Changes in fatigue in rectal cancer patients before and after therapy: a systematic review and meta-analysis



Fatigue is a common problem among rectal cancer patients and can affect their quality of life. This study conducted a systematic review to better understand changes in fatigue severity in rectal cancer patients before, during, and after they undergo therapy.


We used preset keywords to search the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, and ProQuest databases for relevant studies published between 2000 and 2018, and data analysis was performed using Comprehensive Meta-Analysis (CMA) software (version 2.2.048) and SPSS software (version 19.0). In total, nine articles with complete data were included in our meta-analysis.


Fatigue conditions were compared before the start of therapy (baseline) and at 1 month (time 1), 3 months (time 2), 6 months (time 3), and 12 months (time 4) after the start of therapy. The standardized mean differences (SMDs) of the pooling effects size were 1.013 (95% confidence interval (CI) 0.217–1.810), − 0.551 (95% CI − 0.647 to − 0.456), − 0.330 (95% CI − 0.427 to − 0.233), and − 0.149 (95% CI − 0.221 to − 0.078), respectively. Subsequent analysis with a linear mixed effect model revealed that the estimate of the time variable was − 0.226 (p = 0.047), which indicates that the severity of fatigue varies over time and over the course of treatment. The results reveal that fatigue affects rectal cancer patients even before they start therapy.


Although fatigue worsened during the first month after cancer therapy, it gradually improved thereafter.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, Johnson DH, Miaskowski C, Scherr SL, Portenoy RK, Vogelzang NJ (2000) Impact of cancer-related fatigue on the lives of patients: new findings from the fatigue coalition. Oncologist 5:353–360.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Teunissen SC, Wesker W, Kruitwagen C, de Haes HC, Voest EE, de Graeff A (2007) Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manag 34:94–104.

    Article  Google Scholar 

  3. 3.

    Charalambous A, Kouta C (2016) Cancer related fatigue and quality of life in patients with advanced prostate cancer undergoing chemotherapy. Biomed Res Int 2016:3989286.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Chen HL, Liu K, You QS (2018) Self-efficacy, cancer-related fatigue, and quality of life in patients with resected lung cancer. Eur J Cancer Care (Engl) 27:e12934.

    Article  Google Scholar 

  5. 5.

    Fabi A, Falcicchio C, Giannarelli D, Maggi G, Cognetti F, Pugliese P (2017) The course of cancer related fatigue up to ten years in early breast cancer patients: what impact in clinical practice? Breast 34:44–52.

    Article  PubMed  Google Scholar 

  6. 6.

    Grenon NN, Chan J (2009) Managing toxicities associated with colorectal cancer chemotherapy and targeted therapy: a new guide for nurses. Clin J Oncol Nurs 13:285–296.

    Article  PubMed  Google Scholar 

  7. 7.

    Wang XS, Janjan NA, Guo H, Johnson BA, Engstrom MC, Crane CH, Mendoza TR, Cleeland CS (2001) Fatigue during preoperative chemoradiation for resectable rectal cancer. Cancer 92:1725–1732.<1725::aid-cncr1504>;2-d

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Yeom SS, Park IJ, Jung SW, Oh SH, Lee JL, Yoon YS, Kim CW, Lim SB, Kim N, Yu CS, Kim JC (2017) Outcomes of patients with abdominoperineal resection (APR) and low anterior resection (LAR) who had very low rectal cancer. Medicine 96:e8249.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Li Y, Wang J, Ma X, Tan L, Yan Y, Xue C, Hui B, Liu R, Ma H, Ren J (2016) A review of neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Int J Biol Sci 12:1022–1031.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Petersen SH, Harling H, Kirkeby LT, Wille-Jørgensen P, Mocellin S (2012) Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev 3:CD004078.

    Article  Google Scholar 

  11. 11.

    Kim CG, Ahn JB, Shin SJ, Beom SH, Heo SJ, Park HS, Kim JH, Choe EA, Koom WS, Hur H, Min BS, Kim NK, Kim H, Kim C, Jung I, Jung M (2017) Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after preoperative chemoradiation therapy and surgery. BMC Cancer 17:615.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Joanna Briggs Institute (2011) Module 3-the appraisal, extraction and pooling of quantitative data. Accessed 30 August 2019

  13. 13.

    Li SX, Liu BB, Lu JH (2014) Longitudinal study of cancer-related fatigue in patients with colorectal cancer. Asian Pac J Cancer Prev 15:3029–3033.

    Article  PubMed  Google Scholar 

  14. 14.

