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The impact on health-related quality of life in the first 12 months: A randomised comparison of preoperative short-course radiation versus long-course chemoradiation for T3 rectal cancer (Trans-Tasman Radiation Oncology Group Trial 01.04)
European Journal of Cancer, Volume 55, March 2016, Pages 15 - 26
To assess health-related quality of life (HRQOL) in patients participating in a randomised trial of neoadjuvant short course radiation (SC) or long course chemoradiation (LC) for operable rectal cancer.
Patients and methods
Eligible patients with T3N0-2M0 rectal cancer completed the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30) and the colorectal cancer specific module (QLQ C38) at randomisation and 1, 2, 3, 6, 9 and 12 months later.
Of 326 patients randomised, 297 (SC 143, LC 154) were eligible for completion of HRQOL questionnaires. Baseline scores were comparable across the SC and LC groups. Patients reported low scores on sexual functioning and sexual enjoyment. Defaecation problems were the worst of the symptoms at baseline. Surgery had the most profoundly negative effect on HRQOL, seen in both the SC and LC treatment groups to the same extent. The most severely affected domains were physical function and role function and the most severely affected symptoms were fatigue, pain, appetite, weight loss and male sexual problems. Most domains and symptoms returned to baseline levels by 12 months apart from body image, sexual enjoyment and male sexual problems. Future perspective was better than prior to treatment.
There is no overall difference in HRQOL between SC and LC neoadjuvant treatment strategies, in the first 12 months, after surgery. In the immediate postoperative period HRQOL was adversely affected in both groups but for the most part was temporary. Some residual sexual functioning concerns persisted at 12 months.
- We compared health-related quality of life (HRQOL) in patients with rectal cancer having combined modality treatments.
- Surgery had the most profoundly negative effect on HRQOL across multiple domains.
- No differences occurred in HRQOL between neoadjuvant strategies, in the first 12 months.
- HRQOL returned to baseline by 12 months except for body image and sexual functioning.
Keywords: Health-related quality of life, Rectal cancer, Neoadjuvant chemoradiation.
Although surgery is the mainstay of treatment for localised rectal cancer, preoperative radiation has been shown to reduce local recurrence  and . Combined treatment approaches are practiced widely; however the optimal treatment scheduling remains under investigation. There is a paucity of published data on the impact of these treatment modalities on patients' functioning and health-related quality of life (HRQOL). Information of this type may be particularly helpful for future patients and doctors facing decisions about different combinations of treatment.
We performed a randomised trial for clinical stage T3 rectal cancer comparing preoperative short-course (SC) radiotherapy with long-course (LC) chemoradiotherapy . The primary end-point was 3-year local recurrence. Other end-points included relapse-free survival, overall survival, late toxicity and HRQOL. No differences in rates of local or distant recurrence, relapse-free survival, overall survival, or late toxicity were detected. The aim of the current report was to provide a comprehensive account of HRQOL, across the range of dimensions measured by two European Organisation Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ-C30, QLQ-CR38), over the first year of the trial.
2.1. Study population and treatment
Methods of this trial have been reported previously . Between 2001 and 2006, 326 patients with pathologically documented and clinically resectable stage T3 adenocarcinoma of the rectum suitable for a curative resection and preoperative radiotherapy, were randomised to receive LC or SC preoperative therapy (Fig. 1A). Patients in the LC and SC arms were scheduled to received four and six, monthly cycles of 5 Fluorouracil (5FU)-based adjuvant chemotherapy respectively.
