues including sexual function, enjoyment, problems, and intimacy. Females had worse bowel problems, sexual function, and sexual enjoyment than males but better sexual intimacy and less concerns about contaminating their partner. Stage Ta had the highest global health status, followed by T1 and Tis. QOL did not vary by time since diagnosis except for sexual function. The cystectomy group (n= 21) had worse QOL in sexual function, discomfort with sexual intimacy, sexual enjoyment, and male sexual problems than the non-cystectomy group (n= 336).
CONCLUSION
NMIBC survivors face a unique burden associated with their diagnosis and the often-lifelong surveillance and treatment regimens. The finding has important implications for the design of tailored supportive care interventions to improve QOL for NMIBC survivors.
Introduction
Non-muscle-invasive bladder cancer (NMIBC) survivors represent the majority (75%) of incident and prevalent cases of bladder cancer (1). NMIBC survivors are subject to a unique burden, typically lifelong programs of surveillance and repeated treatments. The treatment of NMIBC includes the transurethral resection of bladder tumor (TURBT) with or without intravesical chemotherapy or immunotherapy. Depending on the chosen strategy, these treatments can be associated with several complications in the short- and long-term, such as pain, urinary problems, gastro-intestinal problems, infection, or inflammation (2). Even with the recommended treatments, up to 33% of NMIBC survivors have a recurrence of NMIBC within the first year, increasing to approximately 50% by five years (3). The risk of progression to muscle-invasive bladder cancer (MIBC) is much more heterogeneous. It occurs very rarely in the lower risk majority, but high-risk subgroups of NMIBC survivors face risks of up to 45% within five years (4). Due to the high rate of recurrence or progression, NMIBC survivors are required to have repeated invasive surveillance cystoscopies (as frequent as every three months) and intravesical treatments (5). Thus, NMIBC survivors live with an exceptional burden of surveillance and possible treatment for the rest of their lives after diagnosis, potentially affecting their quality of life (QOL).
Even though most bladder cancer survivors are living with NMIBC, much of the existing QOL literature in bladder cancer addresses the burdens of patients with MIBC, not NMIBC, and focuses primarily on the experience of patients receiving cystectomy with different urinary diversion methods as opposed to chemoradiation (6). Relatively fewer studies have assessed the impact of both the disease and the treatment on QOL in NMIBC patients to date. Moreover, although a few studies have been conducted with a population-based sample of bladder cancer survivors, there is currently no population-based QOL study focused solely on NMIBC survivors (7).
Despite the unique burden of NMIBC survivors, including frequent recurrences, repeated surveillance cystoscopies and treatments, and the highest lifetime medical cost per person among all cancers (8,9), little is known about the impact of NMIBC and its treatment on QOL in NMIBC survivors. Therefore, we aimed to address gaps in our understanding of the disease and treatment effects on QOL in NMIBC survivors. Specifically, the aims of the present study were to: a) describe QOL in a population-based sample of NMIBC survivors; and b) examine the impact of sex, cancer stage, time since diagnosis, and treatment on QOL.
Patients and Methods
Study Population
NMIBC population was identified through the North Carolina Central Cancer Registry (CCR), which is the cancer data center for the population of North Carolina. Eligible individuals: a) had a confirmed diagnosis of NMIBC (stage Ta, T1, or carcinoma in situ); b) were 18 years or older; c) were one to six years post-diagnosis; and d) had completed initial cancer treatment. A total of 5,979 NMIBC patients were listed in the North Carolina CCR who had been diagnosed between 2010 and 2014 and who met the inclusion criteria. Of these, 2,000 potential participants were randomly selected and stratified by sex (1,500 males and 500 females to reflect the sex ratio of the target population).
Data Collection Procedures
The potential participants were contacted by mail, according to Dillman’s method for mailed surveys (10). The initial contact was through a mailed survey packet, which contained a letter of introduction, CCR brochure, consent form, future contact form, and self-administered questionnaire with a postage-paid return envelope. One week after the survey packet was sent, reminder postcards were sent to the potential participants in order to encourage participation. The data were double-entered by the first author and one trained research assistant, and all the discrepancies were corrected by consulting the original survey data. The study was approved by the institutional review board at the University of North Carolina at Chapel Hill.
Measures
Demographics and clinical characteristics were obtained from the North Carolina CCR information and participants’ self-reports. QOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) version 3.0 and a NMIBC-specific module (QLQ-NMIBC24) (11,12). The QLQ-C30 has 30 items and is comprised of a global health status scale, five functional scales (physical, role, emotional, cognitive, and social) and nine symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each item in the global health status scale has a numerical rating scale from 1 to 7, and each item in the function and symptom scales has a four-point Likert scale from 1 (‘not at all’) to 4 (‘very much’). The measure was developed specifically for assessing the health-related QOL of cancer patients and has been used previously in the bladder cancer population (13–15). The QLQ-NMIBC24 is a 24-item questionnaire specifically for patients with NMIBC and assesses 11 domains (urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, risk of contaminating partner, sexual intimacy, sexual enjoyment, sexual function, male sexual problems, and female sexual problems). Each item has a four-point Likert scale from 1 (‘not at all’) to 4 (‘very much’). For scoring the QLQ-C30 and QLQ-NMIBC24, raw scores of each domain were calculated by averaging the response scores of comprised items in each domain. A linear transformation was then performed to standardize the raw scores, such that scores for each domain range from 0 to 100. Higher scores indicate higher (better) levels of global health status or functioning, or higher (worse) levels of symptoms.