    Park HC, Janjan NA, Mendoza TR, Lin EH, Vadhan-Raj S, Hundal M, Zhang Y, Delclos ME, Crane CH, Das P, Wang XS, Cleeland CS, Krishnan S (2009) Temporal patterns of fatigue predict pathologic response in patients treated with preoperative chemoradiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys 75:775–781.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Pucciarelli S, Del Bianco P, Efficace F et al (2011) Patient-reported outcomes after neoadjuvant chemoradiotherapy for rectal cancer: a multicenter prospective observational study. Ann Surg 253:71–77.

    Article  PubMed  Google Scholar 

  16. 16.

    Couwenberg AM, Burbach JPM, van Grevenstein WMU, Smits AB, Consten ECJ, Schiphorst AHW, Wijffels NAT, Heikens JT, Intven MPW, Verkooijen HM (2018) Effect of neoadjuvant therapy and rectal surgery on health-related quality of life in patients with rectal cancer during the first 2 years after diagnosis. Clin Colorectal Cancer 17:e499–e512.

    Article  PubMed  Google Scholar 

  17. 17.

    Schmidt CE, Bestmann B, Küchler T, Longo WE, Kremer B (2005) Prospective evaluation of quality of life of patients receiving either abdominoperineal resection or sphincter-preserving procedure for rectal cancer. Ann Surg Oncol 12:117–123.

    Article  PubMed  Google Scholar 

  18. 18.

    Zhang JK, Fang LL, Zhang DW, Jin Q, Wu XM, Liu JC, Zhang CD, Dai DQ (2016) Type D personality is associated with delaying patients to medical assessment and poor quality of life among rectal cancer survivors. Int J Color Dis 31:75–85.

    CAS  Article  Google Scholar 

  19. 19.

    Grumann MM, Noack EM, Hoffmann IA, Schlag PM (2001) Comparison of quality of life in patients undergoing abdominoperineal extirpation or anterior resection for rectal cancer. Ann Surg 233:149–156.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Monastyrska E, Hagner W, Jankowski M, Głowacka I, Zegarska B, Zegarski W (2016) Prospective assessment of the quality of life in patients treated surgically for rectal cancer with lower anterior resection and abdominoperineal resection. Eur J Surg Oncol 42:1647–1653.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Herrle F, Sandra-Petrescu F, Weiss C, Post S, Runkel N, Kienle P (2016) Quality of life and timing of stoma closure in patients with rectal cancer undergoing low anterior resection with diverting stoma: a multicenter longitudinal observational study. Dis Colon Rectum 59:281–290.

    Article  PubMed  Google Scholar 

  22. 22.

    Väyrynen JP, Tuomisto A, Väyrynen SA, Klintrup K, Karhu T, Mäkelä J, Herzig KH, Karttunen TJ, Mäkinen MJ (2018) Preoperative anemia in colorectal cancer: relationships with tumor characteristics, systemic inflammation, and survival. Sci Rep 8:1126.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Bondurant KL, Lundgreen A, Herrick JS, Kadlubar S, Wolff RK, Slattery ML (2013) Interleukin genes and associations with colon and rectal cancer risk and overall survival. Int J Cancer 132:905–915.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Macciò A, Madeddu C, Gramignano G et al (2015) The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study. Haematologica 100:124–132.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Manocha M, Khan WI (2012) Serotonin and GI disorders: an update on clinical and experimental studies. Clin Transl Gastroenterol 3:e13.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Coleman EA, Goodwin JA, Coon SK, Richards K, Enderlin C, Kennedy R, Stewart CB, McNatt P, Lockhart K, Anaissie EJ, Barlogie B (2011) Fatigue, sleep, pain, mood, and performance status in patients with multiple myeloma. Cancer Nurs 34:219–227.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Bower JE (2014) Cancer-related fatigue--mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 11:597–609.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Johnson RL, Amin AR, Matzo M (2012) Cancer-related fatigue. Am J Nurs 112:57–60.

    Article  PubMed  Google Scholar 

  29. 29.

    O'Higgins CM, Brady B, O'Connor B, Walsh D, Reilly RB (2018) The pathophysiology of cancer-related fatigue: current controversies. Support Care Cancer 26:3353–3364.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Goedendorp MM, Gielissen MF, Verhagen CA, Peters ME, Bleijenberg G (2008) Severe fatigue and related factors in cancer patients before the initiation of treatment. Br J Cancer 99:1408–1414.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Silverman MN, Heim CM, Nater UM, Marques AH, Sternberg EM (2010) Neuroendocrine and immune contributors to fatigue. PM R 2:338–346.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Gil F, Costa G, Hilker I, Benito L (2012) First anxiety, afterwards depression: psychological distress in cancer patients at diagnosis and after medical treatment. Stress Health 28:362–367.

    Article  PubMed  Google Scholar 

  33. 33.

    Turgay AS, Khorshid L, Eser I (2008) Effect of the first chemotherapy course on the quality of life of cancer patients in Turkey. Cancer Nurs 31:E19–E23.