2.2. Health-related QOL assessment
Health-related quality of life was assessed with two validated EORTC questionnaires: the Core Quality of Life Questionnaire QLQ-C30 and the colorectal cancer module QLQ-CR38  and . The QLQ-C30 is a 30-item questionnaire covering issues relevant to cancer patients. It comprises five multi-item function subscales: physical, role, emotional, social and cognitive functioning; three multi-item symptom scales measuring fatigue, pain, and emesis; a global health/overall QL subscale; and six single items to assess financial impact and symptoms such as dyspnoea, sleep disturbance, appetite, diarrhoea and constipation. The QLQ-CR38 has 38 questions which targets issues specific to colorectal cancer. Nineteen items are completed by all patients and the remaining by subsets of patients (men or women; with or without stoma). There are four multi-item function subscales (body image, sexual functioning, sexual enjoyment and future perspective); seven multi-item symptom scales (radiotherapy effects on micturition, chemotherapy side-effects, gastrointestinal (GI) symptoms, defaecation problems, stoma-related problems) and one single symptom item (weight loss). Both questionnaires were scored according to recommended algorithms . All scores range from 0 to 100. A higher score for functional domains indicates better HRQOL whereas a lower score for symptom domains and single items indicates fewer symptoms.
2.3. Collection of HRQL data
In the first year of the trial, patients in both treatment groups were nominated to complete HRQOL questionnaires at randomisation and 1, 2, 3, 6, 9 and 12 months thereafter (Fig. 1A). When possible, questionnaires were completed at the time of scheduled clinic appointments; otherwise they were posted. Patients with a missing questionnaire at a certain time point were still included in the other time points. If physicians had seen the patient at the time a questionnaire was expected but not available they made proxy measurements of HRQOL on a 10 cm linear analogue scale anchored by ‘very poor and excellent’. This allowed missing patient HRQOL scores to be imputed for the purpose of a sensitivity analysis.
3. Statistical analysis
Patients were included in the HRQOL analysis if they had completed a baseline HRQOL questionnaire, did not suffer disease relapse within the first month, and completed at least one other expected HRQOL questionnaire. This group is referred to as the ‘analysed population’. Patients were analysed according to groups as treated. To minimise burden HRQOL questionnaires were not expected at a given time if the patient had relapsed. Compliance with HRQOL questionnaire completion was expressed as the percentage of expected questionnaires completed by the analysed group (see Fig. 2).
The global health /overall QL subscale from the QLQ-C30 was specified a priori as the primary outcome for the HRQOL analysis, remaining subscales and items from the QLQ-C30 and QLQ-C38 were considered secondary outcomes. Data were analysed and graphed according to change from baseline for each of the HRQOL subscales and items. Wilcoxon tests were used to assess change in HRQOL within each arm and to compare across arms. A change in score of 10 points from baseline was defined as clinically significant . In addition an area under the curve (AUC) analysis was performed. The AUC for each arm was calculated from the HRQOL means, and its standard error was obtained from the estimated covariance matrices of the means. The AUC was standardised to represent the mean curve height over the period 0–12 months in order to allow easier interpretations . Longitudinal modelling was not used primarily because HRQOL questionnaires were not collected after relapse. Clinician-rated HRQOL was available when the corresponding patient data were missing. Analysis with and without the clinician ratings was performed.
It became apparent that analysis of the HRQOL data using protocol-defined windows was not sensitive to the different timing and scheduling of treatments between arms. For example, around the time of surgery (the event that had the biggest impact on HRQOL) patients having SC radiation completed HRQOL questionnaires monthly whereas in the LC group, at the time of surgery they were completed every three months. This may have masked any similarities or differences due to the operation. To overcome these deficiencies analyses were performed based on realigning the time scale for each patient to make the date of operation occur at time zero. Windows were defined as a series of contiguous 1 month intervals before and after the date of operation; the date of collection of HRQOL questionnaire determined to which of these windows a value was allocated (Fig. 1B). AUC analyses were performed using protocol-defined windows. No formal adjustment of p-values for multiple comparisons was made. Differences for which p < 0.010 were given more weight for comparisons across treatment arms, at multiple time points. All p-values are two-sided. Analyses were carried out using the R statistical package (version 3.0.1).
