- Research article
- Open Access
Patient-reported outcomes in randomised clinical trials of bladder cancer: an updated systematic review
BMC Urology volume 19, Article number: 86 (2019)
Despite international recommendations of including patient-reported outcomes (PROs) in randomised clinical trials (RCTs), a 2014 review concluded that few RCTs of bladder cancer (BC) report PRO as an outcome. We therefore aimed to update the 2014 review to synthesise current evidence-based knowledge of PROs from RCTs in BC. A secondary objective was to examine whether quality of PRO reporting has improved over time and to provide evidence-based recommendations for future studies in this area.
We conducted a systematic literature search using PubMed/Medline, from April 2014 until June 2018. We included the RCTs identified in the previous review as well as newly published RCTs. Studies were evaluated using a predefined electronic-data extraction form that included information on basic trial demographics, clinical and PRO characteristics and standards of PRO reporting based on recommendation from the International Society of Quality of Life Research.
Since April 2014 only eight new RCTs for BC included PROs as a secondary outcome. In terms of methodology, only the proportion of RCTs documenting the extent of missing PRO data (75% vs 11.1%, p = 0.03) and the identification of PROs in trial protocols (50% vs 0%, p = 0.015) improved. Statistical approaches for dealing with missing data were not reported in most new studies (75%).
Little improvement into the uptake and assessment of PRO as an outcome in RCTs for BC has been made during recent years. Given the increase in (immunotherapy) drug trials with a potential for severe adverse events, there is urgent need to adopt the recommendations and standards available for PRO use in bladder cancer RCTs.
With an estimated 549,000 new cases and 200,000 deaths in 2018 worldwide, bladder cancer is the 10th most common form of cancer . All groups of bladder cancer patients are, not surprisingly, subjected to significant treatment burdens that are emotionally and psychologically taxing. Several symptoms, such as blood in the urine, pain and nausea, associated with different treatments may result in increased prevalence of depression, anxiety and stress and, consequently, decreased quality of life (QoL) . Given this disease burden, there is a need to further evaluate how patient-reported outcomes (PROs) are incorporated in clinical bladder cancer research. Inclusion of QoL or other PROs in clinical trials and methodological rigor already at the stage of protocol writing are essential to eventually generate data that can robustly inform patient care .
Randomized controlled trials (RCTs), across a wide range of cancer malignancies, increasingly include PROs in an effort to better understand overall treatment effectiveness of newer drugs . Inclusion of PROs in cancer research is not only valued by oncologists and patients, but also by regulatory stakeholders. To illustrate, the US Food and Drug Administration (FDA) included PROs as one of the clinical outcomes assessments (COAs) that can be used to determine whether or not a drug has demonstrated treatment benefit . Similarly, the European Medicines Agency (EMA) has issued recent guidelines on the use of PRO endpoints in cancer research .
In the context of bladder cancer, a systematic review encompassing the years 2004–2014 examined the quality of PRO reporting and methodological strengths and weaknesses of RCTs. It concluded that few RCTs report PRO as an outcome and improvement in methodology was required . Another more recent systematic review using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)  specifically evaluated the psychometric properties of PRO measurements in bladder cancer (1990–2017) . No existing PRO stood out as the most appropriate to measure QoL in bladder cancer patients due to heterogeneity of the disease and its treatments and due to lack of validation studies . Moreover, a recent systematic review highlighted the mental health implications in bladder cancer patients  – and hence the potential effects the disease and its treatments can have on QoL.
This study therefore aimed to update the review by Feuerstein et al. , by including all the RCTs of that review as well as newly published RCTs in order to synthesise current evidence-based knowledge of PROs from RCTs in bladder cancer. A secondary objective was to examine whether quality of PRO reporting improved over time and to provide evidence-based recommendations for future studies in this area.
