Patient-reported outcomes after chemoradiotherapy for anal cancer
DOI:
https://doi.org/10.2340/1651-226X.2025.43636Keywords:
anal cancer, chemoradiotherapy, patient reported outcome measures, chronic fatigue, anorectal functionAbstract
Background and purpose: Chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCCA) results in favorable survival. However, treatment intensity must be balanced against late side effects. The aim of this current study was to prospectively investigate patient-reported outcomes (PROs) before CRT and up to 5 years after completed CRT for SCCA.
Patient/material and methods: This prospective study included 120 patients with SCCA receiving CRT to total doses of 54–58 Gy with concomitant mitomycin and 5-fluorouracil. Patients completed PRO questionnaires before CRT, and at 3 months, 1-, 3-, and 5 years after completed CRT. The questionnaires were the EORTC QLQ-C30 and QLQ-CR29, St. Marks incontinence score, Fatigue Questionnaire, the Hospital Anxiety and Depression Scale, and a scoring for neuroticism.
Results: Patients reported a high burden of symptoms and impaired functional outcomes prior to treatment. Tumor-related symptoms, such as buttock pain, improved (difference 11.1, p = 0.002) at a clinically relevant level 3 months after CRT, consistent with tumor response. Other functional outcomes and symptoms, such as body image (difference 11.5, p < 0.001), worsened. While some outcomes, such as anxiety (difference 10.4, p = 0.001), improved over time, several were persistently impaired, in particular anorectal and sexual function, where symptom burden remained high 5 years after CRT. Chronic fatigue (CF) was reported by 28% of patients at 5-year follow-up.
Interpretation: Five years after CRT for SCCA, patients report a persistently high symptom burden regarding anorectal and sexual function, and one-third report CF, demonstrating the long-term impact of treatment.
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Rao S, Guren MG, Khan K, Brown G, Renehan AG, Steigen SE, et al. Anal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up(*). Ann Oncol. 2021;32(9):1087–100.
https://doi.org/10.1016/j.annonc.2021.06.015 DOI: https://doi.org/10.1016/j.annonc.2021.06.015
Sekhar H, Malcomson L, Kochhar R, Sperrin M, Alam N, Chakrbarty B, et al. Temporal improvements in loco-regional failure and survival in patients with anal cancer treated with chemo-radiotherapy: treatment cohort study (1990–2014). Br J Cancer. 2020;122(6):749–58.
https://doi.org/10.1038/s41416-019-0689-x DOI: https://doi.org/10.1038/s41416-019-0689-x
Slørdahl KS, Klotz D, Olsen J, Skovlund E, Undseth C, Abildgaard HL, et al. Treatment outcomes and prognostic factors after chemoradiotherapy for anal cancer. Acta Oncol. 2021;60(7):921–30.
https://doi.org/10.1080/0284186X.2021.1918763 DOI: https://doi.org/10.1080/0284186X.2021.1918763
Besson A, Deftereos I, Chan S, Faragher IG, Kinsella R, Yeung JM. Understanding patient-reported outcome measures in colorectal cancer. Future Oncol. 2019;15(10):1135–46.
https://doi.org/10.2217/fon-2018-0723 DOI: https://doi.org/10.2217/fon-2018-0723
Di Maio M, Basch E, Denis F, Fallowfield LJ, Ganz PA, Howell D, et al. The role of patient-reported outcome measures in the continuum of cancer clinical care: ESMO clinical practice guideline. Ann Oncol. 2022;33(9):878–92.
https://doi.org/10.1016/j.annonc.2022.04.007 DOI: https://doi.org/10.1016/j.annonc.2022.04.007
Fish R, Sanders C, Adams R, Brewer J, Brookes ST, DeNardo J, et al. A core outcome set for clinical trials of chemoradiotherapy interventions for anal cancer (CORMAC): a patient and health-care professional consensus. Lancet Gastroenterol Hepatol. 2018;3(12):865–73.
https://doi.org/10.1016/S2468-1253(18)30264-4 DOI: https://doi.org/10.1016/S2468-1253(18)30264-4
Samuel R, Knight SR, Adams R, Das P, Dorth J, Finch D, et al. International consensus to define outcomes for trials of chemoradiotherapy for anal cancer (CORMAC-2): defining the outcomes from the CORMAC core outcome set. EClinicalMedicine. 2024;78:102939.
https://doi.org/10.1016/j.eclinm.2024.102939 DOI: https://doi.org/10.1016/j.eclinm.2024.102939
Pe M, Voltz-Girolt C, Bell J, Bhatnagar V, Bogaerts J, Booth C, et al. Using patient-reported outcomes and health-related quality of life data in regulatory decisions on cancer treatment: highlights from an EMA-EORTC workshop. Lancet Oncol. 2025;26(6):687–90.