Data Analysis
Chi-squared tests and t-tests were used to determine whether there was a significant difference between the participants and the non-participants. Descriptive statistics were computed to examine the demographics, clinical characteristics, and QOL in NMIBC survivors. T-tests, analysis of variance (ANOVA), and Pearson’s correlation were used to examine whether the QOL varied by sex, cancer stage, time since diagnosis, and treatment. In addition, two sets of post-hoc analyses were conducted: 1) comparing QOL in cystectomy vs. non-cystectomy using t-tests and 2) comparing QOL among the non-cystectomy groups using ANOVA, with step-down tests where necessary. All the statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC).
Results
Sample Characteristics
Of the 2,000 prospective participants who were mailed the surveys, 9 were duplicates, 153 packages were returned undeliverable, and 154 patients did not meet the inclusion criteria (no NMIBC by patient report, n = 6; unable to read and write a questionnaire by family report, n = 9; or deceased, n = 139) (Figure 1). A total of 1,684 survivors were eligible and 398 (23.6%) participants returned their surveys. The participants were more likely to be white than non-participants (94.5% vs. 88.1%, p < .001), but other demographic and clinical characteristic information from the registry did not differ (Table S1: Demographics for the overall study population are provided in supporting information). Twenty-two participants who did not complete the main outcome (QOL) instrument were excluded from the analyses, leaving 376 participants whose responses were included in the analyses. The 22 participants whose data were excluded were more likely to be older than those whose data were included in the analyses (81.5± 6.7 vs. 72.2± 9.2, p < .001), but other demographic and clinical characteristic information from the registry did not differ. Table 1 indicates the sample characteristics of the 376 participants who were included in the analyses. The majority were male, white, and non-Hispanic. Mean age at study enrollment was 72.2 years, and 83.2% (n = 313) were aged 65 years or older. The mean years since diagnosis was 3.4 years. A majority of participants (73.4%, n = 276) reported having received TURBT as the primary treatment whereas only 5.6% (n = 21) had received cystectomy. Of all the participants, 36.2% and 43.4% had received intravesical chemotherapy and immunotherapy, respectively.
Figure 1. Research flowchart.
Abbreviation: NMIBC, non-muscle-invasive bladder cancer.
Table 1.
Included Participants* Demographic and Clinical Characteristics from NC Central Cancer Registry and Survey
| Characteristic | Participants (n=376*) |
|---|---|
| Sex† | |
| Male | 272 (72.3%) |
| Female | 104 (27.7%) |
| Age at diagnosis, years† | |
| Mean (SD), Range | 68.3 (9.2), 34–89 |
| Age at enrollment, years† | |
| Mean (SD), Range | 72.2 (9.2), 39–94 |
| Race† | |
| White | 355 (94.4%) |
| African American | 13 (3.5%) |
| Other | 2 (0.5%) |
| Unknown | 6 (1.6%) |
| Ethnicity† | |
| Non-Hispanic | 369 (98.1%) |
| Hispanic | 1 (0.3%) |
| Unknown | 6 (1.6%) |
| Annual income | |
| < $50,000 | 132 (35.1%) |
| $50,000- $99,999 | 136 (36.2%) |
| ≥$100,000 | 62 (16.5%) |
| No response given | 46 (12.2%) |
| Education | |
| ≤ High school graduate | 89 (23.7%) |
| Some college or technical school/College graduate | 210 (55.9%) |
| Post-graduate | 65 (17.3%) |
| No response given | 12 (3.2%) |
| Marital status | |
| Married/ Living with partner | 284 (75.5%) |
| Never married/ Divorced/ Widowed/ Separated | 80 (21.3%) |
| No response given | 12 (3.2%) |
| Employment | |
| Employed | 71 (18.9%) |
| Unemployed | 20 (5.3%) |
| Retired | 274 (72.9%) |
| No response given | 11 (2.9%) |
| Histology† | |
| Papillary transitional cell carcinoma | 312 (83.0%) |
| Transitional cell carcinoma | 62 (16.5%) |
| Other | 2 (0.5%) |
| Stage at diagnosis† | |
| Ta | 250 (66.5%) |
| Tis | 24 (6.4%) |
| T1 | 102 (27.1%) |
| Years since diagnosis† | |
| Mean (SD), Range | 3.4 (1.5), 1–6 |
| All types of previous treatment | |
| TURBT | 276 (73.4%) |
| Immunotherapy | 163(43.4%) |
| Chemotherapy | 136 (36.2%) |
| Cystectomy | 21 (5.6%) |
| Radiation therapy | 3 (0.8%) |
| Other | 14 (3.7%) |
| No treatment selected | 11 (2.9%) |
| Previous Treatment | |
| TURBT only | 88 (24.7%) |
| TURBT+ Chemotherapy | 94 (26.3%) |
| TURBT+ Immunotherapy | 123 (34.5%) |
| TURBT+ Chemotherapy+ Immunotherapy | 31 (8.7%) |
| Cystectomy | 21 (5.9%) |
| Current treatment status | |
| Not in treatment | 299 (79.5%) |
| Receiving treatment | 71 (18.9%) |
| No response given | 6 (1.6%) |
22 respondents, who did not complete the main outcome (quality of life) instrument, were excluded in the analysis.
Data from NC central cancer registry.
Abbreviations: NC, North Carolina; SD, standard deviation; TURBT, transurethral resection of bladder tumor.