Search strategy and identification of studies
We conducted a systematic literature search using PubMed/Medline, from April 2014 until June 2018. Methodology for study identification and evaluation followed standardised criteria used in the PROMOTION Registry (http://promotion.gimema.it) and was previously described in similar systematic reviews [7, 11, 12]. For the purpose of this updated review on bladder cancer RCTs, the following script was used to identify a PRO component: (“quality of life” OR “health related quality of life” OR “health status” OR “health outcomes” OR “patient outcomes” OR “depression” OR “anxiety” OR “emotional” OR “social” OR “psychosocial” OR “psychological” OR “distress” OR “social functioning” OR “social wellbeing” OR “emotional” OR “patient reported symptom” OR “patient reported outcomes” OR pain OR fatigue OR “patient reported outcome” OR “PRO” OR “PROs” OR “HRQL” OR “QOL” OR “HRQOL” OR “symptom distress” OR “symptom burden” OR “symptom assessment” OR “functional status” OR sexual OR functioning) AND bladder. The search strategy was restricted to RCTs. In case of multiple publications from the same RCT, all relevant data possibly published in secondary articles were combined.
Only English-language reports of RCTs comparing conventional treatments and involving adult patients with bladder cancer were included – irrespective of disease stage. The minimum, overall sample size was set at 50 patients. Screening studies or those involving patients with benign disease were excluded. We did not consider conference abstracts as these did not contain sufficient information. RCTs of interventions that were psychological, behavioural, complementary or alternative were also excluded.
We included all studies evaluating a PRO either as a primary or secondary outcome – either as a multidimensional QoL outcome or any other type of PRO. Those studies evaluating only treatment adherence or satisfaction were also excluded. For comparability purposes, selection criteria of eligible articles were the same as of the previous systematic review . Details on the search strategy and selection process were documented according to the PRISMA guidelines .
Methods of evaluation of studies
Two reviewers (MVH, FS) extracted information from the identified studies and a third reviewer (FE) was consulted in case of disagreement. All data were entered by the reviewers into a password protected online database (REDCap)  by completing a predefined electronic-data extraction form (eDEF). Full details on information contained in the eDEF have been previously reported . A double-blind data entry procedure was performed as each reviewer completed the eDEF independently. Discrepancies in evaluations were electronically recorded and when disagreements occurred in the evaluation of any item included in the eDEF, the reviewers revisited the paper to reconcile any differences until consensus was achieved.
Type of data extraction and data analysis
For the purpose of this review, the following types of information were considered: 1) basic trial demographics; 2) clinical and PRO characteristics and 3) elements of PRO reporting based on recommendation from the International Society of Quality of Life Research (ISOQOL) . Quality of PRO reporting was therefore evaluated with the ISOQOL checklist, which comprises a common set of 17 key issues regardless of PRO being primary or secondary outcome. Eleven additional issues were considered when a PRO is a primary outcome of the study. Each item of the ISOQOL checklist was rated as ‘yes’ if documented in the publication (scored as 1) or ‘no’ if not documented (scored 0). To further refine the investigation of the accuracy of reporting, we divided the ISOQOL item addressing the problem of missing data into two (i.e., reporting the extent of missing data and reporting statistical approaches for dealing with missing data). We thus rated each RCT with a score ranging from 0 to a maximum of 18 (RCT with PRO as a secondary outcome) or 29 (PRO as primary outcome). In both cases, a higher score indicates better quality of the PRO reporting. Our rule of thumb for this analysis was to consider RCTs addressing less than 50% of items included in the ISOQOL recommendations  as having “suboptimal quality”. That is, 9 items out of 18 for RCTs which included PRO as secondary outcome and 15 items out of 29 for RCTs which included PRO as primary outcome.