https://doi.org/10.1016/S1470-2045(25)00150-0 DOI: https://doi.org/10.1016/S1470-2045(25)00150-0
Bentzen AG, Balteskard L, Wanderås EH, Frykholm G, Wilsgaard T, Dahl O, et al. Impaired health-related quality of life after chemoradiotherapy for anal cancer: late effects in a national cohort of 128 survivors. Acta Oncol. 2013;52(4):736–44.
https://doi.org/10.3109/0284186X.2013.770599 DOI: https://doi.org/10.3109/0284186X.2013.770599
Sodergren SC, Vassiliou V, Dennis K, Tomaszewski KA, Gilbert A, Glynne-Jones R, et al. Systematic review of the quality of life issues associated with anal cancer and its treatment with radiochemotherapy. Support Care Cancer. 2015;23(12):3613–23.
https://doi.org/10.1007/s00520-015-2879-2 DOI: https://doi.org/10.1007/s00520-015-2879-2
Lefèvre AC, Serup-Hansen E, Storm KS, Wind KL, Kronborg C, Spindler KG. One-year treatment-related side effects and quality of life after chemoradiotherapy in squamous cell carcinoma of the anus. Int J Radiat Oncol Biol Phys. 2023;115(5):1165–77.
https://doi.org/10.1016/j.ijrobp.2022.09.071 DOI: https://doi.org/10.1016/j.ijrobp.2022.09.071
Cancer registry of Norway. Cancer Registry of Norway, Norwegian Institute of Public Health. Cancer in Norway 2022 – cancer incidence, mortality, survival and prevalence in Norway. Oslo: Cancer Registry of Norway; 2023. Oslo; 2022.
Sobin LH, editor., MKGE, Wittekind C. (Editor). TNM classifiaction of malignant tumours. Oxford, Wiley. 7th ed. 2011. DOI: https://doi.org/10.1002/9780471420194.tnmc26
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.
https://doi.org/10.1093/jnci/85.5.365 DOI: https://doi.org/10.1093/jnci/85.5.365
Whistance RN, Conroy T, Chie W, Costantini A, Sezer O, Koller M, et al. Clinical and psychometric validation of the EORTC QLQ-CR29 questionnaire module to assess health-related quality of life in patients with colorectal cancer. Eur J Cancer. 2009;45(17):3017–26.
https://doi.org/10.1016/j.ejca.2009.08.014 DOI: https://doi.org/10.1016/j.ejca.2009.08.014
Fayers PM AN, Bjordal K, Groenvold M, Curran D, Bottomley A, on Group. botEQoL. The EORTC QLQ-C30 scoring manual. Brussel, European Organisation for Research and Treatment of Cancer. 3rd ed. 2001.
Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16(1):139–44.
https://doi.org/10.1200/JCO.1998.16.1.139 DOI: https://doi.org/10.1200/JCO.1998.16.1.139
Vaizey CJ, Carapeti E, Cahill JA, Kamm MA. Prospective comparison of faecal incontinence grading systems. Gut. 1999;44(1):77–80.
https://doi.org/10.1136/gut.44.1.77 DOI: https://doi.org/10.1136/gut.44.1.77
Johannessen HH, Norderval S, Stordahl A, Falk RS, Wibe A. Interview-based versus self-reported anal incontinence using St Mark’s incontinence score. Int Urogynecol J. 2018;29(5):667–71.
https://doi.org/10.1007/s00192-017-3363-y DOI: https://doi.org/10.1007/s00192-017-3363-y
Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, et al. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147–53.
https://doi.org/10.1016/0022-3999(93)90081-P DOI: https://doi.org/10.1016/0022-3999(93)90081-P
Dahl AA, Grotmol KS, Hjermstad MJ, Kiserud CE, Loge JH. Norwegian reference data on the fatigue questionnaire and the Patient Health Questionnaire-9 and their interrelationship. Ann Gen Psychiatry. 2020;19:60.
https://doi.org/10.1186/s12991-020-00311-5 DOI: https://doi.org/10.1186/s12991-020-00311-5
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.
https://doi.org/10.1111/j.1600-0447.1983.tb09716.x DOI: https://doi.org/10.1111/j.1600-0447.1983.tb09716.x
Eyseneck SBG, Tambs K. Cross-cultural comparison of personality: Norway and England. Scand J Psychol. 1990;31:191–7.