QOL
The average global health status score was 73.6 and the average functioning scores ranged from 83.9 to 86.5 (Table 2). The average scores of the top five symptom scales/items in QLQ-C30 (insomnia, fatigue, dyspnea, pain, and financial difficulties) ranged from 14.1 to 24.3. The average scores for QLQ-NMIBC24 ranged from 5.0 to 48.5. The domains with the lower QOL were sexual function, sexual enjoyment, male/female sexual problems, sexual intimacy, urinary symptoms, future worries, and bloating and flatulence.
Table 2.
Quality of Life Scores
| Measure | Characteristic | n | Mean (SD) | Observed Range |
|---|---|---|---|---|
| EORTC QLQ-C30 |
Global health status | 364 | 73.6 (21.7) | 0 – 100 |
| Physical functioning | 376 | 84.6 (20.3) | 6.7–100 | |
| Role functioning | 376 | 86.5 (23.9) | 0 – 100 | |
| Emotional functioning | 376 | 84.4 (21.0) | 0 – 100 | |
| Cognitive functioning | 376 | 83.9 (21.3) | 0 – 100 | |
| Social functioning | 376 | 84.8 (25.1) | 0 – 100 | |
| Fatigue† | 376 | 23.6 (25.6) | 0 – 100 | |
| Nausea and vomiting† | 376 | 5.1 (12.0) | 0 – 66.7 | |
| Pain† | 376 | 16.4 (25.3) | 0 – 100 | |
| Dyspnea† | 376 | 17.1 (27.2) | 0 – 100 | |
| Insomnia† | 374 | 24.3 (30.4) | 0 – 100 | |
| Appetite loss† | 374 | 9.0 (20.5) | 0 – 100 | |
| Constipation† | 374 | 13.7 (24.9) | 0 – 100 | |
| Diarrhea† | 375 | 9.2 (18.8) | 0 – 100 | |
| Financial difficulties† | 376 | 14.1 (26.2) | 0 – 100 | |
| EORTC QLQ-NMIBC24 | Urinary symptoms† | 375 | 23.5(22.2) | 0 – 100 |
| Malaise† | 376 | 5.0 (11.8) | 0 – 83.3 | |
| Future worries† | 376 | 23. 5 (22.7) | 0 – 100 | |
| Bloating & flatulence† | 376 | 20.5 (21.5) | 0 – 100 | |
| Sexual function | 368 | 31. 5 (27.2) | 0 – 100 | |
| Intravesical treatment issues† | 375 | 7.4 (18.8) | 0 – 100 | |
| Sexual intimacy† | 352 | 27.9 (35.0) | 0 −100 | |
| Risk of contaminating partner† | 350 | 9.7 (23.7) | 0 – 100 | |
| Sexual enjoyment | 327 | 48.1 (38.1) | 0 – 100 | |
| Male sexual problems† | 261 | 48.5 (35.7) | 0 – 100 | |
| Female sexual problems† | 83 | 39.0 (39.2) | 0 – 100 |
Note. Possible range of scores is 0–100. Higher scores denote better quality of life except for those marked with †.
High scores denote poorer quality of life in these domains.
Abbreviations: EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; NMIBC24, 24-item non-muscle-invasive bladder cancer module; SD, standard deviation.
QOL by sex.
Females had significantly higher levels of constipation and diarrhea (both p = .02; Table 3). Males had significantly better sexual function (p < .0001) and sexual enjoyment (p < .0001) than females. However, males reported significantly more discomfort with sexual intimacy (p = .01) and higher levels of concern about contaminating their partners (p = .03).
Table 3.
Quality of Life by Sex, Stage, and Years since Diagnosis
| EORTC QLQ-C30 Mean (SD) |
|||||||
|---|---|---|---|---|---|---|---|
| Global health status (n=364) + |
Physical Functioning (n=376) + |
Role Functioning (n=376) + |
Emotional Functioning (n=376) + |
Cognitive Functioning (n=376) + |
Social Functioning (n=376) + |
Fatigue (n=376) − |
|
| Sex | |||||||
| Male | 72.5 (21.4) | 84.5 (20.6) | 85.7 (24.4) | 85.1 (21.3) | 84.2 (21.4) | 84.5 (25.1) | 23.6 (25.3) |
| Female | 76.7 (22.3) | 84.9 (19.7) | 88.8 (22.5) | 82.8 (20.4) | 82.9 (21.0) | 85.7 (25.3) | 23.3 (26.6) |
| p-valuea | .10 | .89 | .26 | .33 | .57 | .67 | .92 |
| Stage | |||||||
| Ta | 75.7 (20.6) | 86.6 (18.8) | 88.7 (21.5) | 85.8 (19.6) | 85.1 (20.4) | 87.7 (22.2) | 21.1(24.5) |