4.1. Patient characteristics
Three hundred and twenty six patients from 27 Australasian centres were randomly assigned to the study. There were no significant imbalances in patient characteristics between the two study groups (Table 1). The median age was 64 years (range 26–82 years), 73% were male and 58% had an Eastern Co-operative Group performance status of 0.
|Characteristic||SC (n = 143)||LC (n = 154)|
|No. patients||%||No. patients||%|
Abbreviations: SC, short course radiation; LC, long course chemoradiation; ECOG PS, Eastern Co-operative Group performance status; APR, abdomino-perineal resection; AR, anterior resection.
4.2. Compliance with HRQOL assessment
One hundred and sixty one patients in each arm of the study were eligible for HRQOL completion. One hundred and forty three patients treated by SC and 154 treated by LC were included in the ‘analysed’ population (Fig. 2). Compliance with completion of HRQOL questionnaires at follow-up visits was above 80% for all time points in both groups except for month 1 in the SC group which corresponded to the immediate perioperative period, where compliance was 66%.
4.3. Baseline HRQOL
The two study arms had similar baseline HRQOL scores in all domains and items (Table 2). The lowest baseline scores were seen in sexual functioning followed by sexual enjoyment and global health/overall QL. There were good levels of physical and role functioning and body image. Defaecation problems, sleep disturbance, male sexual problems diarrhoea and fatigue indicated the greatest symptom impairments (highest baseline scores). Another item indicating a greater degree of concern at baseline was ‘future perspective’.
|Baseline HRQL scores|
|EORTC QLQ-C30 subscales||Treatment|
|Short course||Long course|
|No. responses N = 143||Mean (SEM)||No. responses N = 154||Mean (SEM)|
|Physical||142||90.7 (1.1)||154||90.9 (1.2)|
|Role||143||85.1 (2.0)||154||86.5 (2.0)|
|Emotional||143||75.0 (1.8)||153||75.0 (1.8)|
|Cognitive||143||88.7 (1.3)||153||84.6 (1.6)|
|Social||143||86.1 (2.0)||153||84.1 (2.0)|
|Global||143||71.0 (1.7)||153||70.0 (1.8)|
|Fatigue||143||21.8 (1.6)||154||21.9 (1.9)|
|Nausea/vomiting||143||4.3 (1.0)||154||3.0 (1.0)|
|Pain||143||17.0 (1.9)||154||16.0 (2.0)|
|Dyspnoea||142||6.1 (1.3)||153||7.0 (1.4)|
|Insomnia||141||25.8 (2.0)||151||27.1 (2.0)|
|Appetite||143||13.0 (1.8)||154||12.0 (1.8)|
|Constipation||143||17.7 (2.2)||152||19.1 (2.3)|
|Diarrhoea||143||24.5 (3.0)||150||24.4 (3.0)|
|EORTC QLQ-C38 subscales|
|Body image||139||89.8 (1.6)||153||90.5 (1.5)|
|Sexual function||131||22.0 (2.0)||143||29.0 (2.2)|
|Sex enjoymenta||67||51.7 (4.2)||77||60.2 (3.8)|
|Future perspective||139||54.9 (3.0)||153||52.7 (3.0)|
|Micturition||141||16.9 (1.0)||153||21.5 (1.0)|
|CT effects||140||7.0 (1.2)||154||6.0 (0.8)|
|GI symptoms||141||22.5 (1.5)||153||21.2 (1.4)|
|Defaecation problems||134||30.0 (1.6)||146||30.0 (1.5)|
|Male||91||23.4 (3.0)||95||27.9 (3.0)|
|Female||8 (of 41)||8||12 (of 41)|
|Weight loss||141||13.2 (2.0)||152||18.4 (2.1)|
a Sexual enjoyment question is applicable to those who reported being sexually active.
Function scales: higher numbers mean better function (100 = excellent function).
Symptom scales: higher numbers mean more symptoms (100 = severe symptoms).