https://doi.org/10.1111/j.1467-9450.1990.tb00830.x DOI: https://doi.org/10.1111/j.1467-9450.1990.tb00830.x
Bøhn SH, Vandraas KF, Kiserud CE, Dahl AA, Thorsen L, Ewertz M, et al. Work status changes and associated factors in a nationwide sample of Norwegian long-term breast cancer survivors. J Cancer Surviv. 2024;18(2):375–84.
https://doi.org/10.1007/s11764-022-01202-2 DOI: https://doi.org/10.1007/s11764-022-01202-2
Dahl AA, Smedsland SK, Vandraas KF, Bøhn SK, Falk RS, Kiserud CE, et al. High neuroticism is associated with common late adverse effects in a nationwide sample of long-term breast cancer survivors. Breast Cancer Res Treat. 2023;202(1):97–104.
https://doi.org/10.1007/s10549-023-07055-2 DOI: https://doi.org/10.1007/s10549-023-07055-2
Grav S, Stordal E, Romild UK, Hellzen O. The relationship among neuroticism, extraversion, and depression in the HUNT study: in relation to age and gender. Issues Ment Health Nurs. 2012;33(11):777–85.
https://doi.org/10.3109/01612840.2012.713082 DOI: https://doi.org/10.3109/01612840.2012.713082
Grov EK, Dahl AA. Is neuroticism relevant for old cancer survivors? A controlled, population-based study (the Norwegian HUNT-3 survey). Support Care Cancer. 2021;29(7):3623–32.
https://doi.org/10.1007/s00520-020-05870-7 DOI: https://doi.org/10.1007/s00520-020-05870-7
Slørdahl KS, Balto A, Guren MG, Wibe A, Kørner H, Norderval S, et al. Patient-reported outcomes after treatment for rectal cancer – a prospective nationwide study. Colorectal Dis. 2024;27(1):e17231.
https://doi.org/10.1111/codi.17231 DOI: https://doi.org/10.1111/codi.17231
Bell ML, Fairclough DL, Fiero MH, Butow PN. Handling missing items in the Hospital Anxiety and Depression Scale (HADS): a simulation study. BMC Res Notes. 2016;9(1):479.
https://doi.org/10.1186/s13104-016-2284-z DOI: https://doi.org/10.1186/s13104-016-2284-z
Helsedirektoratet. Analkreft – handlingsprogram [Internet]. Helsedirektoratet; 2021. Available from: https://www.helsedirektoratet.no/retningslinjer/analkreft-handlingsprogram [Cited date: 02.07.24]
Gilbert A, Adams R, Webster J, Gilbert DC, Abbott NL, Berkman L, et al. Standard versus reduced-dose chemoradiotherapy in anal cancer (PLATO-ACT4): short-term results of a phase 2 randomised controlled trial. Lancet Oncol. 2025;26(6):707–18. DOI: https://doi.org/10.2139/ssrn.5122512
https://doi.org/10.1016/S1470-2045(25)00213-X DOI: https://doi.org/10.1016/S1470-2045(25)00213-X
Caravatta L, Mantello G, Valvo F, Franco P, Gasparini L, Rosa C, et al. Radiotherapy with intensity-modulated (IMRT) techniques in the treatment of anal carcinoma (RAINSTORM): a multicenter study on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group. Cancers (Basel). 2021;13(8):1902.
https://doi.org/10.3390/cancers13081902 DOI: https://doi.org/10.3390/cancers13081902
Gilbert A, Drinkwater K, McParland L, Adams R, Glynne-Jones R, Harrison M, et al. UK national cohort of anal cancer treated with intensity-modulated radiotherapy: one-year oncological and patient-reported outcomes. Eur J Cancer. 2020;128:7–16.
https://doi.org/10.1016/j.ejca.2019.12.022 DOI: https://doi.org/10.1016/j.ejca.2019.12.022
Åsberg RE, Nilsen M, Hjermstad MJ, Reinertsen KV, Karlsen J, Giskeødegård GF, et al. Norwegian general population normative data for the European Organization for Research and Treatment of Cancer questionnaires: the Quality of Life Questionnaire-Core 30, the Sexual Health Questionnaire QLQ-SHQ22 and the sexual domains of the QLQ-BR23/BR45. Eur J Cancer. 2023;190:112943.
https://doi.org/10.1016/j.ejca.2023.112943 DOI: https://doi.org/10.1016/j.ejca.2023.112943
Axelsson A, Johansson M, Haglind E, Li Y, Nilsson PJ, Angenete E. Patient reported long-term side effects from treatment on urinary and sexual function in anal cancer survivors – 3- and 6-year results from the Swedish national ANCA study. Colorectal Dis. 2024;26(7):1359–69.
