Measuring the health-related quality of life and sexual functioning of patients with rectal cancer: Does type of treatment matter?

Authors

  • Marjan J. Traa,

    Corresponding author
    1. CoRPS - Center of Research on Psychology in Somatic Diseases, Department of Medical Psychology, Tilburg University, Tilburg, The Netherlands
    • Correspondence to: Marjan Traa, CoRPS–Department of Medical and Clinical Psychology, Tilburg University, PO Box 90153, 5000 LE Tilburg, The Netherlands, Tel.: +31-13-466-4129, Fax: +31-466-2067, E-mail: m.j.traa@tilburguniversity.edu

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  • Ricardo G. Orsini,

    1. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
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  • Brenda L. Den Oudsten,

    1. CoRPS - Center of Research on Psychology in Somatic Diseases, Department of Medical Psychology, Tilburg University, Tilburg, The Netherlands
    2. Department of Education and Research, St. Elisabeth Hospital, Tilburg, The Netherlands
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  • Jolanda De Vries,

    1. CoRPS - Center of Research on Psychology in Somatic Diseases, Department of Medical Psychology, Tilburg University, Tilburg, The Netherlands
    2. Department of Medical Psychology, St. Elisabeth Hospital, Tilburg, The Netherlands
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  • Jan A. Roukema,

    1. CoRPS - Center of Research on Psychology in Somatic Diseases, Department of Medical Psychology, Tilburg University, Tilburg, The Netherlands
    2. Department of Surgery, St. Elisabeth Hospital, Tilburg, The Netherlands
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  • Sietske J. Bosman,

    1. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
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  • Ralph L. Dudink,

    1. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
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  • Harm J.T. Rutten

    1. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
    2. Research Institute Growth and Development, Maastricht University Medical Center, The Netherlands
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Abstract

The literature on the health-related quality of life (HRQOL) after rectal cancer is growing, however, a comparison between patients with nonadvanced disease (NAD), locally advanced rectal cancer (LARC), locally recurrent rectal cancer (LRRC) and a normative population has not been made. Data on the sexual functioning of patient groups is also scarce. We compared (i) the HRQOL of patients with NAD, LARC, or LRRC, with a special focus on sexual functioning and (ii) the HRQOL of the three treatment groups with a normative population. The EORTC QLQ-C30 and QLQ-CR38 were completed by 80 patients with NAD, 292 LARC patients and 67 LRRC patients. The normative population (n = 350) completed the EORTC QLQ-C30 and the Sexual Functioning and Sexual Enjoyment scales of the CR38. LRRC patients reported a lower Physical Function, Social Function, Future Perspective, Sexual Functioning and more Pain compared with LARC and NAD patients. Also, LRRC patients had a worse Body image than NAD patients and a lower Male Sexual Functioning than LARC patients. More than 75% of men and 50% of women were sexually active preoperative, compared with less than 50% and less than 35% postoperative. Male LRRC patients had more problems with erectile or ejaculatory functioning and felt less masculine than NAD or LARC patients. Women did not differ on Lubrication, Dyspareunia and Body Image. About 10% of patients used aids in order to improve erectile functioning (men) or lubrication (women). The treatment groups reported a lower HRQOL and sexual functioning compared with the normative population.

Rectal cancer is one of the most common malignancies worldwide and has a still increasing incidence and prevalence.[1, 2] In 10–15% of the patients, the rectal cancer is considered locally advanced.[3] In addition, 5–10% of rectal cancer patients develop a local recurrence without metastatic disease which can still be treated with a curative intent.[4]

Treatment for rectal cancer is based on clinical T-stage, pathological lymph nodes and distant metastasis.[5] The standard treatment for nonadvanced rectal cancer in The Netherlands is neoadjuvant radiotherapy followed by a total mesorectal excision with autonomous nerve preservation, except for cT1N0 patients were radiotherapy is not indicated.[5] Patients with locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) are treated with neoadjuvant radiochemotherapy often followed by more extensive extra-anatomical surgery in order to achieve a curative resection. During these procedures an intraoperative radiotherapy (IORT) boost dose can be applied at the area of risk in order to improve local control.[6] The current multidisciplinary treatment for rectal cancer has led to decreased morbidity and a significant improvement of survival.[7-9] However, treatment for LARC of LLRC may still be accompanied by high morbidity rates (15–68%).[10-13] Therefore, the complex and extensive treatment for LARC and LRRC can be very burdensome for the patients.