| Tis | 64.9 (23.8) | 80.6 (22.9) | 83.3 (29.5) | 82.2 (24.2) | 79.8 (23.1) | 79.9 (31.8) | 28.2 (26.6) |
| T1 | 70.8 (22.9) | 80.7 (22.6) | 81.9 (27.3) | 81.6 (23.4) | 81.7 (22.8) | 78.9 (28.8) | 28.5 (27.4) |
| p-valueb | .02 | .03 | .04 | .20 | .25 | .01 | .03 |
| Years since diagnosis | |||||||
| 1 | 72.5 (18.2) | 85.3 (16.4) | 90.8 (20.2) | 89.4 (19.1) | 86.8 (16.3) | 89.1 (22.4) | 20.9 (21.8) |
| 2 | 73.8 (21.0) | 84.1 (21.5) | 87.2 (23.4) | 83.9 (19.9) | 82.8 (18.2) | 85.6 (23.0) | 22.7 (23.6) |
| 3 | 78.0 (20.1) | 87.7 (17.7) | 88.3 (22.3) | 85.2 (22.2) | 88.1 (19.0) | 86.7 (24.9) | 19.7 (23.8) |
| 4 | 67.8 (24.1) | 82.1 (22.9) | 81.3 (28.7) | 80.3 (24.2) | 79.6 (26.2) | 77.6 (31.3) | 27.2 (28.8) |
| 5 | 74.5 (23.8) | 84.8 (21.0) | 85.9 (24.2) | 85.9 (19.0) | 83.3 (23.2) | 85.4 (24.6) | 26.0 (28.1) |
| 6 | 73.8 (19.7) | 83.5 (19.3) | 87.9 (21.4) | 85.3 (19.8) | 83.7 (22.8) | 87.5 (19.9) | 25.1 (26.8) |
| p-valuec | .72 | .64 | .41 | .72 | .48 | .57 | .18 |
| Treatment§ | |||||||
| TURBT only | 74.8 (19.1) | 83.6 (21.3) | 89.2 (22.0) | 87.2 (16.6) | 87.9 (16.3) | 87.3 (24.8) | 21.3 (24.8) |
| TURBT+ Chemo | 68.4 (23.4) | 82.7 (22.1) | 83.2 (25.1) | 83.8 (22.1) | 82.1 (24.0) | 82.1 (25.9) | 27.3 (26.9) |
| TURBT+ Immuno | 76.3 (22.1) | 87.2 (18.5) | 88.8 (21.4) | 84.3 (21.2) | 82.9 (20.5) | 87.3 (21.9) | 21.7 (25.3) |
| TURBT+Chemo+Immuno | 76.1 (21.1) | 85.3 (19.4) | 83.3 (29.5) | 80.4 (26.3) | 86.0 (24.4) | 80.1 (31.5) | 20.4 (27.1) |
| Cystectomy | 75.0 (18.9) | 88.6 (15.1) | 89.7 (17.9) | 81.0 (21.3) | 79.4 (25.2) | 84.9 (21.7) | 23.8 (23.7) |
| p-valueb | .10 | .44 | .28 | .50 | .26 | .36 | .46 |
| p-valued | .79 | .41 | .58 | .45 | .31 | .97 | .90 |
| p-valuee | .05 | .40 | .20 | .43 | .23 | .23 | .31 |
| EORTC QLQ-C30 Mean (SD) |
||||||||
|---|---|---|---|---|---|---|---|---|
| Nausea and Vomiting (n=376) − |
Pain (n=376) − |
Dyspnea (n=376) − |
Insomnia (n=374) − |
Appetite loss (n=374) − |
Constipation (n=374) − |
Diarrhea (n=375) − |
Financial difficulties (n=376) − |
|
| Sex | ||||||||
| Male | 4.4 (10.6) | 16.7 (25.3) | 17.5 (27.3) | 22.5 (29.9) | 9.0 (20.4) | 11.6 (22.5) | 7.6 (16.9) | 14.1 (26.3) |
| Female | 6.7 (15.2) | 15.4 (25.5) | 16.0 (27.1) | 29.1 (31.2) | 9.1 (20.1) | 19.3 (29.8) | 13.6 (22.6) | 14.1 (26.2) |
| p-valuea | .09 | .65 | .63 | .06 | .97 | .02 | .02 | .99 |
| Stage | ||||||||
| Ta | 4.1 (11.4) | 14.9 (24.8) | 14.7 (25.1) | 22.9 (30.1) | 8.2 (19.4) | 12.4 (22.4) | 7.9 (17.3) | 10.7 (22.4) |
| Tis | 7.6 (13.9) | 20.2 (27.8) | 25.0 (39.6) | 29.2 (33.1) | 11.1 (23.4) | 18.2 (32.1) | 10.1 (15.7) | 20.8 (30.8) |
| T1 | 6.7 (12.9) | 19.1 (25.8) | 21.2 (28.1) | 26.7 (30.6) | 10.6 (22.6) | 16.0 (28.8) | 12.4 (22.5) | 20.9 (31.8) |
| p-valueb | .11 | .27 | .04 | .41 | .54 | .32 | .12 | < .01 |
| Years since diagnosis | ||||||||
| 1 | 3.5 (8.2) | 17.2 (19.2) | 16.1 (27.6) | 25.3 (26.2) | 14.9 (26.1) | 8.0 (19.2) | 5.7 (12.8) | 12.6 (27.3) |
| 2 | 3.8 (10.4) | 15.3 (21.6) | 18.1 (26.5) | 25.7 (30.4) | 8.8 (20.2) | 14.9 (25.1) | 10.1 (20.6) | 14.6 (25.5) |
| 3 | 5.2 (12.9) | 13.1 (23.5) | 12.1 (20.7) | 22.4 (31.5) | 5.5 (18.0) | 11.7 (26.6) | 11.2 (20.5) | 13.3 (26.3) |
| 4 | 6.2 (12.3) | 20.2 (32.3) | 21.4 (31.1) | 25.8 (31.9) | 8.0 (19.3) | 15.2 (24.9) | 9.6 (19.2) | 19.4 (31.3) |
| 5 | 7.3 (15.1) | 17.2 (27.2) | 13.5 (26.4) | 25.5 (31.8) | 13.0 (24.2) | 15.1 (23.7) | 7.3 (15.1) | 10.4 (23.7) |
| 6 | 3.3 (10.1) | 17.1 (25.2) | 24.2 (32.9) | 20.0 (27.0) | 7.5 (16.0) | 14.5 (27.4) | 8.3 (19.6) | 12.5 (20.9) |