Abbreviations: SEM, standard error of the mean; HRQOL, health-related quality of life; EORTC, European Organisation Research and Treatment of Cancer; QOL, quality of life questionnaires; CT, computed tomography; GI, gastrointestinal.
4.4. Change in HRQOL
In the analysis of the change from the time of randomisation, global health/overall QL was significantly more impaired in the SC treatment group than the LC group, in months 1 and 2 (Fig. 3A). This time period coincided with definitive rectal surgery in the SC group while the LC group received preoperative chemoradiation. The AUC analysis, however, which provides a more balanced estimate of overall HRQOL during the first 12 months, indicated that there was no evident difference between treatment arms in global health status/QL or other aspects of HRQOL (Table 3, online). Analyses with and without the imputed clinician ratings were not different.
After amending the analysis to use date of operation for each patient as time zero, to account for the different timings of treatment modalities, the two study arms had similar global health/overall QL subscale change scores over the 12 month postoperative period (Fig. 3B). In the LC treatment group preoperative combined chemoradiation coincided with a modest deterioration (5–10 points out of 100) in HRQOL during the 6-week treatment period (Fig 3, Fig 4, and Fig 5). The impact of surgery in both treatment groups was more pronounced. As seen in Fig. 3B, global health/overall QL declined substantially and to the same degree in both treatment groups in the first month postoperatively (decline of 30–35 points out of 100). There was a gradual improvement in global health/overall QL in both groups over the next few months despite 85% of the SC group and 86% of the LC group receiving adjuvant chemotherapy during this time. Twelve months after surgery the global health/overall QL of patients in both treatment arms had recovered to pre-surgery levels. There was a similar profile seen postoperatively in patients in both treatment groups with respect to other functioning subscales (Fig. 4); physical function (declined 40–46), role function (declined 66–70) and social function (declined 45–52). Correspondingly there was gradual recovery over the ensuing months, however at the 12-month time point scores for these domains remained significantly lower (5–10 points) than pre-surgery values (Table 4 online). Similar profiles were seen for fatigue, pain and appetite loss (Fig. 5). These symptoms worsened in both treatment groups (by 30–50 points) in the immediate postoperative period and then gradually improved. Appetite loss returned to pre-surgery levels by 12 months in both treatment groups; however pain was slightly better in the SC arm and fatigue was slightly worse in the LC arm compared to before surgery for these symptoms.
Three subscales of the QLQ-CR38 pertain to GI symptoms and bowel function. The GI tract subscale relates to abdominal swelling, pain, flatulence and belching. Overall the GI tract subscale scores worsened in both treatment groups to the same extent during the first month after surgery and then improved quickly to have recovered to baseline values by 2 months and be marginally better than baseline by 12 months. The AUC analysis incorporating the whole postoperative 12 month period showed no overall difference in GI tract concerns between the two treatment groups (p = 0.37). There are two additional subscales on the QLQ-CR38 referring to 1) defaecation difficulties in those with intact sphincters; or 2) stoma-related problems. Ninety seven percent of patients in the SC group and 92% in the LC had either a temporary or permanent stoma fashioned at the time of surgery. The majority of patients had temporary stomas closed within 12 months of surgery. In patients with an intact sphincter at 12 months there was no difference between SC and LC groups in defaecation problems (p = 0.47). Similarly in those with stomas in place after 12 months there were no differences between treatment groups for stoma-related issues (p = 0.64).
