Skip to main content
Log in

Patient-reported outcomes in randomised controlled trials of colorectal cancer: an analysis determining the availability of robust data to inform clinical decision-making

  • Review – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript



Randomised controlled trials (RCTs) are the most robust study design measuring outcomes of colorectal cancer (CRC) treatments, but to influence clinical practice trial design and reporting of patient-reported outcomes (PROs) must be of high quality. Objectives of this study were as follows: to examine the quality of PRO reporting in RCTs of CRC treatment; to assess the availability of robust data to inform clinical decision-making; and to investigate whether quality of reporting improved over time.


A systematic review from January 2004–February 2012 identified RCTs of CRC treatment describing PROs. Relevant abstracts were screened and manuscripts obtained. Methodological quality was assessed using International Society for Quality of Life Research—patient-reported outcome reporting standards. Changes in reporting quality over time were established by comparison with previous data, and risk of bias was assessed with the Cochrane risk of bias tool.


Sixty-six RCTs were identified, seven studies (10 %) reported survival benefit favouring the experimental treatment, 35 trials (53 %) identified differences in PROs between treatment groups, and the clinical significance of these differences was discussed in 19 studies (29 %). The most commonly reported treatment type was chemotherapy (n = 45; 68 %). Improvements over time in key methodological issues including the documentation of missing data and the discussion of the clinical significance of PROs were found. Thirteen trials (20 %) had high-quality reporting.


Whilst improvements in PRO quality reporting over time were found, several recent studies still fail to robustly inform clinical practice. Quality of PRO reporting must continue to improve to maximise the clinical impact of PRO findings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


  • Bauhofer A et al (2007) Perioperative prophylaxis with granulocyte colony-stimulating factor (G-CSF) in high-risk colorectal cancer patients for an improved recovery: a randomized, controlled trial. Surgery 141:501–510. doi:10.1016/j.surg.2006.09.004

    Article  PubMed  Google Scholar 

  • Brundage M et al (2012) Patient-reported outcomes in randomized clinical trials: development of ISOQOL reporting standards. Qual Life Res 22:1161–1175. doi:10.1007/s11136-012-0252-1

    Article  PubMed Central  PubMed  Google Scholar 

  • Calvert M, Blazeby J, Altman DG, Revicki DA, Moher D, Brundage MD, Group CP (2013) Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA 309:814–822. doi:10.1001/jama.2013.879

    Article  CAS  PubMed  Google Scholar 

  • Chan A-W et al (2013) SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. doi:10.1136/bmj.e7586

    Google Scholar 

  • Claassens L et al (2011) Health-related quality of life in non-small-cell lung cancer: an update of a systematic review on methodologic issues in randomized controlled trials. J Clin Oncol 29:2104–2120. doi:10.1200/JCO.2010.32.3683

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cocks K, King MT, Velikova G, Fayers PM, Brown JM (2008) Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials. Eur J Cancer 44:1793–1798. doi:10.1016/j.ejca.2008.05.008

    Article  PubMed  Google Scholar 

  • Coleman MP et al (2011) Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet 377:127–138. doi:10.1016/S0140-6736(10)62231-3

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Coulman KD, Abdelrahman T, Owen-Smith A, Andrews RC, Welbourn R, Blazeby JM (2013) Patient-reported outcomes in bariatric surgery: a systematic review of standards of reporting. Obes Rev Off J Int Assoc Study Obes. doi:10.1111/obr.12041

    Google Scholar 

  • de Kort SJ, Willemse PHB, Habraken JM, de Haes HCJM, Willems DL, Richel DJ (2006) Quality of life versus prolongation of life in patients treated with chemotherapy in advanced colorectal cancer: a review of randomized controlled clinical trials. Eur J Cancer 42:835–845. doi:10.1016/j.ejca.2005.10.026

    Article  PubMed  Google Scholar 

  • Denlinger CS, Barsevick AM (2009) The challenges of colorectal cancer survivorship. J Natl Compr Cancer Netw JNCCN 7:883–893 (quiz 894)

    PubMed  Google Scholar 

  • Douillard JY et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705. doi:10.1200/JCO.2009.27.4860

    Article  CAS  PubMed  Google Scholar 

  • Ducreux M et al (2011) Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer. Int J Cancer 128:682–690. doi:10.1002/ijc.25369

    Article  CAS  PubMed  Google Scholar 

  • Efficace F, Bottomley A, Osoba D, Gotay C, Flechtner H, D’Haese S, Zurlo A (2003) Beyond the development of health-related quality-of-life (HRQOL) measures: a checklist for evaluating HRQOL outcomes in cancer clinical trials—Does HRQOL evaluation in prostate cancer research inform clinical decision making? J Clin Oncol 21:3502–3511. doi:10.1200/JCO.2003.12.121