| p-valuec | .29 | .49 | .41 | .60 | .92 | .42 | .70 | .72 |
| Treatment§ | ||||||||
| TURBT only | 3.6 (10.6) | 15.3 (24.5) | 17.0 (26.3) | 26.5 (29.5) | 8.3 (19.7) | 14.3 (24.8) | 8.4 (19.2) | 11.4 (23.1) |
| TURBT+ Chemo | 7.1 (14.8) | 20.4 (28.0) | 22.0 (29.2) | 24.4 (31.1) | 11.6 (22.9) | 14.5 (27.0) | 9.6 (19.3) | 15.6 (25.3) |
| TURBT+ Immuno | 4.2 (10.4) | 13.4 (22.6) | 13.6 (25.6) | 21.9 (29.9) | 8.4 (20.3) | 11.4 (22.9) | 7.3 (15.7) | 13.6 (28.3) |
| TURBT+Chemo+Immuno | 4.3 (10.5) | 17.2 (26.7) | 12.9 (26.8) | 22.6 (30.3) | 5.4 (21.3) | 12.9 (25.4) | 9.7 (17.6) | 12.9 (26.8) |
| Cystectomy | 8.7 (16.4) | 11.9 (18.4) | 15.9 (27.1) | 23.8 (30.1) | 12.7 (19.7) | 15.9 (27.1) | 17.5 (29.1) | 19.0 (27.0) |
| p-valueb | .16 | .29 | .20 | .86 | .53 | .86 | .24 | .71 |
| p-valued | .30 | .44 | .88 | .99 | .43 | .63 | .18 | .34 |
| p-valuee | .19 | .23 | .12 | .73 | .47 | .77 | .80 | .75 |
| EORTC QLQ-NMIBC24 Mean (SD) |
||||||
|---|---|---|---|---|---|---|
| Urinary symptoms (n=375) − |
Malaise (n=376) − |
Future worries (n=376) − |
Bloating & flatulence (n=376) − |
Intravesical treatment issues (n=375) − |
Risk of contaminating partner (n=350) − |
|
| Sex | ||||||
| Male | 23.2 (22.6) | 5.3 (12.3) | 23.1 (22.6) | 19.6 (19.7) | 7.1 (18.1) | 11.4 (25.7) |
| Female | 24.5 (21.3) | 4.0 (10.3) | 24.3 (23.2) | 23.1 (25.8) | 8.0 (20.5) | 5.0 (16.3) |
| p-valuea | .60 | .29 | .66 | .21 | .69 | .03 |
| Stage | ||||||
| Ta | 21.9 (20.5) | 4.1 (10.2) | 22.6 (21.4) | 20.1 (21.5) | 6.1 (18.1) | 9.4 (23.3) |
| Tis | 31.6 (30.1) | 7.6 (13.9) | 30.0 (30.1) | 19.5 (20.1) | 16.7 (29.5) | 16.7 (32.6) |
| T1 | 25.8 (23.8) | 6.4 (14.5) | 24.1 (23.8) | 21.7 (22.1) | 8.2 (16.6) | 8.8 (21.9) |
| p-valueb | .06 | .14 | .30 | .79 | .03 | .32 |
| Years since diagnosis | ||||||
| 1 | 22.6 (18.7) | 5.2 (10.1) | 23.3 (20.9) | 19.6 (23.2) | 0 (0) | 6.4 (21.1) |
| 2 | 23.5 (22.9) | 4.7 (12.5) | 24.7 (24.4) | 22.2 (23.4) | 5.9 (16.0) | 14.6 (28.6) |
| 3 | 22.7 (24.0) | 4.4 (11.2) | 20.5 (22.7) | 20.0 (21.0) | 5.8 (13.8) | 7.3 (20.2) |
| 4 | 25.6 (24.3) | 7.7 (15.2) | 28.0 (23.7) | 22.9 (22.3) | 13.9 (27.3) | 6.3 (18.7) |
| 5 | 22.3 (21.3) | 4.7 (9.6) | 23.0 (21.9) | 17.7 (19.4) | 9.4 (20.1) | 10.6 (23.4) |
| 6 | 24.5 (17.4) | 2.5 (8.1) | 19.6 (19.0) | 18.8 (19.3) | 5.0 (17.8) | 10.0 (26.4) |
| p-valuec | .81 | .69 | .63 | .40 | .07 | .61 |
| Treatment§ | ||||||
| TURBT only | 20.7 (18.5) | 4.0 (9.8) | 19.7 (20.1) | 19.1 (21.7) | 4.2 (17.4) | 2.8 (11.9) |
| TURBT+ Chemo | 27.3 (23.5) | 5.9 (12.9) | 26.6 (22.4) | 22.0 (23.3) | 9.9 (20.6) | 10.6 (24.8) |
| TURBT+ Immuno | 23.3 (22.1) | 4.8 (12.2) | 24.1 (23.9) | 20.9 (20.9) | 8.2 (20.2) | 12.3 (27.1) |
| TURBT+Chemo+Immuno | 27.0 (27.1) | 5.4 (9.0) | 23.9 (26.1) | 20.4 (19.1) | 6.5 (15.9) | 13.8 (26.0) |
| Cystectomy | N/A | 3.2 (10.0) | 20.6 (22.5) | 15.9 (20.7) | 6.3 (13.4) | 13.3 (27.4) |
| p-valueb | N/A | .78 | .33 | .77 | .34 | .04 |
| p-valued | N/A | .50 | .56 | .32 | .79 | .48 |
| p-valuee | .19 | .74 | .24 | .85 | .23 | .02 |
| EORTC QLQ-NMIBC24 Mean (SD) |
|||||
|---|---|---|---|---|---|
| Sexual function (n=368) + |
Sexual intimacy (n=352) − |
Sexual enjoyment (n=327) + |
Male sexual problems (n=261) − |
Female sexual problems (n=83) − |
|
| Sex | N/A | N/A | |||
| Male | 35.9 (27.2) | 30.6 (35.5) | 53.2 (37.4) | ||
| Female | 19.8 (23.7) | 20.3 (32.8) | 32.9 (35.7) | ||
| p-valuea | < .0001 | .01 | < .0001 | ||
| Stage | |||||
| Ta | 33.2 (27.6) | 25.7 (33.8) | 48.2 (37.4) | 47.2 (35.1) | 42.2 (40.0) |
| Tis | 29.2 (28.8) | 34.7 (37.4) | 49.2 (43.0) | 53.5 (35.0) | 25.0 (31.9) |