https://doi.org/10.1111/codi.17040 DOI: https://doi.org/10.1111/codi.17040
Bentzen AG, Guren MG, Vonen B, Wanderås EH, Frykholm G, Wilsgaard T, et al. Faecal incontinence after chemoradiotherapy in anal cancer survivors: long-term results of a national cohort. Radiother Oncol. 2013;108(1):55–60.
https://doi.org/10.1016/j.radonc.2013.05.037 DOI: https://doi.org/10.1016/j.radonc.2013.05.037
Reinertsen KV, Cvancarova M, Loge JH, Edvardsen H, Wist E, Fosså SD. Predictors and course of chronic fatigue in long-term breast cancer survivors. J Cancer Surviv. 2010;4(4):405–14.
https://doi.org/10.1007/s11764-010-0145-7 DOI: https://doi.org/10.1007/s11764-010-0145-7
Eikeland SA, Smeland KB, Simensen VC, Fagerli UM, Bersvendsen HS, Kiserud CE, et al. Chronic fatigue in long-term survivors of Hodgkin’s lymphoma after contemporary risk-adapted treatment. Acta Oncol. 2023;62(1):80–8.
https://doi.org/10.1080/0284186X.2023.2168215 DOI: https://doi.org/10.1080/0284186X.2023.2168215
Huynh TM, Falk RS, Hellebust TP, Dale E, Astrup GL, Hjermstad MJ, et al. Chronic fatigue in long-term survivors of head and neck cancer treated with radiotherapy. Radiother Oncol. 2024;195:110231.
https://doi.org/10.1016/j.radonc.2024.110231 DOI: https://doi.org/10.1016/j.radonc.2024.110231
Nilsson MP, Undseth C, Albertsson P, Eidem M, Havelund BM, Johannsson J, et al. Nordic anal cancer (NOAC) group consensus guidelines for risk-adapted delineation of the elective clinical target volume in anal cancer. Acta Oncol. 2023;62(8):897–906.
https://doi.org/10.1080/0284186X.2023.2240490 DOI: https://doi.org/10.1080/0284186X.2023.2240490
ISRCTN. PLATO trial: personalising anal cancer radioTherapy dOse – incorporating ACT3, ACT4 and ACT5 2016: ISRCTN88455282.
https://doi.org/10.1186/ISRCTN88455282 DOI: https://doi.org/10.1186/ISRCTN88455282
Guren MG, Sebag-Montefiore D, Franco P, Johnsson A, Segelov E, Deutsch E, et al. Treatment of squamous cell carcinoma of the anus, unresolved areas and future perspectives for research: perspectives of research needs in anal cancer. Clin Colorectal Cancer. 2021;20(4):279–87.
https://doi.org/10.1016/j.clcc.2021.09.006 DOI: https://doi.org/10.1016/j.clcc.2021.09.006
Wiltink LM, White K, King MT, Rutherford C. Systematic review of clinical practice guidelines for colorectal and anal cancer: the extent of recommendations for managing long-term symptoms and functional impairments. Support Care Cancer. 2020;28(6):2523–32.
https://doi.org/10.1007/s00520-020-05301-7 DOI: https://doi.org/10.1007/s00520-020-05301-7
Helsedirektoratet. Seneffekter etter kreftbehandling. 2020. Oslo, Helsedirektoratet. Contract No.: ISBN 978-82-8081-610-8.
Fabi A, Bhargava R, Fatigoni S, Guglielmo M, Horneber M, Roila F, et al. Cancer-related fatigue: ESMO Clinical Practice Guidelines for diagnosis and treatment. Ann Oncol. 2020;31(6):713–23.
https://doi.org/10.1016/j.annonc.2020.02.016 DOI: https://doi.org/10.1016/j.annonc.2020.02.016
Haas S, Mikkelsen AH, Kronborg C, Oggesen BT, Faaborg PM, Serup-Hansen E, et al. Management of late adverse effects after chemoradiation for anal cancer. Acta Oncol. 2021;60(12):1688–701.
https://doi.org/10.1080/0284186X.2021.1983208 DOI: https://doi.org/10.1080/0284186X.2021.1983208
Kronborg CJ, Pedersen BG, Klemmensen J, Lefévre AC, Wind KL, Spindler KG. Pelvic insufficiency fractures and bone pain after radiation therapy for anal cancer: relation to pelvic bone dose-volume parameters. Adv Radiat Oncol. 2023;8(1):101110.
https://doi.org/10.1016/j.adro.2022.101110 DOI: https://doi.org/10.1016/j.adro.2022.101110
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