    Article  PubMed  Google Scholar 

  • Efficace F, Bottomley A, Vanvoorden V, Blazeby JM (2004) Methodological issues in assessing health-related quality of life of colorectal cancer patients in randomised controlled trials. Eur J Cancer 40:187–197

    Article  CAS  PubMed  Google Scholar 

  • Efficace F et al (2013) Patient-reported outcomes in randomised controlled trials of prostate cancer: methodological quality and impact on clinical decision making. Eur Urol. doi:10.1016/j.eururo.2013.10.017

    PubMed Central  PubMed  Google Scholar 

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) GLOBOCAN 2008, Cancer incidence and mortality worldwide: IARC CancerBase No. 10. International Agency for Research on Cancer. Accessed 23 Oct 2013

  • Greenhalgh J (2009) The applications of PROs in clinical practice: What are they, do they work, and why? Qual Life Res 18:115–123. doi:10.1007/s11136-008-9430-6

    Article  PubMed  Google Scholar 

  • Gujral S, Avery KN, Blazeby JM (2008) Quality of life after surgery for colorectal cancer: clinical implications of results from randomised trials. Support Care Cancer 16:127–132. doi:10.1007/s00520-007-0356-2

    Article  PubMed  Google Scholar 

  • Hedges LV, Olkin I (1985) Statistical methods for meta-analysis. Academic Press, Orlando

    Google Scholar 

  • Higgins JPT, Green S (eds) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration.

  • Janson M, Lindholm E, Anderberg B, Haglind E (2007) Randomized trial of health-related quality of life after open and laparoscopic surgery for colon cancer. Surg Endosc 21:747–753. doi:10.1007/s00464-007-9217-9

    Article  PubMed  Google Scholar 

  • Jayne DG, Brown JM, Thorpe H, Walker J, Quirke P, Guillou PJ (2005) Bladder and sexual function following resection for rectal cancer in a randomized clinical trial of laparoscopic versus open technique. Br J Surg 92:1124–1132. doi:10.1002/bjs.4989

    Article  CAS  PubMed  Google Scholar 

  • Jonker DJ et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048. doi:10.1056/NEJMoa071834

    Article  CAS  PubMed  Google Scholar 

  • Juni P, Holenstein F, Sterne J, Bartlett C, Egger M (2002) Direction and impact of language bias in meta-analyses of controlled trials: empirical study. Int J Epidemiol 31:115–123

    Article  PubMed  Google Scholar 

  • Lee CW, Chi KN (2000) The standard of reporting of health-related quality of life in clinical cancer trials. J Clin Epidemiol 53:451–458

    Article  CAS  PubMed  Google Scholar 

  • Lembersky BC et al (2006) Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol 24:2059–2064. doi:10.1200/JCO.2005.04.7498

    Article  CAS  PubMed  Google Scholar 

  • Liberati A et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. doi:10.1136/bmj.b2700

    Article  PubMed Central  PubMed  Google Scholar 

  • Macefield RC, Avery KN, Blazeby JM (2013) Integration of clinical and patient-reported outcomes in surgical oncology. Br J Surg 100:28–37. doi:10.1002/bjs.8989

    Article  CAS  PubMed  Google Scholar 

  • Macefield RC et al (2014) Developing core outcomes sets: methods for identifying and including patient-reported outcomes (PROs). Trials 15:49. doi:10.1186/1745-6215-15-49

    Article  PubMed Central  PubMed  Google Scholar 

  • Main BG, Strong S, McNair AG, Falk SJ, Crosby T, Blazeby JM (2014) Reporting outcomes of definitive radiation-based treatment for esophageal cancer: a review of the literature Diseases of the esophagus: official journal of the International Society for Diseases of the Esophagus/ISDE. doi:10.1111/dote.12168

    Google Scholar 

  • Moher D, Pham B, Klassen TP, Schulz KF, Berlin JA, Jadad AR, Liberati A (2000) What contributions do languages other than English make on the results of meta-analyses? J Clin Epidemiol 53:964–972

    Article  CAS  PubMed  Google Scholar 

  • Moher D et al (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. doi:10.1136/bmj.c869

    Google Scholar 

  • Odom D et al (2011) Health-related quality of life and colorectal cancer-specific symptoms in patients with chemotherapy-refractory metastatic disease treated with panitumumab. Int J Colorectal Dis 26:173–181. doi:10.1007/s00384-010-1112-5