Main characteristics of eligible studies were reported by proportions, means and standard deviation, according to the type of variable. Differences between studies were assessed by Fisher exact test or Wilcoxon-Mann-Whitney test. Based on the ISOQOL checklist score, comparisons of reporting quality were performed. To ensure comparability between studies with PRO as primary or secondary outcome, for each study the raw score was standardised dividing it by the number of applicable items (18 for secondary or 29 for primary), then multiplied by 100. This way, we obtained an adjusted checklist score ranging from 0 (worst quality) to 100 (best quality). Based on such score, we compared studies with PRO as secondary outcome (studies until March 2014 vs those from April 2014), studies with PRO as primary vs. studies with PRO as secondary outcome and studies using a validated PRO measure or not. In addition, we computed the proportion of studies that had a checklist score below or equal to the cut-off value of 50. All tests were two-sided and statistical significance was set at α = 0.05. Analyses were performed by SAS software v. 9.4 (SAS Institute Inc., Cary, NC).
Overview of RCT characteristics
The search identified 586 abstracts published in the period 2014–2018. Eight studies fulfilled the eligibility criteria (Fig. 1). In all the newly identified RCTs [16,17,18,19,20,21,22,23], PROs were secondary outcome, whereas of the nine old studies [24,25,26,27,28,29,30,31,32,33] five RCTs (55.6%) employed PROs as primary outcome [27,28,29,30, 33]. All but one of the newly identified RCTs were not supported by industry (87.5%) and none of the RCTs was carried out in a multinational context. The majority of new trials (5, 62.5%) enrolled patients with non-metastatic disease. Compared to the old studies, where two RCTs (22.2%) enrolled more than 200 patients, only one of the newly identified RCTs (12.5%) enrolled more than 200 patients overall. Six new RTCs (75%) assessed PROs over a time period of 6 months, one study (12.5%) up to 1 year and in one study (12.5%) the length of assessment was more than 1 year. Details are reported in Table 1.
Most recent (2014–2018) evidence of bladder cancer RCTs with PROs
Among the eight newly identified RCTs, only three [18, 19, 23] used a multidimensional PRO instrument (e.g. the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) ) and of these, two used a bladder cancer-specific questionnaire (the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) and the FACT-Vanderbilt Cystectomy Index (VCI) questionnaires) (Table 2). In three studies [16, 17, 20], no differences in pain scores were detected between the experimental treatment arms (solifenacin, sevoflurane and glycopyrrolate, respectively) and the control arms (standard care, desflurane and atropine, respectively). In the study conducted by Huang et al. , VAS scores for bladder pain were significantly lower at the end of the induction cycle in the group treated with pirarubicin combined with hyaluronic acid compared to pirarubicin alone, while dexmedetomidine was associated with lower postoperative pain scores compared to placebo . Low dose of Bacillus Calmette-Guerin (BCG) was associated with better outcomes in terms of global QoL, role functioning and financial problems, as assessed by the EORTC QLQ-C30, compared to standard dose . No differences in QoL, as assessed with the FACT-BI, were found between laparoscopic and robot-assisted radical cystectomy . Finally, no difference in QoL, as assessed by the FACT-VCI, was detected between robot-assisted radical cystectomy and open radical cystectomy .
Comparison of PRO quality reporting between 2004 and 2014 and 2014–2018
Only one (12.5%) of the eight new RCTs reported a PRO hypothesis  and two (25%) reported the statistical approach for dealing with missing data [19, 23]. Three RCTs (37.5%) documented the mode of PRO administration [16, 17, 21], four (50%) documented the rationale for the choice of PRO instrument [16, 19, 21, 23], whereas two RCTs (25%) reported generalisability issues [17, 21] or interpretation in terms of clinical significance [21, 22].
Compared to previous studies, only two statistically significant improvements were noted: there was an increase in proportion of RCTs documenting the extent of missing PRO data (75% vs 11.1%, p = 0.015) and an increase of RCTs documenting PROs in trial protocols (50% vs 0%, p = 0.03). Further details are reported in Table 3.
We compared the ISOQOL scores for studies with a PRO as secondary outcome identified in the previous review with those identified in this update. The quality of PRO reporting was considered as “suboptimal” for all of the old studies, while this was not the case for the new RCTs, whose quality was considered suboptimal in 50% of the studies. The mean standardized score for the old studies was 30.5 (median 33.3), while for the new studies the mean score was 48.6 (median 50). However, this positive trend was not statistically significant (p = 0.072).