The sexual functioning items of the QLQ-CR38 refer to degree of interest in sex and extent of sexual activity. Both men and women reported sexual functioning to be substantially impaired prior to surgery (Table 2). It then worsened substantially (16–22 points) in the postoperative period to the same degree in both groups (Fig. 4C). There was a level of subsequent recovery; however sexual functioning remained 5–10 points worse than pre-surgery values at 12 months (Table 4 online). The sexual enjoyment question was applicable only to those who were sexually active. Forty-eight percent answered this question at study entry and indicated a moderate level of concern (Table 2). This parameter worsened substantially in both treatment groups and remained significantly worse at 12 months (by 13–20 points). Eighty seven percent of males and 24% of females answered the ‘male and female sexual problems’ questions (difficulty with erection and ejaculation in men, and vaginal dryness and dyspareunia in women). Sexual problems in men and women in both treatment groups worsened by 30–50 points from baseline and remained problematic at 12 months (Fig. 5C). It was the only HRQOL domain to remain >20 points more impaired than pre-surgery, at 12 months. Body image was well preserved at baseline (Table 2). This, deteriorated postoperatively, and then improved but not quite to pre-surgery levels (13 points below). At baseline patients were moderately worried about their future health but 12 months later they were more optimistic than before surgery (by 10–20 points) (Fig. 4D).
We previously reported a randomised trial comparing two treatment options to reduce local recurrence rates in patients with operable rectal cancer . No significant differences were detected in local control or overall survival between the preoperative long course and short course therapy groups. Similarly in this report of HRQOL over the first 12 months, no difference was seen between the two treatment groups in any of the measured domains or symptoms. This was counter to our expectation that the LC chemoradiation would result in a more protracted worsening of HRQOL than SC radiation. We based the primary analysis on an AUC calculation for this reason as it provides a balanced estimate of the overall HRQOL during the first 12 months.
Even though no difference in HRQOL was detected between the SC and LC treatment groups some important observations can be made about the impact of different treatment modalities on HRQOL during the first 12 months. Surgery had the most profound negative effect on HRQOL, seen in both treatment groups to the same extent. The most severely affected domains were physical function and role function and the most severely affected symptoms were fatigue, pain, appetite, weight loss and male sexual problems. The negative impact of surgery on HRQOL was temporary. Most domains and symptoms returned to baseline levels by 12 months, with some notable exceptions. Body image and sexual enjoyment and male sexual problems were substantially worse and future perspective better than prior to treatment. In contrast preoperative combined LC chemoradiation treatment resulted in only modest deteriorations in HRQOL and symptoms; these declines were short-lived and recovered by the time of definitive surgery. Smaller prospective studies after surgery for rectal cancer have also shown that HRQOL is generally worst in the early postoperative period particularly in those dimensions that assess physical performance  and .
Evaluation of bowel function according to the QLQ-C38 subscales was challenging in this patient group given that different questions apply according to the presence of a stoma. Most patients had a stoma fashioned at the time of surgery but a significant number of these were temporary and reversed during the first 12 months. Nevertheless we found no difference at 12 months between treatment groups in terms of bowel function in those with either intact sphincters or stomas.
Sexual dysfunction is a recognised complication of both rectal cancer and its treatment . In the current study very low scores for sexual function (interest and activity) were reported prior to the commencement of treatment. Men reported a significant further decline in sexual functioning, enjoyment, and worsening male sexual problems after surgery which did not return to baseline levels at 12 months. Approximately one quarter of the study participants were women and only a small proportion of these women completed questions relating to sexual activity. This may in part relate to the way the questions are framed. For example the sexual enjoyment questions and female sexual problem questions only apply if they were engaging in sexual intercourse. Women's reluctance to answer questions concerning sexuality has been reported in several other studies  and . Consequently we do not have a good understanding of the effects of these treatments on women's sex lives. A more in-depth inquiry of the multifaceted construct of psychosexual functioning may need different questionnaires or a more qualitative approach, to better reveal the difficulties experienced by women in this domain  and . Our study and others demonstrate that impairments in sexual functioning, sexual enjoyment and perception of body image can persist beyond 1 year of treatment and may be permanent  and . Despite this, once treatment is completed patients report being more optimistic about their future health. Nevertheless our data call for an increased focus on interventions targeted to enhance this underappreciated survivorship issue.
