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
Open accessAbstract
Purpose: Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision (TME). This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 × 5 Gy radiotherapy and TME. Also, hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment. Patients and Methods: Long-term morbidity was assessed in patients from the prospective randomized TME trial, which investigated the efficacy of 5 × 5 Gy before TME surgery for mobile rectal cancer. Dutch patients without recurrent disease were sent a questionnaire. Results: Results were obtained from 597 patients, with a median follow-up of 5.1 years. Stoma function, urinary function, and hospital treatment rates did not differ significantly between the treatment arms. However, irradiated patients, compared with nonirradiated patients, reported increased rates of fecal incontinence (62% v 38%, respectively; P < .001), pad wearing as a result of incontinence (56% v 33%, respectively; P < .001), anal blood loss (11% v 3%, respectively; P = .004), and mucus loss (27% v 15%, respectively; P = .005). Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone. Conclusion: Although preoperative short-term radiotherapy for rectal cancer results in increased local control, there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone. Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME. Future strategies should be aimed at selecting patients for radiotherapy who are at high risk for local failure.
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There was no significant difference between preoperative chemoradiotherapy and preoperative radiotherapy alone in sphincter preservation or survival rate.
“and there was no significant difference between the two groups in terms of sphincter preservation or survival rate [111–118].”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [114]
The Introduction reports no difference in overall survival in a radiotherapy-and-TME trial, but it does not compare preoperative chemoradiotherapy with radiotherapy alone. The Discussion mentions sphincter-saving surgery without reporting a between-group difference in sphincter preservation. The claimed treatment comparison and sphincter-preservation result are therefore unsupported by this copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredIncidences of sexual dysfunction and bowel dysfunction were higher in the preoperative radiation combination therapy group than in the surgery-alone group.
“The incidences of sexual dysfunction and bowel dysfunction were higher in the preoperative radiation combination therapy group than in the surgery-alone group [113, 114].”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [114]
Pathologic complete response rates were significantly higher in the preoperative chemoradiotherapy groups than in the preoperative radiotherapy alone groups.
“but the pathologic complete response rates (pCR) were significantly higher than in the preoperative radiotherapy alone groups.”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [114]
The Introduction discusses preoperative radiotherapy and local recurrence, while the Discussion focuses on late bowel dysfunction; neither reports pathologic complete response rates. Searches for pCR and for a comparison of preoperative chemoradiotherapy with radiotherapy alone found no passage addressing the claimed difference. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn Europe, four randomized controlled trials were performed to investigate the usefulness of adding chemotherapy to preoperative radiotherapy.
“In Europe, four randomized controlled trials, including the EORTC trial, were performed to investigate the usefulness of adding chemotherapy to preoperative radiotherapy.”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [114]
The Introduction discusses randomized trials of radiotherapy, and Study Population describes a trial comparing preoperative radiotherapy plus surgery with surgery alone. Neither section says that four European trials, including an EORTC trial, investigated adding chemotherapy to preoperative radiotherapy. Searches for that trial count and for chemotherapy combined with preoperative irradiation found no supporting passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn two trials, the local recurrence rate was significantly lower in the preoperative chemoradiotherapy group than in the preoperative radiotherapy alone group.
“In two trials, the exception being the short-course radiotherapy trial, the local recurrence rate was significantly lower in the preoperative chemoradiotherapy group”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [114]
The Introduction reports lower local recurrence with preoperative radiotherapy than with surgery alone, and the Study Population describes a trial of radiotherapy plus total mesorectal excision versus excision alone. Neither passage addresses two trials comparing preoperative chemoradiotherapy with preoperative radiotherapy alone; searches for that comparison and for chemotherapy found no such result in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measured
The incidence of acute-phase adverse events was significantly higher in the preoperative chemoradiotherapy groups than in the preoperative radiotherapy alone groups.
“The incidence of acute-phase adverse events was significantly higher in the preoperative chemoradiotherapy groups”
From Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer (2018) · cites this paper as [114]
The Introduction and Discussion (page unavailable) discuss acute toxicity after preoperative radiotherapy, but the study compares radiotherapy plus surgery with surgery alone and focuses on late side effects. A search for chemoradiotherapy and acute adverse events found no comparison of preoperative chemoradiotherapy with radiotherapy alone in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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“The incidences of sexual dysfunction and bowel dysfunction were higher in the preoperative radiation combination therapy group than in the surgeryalone group [113, 114].”
Backgroundvan Gijn, W., Marijnen, C. A., Nagtegaal, I. D., Kranenbarg, E. M.-K., Putter, H., Wiggers, T., Rutten, H. J., Påhlman, L., Glimelius, B., & van de Velde, C. J. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70097-3 · Cited by 1,888 · see citing works
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- Authors
- Peeters, K. C. M. J., van de Velde, C. J. H., Leer, J. W. H., Martijn, H., Junggeburt, J. M. C., Kranenbarg, E. K., Steup, W. H., Wiggers, T., Rutten, H. J., & Marijnen, C. A. M.
- Affiliations
- University Medical Center Groningen (NL)
- From the Departments of Surgery and Clinical Oncology, Leiden University Medical Center, Leiden; Department of Radiotherapy, St. Radboud University Medical Center, Nijmegen; Departments of Radiotherapy and Surgery, Catharina Ziekenhuis, Eindhoven; Department of Surgery, Leyenburg Hospital, The Hague; and Department of Surgical Oncology, Groningen University Hospital, Groningen, the Netherlands
- Venue
- Journal of Clinical Oncology
- Published
- 2005-09-01
- Volume
- 23
- Issue
- 25
- Pages
- 6199-6206
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2149273511
- Cited by
- 943
- References
- 29
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 34 · 2023: 41 · 2022: 50 · 2021: 54 · 2020: 57 · 2019: 44 · 2018: 48 · 2017: 48 · 2016: 51 · 2015: 53 · 2014: 64 · 2013: 53 · 2012: 45
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Cancerfonden
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Surgery › Colorectal and Anal Carcinomas
- Health Sciences › Medicine › Rheumatology › Pelvic floor disorders treatments
- Keywords
- rectal cancer, preoperative radiotherapy, total mesorectal excision, late effects, bowel dysfunction, fecal incontinence, stoma function, urinary function, long-term morbidity, patient satisfaction
- MeSH terms
- Adult, Aged, Aged, 80 and over, Combined Modality Therapy, Fecal Incontinence, Female, Follow-Up Studies, Humans, Male, Middle Aged, Morbidity, Radiation Injuries, Rectal Neoplasms, Patient Satisfaction, Dose Fractionation, Radiation, Neoadjuvant Therapy
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