| T1 | 28.0 (25.6) | 31.6 (37.3) | 47.6 (38.5) | 50.0 (37.3) | 28.9 (37.5) |
| p-valueb | .25 | .24 | .98 | .70 | .39 |
| Years since diagnosis | |||||
| 1 | 26.4 (28.7) | 22.2 (37.0) | 37.3 (41.2) | 38.0 (37.4) | 33.3 (43.6) |
| 2 | 30.0 (26.1) | 24.2 (33.8) | 45.5 (38.7) | 44.6 (33.7) | 37.3 (42.3) |
| 3 | 30.3 (27.3) | 24.1 (31.8) | 48.0 (37.1) | 46.5 (34.6) | 42.1 (36.6) |
| 4 | 32.3 (27.9) | 36.4 (38.1) | 48.6 (37.8) | 51.0 (34.4) | 30.6 (46.0) |
| 5 | 30.6 (25.6) | 31.1 (35.7) | 52.7 (40.4) | 59.8 (40.0) | 41.2 (34.4) |
| 6 | 41.2 (29.2) | 28.3 (35.0) | 53.5 (32.5) | 48.2 (35.8) | 46.7 (42.2) |
| p-valuec | .04 | .10 | .06 | .12 | .56 |
| Treatment§ | |||||
| TURBT only | 29.6 (28.9) | 26.8 (33.9) | 48.9 (38.9) | 52.3 (35.0) | 29.5 (38.1) |
| TURBT+ Chemo | 31.2 (27.0) | 27.6 (34.2) | 46.7 (39.2) | 48.7 (36.8) | 31.9 (34.1) |
| TURBT+ Immuno | 34.8 (26.2) | 23.9 (33.3) | 52.9 (36.4) | 41.1 (32.7) | 54.4 (41.9) |
| TURBT+Chemo+Immuno | 29.4 (26.5) | 29.8 (35.5) | 42.9 (37.3) | 57.9 (36.4) | 51.9 (37.7) |
| Cystectomy | 15.8 (20.6) | 50.0 (39.7) | 26.3 (36.1) | 66.7 (36.5) | 33.3 (57.7) |
| p-valueb | .06 | .04 | .07 | .03 | .18 |
| p-valued | < .01 | < .01 | .01 | .03 | .81 |
| p-valuee | .51 | .80 | .53 | .11 | .09 |
Note. Possible range of scores is 0–100.
Higher score indicates better QOL;
Higher score indicates worse QOL.
p-value from t-test;
p-value from one-way ANOVA;
p-value from Pearson’s correlation;
p-value for post-hoc t-test of cystectomy vs. non-cystectomy;
p-value for post-hoc ANOVA within the 4 non-cystectomy treatments (i.e., excluding cystectomy).
Treatment data were not complete; n=345 for global health status; n=357 for function, symptom, malaise, future worries, and bloating & flatulence; n=356 for urinary symptom, intravesical treatment issues; n=349 for sexual function; n=333 for sexual intimacy; n=331 for risk of contaminating partner; n=309 for sexual enjoyment; n=246 for male sexual problems; n=80 for female sexual problems.
Abbreviations: EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; N/A, not applicable; NMIBC24, 24-item non-muscle-invasive bladder cancer module; SD, standard deviation; TURBT, transurethral resection of bladder tumor.
QOL by cancer stage at initial diagnosis.
Global health status, physical functioning, role functioning, social functioning, fatigue, dyspnea, financial difficulties, and intravesical treatment issues varied significantly by cancer stage at initial diagnosis (all p < .05; Table 3). The highest level of global health status was shown in stage Ta, followed by stages T1 and Tis. Step-down tests indicated the only significant pairwise difference in global health status was between stages Ta and Tis (p = .02). Stage Ta had the best physical, role, and social functioning, and had the least fatigue, dyspnea, and financial difficulties. Stage Tis had the worst physical functioning and dyspnea; Stage T1 had the worst role functioning, social functioning, fatigue, and financial difficulties. However, step-down tests indicated only stages Ta and T1 differed significantly in physical functioning (p = .01), role functioning (p = .01), social functioning (p < .01), fatigue (p = .01), dyspnea (p = .04), and financial difficulties (p < .001). The highest level of intravesical treatment issues was reported in stage Tis, followed by stage T1 and stage Ta. Step-down tests showed stages Ta and T1 both had significantly lower intravesical treatment issues than stage Tis (both p < .05).