The main limitation of this study was in the design of HRQOL time points. Regular assessments were pre-specified and matched in both treatment groups according to point of randomisation rather than according to differences in the treatment schedules. This format was influenced by practical considerations. By coinciding questionnaire completion with clinic visits we aimed to minimise burden on the patients and study personnel thereby optimising compliance. In retrospect, event-driven rather than time-driven scheduling of HRQOL assessments would have been more appropriate. Although more complex to execute, more frequent assessments during times of greater treatment intensity and duration may have better reflected patients' experience across the two different treatment strategies. However, our novel statistical analysis represents one practical approach to reconcile utility of data collection and accurate comparative analysis.
Overall compliance with questionnaire completion was excellent given the complex, multi-disciplinary, multi-institutional nature of the study; however it was lowest in the SC arm in the immediate postoperative period. This occurred because patients were not attending clinical visits where collection of HRQOL questionnaires occurred. They were likely recovering from the acute effects of surgery.
Despite these stated limitations, our study has major strengths. Well-validated disease and treatment specific self-reporting HRQOL questionnaires were applied to a large group of patients in the context of a randomised trial of different treatment approaches. It was measured prospectively starting prior to the commencement of any treatment. This allowed for assessment of treatment related changes to HRQOL over the first 12 months. Several HRQOL domains had not recovered to baseline levels at 12 months. The permanency of this effect is not evident from our data; however HRQOL was collected from patients in both the SC and LC groups for 5 years. It is something we could evaluate in the future.
The results of this study provide important information about the adverse HRQOL effects of combined modality treatment. Doctors can inform their patients who are contemplating such treatments that there is no overall difference in HRQOL between SC and LC preoperative radiation treatment strategies, in the first 12 months. They need to be advised however that adverse effects in physical dimensions, sexual functioning, and body image can occur with both treatments during the first 12 months. This HRQOL information is critical so that patients expectations about post-treatment functioning can be realistic and adequate support can be provided.
Although there is no difference in any HRQOL parameter between the two strategies, LC is more protracted by 1 month, may involve a central venous access device and pump, but has a lower rate of permanent stoma. The longer term HRQOL effects and comparative resource utilisation are important matters and will be the subject of future evaluations.
Conception and design: Sue-Anne McLachlan, Samuel Y. Ngan, Bryan Burmeister, Richard J. Fisher, Michael Solomon, David Goldstein, Stephen P. Ackland, John R. Zalcberg, John Mackay.
Administrative support: Samuel Y. Ngan, Sue-Anne McLachlan, Bev McClure.
Provision of study materials or patients: Sue-Anne McLachlan, Samuel Y. Ngan, Bryan Burmeister, Michael Solomon, David Goldstein, Stephen P. Ackland, Joseph McKendrick, Trevor Leong, John Mackay.
Collection and assembly of data: Sue-Anne McLachlan, Samuel Y. Ngan, Richard J. Fisher, Bev McClure.
Data analysis and interpretation: Sue-Anne McLachlan, Samuel Y. Ngan, Richard J. Fisher, Michael Solomon, David Goldstein, Stephen P. Ackland, Bev McClure, John R. Zalcberg.
Manuscript writing: All authors.
Final approval of manuscript: All authors.
Acknowledgment: Presented at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, 2008.
National Health and Medical Research Council #209123, Cancer Council Victoria, and the Royal Australian and New Zealand College of Radiologists.
Conflict of interest statement
This trial was performed under the auspices of the Trans-Tasman Radiation Oncology Group (TROG), Australian Gastrointestinal Trials Group (AGITG), Colorectal Surgical Society of Australia and New Zealand (CSSANZ), and The Royal College of Surgeons of Australasia (RACS).