The quality of PRO reporting among all of the studies published between 2004 and 2018 was found to be poor. Overall, only six studies (35.3%) addressed 50% or more of the issues recommended by the ISOQOL checklist (data not shown). The mean standardised ISOQOL score for all these studies was 44.7, below the cut-off value of 50. For three of the five RCTs with PRO as primary outcome (60%) the quality of PRO reporting was considered as “suboptimal”. This percentage was higher for RCTs with a PRO as secondary outcomes, with eight of the twelve studies (66.6%) considered as “suboptimal”. The mean standardised ISOQOL score for the RCTs with PRO as primary outcome was 49.7, while for RCTs with PRO as secondary outcome was 42.6. No statistically significant differences in the ISOQOL score were found between RCTs with PRO as primary or secondary outcomes (p = 0.459).
It needs to be noted that only one of the seven (14.3%) studies using validated PRO instruments (e.g. EORTC QLQ-C30) had a high level of quality of PRO reporting, compared to those using non-validated instruments (5 RCTs, 50%). No differences were found in the mean standardised ISOQOL scores between the studies that used validated PRO instruments and those using non-validated instruments.
Since April 2014 only eight new RCTs for bladder cancer that also included a PRO component, were identified and in all these studies PROs were considered as secondary outcomes. Also, during this time period little improvements were noted in the quality of PRO reporting. Indeed, when comparing the new studies identified in this update with previously published RCTs between January 2004 and March 2014 , we did not find significant improvement in the mean standardised ISOQOL checklist scores, possibly due to the small number of studies considered. When comparing each individual item of the ISOQOL checklist over time, we only observed two statistically significant improvements with respect to the reporting of missing data and the identification of PROs in trial protocols. Some of the key recommended issues (e.g. reporting of statistical approaches for dealing with missing data, PRO hypothesis statement and generalizability issues regarding the PRO results) are still poorly documented.
The number of newly conducted RCTs of bladder cancer with a PRO component published from 2014 is strikingly low when compared with the number of RCTs conducted in other cancer types, such as breast, lung and prostate cancer [4, 36, 37]. Nevertheless, in the current era of immunotherapy development, including monoclonal antibodies directed against inhibitory checkpoints receptors on T-cells (known as immune checkpoint inhibitors, ICIs), a vast number of trials for bladder cancer are under way – with several of them also assessing PROs. For instance, CHECKMATE 274 (ClinicalTrials.gov Identifier: NCT02632409) is an RCT of the ICI nivolumab versus placebo in patients who have undergone radical cystectomy for muscle-invasive bladder cancer (MIBC). In this study PROs are evaluated as an exploratory outcome using a multidimensional QoL measure. Another study of an ICI, avelumab, in the maintenance setting following first line chemotherapy (JAVELIN; ClinicalTrials.gov Identifier: NCT02603432) also evaluates PRO as a secondary outcome. POTOMAC (ClinicalTrials.gov Identifier: NCT03528694), a trial of the ICI durvalumab plus Bacillus Calmette-Guerin (BCG) versus BCG alone in patients with high risk non-muscle invasive bladder cancer (NMIBC) assesses several PROs as secondary outcome measures. Of note however, many currently ongoing studies in bladder cancer, including those evaluating PARP-inhibitors, FGFR-inhibitors and tyrosine kinase inhibitors do not include PRO assessments [38, 39].
Important International PRO initiatives are ongoing, for example, the standardisation of statistical analyses of PRO data in clinical trials . Also, an international, consensus-based, PRO-specific guidance, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension, was recently made available . This guidance aims to support investigators with protocol writing and to ensure that all methodological issues are appropriately considered. Finally, the CONSORT PRO Extension has been published in 2013 and this is particularly helpful to investigators at the time of publishing final results of RCTs with a PRO component . Taken together these recommendations will hopefully help investigators improving the design of clinical trials and the assessment of PROs, thus ensuring high-quality data that may inform patient-centred care. Furthermore, it is worth highlighting that the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group has developed various tumour and treatment-specific QoL Modules – with several currently in development, including specific ones for non-muscle invasive BC, muscle invasive BC, and metastatic bladder cancer . Finally, it is important to note, however, that word limits in journal guidelines may sometimes limit authors in the opportunity to report on secondary outcomes (i.e. PROs) for their trials  – especially if the results for the primary outcome are negative.
This study has limitations. First, despite our comprehensive search strategy, it is possible that some RCTs with a PRO component might have been missed. Another limitation is the exclusion of non–English language papers. However, it is unlikely that such omission would have significantly altered the conclusion of this review . In addition, we did not compare the published RCT results with their respective protocols, although this might have provided further information. Finally, our results cannot be generalised to RCTs investigating non-conventional medical interventions. A strength of the current review is that we used a formal, objective approach to evaluate PRO reporting in the bladder cancer literature. Since all studies use different reporting criteria and methods, the information was extracted and assessed by two independent researchers. In case of inconsistencies, a third arbiter helped achieving consensus.
The current systematic review identified little improvement in the uptake and assessment of PROs in RCTs for bladder cancer during the last 4 years. Therefore, given the scarcity of rigorous PRO data, it is difficult to draw meaningful conclusions that can robustly inform patient care and support clinical decision-making. Given the increase in (immunotherapy) drug trials with a potential for severe adverse events in bladder cancer patients, there is urgent need to adopt the recommendations and standards available for PRO use in bladder cancer RCTs.
Availability of data and materials
All data was taken from publicly available resources and collated in the PROMOTION Registry. Data can be obtained on request: email@example.com.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
Rutherford C, Costa DSJ, King MT, Smith DP, Patel MI. A conceptual framework for patient-reported outcomes in non-muscle invasive bladder cancer. Support Care Cancer. 2017;25(10):3095–102.
Calvert M, Kyte D, Mercieca-Bebber R, Slade A, Chan AW, King MT, et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols: the SPIRIT-PRO extension. JAMA. 2018;319(5):483–94.
Efficace F, Fayers P, Pusic A, Cemal Y, Yanagawa J, Jacobs M, et al. Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: a pooled analysis of 557 trials. Cancer. 2015;121(18):3335–42.
U.S. Food and Drug Administration: Guidance for Industry and FDA Staff Qualification Process for Drug Development Tools, 2014. https://www.fda.gov/downloads/drugs/guidances/ucm230597.pdf. Accessed 14 June 2017.
European Medicine Agency. The use of patient-reported outcome (PRO) measures in oncology studies. Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man. 2016. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2016/04/WC500205159.pdf Accessed 9 July 2017.
Feuerstein MA, Jacobs M, Piciocchi A, Bochner B, Pusic A, Fayers P, et al. Quality of life and symptom assessment in randomized clinical trials of bladder cancer: A systematic review. Urol Oncol. 2015;33(7):331 e17–23.
Prinsen CAC, Mokkink LB, Bouter LM, Alonso J, Patrick DL, de Vet HCW, et al. COSMIN guideline for systematic reviews of patient-reported outcome measures. Qual Life Res. 2018;27(5):1147–57.
Mason SJ, Catto JWF, Downing A, Bottomley SE, Glaser AW, Wright P. Evaluating patient-reported outcome measures (PROMs) for bladder cancer: a systematic review using the COnsensus-based standards for the selection of health measurement INstruments (COSMIN) checklist. BJU Int. 2018;122(5):760–73.
Pham H, Torres H, Sharma P. Mental health implications in bladder cancer patients: a review. Urol Oncol. 2019;37(2):97–107.
Efficace F, Feuerstein M, Fayers P, Cafaro V, Eastham J, Pusic A, et al. Patient-reported outcomes in randomised controlled trials of prostate cancer: methodological quality and impact on clinical decision making. Eur Urol. 2014;66(3):416–27.
Mercieca-Bebber RL, Perreca A, King M, Macann A, Whale K, Soldati S, et al. Patient-reported outcomes in head and neck and thyroid cancer randomised controlled trials: a systematic review of completeness of reporting and impact on interpretation. Eur J Cancer. 2016;56:144–61.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–12.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.
Brundage M, Blazeby J, Revicki D, Bass B, de Vet H, Duffy H, et al. Patient-reported outcomes in randomized clinical trials: development of ISOQOL reporting standards. Qual Life Res. 2013;22(6):1161–75.
Chung JM, Ha HK, Kim DH, Joo J, Kim S, Sohn DW, et al. Evaluation of the efficacy of Solifenacin for preventing catheter-related bladder discomfort after transurethral resection of bladder tumors in patients with non-muscle invasive bladder Cancer: a prospective, randomized, Multicenter Study. Clin Genitourin Cancer. 2017;15(1):157–62.
Kim HC, Hong WP, Lim YJ, Park HP. The effect of sevoflurane versus desflurane on postoperative catheter-related bladder discomfort in patients undergoing transurethral excision of a bladder tumour: a randomized controlled trial. Can J Anaesth. 2016;63(5):596–602.
Yokomizo A, Kanimoto Y, Okamura T, Ozono S, Koga H, Iwamura M, et al. Randomized controlled study of the efficacy, safety and quality of life with low dose bacillus Calmette-Guerin instillation therapy for nonmuscle invasive bladder Cancer. J Urol. 2016;195(1):41–6.
Khan MS, Gan C, Ahmed K, Ismail AF, Watkins J, Summers JA, et al. A single-Centre early phase randomised controlled three-arm trial of open, robotic, and laparoscopic radical cystectomy (CORAL). Eur Urol. 2016;69(4):613–21.
Kim HC, Lim SM, Seo H, Park HP. Effect of glycopyrrolate versus atropine coadministered with neostigmine for reversal of rocuronium on postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor: a prospective randomized study. J Anesth. 2015;29(6):831–5.
Huang W, Wang F, Wu C, Hu W. Efficacy and safety of pirarubicin combined with hyaluronic acid for non-muscle invasive bladder cancer after transurethral resection: a prospective, randomized study. Int Urol Nephrol. 2015;47(4):631–6.
Kim HC, Lee YH, Jeon YT, Hwang JW, Lim YJ, Park JE, et al. The effect of intraoperative dexmedetomidine on postoperative catheter-related bladder discomfort in patients undergoing transurethral bladder tumour resection: a double-blind randomised study. Eur J Anaesthesiol. 2015;32(9):596–601.
Parekh DJ, Reis IM, Castle EP, Gonzalgo ML, Woods ME, Svatek RS, et al. Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial. Lancet. 2018;391(10139):2525–36.
James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012;366(16):1477–88.
Sabichi AL, Lee JJ, Grossman HB, Liu S, Richmond E, Czerniak BA, et al. A randomized controlled trial of celecoxib to prevent recurrence of nonmuscle-invasive bladder cancer. Cancer Prev Res (Phila). 2011;4(10):1580–9.
Koga H, Ozono S, Tsushima T, Tomita K, Horiguchi Y, Usami M, et al. Maintenance intravesical bacillus Calmette-Guerin instillation for ta, T1 cancer and carcinoma in situ of the bladder: randomized controlled trial by the BCG Tokyo strain study group. Int J Urol. 2010;17(9):759–66.
Marandola M, Antonucci A, Tellan G, Fegiz A, Fazio R, Scicchitano S, et al. Subarachnoid sufentanil as sole agent vs standard spinal bupivacaine in transurethral resection of the bladder. Minerva Anestesiol. 2005;71(3):83–91.
Ozyuvaci E, Altan A, Karadeniz T, Topsakal M, Besisik A, Yucel M. General anesthesia versus epidural and general anesthesia in radical cystectomy. Urol Int. 2005;74(1):62–7.
Gontero P, Oderda M, Mehnert A, Gurioli A, Marson F, Lucca I, et al. The impact of intravesical gemcitabine and 1/3 dose Bacillus Calmette-Guerin instillation therapy on the quality of life in patients with nonmuscle invasive bladder cancer: results of a prospective, randomized, phase II trial. J Urol. 2013;190(3):857–62.