QOL by time since diagnosis.
The only significant relationship was with sexual function, which was better further from diagnosis (p = .04; Table 3).
QOL by treatment.
Sexual intimacy, risk of contaminating partner, and male sexual problems varied significantly by treatment (Table 3). The cystectomy group had the highest level of discomfort with sexual intimacy and the most male sexual problems, whereas the TURBT + immunotherapy group had the lowest discomfort with sexual intimacy and the least male sexual problems. The highest level of concerns about contaminating partner was found in the TURBT + chemotherapy + immunotherapy group, and the lowest was in TURBT only.
After observing the large QOL differences between cystectomy and non-cystectomy treatments, we conducted post-hoc analyses with the goal of understanding how cystectomy was associated with QOL and how QOL varied within the non-cystectomy treatments. When comparing cystectomy vs. non-cystectomy, non-cystectomy had significantly better sexual function (p < .01), better sexual intimacy (p < .01), higher sexual enjoyment (p = .01), and lower levels of male sexual problems (p = .03) than cystectomy. In comparing the non-cystectomy groups, the concern about contaminating partner varied significantly by treatment. Step-down tests showed the TURBT with intravesical chemotherapy, TURBT with intravesical immunotherapy, and TURBT with intravesical chemotherapy and immunotherapy had significantly higher concerns about the risk of contaminating partners than TURBT only (p = .03, p < .01, and p = .03, respectively). However, the concern about the contaminating partner was not significantly different between TURBT with intravesical immunotherapy and TURBT with intravesical chemotherapy.
Discussion
This study provides further insight into the QOL of the NMIBC population. To the best of our knowledge, there have been no NMIBC QOL studies in which population-based sampling was used. Our study sample was randomly selected from the NMIBC population in North Carolina, which is similar to the demographics of those in the US.
Our findings about the average QLQ-C30 global health status and functioning scores were consistent with those from other studies of NMIBC patients (13,15,16), even though the mean time since diagnosis in our study (3.4 ± 1.5 years, range 1–6 years) was longer than other studies (right after the induction instillation cycle – up to two years post-diagnosis). Although there is a limitation in direct comparison, our evidence suggests there is little to no benefit farther from time of diagnosis in the global health status and functioning. The average symptom scores of QLQ-C30 were similar to other studies (13,15,16) except for fatigue, insomnia, and financial difficulties. In our study, the NMIBC survivors, whose mean time since diagnosis was 3.4 ± 1.5 years, had worse symptoms of fatigue and insomnia and higher financial difficulties than the survivors in other NMIBC studies in which they were measured after the intravesical treatment or one year after the end of the maintenance cycle (two years post-diagnosis) (13,15,16).
The higher financial difficulties in our study (longer mean time since diagnosis) than those in the other studies may suggest NMIBC survivors continuously face financial problems due to bladder cancer care and surveillance. Multiple studies defined bladder cancer as having the highest cost to the health system per patient, from diagnosis to death among all cancer types (8,9). However, little work has been done to understand how financial burden affects the NMIBC survivors and their access to medical care. While we are learning more about financial toxicity in cancer patients (17,18), further research is needed to understand the financial burden in NMIBC populations to ultimately reduce their financial burden.
The global health status of our study (73.6 ± 21.7) was better than genitourinary cancer patients (62.6 ± 22.2) in the EORTC reference (19) and patients with bladder cancer (both NMIBC and MIBC; 43.5 ± 22.8) in a previous study (14). Also, the average functioning and symptoms scores of QLQ-C30 in our study indicate better QOL than those of the genitourinary cancer patients in the EORTC reference and the bladder cancer patients in the previous study (14). However, the genitourinary cancer of the EORTC reference were mainly kidney cancer (76%), followed by other genitourinary cancer (18%) and bladder cancer (5%). Also, the participants of the previous study (14) had mostly MIBC (64%), and only 26% had NMIBC (another 10% were unknown). Because 82% of the participants had cystectomies in the previous study (14), we suspect these participants had lower global health status, lower functioning, and worse symptoms than those in our study.
Although NMIBC-specific symptoms and sexual function in this study seemed to be better than those right after induction intravesical therapy and one year after the end of the maintenance intravesical therapy in the other NMIBC study (13) using the same instrument (QLQ-NMIBC 24), we found one- to six-year NMIBC survivors still reported urinary symptoms, future worries, sexual intimacy problems, and male/female sexual problems (erectile difficulty, ejaculation problem, or vaginal dryness). One possible reason for persistent symptoms is prevalent use of maintenance therapy in high risk NMIBC. Our findings about sexual problems are supported by a previous mixed-methods study (20). The previous study also demonstrated that NMIBC participants (mean age was 65 years), who had been diagnosed within four years, reported sexual dysfunction such as erectile difficulty (60% of sexually active males), ejaculation problem (43% of sexually active males), and vaginal dryness (63% of sexually active females). This prevalence of sexual dysfunction in NMIBC survivors was much higher than that in another study with community-dwelling older adults (57 to 85 years) in the US (21). This study reported that, in community-dwelling older adults, 37% of sexually active males experienced erectile difficulty and 39% of sexually active females experienced vaginal dryness.
In our study, global health status and most functions and symptoms did not vary by sex, but bowel problems and sexual issues did. Schmidt et al. (22) found no difference in QOL (physical, mental, urinary, bowel, and sexual QOL) by sex in NMIBC patients within a year of diagnosis. The findings could be different from ours due to the use of different QOL instruments and time since diagnosis (our study population was at least one-year post-diagnosis). However, the differences in sexual issues by sex are also shown in some other studies (20,23), which reported males were significantly more sexually active than females.
