Sexual Function and Wellbeing in Females With Rectal Cancer

• Sponsor: Karolinska Institutet (Other)
• Overall Status: Completed
• CT.gov ID: NCT01216189
• Collaborator: Swedish Cancer Society (Other)
• Enrollment: 142
• Locations: 5
• Duration (Months): 90
• Patients Per Site: 28.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Radiation: Preoperative radiotherapy

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 142 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Sexual Function and Wellbeing in Females Diagnosed With Rectal Cancer
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Preoperative radiotherapy Women with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Radiation: Preoperative 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.
No preoperative radiotherapy Women with rectal cancer treated with surgery alone (no RT).

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Linköping University Hospital	Linköping		Sweden
2	Norrköping Hospital	Norrköping		Sweden
3	Ersta Hospital	Stockholm		Sweden
4	Karolinska University Hospital	Stockholm		Sweden
5	Örebro University Hospital	Örebro		Sweden

Sponsors and Collaborators

• Karolinska Institutet
• Swedish Cancer Society

Investigators

• Principal Investigator: Anna Martling, Karolinska Institutet

Study Documents (Full-Text)

None provided.

More Information

Publications

• Segelman J, Martling A, Machado M, Holm T, Bergmark K, Flöter Rådestad A. Preoperative sexual function in women with rectal cancer. Eur J Surg Oncol. 2013 Oct;39(10):1079-86. doi: 10.1016/j.ejso.2013.07.091. Epub 2013 Aug 15.

• Responsible Party: Anna Martling, Professor, Senior Consultant Surgeon, Karolinska Institutet
• ClinicalTrials.gov Identifier: NCT01216189
• Other Study ID Numbers: 2008/247-31/3
• First Posted: Oct 7, 2010
• Last Update Posted: Apr 9, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Anna Martling, Professor, Senior Consultant Surgeon, Karolinska Institutet: Rectal cancer; Preoperative radiotherapy; Pelvic surgery; Sexual function; Wellbeing; Hormone levels
• Additional relevant MeSH terms: Rectal Neoplasms

Study Results

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.

Arm/Group Title	Preoperative Radiotherapy	No Preoperative Radiotherapy
Arm/Group Description	Women with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Women with rectal cancer treated with surgery alone (no RT).
Period Title: Overall Study
STARTED	110	32
COMPLETED	85	27
NOT COMPLETED	25	5

Baseline Characteristics

Arm/Group Title	Preoperative Radiotherapy	No Preoperative Radiotherapy	Total
Arm/Group Description	Women with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Women with rectal cancer treated with surgery alone (no RT).	Total of all reporting groups
Overall Participants	110	32	142
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	69	65.5
Sex: Female, Male (Count of Participants)
Female	110 100%	32 100%	142 100%
Male	0 0%	0 0%	0 0%
BMI (kg/m2) [Median (Full Range) ]
Median (Full Range) [kg/m2]	24.2	24.4	24.3
ASA score (Count of Participants)
I	35 31.8%	7 21.9%	42 29.6%
II	58 52.7%	13 40.6%	71 50%
III	16 14.5%	9 28.1%	25 17.6%
Missing	1 0.9%	3 9.4%	4 2.8%
Tumour distance from anal verge (Count of Participants)
0-4 cm	45 40.9%	4 12.5%	49 34.5%
5-10 cm	40 36.4%	14 43.8%	54 38%
11-15 cm	23 20.9%	12 37.5%	35 24.6%
Missing	2 1.8%	2 6.3%	4 2.8%
Type of preoperative RT (Count of Participants)
Short course (5Gy x5)	73 66.4%	0 0%	73 51.4%
Long course (2 Gy x25 or 1.8 x28)	37 33.6%	0 0%	37 26.1%
No RT	0 0%	32 100%	32 22.5%
Type of Surgery (Count of Participants)
Anterior resection	54 49.1%	20 62.5%	74 52.1%
Abdominal excision	53 48.2%	8 25%	61 43%
No abdominal surgery	2 1.8%	2 6.3%	4 2.8%
Missing	1 0.9%	2 6.3%	3 2.1%
Resection of gynaecological organs (Count of Participants)
Hysterectomy	13 11.8%	5 15.6%	18 12.7%
Unilateral/bilateral oophorectomy	16 14.5%	4 12.5%	20 14.1%
Partial vaginal resection	9 8.2%	0 0%	9 6.3%
No resection	71 64.5%	21 65.6%	92 64.8%
Missing	1 0.9%	2 6.3%	3 2.1%
Pathological tumour stage (Count of Participants)
0	10 9.1%	1 3.1%	11 7.7%
I	24 21.8%	8 25%	32 22.5%
II	29 26.4%	6 18.8%	35 24.6%
III	39 35.5%	13 40.6%	52 36.6%
IV	4 3.6%	1 3.1%	5 3.5%
Missing	4 3.6%	3 9.4%	7 4.9%
Neoadjuvant chemotherapy (Count of Participants)
Yes	35 31.8%	1 3.1%	36 25.4%
No	74 67.3%	29 90.6%	103 72.5%
Missing	1 0.9%	2 6.3%	3 2.1%
Adjuvant chemotherapy (Count of Participants)
Yes	36 32.7%	9 28.1%	45 31.7%
No	73 66.4%	21 65.6%	94 66.2%
Missing	1 0.9%	2 6.3%	3 2.1%

