Sexual Function and Wellbeing in Males With Rectal Cancer

• Sponsor: Karolinska Institutet (Other)
• Overall Status: Completed
• CT.gov ID: NCT01216202
• Collaborator: Swedish Cancer Society (Other)
• Enrollment: 178
• Locations: 2
• Duration (Months): 73
• Patients Per Site: 89
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Preoperative radiotherapy and pelvic surgery is recommended to many patients with rectal cancer. For men there are theoretical reasons to believe that the treatment may effect hormone levels, spermatogenesis, sexual function and wellbeing. To address these questions a longitudinal observational study was initiated where measurements of androgen hormone levels, semen samples 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

Men with rectal cancer stage I to III planned for resection was included in the study. Men treated with preoperative RT were assigned to the exposed group and men treated with surgery alone were assigned to the unexposed group. Eighteen months after start of inclusion, less than 10% of the participants were treated with surgery alone. To increase the sample size of the unexposed group, men with prostate cancer stage I to III and scheduled for robot-assisted prostatectomy were also included.

Participants with rectal cancer were enrolled at two centres in Stockholm (Karolinska University Hospital and Ersta Hospital) between 2010 and 2014. Participants with prostate cancer were enrolled at the Urology department of the Karolinska University Hospital in Stockholm between 2012 and 2013.

Patient data, fasting venous blood samples, semen samples and questionnaires regarding sexual function and well being were collected before start of oncological treatment (baseline), 1 and 2 years after surgery. Men treated with preoperative RT for rectal cancer had an additional venous blood sample during the week before surgery. Men with rectal cancer under 55 years of age were offered semen cryopreservation.

Participants could choose if they wanted to participate in one, two or three of the following parts; hormone analysis, semen analysis and/ or questionnaires regarding sexual function and well being. Semen sampling and cryopreservation was not performed in men with prostate cancer.

Changes in hormone levels, semen measurements and sexual function during follow-up were assessed, and compared between exposed and unexposed participants.

Study Design

• Study Type: Observational
• Actual Enrollment: 178 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Sexual Function and Wellbeing in Males Diagnosed With Rectal Cancer
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Preoperative RT Men 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. Testicular doses (TDs) was calculated from planning CT-scans and reported as mean cumulative testicular dose. Relative TD was calculated based in the assumption that RT regimens for rectal cancer are bioequivalent and referred to as proportion of prescribed dose absorbed by the testes.
No preoperative RT Men with rectal cancer or prostate cancer treated with surgery alone (no RT).

Outcome Measures

Primary Outcome Measures

1. Change in Serum Testosterone Levels Between Baseline and After Preoperative Radiotherapy. [Baseline and after RT/before surgery.]

   Fasting morning venous blood samples were collected at baseline, eg prior to oncological treatment. Men with rectal cancer treated with preoperative radiotherapy (RT) had a second blood sample taken afte RT and before surgery, collected the week before surgery and defined as "after RT/before surgery". Elapsed time between start of RT and the second blood sample was median 38 days, ranging from 3 to 195 days depending on the type of preoperative oncological treatment regimen. Testosterone (T) was analysed at the Department of Clinical Chemistry, Karolinska University Hospital, using commercial assays.

2. Change in Total Number of Sperms Per Ejaculate Between Baseline and Two Year Follow-up. [Baseline, 1 and 2 years after surgery.]

   Semen samples were collected at the Department of Reproductive Medicine of Karolinska University Hospital after 72h of sexual abstinence and analysed according to World Health Organization 2010 standard. Total number of sperms (million spermatozoa per ejaculate), was calculated by multiplying sperm concentration (million spermatozoa per millilitre semen) with semen volume (milliliter semen/ejaculate). Total number of sperms below 39 million per ejaculate was defined as oligospermia, and 0 million per ejaculate was defined as azoospermia. Semen samples were only collected in men with rectal cancer, not prostate cancer.

3. Sexual Function [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males diagnosed with rectal cancer stadium I-III, planned for surgery with or without preoperative radiotherapy or males with prostate cancer stadium I-III planned for robot-assisted prostatectomy without preoperative radiotherapy.