Interestingly, QOL did not vary by time since diagnosis except for sexual function in this study, which is consistent with other studies (20,24,25). These findings suggest NMIBC survivors had lifelong burdens different from those associated with other cancers. For many other cancers, including MIBC, there is a relatively intense period of treatment (major surgery and potentially chemotherapy/radiation) shortly after diagnosis; patients then shift into survivorship mode, which is often relatively static, with noninvasive (scan-based) surveillance, and relatively less frequent recurrence. However, the NMIBC population has much higher rates of recurrence (> 40%) than most cancers, requiring frequent invasive surveillance and prevalent intravesical treatments, and this might be a burden affecting their QOL for the rest of their lives. Allareddy et al. (24) showed QOL did not differ by time since diagnosis in long-term bladder cancer survivors (both NMIBC and MIBC). In addition, one cross-sectional study (25), which compared two independent bladder cancer cohorts (patients who completed the survey before diagnosis and individuals who completed the survey after diagnosis), reported significant differences of mental and physical QOL between the pre- and post-diagnoses (5 years for mental QOL; 10 years for physical QOL) groups. The post-diagnosis group had lower mental and physical QOL than the pre-diagnosis group. These findings suggest that QOL decreases significantly after a cancer diagnosis and does not improve for many years. However, these findings should be interpreted with caution, because of their cross-sectional nature (24,25). Thus, a longitudinal study should provide a better understanding of QOL by time since diagnosis. In our study, sexual function (the extent of sexual activity and interest in sex) was better in survivors who were farther from the time of diagnosis. Kowalkowski et al. (20) also found time since diagnosis was significantly longer in participants who had an interest in sex than those who had no interest in sex.
Stage Ta had significantly better global health status than Tis and better QOL (physical, role, and social functions, fatigue, dyspnea, and financial difficulties) than T1. Stages Ta and T1 had significantly lower intravesical treatment issues than Tis. One possible explanation for these findings is that at stage Ta there is often a lower risk of progression, so patients diagnosed at stage Ta less commonly receive intravesical immunotherapy or other treatments. However, considering intravesical immunotherapy is generally used more in Tis, as well as T1, the finding where only Tis appears to be substantially different to the other two (T1 and Ta) for intravesical treatment issues may be explained in part by the small number of participants at stage Tis (n=24, 6.4%). Stage Tis may also have a different intrinsic symptom burden related to the cancer itself.
The cystectomy group had more sexual issues than the non-cystectomy group, which is in agreement with previous studies (24,26). However, there were no significant differences in general health status, functions (physical, role, emotional, cognitive, and social functions), and common cancer symptoms between the cystectomy and the non-cystectomy groups. In addition, our findings suggest the TURBT only group had significantly less concerns about the risk of contaminating their partners than the other treatment groups (TURBT + chemotherapy, TURTB + immunotherapy, TURBT + chemotherapy + immunotherapy), whereas there were no significant differences between the immunotherapy and chemotherapy groups.
This study has several limitations. Firstly, because we used a cross-sectional design, we are not able to infer longitudinal changes in QOL. Also, we did not have pre-treatment baseline QOL data for comparison; thus, potential differences in the baseline characteristics of participants exist. A longitudinal study, which is currently lacking in the literature on QOL in the NMIBC population, would provide better information about QOL changes over time. Another limitation of this study is the lower response rate (23.6%). Population-based sample from state registry without a physician’s letter for recruitment may have affected the response rate. Third, while the NMIBC population was predominantly white (89.5%, this is reflective of the demographics of bladder cancer in the US in general), the participants were more likely white (94.5%) than non-participants (88.1%). Little is known about QOL in minority populations with NMIBC. Thus, more studies should be conducted in a more diverse NMIBC population to confirm the generalizability of our findings to diverse populations. Lastly, the number of survivors in the cystectomy group was low (n=21). Also, the QLQ-NMIBC24 was used to measure QOL for the cystectomy group in this study as we wanted to have a uniform comparison using the same instrument across the whole NMIBC population. The QLQ-BLM-30, which is designed to assess post-urinary-diversion problems, might be considered to assess QOL specifically for the cystectomy group in future work.
In conclusion, this population-based cross-sectional study showed one to six-year NMIBC survivors had symptoms that persisted including urinary and bowel symptoms, sexual problems, and future worries. Moreover, global health status, functioning (physical, role, social), and financial difficulties differed by cancer stage; and sexual QOL differed by sex and type of treatment. These findings suggest healthcare providers should regularly assess these burdens across the continuum of cancer care for NMIBC survivors through survivorship visits regardless of time since diagnosis. Furthermore, healthcare providers should consider sex, cancer stage, and treatment differences in symptom effects on QOL and provide appropriate care and advice by sex, stage, and treatment. When patients are diagnosed with NMIBC, healthcare providers should give the information about how the diagnosis and treatment can affect QOL and help the patients to make an informed decision about treatment. In addition, more longitudinal studies are needed to better understand the unique needs and other studies are needed to develop and test appropriate supportive care interventions for NMIBC survivors throughout their cancer journey.
Supplementary Material
Acknowledgments
Ahrang Jung is supported by Cancer Outcomes Research Program Research Award, Lineberger Comprehensive Cancer Center, UNC; Sigma Theta Tau International, Alpha Alpha Chapter Research Grant; and Linda Waring Matthews Research Fund Scholarship.
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