Outcome Measures

1. Primary Outcome

Title	Change in Serum Testosterone Levels Between Baseline and 1 Year After Surgery.
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Preoperative Radiotherapy	No Preoperative Radiotherapy
Arm/Group Description	Women with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Women with rectal cancer treated with surgery alone (no RT).
Measure Participants	98	27
Baseline	0.6	0.6
After RT/before surgery	0.6
1 year after surgery	0.5	0.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preoperative Radiotherapy
	Comments	The change in serum testosterone levels between baseline and 1 year was assessed using longitudinal regression analysis (GEE).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	The threshold for statistical significance was p = 0.05.
	Method	Regression, Linear
	Comments	Model adjusted for menopausal status.
Method of Estimation	Estimation Parameter	Mean change
	Estimated Value	-0.138
	Confidence Interval	(2-Sided) 95%; -0.232 to -0.044
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	No Preoperative Radiotherapy
	Comments	The change in serum testosterone levels between baseline and 1 year was assessed using longitudinal regression analysis (GEE).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.805
	Comments	The threshold for statistical significance was p=0.05.
	Method	Regression, Linear
	Comments	Model adjusted for menopausal status.
Method of Estimation	Estimation Parameter	Mean change
	Estimated Value	-0.011
	Confidence Interval	(2-Sided) 95%; -0.097 to 0.075
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change in Sexual Function (Total FSFI Scores) Between Baseline and 2 Years Follow-up.
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Preoperative Radiotherapy	No Preoperative Radiotherapy
Arm/Group Description	Women with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Women with rectal cancer treated with surgery alone (no RT).
Measure Participants	109	30
Baseline	18.5	6.7
1 year after surgery	11.1	5.8
2 years after surgery	10.8	6.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preoperative Radiotherapy, No Preoperative Radiotherapy
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	The threshold for statistical significance was p=0.05.
	Method	Regression, Linear
	Comments	Model adjusted for Age, Psychological General Well-being total score and relationship with partner.
Method of Estimation	Estimation Parameter	Mean change in FSFI scores
	Estimated Value	-9.33
	Confidence Interval	(2-Sided) 95%; -16.66 to -1.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	Adverse Events were not monitored.
Arm/Group Title	Preoperative RT		No Preoperative RT
Arm/Group Description	Women with rectal cancer treated with preoperative radiotherapy (RT) and surgery.		Women with rectal cancer treated with surgery alone (no RT).
All Cause Mortality
	Preoperative RT		No Preoperative RT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/110 (3.6%)		2/32 (6.3%)
Serious Adverse Events
	Preoperative RT		No Preoperative RT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Preoperative RT		No Preoperative RT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.