Even though the importance of patient-reported outcomes and quality of life are increasingly recognized, research on LARC or LRRC has predominantly focused on assessing local or distance control and overall survival. A recent review concluded that only seven studies evaluated the patients' health-related quality of life (HRQOL) after treatment for LARC or LRRC.[3] These studies reported that the HRQL in LRRC and LARC was lower compared with patients with nonadvanced disease (NAD) and normative populations.[3, 14, 15] However, these findings were based on small sample sizes.[3] Furthermore, information on sexual dysfunction is lacking.[3, 14] Therefore, the objectives of this cross-sectional study were (i) to compare the HRQOL of three patient populations (i.e. NAD, LARC and LRRC), with a special focus on sexual functioning and (ii) to compare the HRQOL of the three treatment groups with a normative population.

Material and Methods

Patients and procedure

The Catharina Hospital (Eindhoven, the Netherlands) is a tertiary referral center for patients with LARC or LRRC. In the period between 2000 and 2010 a total of 841 patients received surgery for primary rectal cancer (112 patients with a NAD and 726 patients with a LARC) and 222 patients received surgery for a LRRC. All patients who were still alive in 2010 were contacted to ask them if they were willing to participate in this study. If patients agreed to participate they were asked to complete the set of standardized surveys investigating their HRQOL at home. The local ethics committees approved the study.

Normative sample data were derived from CentERdata (an online household panel) in which 1,731 (81%) members of this panel completed questionnaires.[16] The description for the data collection is described elsewhere.[16] For this analysis, an age and sex-matched normative population, in which a similar distribution of ages as in the patient was obtained, was included (n = 350). The data will be available for noncommercial scientific research, subject to study question, privacy and confidentiality restrictions and registration (www.profilesregistry.nl).[17]

Multidisciplinary treatment

All tumors were identified by endoscopy and confirmed by biopsy. In addition, all patients received a preoperative magnetic resonance imaging (MRI) of the pelvis for accurate staging. A pretreatment computerized tomography (CT) was also used to exclude distant metastasis.

Patients with a primary cT1-T3 tumor without threatened margin or pathological lymph nodes (N0) are classified with a mobile primary tumor (NAD group). Patients with primary cT3+ or any cT stage with pathological lymph nodes (N1 of greater) are considered locally advanced (LARC group). According to the Dutch national guidelines only patients with cT1 without positive lymph nodes are not treated with neoadjuvant therapy.[5] Therefore, most of the patients with NAD received course neoadjuvant radiotherapy with 5 × 5 Gray (Gy).[18] Most patients with LARC received neoadjuvant radiochemotherapy up to 50.4 Gy in 28 fractions to achieve downstaging in order to allow a radical resection.[19] During the study period different treatment schemes of neo-adjuvant radiochemotherapy have been used. These schemes and the influence on oncological outcome have been described elsewhere.[19]

For LRRC, tumor growth is not confined to a specific compartment lined by fascias, because these fascias have been severed and removed during the primary surgery. This facilitates recurrent tumors to grow into surrounding compartments. However, for LRRC patients, neoadjuvant treatment options are more limited since patients already received radio(-chemo)therapy during the treatment of the primary tumor. Due to dose accumulation, toxicity tissue tolerance for reirradiation was limited to 30 Gy.[10]

After neoadjuvant treatment, most patients with LARC or LRRC received a preoperative MRI to see whether downstaging had occurred. In almost all cases of LARC and LRRC, surgery was planned 8–10 weeks after completion of the neoadjuvant treatment. In patients with NAD there was no waiting period after neoadjuvant treatment and before surgery. Patients with NAD and patients with an advanced disease stage without involved rectal margins underwent either a low anterior resection with sphincter preservation and a (temporary) colostomy (LAR) or an abdominoperineal resection with permanent colostomy (APR). Patients with an advanced disease stage and involved rectal margins or patients with local recurrence were treated with a LAR or APR including extra-anatomical resections in order to achieve a radical resection. An IORT boost of 10–12.5 GY was used when an involved resection margin was expected. IORT is useful in overcoming dose limitations since it can apply a dose of IORT at a well defined specific area. Details on this multimodality treatment strategy have been described previously.[10, 20, 21] After treatment, patients were referred to a gynecologist or an urologist when needed.

Medical records

Data were retrieved from a prospective database where information on all rectal cancer patients treated in the Catharina Hospital is registered. This information includes patient and tumor characteristics, treatment, preoperative, perioperative and postoperative clinical course.

Questionnaires

Patients completed the European Organization for Research and Treatment of Cancer (EORTC) general HRQOL Questionnaire (QLQ-C30)[22] and the disease specific EORTC – ColoRectal 38 (QLQ-CR38).[23] Both are validated for use within the Dutch population. The QLQ-C30 assesses global health status, functional health and symptom burden, and includes a global HRQOL scale, and five scales on Physical, Role, Cognitive, Emotional and Social Functioning. It also comprises three symptoms scales on Fatigue, Nausea and Vomiting and Pain, and six single items assessing Dyspnea, Insomnia, Loss of Appetite, Constipation, Diarrhea and Financial Impact. The QLQ-CR38 assesses colorectal cancer specific functional health and symptom burden. It consists of scales or single items measuring Body Image, Sexual Functioning, Sexual Enjoyment and Future Perspective. The symptom scales assess Micturition Problems, Defecation Problems, Gastrointestinal Symptoms, Stoma-related Problems, Chemotherapy Side effects, Male Sexual Functioning and Female Sexual Functioning. A single item assessed weight Loss. For both questionnaires, the items are ranged on a 4-point scale ranging from 1 (not at all) to 4 (very much) with the exception of the global health status scale, which is scored on a 7-point scale ranging from 1 (very poor) to 7 (excellent). All scales were linearly converted to a 0–100 scale according to standard scoring procedures. For the functioning scales and single items, higher scores indicate better functioning; for the symptom scales and single item, higher scores indicate higher symptom burden.

In addition, patients were asked two additional questions. All patients were asked to what extent they were sexually active preoperatively. This question was answered on a 4-point scale: 1 = As usual, 2 = To a lesser extent, 3 = Barely, 4 = Not sexually active. In addition, men were asked if the used aids in order to get an erection. This question was answered on a 4-point scale: 1 = No, 2 = Yes, pills (e.g. Viagra), 3 = Yes, injections and 4 = Yes, mechanical devices. The women were asked if they used aids in order to improve lubrication. This question was answered on a 3-point scale: 1= No, 2 = Yes, medication (e.g. Synapauze), 3 = Other aids (e.g. lubricants).

The normative sample completed the EORTC QLQ-C30 and the EORTC QLQ-CR38 subscales Sexual Functioning and Sexual Enjoyment.

Statistical analyses

Analyses of variance (ANOVA's) and chi-square tests were conducted when appropriate to present the sociodemographic and clinical characteristics for the three treatment groups (i.e. NAD, LARC and LRRC). For patients, the EORTC-QLQ-C30 and QLQ-CR38 mean scores, stratified by group, were compared with analysis of covariance (ANCOVA). Confounding background variables included for adjustment in these analyses were determined a priori and chosen to be age, sex and time since surgery. The estimated marginal means were examined in order to determine which groups differed significantly from each other (a Bonferroni correction was applied). Next, similar ANCOVA's were conducted to compare the three groups with a normative population on the EORTC QLQ-C30 and EORTC QLQ-CR38 subscales Sexual Functioning and Sexual Enjoyment. However, time since surgery was no longer a confounding background variable, since this was not applicable for the normative population. In order to examine the effect of disease progression (metastasis or a not surgically treated local recurrence), secondary ANCOVAs were conducted in which patients with disease progression were excluded. Next, for the three treatment groups, the scores on the sexuality questions were dichotomized in order to determine the prevalence of sexual problems. Patients who reported no problems at all or minor problems (not at all—a little bit) were categorized as not having sexual problems, while patients who reported more severe problems (quite some—very much) were categorized as having sexual problems. In addition, questions regarding sexual activity were dichotomized into 0 (not sexually active) or 1 (sexually active). Furthermore, the scores on the aids questions were dichotomized into 0 (no resources used) and 1 (resources used). Means and standard deviations are provided as (M ± SD). Statistical differences were indicated if p < 0.05 (two-sided). All statistical analyses were performed using SPSS17.0.

Results

Study population

In total, 80 patients with NAD, 292 patients with LARC, 67 patients with LRRC returned the completed questionnaire and were included in the current study. This reflected an 85% response rate. The sociodemographic and clinical characteristics of the patients are presented in Table 1. The patients with NAD patients mostly received neoadjuvant short course radiotherapy (86.3%) while patients with LARC received neoadjuvant chemoradiation (84.6%). Patients with LRRC received neoadjuvant reirradiation combined with chemotherapy (56.7%) or full course chemoradiation (37.3%). In addition, type of surgery differed per group. In the NAD group, a LAR was more often performed (67.5%) than an APR (28.8%); for the LARC group, these percentages were more equal (47.6 vs. 43.2%, respectively). As can be expected, the percentage of multivisceral resections was higher in the LRRC group (53.7%) than the LARC (39%) and NAD group (1.6%). The normative sample consisted of 200 men (age 66.6 ± 10.0) and 150 women (age 66.1 ± 10.9). Further information about the normative sample is published elsewhere.[24, 25]

Table 1. Demographic and clinical characteristics of patients the tree treatment groups
 NAD (n = 80)LARC (n = 292)LRRC (n = 67)
Age at time of survey (mean ± SD)70.4 ± 9.765.6 ± 9.763.7 ± 9.8
Years since surgery (median [range])4.5 [0–11]2.3 [0–11]3.3 [0–10]
 N (%)N (%)N (%)
Male (yes)46 (57.5)169 (57.9)44 (65.7)
Neoadjuvant treatment
No neoadjuvant treatment10 (132.5)1 (0.3)2 (3)
Short-course radiotherapy (5 × 5 Gy)69 (86.3)18 (6.2)NA
Long-course radiotherapy26 (8.9)NA
Chemoradiaton1 (1.3)247 (84.6)NA
 Reirradiation with chemotherapyNANA38 (56.7)
 Reirradiation without chemotherapyNANA1 (1.5)
Full-course irradiation with chemotherapyNANA25 (37.3)
Full-course irradiationNANA1 (1.5)
Type of surgery
Low anterior resection54 (67.5)139 (47.6)8 (11.9)
Abdominoperineal resection23 (28.8)126 (43.2)15 (22.4)
Abdominosacral resection5 (1.7)19 (28.4)
Exenteration (anterior/pelvic)11 (3.8)9 (13.4)
Hartmann3 (3.8)11 (3.8)3 (4.5)
Other1 (0.4)
Multivisceral (including prostate/uterus/vesiculae)2 (1.6)114 (39.0)31 (53.7)
Intraoperative radiotherapy (IORT)189 (64.7)58 (86.6)
Radical treatment
Radical78 (97.5)265 (90.8)51 (76.1)
Microscopic focal irradical26 (8.9)16 (23.9)
Missing2 (2.5)1 (0.3)
Not surgically treated local recurrence0 (0.0)6 (2.1)
Distant metastases2 (2.5)33 (11.3)11 (16.4)
Clinical T stage
T1-240 (50.0)3 (1.0)NA
T340 (50.0)107 (36.6)NA
T4177 (60.6)NA
Missing5 (1.7)NA
Clinical N stage
N080 (100)97 (33.2)NA
N192 (31.5)NA
N259 (20.2)NA
Missing44 (15.1)NA
Clinical M1 stage15 (5.3)NA
Postoperative abdominal complications
Presacral abscess10 (12.5)25 (8.6)5 (7.5)
Anastomic leakage3 (3.8)15 (4.1)2 (3)

Scores on the EORTC QLQ-C30 and EORTC QLQ-CR38

After adjusting for age, sex and time since diagnosis, LRRC patients reported a lower Physical Function, Social Function, Future Perspective, Sexual Functioning and more Pain compared with LARC patients and patients with NAD (p's < 0.05, see Table 2). Furthermore, LRRC patients experienced a worse Body image compared with NAD patients (p = 0.016) and a lower Male Sexual Functioning compared with LARC patients (p = 0.018). Excluding patients with a disease progression resulted in similar results, with exception of the Male Sexual Functioning and Future Perspective scale for which the differences were no longer statistically significant (results not shown).

Table 2. Mean scores on the EORTC QLQ-C30 and QLQ-CR38
 NAD (n = 80)LARC (n = 292)LRRC (n = 67)p*Norm. Popp**
  • 1

    Higher scores indicate better functioning.

  • 2

    Higher scores indicate more problems.

  • *

    p Value for the comparison between the three treatment groups, adjusted for age, sex and time since diagnosis.

  • **

    p Value for the comparison between all four groups, adjusted for age and sex. Significant p Values (p < 0.05) are marked in bold. The mean scores on the subscale Defecation Problems are not computed because this is not applicable for most patients since they have a stoma.

  • Abbreviation: Norm.pop, normative population.

EORTC C30 subscales
Global quality of life170.5 ± 22.168.1 ± 23.464.0 ± 24.00.31377.2 ± 17.4<0.0001
Physical function180.3 ± 19.179.5 ± 20.471.9 ± 22.80.02286.0 ± 17.1<0.0001
Role function175.0 ± 28.475.3 ± 28.169.6 ± 31.60.31586.4 ± 21.6<0.0001
Emotional function184.8 ± 18.882.6 ± 20.781.1 ± 22.60.63090.3 ± 15.0<0.0001
Cognitive function184.4 ± 20.983.7 ± 21.180.9 ± 22.10.49890.8 ± 14.1<0.0001
Social function182.7 ± 22.479.2 ± 25.269.6 ± 29.20.00993.1 ± 16.8<0.0001
Fatigue223.1 ± 22.326.8 ± 23.926.2 ± 22.10.52617.8 ± 20.5<0.0001
Nausea/vomiting23.0 ± 8.34.4 ± 11.84.0 ± 11.60.7363.0 ± 11.80.311
Pain214.8 ± 21.315.8 ± 22.841.9 ± 22.3<0.000117.8 ± 23.0<0.0001
Dyspnoea216.0 ± 24.413.8 ± 22.512.4 ± 19.30.6139.4 ± 19.60.028
Insomnia219.4 ± 27.518.7 ± 26.521.3 ± 30.40.77114.9 ± 22.00.067
Appetite loss23.8 ± 10.76.7 ± 17.73.2 ± 9.90.1943.3 ± 12.00.019
Constipation28.4 ± 16.49.1 ± 20.59.3 ± 23.70.9515.6 ± 15.30.037
Diarrhoea221.5 ± 27.818.7 ± 25.319.4 ± 26.00.5124.5 ± 15.1<0.0001
Financial problems25.6 ± 17.311.9 ± 23.38.2 ± 19.90.4363.0 ± 12.0<0.0001
EORTC CR38 subscales
Body image180.1 ± 22.873.5 ± 26.465.5 ± 29.90.016
Future perspective171.4 ± 26.266.7 ± 27.357.2 ± 34.20.018
Sexual Functioning125.5 ± 27.121.6 ± 24.815.2 ± 19.50.00931.4 ± 25.5<0.0001
Sexual Enjoyment158.1 ± 25.856.8 ± 27.766.7 ± 26.10.47164.3 ± 25.1<0.0001
Micturition problems225.3 ± 17.224.9 ± 16.325.1 ± 17.90.945
Chemotherapy side effects211.0 ± 13.414.7 ± 17.411.1 ± 12.70.228
Gastrointestinal problems217.3 ± 15.420.3 ± 14.821.7 ± 14.70.381
Male Sexual Functioning269.9 ± 31.369.3 ± 32.586.3 ± 23.20.014
Female Sexual Functioning229.5 ± 27.337.2 ± 33.941.7 ± 41.90.747
Stoma-related problems223.2 ± 22.425.7 ± 18.824.5 ± 19.60.987
Weight loss28.0 ± 18.710.8 ± 21.49.1 ± 18.30.711

In-depth analyses of the sexuality items revealed that more than 75% of men were sexually active preoperative, regardless of their treatment (p = 0.397, see Table 3). After treatment, these percentages dropped to less than 50%. LRRC patients more often had problems with erectile functioning and felt less masculine (see Table 4) compared with NAD or LARC patients (p's< 0.05). However, less than 10% of the patients used aids to enhance erectile functioning (p = 0.610).

Table 3. The effect of treatment on sexual functioning for men and women
 MenWomen
 NAD (n = 45)LARC (n = 170)LRRC (n = 44)pNAD (n = 35)LARC (n = 122)LRRC (n = 23)p
  1. In both tables, the scores on the individual EORTC QLQ-CR38 items were dichotomized into two categories (not at all—a bit = 0 and some problems—very much problems = 1). NA, not applicable; since these questions were intercourse related for the women they were not applicable for some women. Significant p values (p < 0.05) are marked in bold.

Sexual active preoperative
Yes42 (93.3%)141 (82.9%)35 (79.5%)0.39724 (68.6%)75 (61.5%)12 (52.2%)0.071
No2 (4.4%)17 (10.0%)5 (11.4%) 5 (14.3%)16 (13.1%)8 (34.8%) 
Missing1 (2.2%)12 (7.1%)4 (9.1%) 6 (17.1%)31 (25.4%)3 (13.0%) 
Sexually active postoperative
Yes21 (46.7%)75 (44.1%)11 (25.0%)0.05412 (34.3%)28 (23.0%)6 (26.1%)0.427
No23 (51.1%)93 (54.7%)32 (72.7%) 17 (48.6%)70 (57.4%)13 (56.5%) 
Missing1 (2.2%)2 (1.2%)1 (2.3%) 6 (17.1%)24 (19.7%)4 (17.4%) 
Erectile functioning (♂)/lubrication (♀)   0.010   0.571
No problems7 (15.6%)39 (22.9%)2 (4.5 %) 10 (28.6%)33 (27.0%)3 (13.0%) 
Problems to some extent31 (68.9%)113 (66.5%)41 (93.2%) 5 (14.3%)24 (19.7%)4 (17.4%) 
Missing7 (15.6%)18 (10.6%)1 (2.3%) 20 (57.1%)65 (53.3%)16 (69.6%) 
Ejaculatory functioning (♂)/Dyspareunia (♀)   0.059   0.235
No problems11 (24.4%)50 (29.4%)6 (13.6%) 14 (40.0%)37 (30.3%)2 (8.7%) 
Problems to some extent26 (57.8%)98 (57.6%)35 (79.5%) 2 (5.7%)15 (12.3%)2 (8.7%) 
Missing/NA8 (17.8%)22 (12.9%)3 (6.8%) 19 (54.3%)70 (57.4%)19 (82.6%) 
Aids used to enhance erectile functioning*   0.610   0.703
No37 (82.2%)131 (77.1%)36 (81.8%) 15 (42.9%)50 (41.0%)5 (21.7%) 
Yes2 (4.4%)15 (8.8%)4 (9.1%) 5 (14.3%)10 (8.2%)1 (4.3%) 
Missing6 (13.3%)24 (14.1%)4 (9.1%) 15 (42.9%)62 (50.8%)17 (73.9%) 
Table 4. The effect of treatment on body image for men and women
 MenWomen
 NAD (n = 45)LARC (n = 170)LRRC (n = 44)pNAD (n = 36)LARC (n = 121)LRRC (n = 23)p
  1. In both tables, the scores on the individual EORTC QLQ-CR38 items were dichotomized into two categories (not at all—a bit = 0 and some—very much problems = 1). Significant p values (p < 0.05) are marked in bold.

Feeling less attractive due to disease/treatment   0.061   0.460
Yes4 (8.9%)27 (15.9%)12 (27.3%) 6 (17.1%)28 (23.0%)3 (13.0%) 
No41 (91.1%)142 (83.5%)32 (72.2%) 29 (82.9%)90 (73.8%)19 (82.6%) 
Missing0 (0.0%)1 (0.6%)0 (0.0%) 0 (0.0%)4 (3.3%)1 (4.3%) 
Feeling less masculine/feminine   0.046   0.526
Yes11 (24.4%)46 (27.1%)20 (45.5%) 3 (8.6%)20 (16.4%)3 (13.0%) 
No33 (73.3%)123 (72.4%)24 (54.5%) 30 (85.7%)98 (80.3%)19 (82.6%) 
Missing1 (2.2%)1 (0.6%)0 (0.0%) 2 (5.7%)4 (3.3%)1 (4.3%) 
Dissatisfied with body   0.723   0.262
Yes9 (20.0%)34 (20.0%)11 (25.0%) 5 (14.3%)30 (24.6%)7 (30.4%) 
No36 (80.0%)135 (79.4%)32 (72.7%) 29 (82.9%)90 (73.8%)14 (60.9%) 
Missing0 (0.0%)1 (0.6%)1 (2.3%) 1 (2.9%)2 (1.6%)2 (8.7%) 

More than 50% of women were sexually active preoperative. However, after treatment 34.3% of NAD, 23.0% of LARC and 26.1% of LRRC patients were still sexually active (p = 0.427). Women did not differ on Lubrication, Dyspareunia and their Body Image. Less than 15% of women used aids to enhance lubrication. However, more than 50% of women did not answer the questions on lubrication, dyspareunia and aids used to enhance lubrication.

Comparison with a normative population

Compared with the normative population, rectal cancer patients had lower scores on Global Quality of Life, Role Function, Cognitive Function, Emotional Function, Social Function and Sexual Enjoyment and more Constipation and Diarrhea, regardless of treatment (p's < 0.05; see Table 2). In addition, LARC and LRRC patients experienced a lower Physical Function, Sexual Functioning but more Fatigue than the normative population (p's< 0.05). Finally, LRRC patients reported more Pain (p < 0.0001) than the normative population, while the LARC group reported more Appetite Loss (p = 0.017), Dyspnoea (n = 0.026) and Financial problems (p < 0.0001) compared with the normative population. Excluding patients with a disease progression resulted in similar results (results not shown).

Discussion

Patients with a LRRC reported a lower HRQOL compared with both LARC patients and patients with NAD. These results are consistent with the results of Palmer et al. who described that patients with an extensive disease had a lower HRQL compared with patients with NAD.[14] However, they pooled the LARC and LRRC patients in one group, while our study clearly shows that the LRRC group experiences a lower HRQOL compared with the LARC group. This could be due to the fact that patients with a LRRC were treated with more extensive treatment to achieve radical surgery (e.g. extra-anatomical resections), which may have influenced the physical condition and psychological state of the patient. In this study, no significant differences between the LARC and NAD groups were found. The study of Austin et al.[15] also reported that patients with pelvic exenteration did not differ on physical, social, emotional and functional well-being compared with patients who underwent a low anterior resection or an abdominoperineal resection. Compared with a Dutch normative population all three groups had a lower HRQOL, which is in line with earlier studies.[14, 15]

Compared with the preoperative percentages, the percentage of patients that were still sexually active at time of questionnaire completion had dropped dramatically. For men, more than 75% of patients were sexually active preoperative compared with less than 50% postoperative. For women, these percentages were lower; more than 50% of women were sexually active preoperative compared with less than 35% postoperative. Moreover, patients with LRRC or LARC reported a lower Sexual Functioning than NAD patients and LRRC patients reported a worse Male Sexual Functioning than LARC patients. Furthermore, LRRC patients most often experienced problems with erectile functioning and they more often reported to feel less masculine. For women, no differences were reported for lubrication problems, dyspareunia and body image. The substantial decline in the percentage of sexually active participants could also partly reflect normal effects of aging, since the mean time since surgery was 2.0 (range 0–11 years). However, the fact remains that all three groups reported a lower sexual functioning (which includes sexual activity) and sexual enjoyment compared with the normative population. Based on these results it may be expected that age does not fully explain the lower levels of functioning and sexual enjoyment in our population.

Even though a high prevalence of sexual dysfunction was found, less than 15% of patients reported to use aids in order to improve erectile functioning (men) or lubrication (women). The discrepancy between the presence of sexual dysfunction and the frequency by which aids are used in an attempt to improve sexual functioning is remarkable. These numbers may be due to an insufficient knowledge of patients about the possible treatments for sexual dysfunction. Previous studies have already shown that although it was important for most of the patients to discuss sexuality, these discussions do not always occur.[26] [27] Furthermore, not all patients may feel inclined to seek help for their problems; perhaps, they have found other ways to maintain a satisfactory relationship. There may be a still existing taboo on discussing sexuality, in both health care professionals as patients. Psychosexual education before and after treatment may play an important role in increasing the patients' knowledge. In this way, professionals normalize patients' concerns, which may lower the threshold for patients to seek adequate support. Furthermore, it is imperative that health care professionals adequately assess, evaluate and manage potential sexual problems.

The merits of the current study are the fact that this study achieved a high response rate (85%). To our knowledge, this is the first study to investigate the HRQOL in NAD, LARC and LRRC. In addition, the comparison of these three groups with a normative population was not yet performed. Finally, we used validated and reliable questionnaires. However, there are also some limitations that need to be acknowledged. For instance, the cross-sectional nature of this study presents an inherent limitation. Furthermore, no information was known about the patients' functioning before treatment, except of knowledge on whether or not patients were sexually active preoperative, which limits the determination of the effect of a cancer diagnosis and treatment on functioning. In addition, it is possible that the question on preoperative sexual activity was not clear for the LRRC group. It is a possibility that the LRRC group thought that the question referred to their sexual activity before the first surgery (for the primary cancer) instead of the second surgery, which may explain the remarkable difference between the percentage of postoperative sexual active patients in the NAD group and the preoperative sexual active patients in the LRRC group. Furthermore, even though the EORTC QLQ-CR38 is one of the most used questionnaires to assess sexual functioning, it provides limited information since sexual functioning is assessed with only five questions. Finally, more than 50% of women did not answer the questions regarding lubrication, dyspareunia and aids used to enhance lubrication. This may be attributed to the way these questions are postulated. The questions “Did you have a dry vagina during intercourse” and “Did you have pain during intercourse” imply that a women needs to be sexually active in order to encounter possible problems. However, women may not be sexually active due to these problems; therefore, the causality implied is not correct. Future research should use questionnaires designed to assess sexuality more adequately. In addition, according to the Dutch national guideline only patients with cT1N0 are not treated with neoadjuvant treatment.[5] In our study, only eight patients with a NAD had a cT1N0 tumor and did therefore not receive neoadjuvant radiotherapy. However, negative effects of neoadjuvant radiotherapy on HRQOL has been previously reported.[28, 29] The fact that almost all patients received neoadjuvant treatment may therefore, to some extent, explain the lack of differences in HRQOL between the LARC and NAD group. Moreover, with the introduction of the new guidelines for rectal cancer treatment patients with cT2N0 rectal cancers will no longer be eligible for neoadjuvant radiotherapy. Therefore, future studies will be able to examine two subgroups within NAD: those who received neoadjuvant treatment (cT3N0) and those who did not (cT1N0 or cT2NO). In this way, the potential effects of neoadjuvant radiotherapy in patients with NAD can be evaluated more specifically. Furthermore, in the Catharina hospital patients receive IORT when an involved surgical margin can be expected. Multiple studies about the effectiveness of IORT in LARC patients are performed.[7, 30, 31] These studies report an additional benefit of IORT on local control and outcome. However, IORT may have a negative impact on HRQOL, particularly on the sexuality and uro-genital items. In this study, only minor differences between the NAD and LARC patients were found. Nevertheless, future studies are still warranted to examine the effects of IORT on HRQOL more specifically. Finally, since our study population was already stratified into three groups (NAD, LARC, LRRC), it was no possible to conduct the analyses specifically for patients with a stoma or to include stoma as a covariate as this would, unfortunately, have resulted in too low sample sizes. Therefore, it would be beneficial if upcoming studies provide further insights in the influence of a (temporary) stoma on (HR)QOL.

In conclusion, this study showed that patients with LRRC reported the lowest HRQOL compared with LARC or NAD patients. All three groups reported low scores on sexual functioning compared with the normative population, while only few patients reported to used aids to improve this functioning.

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