• Informed consent

• Fluent in Swedish

• Residents of the Stockholm county area

Exclusion Criteria:

• Rectal cancer stadium IV

• Previous radiotherapy to the pelvic region

• History or evidence of a second pelvic malignancy

• Androgen deprivation therapy, Testosterone replacement or Androgen abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ersta Hospital	Stockholm		Sweden
2	Karolinska University Hospital	Stockholm		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

• Buchli C, Al Abani M, Ahlberg M, Holm T, Fokstuen T, Bottai M, Frödin JE, Lax I, Martling A. Assessment of testicular dose during preoperative radiotherapy for rectal cancer. Acta Oncol. 2016;55(4):496-501. doi: 10.3109/0284186X.2015.1073349. Epub 2015 Sep 11.
• Buchli C, Tapper J, Bottai M, Holm T, Arver S, Blomqvist L, Martling A. Testosterone and body composition in men after treatment for rectal cancer. J Sex Med. 2015 Mar;12(3):774-82. doi: 10.1111/jsm.12751. Epub 2014 Nov 12.
• Tapper J, Arver S, Holm T, Bottai M, Machado M, Jasuja R, Martling A, Buchli C. Acute primary testicular failure due to radiotherapy increases risk of severe postoperative adverse events in rectal cancer patients. Eur J Surg Oncol. 2020 Jan;46(1):98-104. doi: 10.1016/j.ejso.2019.07.023. Epub 2019 Jul 19.

• Responsible Party: Anna Martling, Professor, Senior Consultant Surgeon, Karolinska Institutet
• ClinicalTrials.gov Identifier: NCT01216202
• Other Study ID Numbers: 2009/1860-31/2
• First Posted: Oct 7, 2010
• Last Update Posted: May 6, 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; Spermatogenesis
• Additional relevant MeSH terms: Rectal Neoplasms

Study Results

Participant Flow

Recruitment Details

Participants with rectal cancer stage I to III planned for rectal resection eligible for the study were enrolled at a tertiary (Karolinska University Hospital) and secondary hospital (Ersta Hospital) in Stockholm during April 2010 and May 2014. Of 372 men with rectal cancer assessed for eligibility, 115 were included in the study.

Pre-assignment Detail

18 months after start of inclusion, less than 10% of the participants were treated with surgery alone. To increase the sample size of the unexposed group (no preoperative radiotherapy), 63 men with prostate cancer I to III scheduled for robot assisted prostatectomy were included. Participants with prostate cancer were enrolled at the Urology department at Karolinska University Hospital between May 2012 and January 2013.

Arm/Group Title	Preoperative RT	No Preoperative RT
Arm/Group Description	Men with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Men with rectal cancer or prostate cancer treated with surgery alone (no RT).
Period Title: Overall Study
STARTED	101	77
Analysed at Baseline	93	75
Analysed After RT	79	0
COMPLETED	79	75
NOT COMPLETED	22	2

Baseline Characteristics

Arm/Group Title	Preoperative RT	No Preoperative RT	Total
Arm/Group Description	Men with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Men with rectal cancer or prostate cancer treated with surgery alone (no RT).	Total of all reporting groups
Overall Participants	93	75	168
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.3 (11.3)	63.3 (6.7)	61.6 (9.6)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	93 100%	75 100%	168 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.3 (4.1)	26.4 (3.0)	25.8 (3.7)
ASA score (Count of Participants)
I	21 22.6%	25 33.3%	46 27.4%
II	51 54.8%	41 54.7%	92 54.8%
III	21 22.6%	7 9.3%	28 16.7%
Missing data	0 0%	2 2.7%	2 1.2%
Preoperative RT (Count of Participants)
Short course RT (5x5 Gy)	68 73.1%	0 0%	68 40.5%
Long course RT (1.8x28 Gy)	25 26.9%	0 0%	25 14.9%
No RT	0 0%	75 100%	75 44.6%
Preoperative chemotherapy (Count of Participants)
Concomitant chemotherapy	23 24.7%	0 0%	23 13.7%
Full dose chemotherapy	11 11.8%	0 0%	11 6.5%
No chemotherapy	59 63.4%	75 100%	134 79.8%