    Article  PubMed  Google Scholar 

  34. 34.

    Park IJ, You YN, Agarwal A, Skibber JM, Rodriguez-Bigas MA, Eng C, Feig BW, Das P, Krishnan S, Crane CH, Hu CY, Chang GJ (2012) Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol 30:1770–1776.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Given B, Given CW, McCorkle R, Kozachik S, Cimprich B, Rahbar MH, Wojcik C (2002) Pain and fatigue management: results of a nursing randomized clinical trial. Oncol Nurs Forum 29:949–956.

    Article  PubMed  Google Scholar 

  36. 36.

    Saber MM, Al-Mahallawi AM, Nassar NN, Stork B, Shouman SA (2018) Targeting colorectal cancer cell metabolism through development of cisplatin and metformin nano-cubosomes. BMC Cancer 18:822.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Banipal RPS, Singh H, Singh B (2017) Assessment of cancer-related fatigue among cancer patients receiving various therapies: a cross-sectional observational study. Indian J Palliat Care 23:207–211.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR (2007) Cancer-related fatigue: the scale of the problem. Oncologist 12:4–10.

    Article  PubMed  Google Scholar 

  39. 39.

    Piper BF, Borneman T, Sun VC, Koczywas M, Uman G, Ferrell B, James RL (2008) Cancer-related fatigue: role of oncology nurses in translating National Comprehensive Cancer Network assessment guidelines into practice. Clin J Oncol Nurs 12:37–47.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Okuyama T, Akechi T, Kugaya A et al (2000) Development and validation of the cancer fatigue scale: a brief, three-dimensional, self-rating scale for assessment of fatigue in cancer patients. J Pain Symptom Manag 19:5–14.

    CAS  Article  Google Scholar 

  41. 41.

    Wu HS, McSweeney M (2001) Measurement of fatigue in people with cancer. Oncol Nurs Forum 28:1371–1384

    CAS  PubMed  Google Scholar 

  42. 42.

    Cleeland CS, Mendoza TR, Wang XS et al (2000) Assessing symptom distress in cancer patient: the M. D. Anderson Symptom Inventory. Cancer 89:1634–1646.<1634::aid-cncr29>;2-v

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Greimel ER, Kuljanic Vlasic K, Waldenstrom AC, Duric VM, Jensen PT, Singer S, Chie W, Nordin A, Bjelic Radisic V, Wydra D, European Organization for Research and Treatment of Cancer Quality-of-Life Group (2006) The European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire cervical cancer module: EORTC QLQ-CX24. Cancer 107:1812–1822.

    Article  PubMed  Google Scholar 

  44. 44.

    Knobel H, Loge JH, Brenne E, Fayers P, Hjermstad MJ, Kaasa S (2003) The validity of EORTC QLQ-C30 fatigue scale in advanced cancer patients and cancer survivors. Palliat Med 17:664–672.

    Article  PubMed  Google Scholar 

  45. 45.

    Glaus A (1993) Assessment of fatigue in cancer and non-cancer patients and in healthy individuals. Support Care Cancer 1:305–315.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Munch TN, Strömgren AS, Pedersen L, Petersen MA, Hoermann L, Groenvold M (2006) Multidimensional measurement of fatigue in advanced cancer patients in palliative care: an application of the multidimensional fatigue inventory. J Pain Symptom Manag 31:533–541.

    Article  Google Scholar 

  47. 47.

    Jean-Pierre P, Figueroa-Moseley CD, Kohli S, Fiscella K, Palesh OG, Morrow GR (2007) Assessment of cancer-related fatigue: implications for clinical diagnosis and treatment. Oncologist 12:11–21.

    Article  PubMed  Google Scholar 

Download references


We thank the anonymous reviewers and editor for their comments.

Author information




Conceptualization: Wen-Pei Chang; Hsiu-Ju Jen.

Data curation: Wen-Pei Chang.

Formal analysis: Wen-Pei Chang; Hsiu-Ju Jen.

Methodology: Wen-Pei Chang.

Project administration: Wen-Pei Chang.

Resources: Wen-Pei Chang.

Software: Wen-Pei Chang; Hsiu-Ju Jen.

Supervision: Wen-Pei Chang.

Validation: Wen-Pei Chang; Hsiu-Ju Jen.

Visualization: Wen-Pei Chang.

Writing, original draft: Wen-Pei Chang.

Writing, review and editing: Wen-Pei Chang.

Corresponding author

Correspondence to Chang Wen-Pei.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wen-Pei, C., Hsiu-Ju, J. Changes in fatigue in rectal cancer patients before and after therapy: a systematic review and meta-analysis. Support Care Cancer 28, 2513–2522 (2020).

Download citation


  • Rectum cancer
  • Tiredness
  • Treatment