Karl A, Buchner A, Becker A, Staehler M, Seitz M, Khoder W, et al. A new concept for early recovery after surgery for patients undergoing radical cystectomy for bladder cancer: results of a prospective randomized study. J Urol. 2014;191(2):335–40.
Skinner EC, Skinner DG. Does reflux in orthotopic diversion matter? A randomized prospective comparison of the Studer and T-pouch ileal neobladders. World J Urol. 2009;27(1):51–5.
Ahmadi H, Skinner EC, Simma-Chiang V, Miranda G, Cai J, Penson DF, et al. Urinary functional outcome following radical cystoprostatectomy and ileal neobladder reconstruction in male patients. J Urol. 2013;189(5):1782–8.
Johnson MH, Nepple KG, Peck V, Trinkaus K, Klim A, Sandhu GS, et al. Randomized controlled trial of oxybutynin extended release versus placebo for urinary symptoms during intravesical Bacillus Calmette-Guerin treatment. J Urol. 2013;189(4):1268–74.
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–76.
Calvert M, Blazeby J, Altman DG, Revicki DA, Moher D, Brundage MD. Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA. 2013;309(8):814–22.
Fiteni F, Anota A, Westeel V, Bonnetain F. Methodology of health-related quality of life analysis in phase III advanced non-small-cell lung cancer clinical trials: a critical review. BMC Cancer. 2016;16:122.
Efficace F, Aaronson NK, Sparano F, Sprangers M, Fayers P, Pusic AL, et al. Quality of Patient-Reported Outcome (PRO) reporting in Randomized Controlled Trials (RCTs) over time. Evidence from 480 RCTs from 2004 to 2016. 24th Annual Conference of the International Society for Quality of Life Research (ISOQOL), Philadelphia, USA. Qual Life Res. 2017;26(1):139 (abs.3056).
Rimar KJ, Tran PT, Matulewicz RS, Hussain M, Meeks JJ. The emerging role of homologous recombination repair and PARP inhibitors in genitourinary malignancies. Cancer. 2017;123(11):1912–24.
Nogova L, Sequist LV, Perez Garcia JM, Andre F, Delord JP, Hidalgo M, et al. Evaluation of BGJ398, a fibroblast growth factor receptor 1-3 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: results of a global phase I, dose-escalation and dose-expansion study. J Clin Oncol. 2017;35(2):157–65.
Pe M, Dorme L, Coens C, Basch E, Calvert M, Campbell A, et al. Statistical analysis of patient-reported outcome data in randomised controlled trials of locally advanced and metastatic breast cancer: a systematic review. Lancet Oncol. 2018;19(9):e459–e69.
EORTC Quality of Life Group. EORTC Quality of Life 2019 Available from: https://www.eortc.org/research_field/quality-of-life/.
Marandino L, La Salvia A, Sonetto C, De Luca E, Pignataro D, Zichi C, et al. Deficiencies in health-related quality-of-life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016. Ann Oncol. 2018;29(12):2288–95.
Morrison A, Polisena J, Husereau D, Moulton K, Clark M, Fiander M, et al. The effect of English-language restriction on systematic review-based meta-analyses: a systematic review of empirical studies. Int J Technol Assess Health Care. 2012;28(2):138–44.
We would like to thank the Dianne and Graham Roberts Charitable Settlement for their support.
We would like to thank the Dianne and Graham Roberts Charitable Settlement for their support.
Ethics approval and consent to participate
As this was a systematic review, all data used for analysis in this work was publicly available.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Van Hemelrijck, M., Sparano, F., Josephs, D. et al. Patient-reported outcomes in randomised clinical trials of bladder cancer: an updated systematic review. BMC Urol 19, 86 (2019). https://doi.org/10.1186/s12894-019-0518-9
- Quality of life
- Outcome measurement
- Bladder cancer