Outcome Measures

1. Primary Outcome

Title	Change in Serum Testosterone Levels Between Baseline and After Preoperative Radiotherapy.
Description	Fasting morning venous blood samples were collected at baseline, eg prior to oncological treatment. Men with rectal cancer treated with preoperative radiotherapy (RT) had a second blood sample taken afte RT and before surgery, collected the week before surgery and defined as "after RT/before surgery". Elapsed time between start of RT and the second blood sample was median 38 days, ranging from 3 to 195 days depending on the type of preoperative oncological treatment regimen. Testosterone (T) was analysed at the Department of Clinical Chemistry, Karolinska University Hospital, using commercial assays.
Time Frame	Baseline and after RT/before surgery.

Outcome Measure Data

Analysis Population Description

For participants in "No preoperative RT", no blood samples were collected at the time point "after RT/before surgery".

Arm/Group Title	Preoperative RT	No Preoperative RT
Arm/Group Description	Men with rectal cancer treated with preoperative radiotherapy (RT) and surgery.	Men with rectal cancer or prostate cancer treated with surgery alone (no RT).
Measure Participants	93	75
Baseline	11.3 (3.4)	11.9 (4.0)
After RT/before surgery	9.3 (3.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preoperative RT, No Preoperative RT
	Comments	The association between change in serum testosterone levels and cumulative mean testicular radiation dose was assessed using longitudinal regression analysis (GEE). No preoperative RT contributed with baseline values.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments	The threshold for statistical significance was p = 0.05.
	Method	Regression, Linear
	Comments

2. Primary Outcome

Title	Change in Total Number of Sperms Per Ejaculate Between Baseline and Two Year Follow-up.
Description	Semen samples were collected at the Department of Reproductive Medicine of Karolinska University Hospital after 72h of sexual abstinence and analysed according to World Health Organization 2010 standard. Total number of sperms (million spermatozoa per ejaculate), was calculated by multiplying sperm concentration (million spermatozoa per millilitre semen) with semen volume (milliliter semen/ejaculate). Total number of sperms below 39 million per ejaculate was defined as oligospermia, and 0 million per ejaculate was defined as azoospermia. Semen samples were only collected in men with rectal cancer, not prostate cancer.
Time Frame	Baseline, 1 and 2 years after surgery.

Outcome Measure Data

Analysis Population Description

Of the 115 men with rectal cancer included in the study, 21 men left at least one semen sample during the study period and was included in the analysis. 20 of 21 men had RT. In total 40 semen samples was analysed. During follow-up three participants with RT dropped out of the study. Number analysed at each time points represents number of available semen samples at each time point; 19 of 21 at baseline, 9 of 18 1 year after surgery, 12 of 18 2 year after surgery.

Arm/Group Title	Preoperative RT	No Preoperative RT
Arm/Group Description	Men with rectal cancer treated with preoperative therapy (RT) and surgery with available semen samples.	Men with rectal cancer treated with surgery alone (no RT) with available semen samples.
Measure Participants	20	1
Measure Semen samples	39	1
Baseline	164.0
1 year after surgery	3.15	0.0
2 years after surgery	32.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preoperative RT
	Comments	The association between change in total number of sperms per ejaculate and relative mean testicular dose was assessed using longitudinal regression analysis (GEE).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments	The threshold for statistical significance was p=0.05.
	Method	Regression, Linear
	Comments	Model adjusted for time between preoperative radiotherapy (RT) and surgery.
Method of Estimation	Estimation Parameter	Estimated mean change
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -6.9 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Sexual Function
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Adverse events were not monitored.
Arm/Group Title	Preoperative RT		No Preoperative RT
Arm/Group Description	Men with rectal cancer treated with preoperative therapy (RT) and surgery.		Men with rectal cancer or prostate cancer treated with surgery alone (no RT).
All Cause Mortality
	Preoperative RT		No Preoperative RT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0%)		2/77 (2.6%)
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.