    Article  PubMed Central  PubMed  Google Scholar 

  • Peeters KC et al (2005) Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients—a Dutch colorectal cancer group study. J Clin Oncol 23:6199–6206. doi:10.1200/JCO.2005.14.779

    Article  CAS  PubMed  Google Scholar 

  • Peeters M et al (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28:4706–4713. doi:10.1200/JCO.2009.27.6055

    Article  CAS  PubMed  Google Scholar 

  • Sibbald B, Roland M (1998) Understanding controlled trials: Why are randomised controlled trials important? BMJ 316:201. doi:10.1136/bmj.316.7126.201

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Staquet M, Berzon R, Osoba D, Machin D (1996) Guidelines for reporting results of quality of life assessments in clinical trials. Qual Life Res 5:496–502

    Article  CAS  PubMed  Google Scholar 

  • Stephens RJ et al (2010) Impact of short-course preoperative radiotherapy for rectal cancer on patients’ quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. J Clin Oncol 28:4233–4239. doi:10.1200/JCO.2009.26.5264

    Article  PubMed  Google Scholar 

  • Stucky CC et al (2011) Long-term follow-up and individual item analysis of quality of life assessments related to laparoscopic-assisted colectomy in the COST trial 93-46-53 (INT 0146). Ann Surg Oncol 18:2422–2431. doi:10.1245/s10434-011-1650-2

    Article  PubMed Central  PubMed  Google Scholar 

  • Thong MS, Mols F, Wang XS, Lemmens VE, Smilde TJ, van de Poll-Franse LV (2013) Quantifying fatigue in (long-term) colorectal cancer survivors: a study from the population-based patient reported outcomes following initial treatment and long term evaluation of survivorship registry. Eur J Cancer 49:1957–1966. doi:10.1016/j.ejca.2013.01.012

    Article  PubMed Central  PubMed  Google Scholar 

  • Tournier-Rangeard L et al (2008) Radiochemotherapy of locally advanced anal canal carcinoma: prospective assessment of early impact on the quality of life (randomized trial ACCORD 03). Radiother Oncol 87:391–397. doi:10.1016/j.radonc.2007.12.004

    Article  CAS  PubMed  Google Scholar 

  • UK CR (2009) Bowel Cancer Incidence Statistics. Accessed 31 Aug 2012

  • van Hooft JE et al (2011) Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial. Lancet Oncol 12:344–352. doi:10.1016/S1470-2045(11)70035-3

    Article  PubMed  Google Scholar 

  • Ward JA, Potter S, Blazeby JM (2012) Outcome reporting for reconstructive breast surgery: the need for consensus, consistency and core outcome sets. Eur J Surg Oncol 38:1020–1021. doi:10.1016/j.ejso.2012.07.108

    Article  CAS  PubMed  Google Scholar 

  • Whistance RN, Blencowe NS, Blazeby JM (2012) The need for standardised outcome reporting in colorectal surgery. Gut 61:472. doi:10.1136/gutjnl-2011-300676

    Article  CAS  PubMed  Google Scholar 

  • Whistance RN et al (2013) A systematic review of outcome reporting in colorectal cancer surgery. Colorectal Dis 15:e548–e560. doi:10.1111/codi.12378

    Article  CAS  PubMed  Google Scholar 

  • Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, Tugwell P (2012) Developing core outcome sets for clinical trials: issues to consider. Trials 13:132. doi:10.1186/1745-6215-13-132

    Article  PubMed Central  PubMed  Google Scholar 

Download references


This paper forms part of a larger project, the Patient-Reported Outcome Measurements Over Time In ONcology-PROMOTION Registry funded in part by a research grant from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group. Also, additional support for the conduct of the study was provided by the Italian Group for Adult Hematologic Diseases (GIMEMA) and the MRC ConDuCT-II Hub for Trials Methodology Research in Bristol. We also acknowledge Alessandro Perreca and Salvatore Soldati, from the GIMEMA, for their contribution to data management. J.R. Rees is funded by the National Institute of Health Research Academic Clinical Lecturer programme.

Conflict of interest


Author information

Authors and Affiliations


Corresponding author

Correspondence to Jonathan R. Rees.

Additional information

On behalf of EORTC Quality of Life Group.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 38 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rees, J.R., Whale, K., Fish, D. et al. Patient-reported outcomes in randomised controlled trials of colorectal cancer: an analysis determining the availability of robust data to inform clinical decision-making. J Cancer Res Clin Oncol 141, 2181–2192 (2015).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: