Rectal Cancer
Conditions
Keywords
Rectal cancer, Preoperative radiotherapy, Pelvic surgery, Sexual function, Wellbeing, Hormone levels
Brief summary
Preoperative radiotherapy (RT) and pelvic surgery is recommended to many patients with rectal cancer. For women there are theoretical reasons to believe that the treatment may affect hormone levels, sexual function and wellbeing. To address these questions a longitudinal observational study was initiated where androgen levels and sexual function were assessed before treatment (baseline) and during a follow-up period of two years.
Detailed description
Women with rectal cancer stage I to III planned for abdominal surgery was included in the study. Women treated with preoperative RT were assigned to the exposed group and women treated with surgery alone were assigned to the unexposed group. 142 participants were enrolled at five outpatient rectal cancer centres in Sweden between 2008 and 2013. Patient data, fasting venous blood samples and questionnaires regarding sexual function and well-being were collected at a baseline visit before start of oncologic treatment, 1 year after surgery and 2 years after surgery (only questionnaires). Women treated with preoperative RT for rectal cancer had an additional venous blood sample taken the day before surgery. Changes in serum levels of testosterone and sexual function during follow-up was assessed and compared between exposed and unexposed participants.
Interventions
RADIATIONPreoperative radiotherapy
Preoperative radiotherapy (RT) was administered as either short course (5Gy x5) or long-course (2Gy x25 or 1.8 Gy x25 with or without 3 fractions of boost to the primary tumor and radiologically malignant lymph nodes) treatment with or without concomitant or sequential chemotherapy. Oncological treatment was decided at a multidisciplinary team conference.
Sponsors
Swedish Cancer Society
Karolinska Institutet
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females diagnosed with rectal cancer stadium I-III, planned surgery with or without preoperative radiotherapy.
Exclusion criteria
* Rectal cancer stadium IV * Previous radiotherapy to the pelvic region * Inability to provide informed consent. * Life expectancy less than 2 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery. | Baseline, the week before surgery and 1 year after surgery. | Fasting venous blood samples were collected at baseline visit (prior to oncological treatment) and 1 year follow-up. Participants treated with preoperative radiotherapy (RT) had an additional blood sample taken the day before surgery. Serum testosterone levels (T) were measured with liquid chromatography-mass spectrometry using the LC-MS/MS Quattro Premier Xevo TQ MS (Waters Corporation, Milford, MA, USA). The total coefficients of variation (CVtot) were 7% at 2.8 nmol/L and 6% at 15 nmol/L. |
| Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up. | Baseline, 1 year after surgery and 2 years after surgery. | Sexual function was assessed using the Female Sexual Function Index (FSFI). The FSFI questionnaire is a 19-item multiple-choice, self-assessment tool validated for use in the general population as well as for patients with cancer. It covers six domains of sexual function in women; desire (2 items), arousal (4 items), lubrication (4 items), orgasm (3 items), satisfaction (3 items) and pain (3 items). Items scores between 0 or 1 to 5, with lower scores indicating worse function. A total FSFI score can be calculated when all items are completed. Minimal total score is 4 points and maximal score is 95 points, with lower scores indicating worse function. A total FSFI score of less than 26.55 points was used to define overall sexual dysfunction. |
Countries
Sweden
Participant flow
Recruitment details
Participants were recruited from five Swedish outpatient rectal cancer centres in Sweden (Karolinska University Hospital, Ersta Hospital, Örebro University Hospital, Linköping University Hospital and Norrköping Hospital) between June 2008 and August 2013. Of 404 women with rectal cancer assessed for eligibility, 142 were included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Preoperative Radiotherapy Women with rectal cancer treated with preoperative radiotherapy (RT) and surgery. | 110 |
| No Preoperative Radiotherapy Women with rectal cancer treated with surgery alone (no RT). | 32 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 2 |
| Overall Study | Lost to Follow-up | 21 | 3 |
Baseline characteristics
| Characteristic | Total | Preoperative Radiotherapy | No Preoperative Radiotherapy |
|---|---|---|---|
| Adjuvant chemotherapy Missing | 3 Participants | 1 Participants | 2 Participants |
| Adjuvant chemotherapy No | 94 Participants | 73 Participants | 21 Participants |
| Adjuvant chemotherapy Yes | 45 Participants | 36 Participants | 9 Participants |
| Age, Continuous | 65.5 years | 62 years | 69 years |
| ASA score I | 42 Participants | 35 Participants | 7 Participants |
| ASA score II | 71 Participants | 58 Participants | 13 Participants |
| ASA score III | 25 Participants | 16 Participants | 9 Participants |
| ASA score Missing | 4 Participants | 1 Participants | 3 Participants |
| BMI | 24.3 kg/m2 | 24.2 kg/m2 | 24.4 kg/m2 |
| Neoadjuvant chemotherapy Missing | 3 Participants | 1 Participants | 2 Participants |
| Neoadjuvant chemotherapy No | 103 Participants | 74 Participants | 29 Participants |
| Neoadjuvant chemotherapy Yes | 36 Participants | 35 Participants | 1 Participants |
| Pathological tumour stage 0 | 11 Participants | 10 Participants | 1 Participants |
| Pathological tumour stage I | 32 Participants | 24 Participants | 8 Participants |
| Pathological tumour stage II | 35 Participants | 29 Participants | 6 Participants |
| Pathological tumour stage III | 52 Participants | 39 Participants | 13 Participants |
| Pathological tumour stage IV | 5 Participants | 4 Participants | 1 Participants |
| Pathological tumour stage Missing | 7 Participants | 4 Participants | 3 Participants |
| Resection of gynaecological organs Hysterectomy | 18 Participants | 13 Participants | 5 Participants |
| Resection of gynaecological organs Missing | 3 Participants | 1 Participants | 2 Participants |
| Resection of gynaecological organs No resection | 92 Participants | 71 Participants | 21 Participants |
| Resection of gynaecological organs Partial vaginal resection | 9 Participants | 9 Participants | 0 Participants |
| Resection of gynaecological organs Unilateral/bilateral oophorectomy | 20 Participants | 16 Participants | 4 Participants |
| Sex: Female, Male Female | 142 Participants | 110 Participants | 32 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Tumour distance from anal verge 0-4 cm | 49 Participants | 45 Participants | 4 Participants |
| Tumour distance from anal verge 11-15 cm | 35 Participants | 23 Participants | 12 Participants |
| Tumour distance from anal verge 5-10 cm | 54 Participants | 40 Participants | 14 Participants |
| Tumour distance from anal verge Missing | 4 Participants | 2 Participants | 2 Participants |
| Type of preoperative RT Long course (2 Gy x25 or 1.8 x28) | 37 Participants | 37 Participants | 0 Participants |
| Type of preoperative RT No RT | 32 Participants | 0 Participants | 32 Participants |
| Type of preoperative RT Short course (5Gy x5) | 73 Participants | 73 Participants | 0 Participants |
| Type of Surgery Abdominal excision | 61 Participants | 53 Participants | 8 Participants |
| Type of Surgery Anterior resection | 74 Participants | 54 Participants | 20 Participants |
| Type of Surgery Missing | 3 Participants | 1 Participants | 2 Participants |
| Type of Surgery No abdominal surgery | 4 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 110 | 2 / 32 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery.
Fasting venous blood samples were collected at baseline visit (prior to oncological treatment) and 1 year follow-up. Participants treated with preoperative radiotherapy (RT) had an additional blood sample taken the day before surgery. Serum testosterone levels (T) were measured with liquid chromatography-mass spectrometry using the LC-MS/MS Quattro Premier Xevo TQ MS (Waters Corporation, Milford, MA, USA). The total coefficients of variation (CVtot) were 7% at 2.8 nmol/L and 6% at 15 nmol/L.
Time frame: Baseline, the week before surgery and 1 year after surgery.
Population: 17 of the included 142 participants were excluded due to history of oophorectomy, resulting in 125 participants analysed. Participants in the group No preoperative radiotherapy had no blood samples taken at the time point After RT/before surgery.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Preoperative Radiotherapy | Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery. | Baseline | 0.6 nmol/l |
| Preoperative Radiotherapy | Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery. | After RT/before surgery | 0.6 nmol/l |
| Preoperative Radiotherapy | Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery. | 1 year after surgery | 0.5 nmol/l |
| No Preoperative Radiotherapy | Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery. | Baseline | 0.6 nmol/l |
| No Preoperative Radiotherapy | Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery. | 1 year after surgery | 0.6 nmol/l |
Comparison: The change in serum testosterone levels between baseline and 1 year was assessed using longitudinal regression analysis (GEE).p-value: 0.00495% CI: [-0.232, -0.044]Regression, Linear
Comparison: The change in serum testosterone levels between baseline and 1 year was assessed using longitudinal regression analysis (GEE).p-value: 0.80595% CI: [-0.097, 0.075]Regression, Linear
Primary
Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up.
Sexual function was assessed using the Female Sexual Function Index (FSFI). The FSFI questionnaire is a 19-item multiple-choice, self-assessment tool validated for use in the general population as well as for patients with cancer. It covers six domains of sexual function in women; desire (2 items), arousal (4 items), lubrication (4 items), orgasm (3 items), satisfaction (3 items) and pain (3 items). Items scores between 0 or 1 to 5, with lower scores indicating worse function. A total FSFI score can be calculated when all items are completed. Minimal total score is 4 points and maximal score is 95 points, with lower scores indicating worse function. A total FSFI score of less than 26.55 points was used to define overall sexual dysfunction.
Time frame: Baseline, 1 year after surgery and 2 years after surgery.
Population: Of the 142 participants included in the study, 3 were excluded due to not answering FSFI questionnaires at any timepoint. Total FSFI scores were only calculated for available questionnaires without missing items.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Preoperative Radiotherapy | Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up. | Baseline | 18.5 score on a scale |
| Preoperative Radiotherapy | Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up. | 1 year after surgery | 11.1 score on a scale |
| Preoperative Radiotherapy | Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up. | 2 years after surgery | 10.8 score on a scale |
| No Preoperative Radiotherapy | Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up. | Baseline | 6.7 score on a scale |
| No Preoperative Radiotherapy | Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up. | 1 year after surgery | 5.8 score on a scale |
| No Preoperative Radiotherapy | Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up. | 2 years after surgery | 6.5 score on a scale |
Comparison: The association between mean change in total FSFI score and preoperative RT was assessed using longitudinal regression analysis (GEE), using no preoperative radiotherapy as the reference group.p-value: 0.01395% CI: [-16.66, -1.99]Regression, Linear