-  C. Camma, M. Giunta, F. Fiorica, L. Pagliaro, A. Craxì, M. Cottone. Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA. 2000;284:1008-1015 Crossref
-  Colorectal Cancer Collaborative G. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet. 2001;358:1291-1304
-  S.Y. Ngan, B. Burmeister, R.J. Fisher, M. Solomon, D. Goldstein, D. Joseph, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012;30:3827-3833 Crossref
-  N.K. Aaronson, S. Ahmedzai, B. Bergman, M. Bullinger, A. Cull, N.J. Duez, 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;85:365-376 Crossref
-  M.A. Sprangers, A. te Velde, N.K. Aaronson. The construction and testing of the EORTC colorectal cancer-specific quality of life questionnaire module (QLQ-CR38). European Organization for Research and Treatment of Cancer Study Group on Quality of Life. Eur J Cancer. 1999;35:238-247 Crossref
-  P.M. Fayers, N.K. Aaronson, K. Bjordal, M. Sullivan. EORTC QLQ-C30 scoring manual. (European Organisation for Research and Treatment of Cancer, 2001)
-  D. Osoba, G. Rodrigues, J. Myles, B. Zee, J. Pater. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16:139-144
-  J. Spritzler, V. DeGruttola, L. Pei. Two-sample tests of area-under-the-curve in the presence of missing data (section 3). Int J Biostat. 2008;4:1
-  G. Palmer, A. Martling, P. Lagergren, B. Cedermark, T. Holm. Quality of life after potentially curative treatment for locally advanced rectal cancer. Ann Surg Oncol. 2008;15:3109-3117 Crossref
-  J. Camilleri-Brennan, R.J. Steele. Prospective analysis of quality of life and survival following mesorectal excision for rectal cancer. Br J Surg. 2001;88:1617-1622 Crossref
-  M.J. Traa, J. De Vries, J.A. Roukema, B.L. Den Oudsten. Sexual (dys)function and the quality of sexual life in patients with colorectal cancer: a systematic review. Ann Oncol. 2012;23:19-27 Crossref
-  J.S. Ford, T. Kawashima, J. Whitton, W. Leisenring, C. Laverdière, M. Stovall, et al. Psychosexual functioning among adult female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2014;32:3126-3136 Crossref
-  R.J. Stephens, L.C. Thompson, P. Quirke, R. Steele, R. Grieve, J. Couture, et al. 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. 2010;28:4233-4239 Crossref
-  M.J. Traa, J. De Vries, J.A. Roukema, H.J. Rutten, B.L. Den Oudsten. The sexual health care needs after colorectal cancer: the view of patients, partners, and health care professionals. Support Care Cancer. 2014;22:763-772 Crossref
-  S. Bregendahl, K.J. Emmertsen, J.C. Lindegaard, S. Laurberg. Urinary and sexual dysfunction in women after resection with and without preoperative radiotherapy for rectal cancer: a population-based cross-sectional study. Colorectal Dis. 2015;17:26-37 Crossref
-  L.M. Wiltink, T.Y. Chen, R.A. Nout, E.M. Kranenbarg, M. Fiocco, S. Laurberg, et al. Health-related quality of life 14 years after preoperative short-term radiotherapy and total mesorectal excision for rectal cancer: report of a multicenter randomised trial. Eur J Cancer. 2014;50:2390-2398 Crossref
a Peter MacCallum Cancer Centre, Australia
b St Vincent's Hospital, Fitzroy, Australia
c Royal Prince Alfred Hospital, Newtown, Australia
d Princess Alexandra Hospital, Woolloongabba, Australia
e Prince of Wales Hospital, Randwick, Australia
f Calvary Mater Hospital, Newcastle, Australia
g Box Hill Hospital, Box Hill, Australia
h The University of Melbourne, Parkville, Australia
i University of Sydney, Sydney, Australia
j The University of Queensland, Brisbane, Australia
k The University of New South Wales, Kensington, Australia
l The University of Newcastle, Callaghan, Australia
m Monash University, Clayton, Australia
∗ Corresponding author: Department of Oncology, St Vincent's Hospital, PO Box 2900 , Fitzroy 3065, Victoria, Australia. Tel.: +61 3 92883156; fax: +61 39288 3172.
© 2015 Elsevier Ltd, All rights reserved.