Rectal Cancer
Conditions
Keywords
Rectal cancer, Preoperative radiotherapy, Pelvic surgery, Sexual function, Wellbeing, Hormone levels, Spermatogenesis
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.
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.
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. 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.
Sponsors
Swedish Cancer Society
Karolinska Institutet
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Sexual Function | 2 years | — |
Countries
Sweden
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Preoperative RT Men with rectal cancer treated with preoperative radiotherapy (RT) and surgery. | 93 |
| No Preoperative RT Men with rectal cancer or prostate cancer treated with surgery alone (no RT). | 75 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
| Overall Study | Lost to Follow-up | 14 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 0 |
Baseline characteristics
| Characteristic | Total | Preoperative RT | No Preoperative RT |
|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 9.6 | 60.3 years STANDARD_DEVIATION 11.3 | 63.3 years STANDARD_DEVIATION 6.7 |
| ASA score I | 46 Participants | 21 Participants | 25 Participants |
| ASA score II | 92 Participants | 51 Participants | 41 Participants |
| ASA score III | 28 Participants | 21 Participants | 7 Participants |
| ASA score Missing data | 2 Participants | 0 Participants | 2 Participants |
| BMI | 25.8 kg/m^2 STANDARD_DEVIATION 3.7 | 25.3 kg/m^2 STANDARD_DEVIATION 4.1 | 26.4 kg/m^2 STANDARD_DEVIATION 3 |
| Preoperative chemotherapy Concomitant chemotherapy | 23 Participants | 23 Participants | 0 Participants |
| Preoperative chemotherapy Full dose chemotherapy | 11 Participants | 11 Participants | 0 Participants |
| Preoperative chemotherapy No chemotherapy | 134 Participants | 59 Participants | 75 Participants |
| Preoperative RT Long course RT (1.8x28 Gy) | 25 Participants | 25 Participants | 0 Participants |
| Preoperative RT No RT | 75 Participants | 0 Participants | 75 Participants |
| Preoperative RT Short course RT (5x5 Gy) | 68 Participants | 68 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 168 Participants | 93 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 2 / 77 |
| 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 After Preoperative Radiotherapy.
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.
Population: For participants in No preoperative RT, no blood samples were collected at the time point after RT/before surgery.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Preoperative RT | Change in Serum Testosterone Levels Between Baseline and After Preoperative Radiotherapy. | Baseline | 11.3 nmol/L | Standard Deviation 3.4 |
| Preoperative RT | Change in Serum Testosterone Levels Between Baseline and After Preoperative Radiotherapy. | After RT/before surgery | 9.3 nmol/L | Standard Deviation 3.5 |
| No Preoperative RT | Change in Serum Testosterone Levels Between Baseline and After Preoperative Radiotherapy. | Baseline | 11.9 nmol/L | Standard Deviation 4 |
Comparison: 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.p-value: 0.014Regression, Linear
Primary
Change in Total Number of Sperms Per Ejaculate Between Baseline and Two Year Follow-up.
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.
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Preoperative RT | Change in Total Number of Sperms Per Ejaculate Between Baseline and Two Year Follow-up. | 1 year after surgery | 3.15 million spermatozoa per ejaculate |
| Preoperative RT | Change in Total Number of Sperms Per Ejaculate Between Baseline and Two Year Follow-up. | 2 years after surgery | 32.6 million spermatozoa per ejaculate |
| Preoperative RT | Change in Total Number of Sperms Per Ejaculate Between Baseline and Two Year Follow-up. | Baseline | 164.0 million spermatozoa per ejaculate |
| No Preoperative RT | Change in Total Number of Sperms Per Ejaculate Between Baseline and Two Year Follow-up. | 1 year after surgery | 0.0 million spermatozoa per ejaculate |
Comparison: The association between change in total number of sperms per ejaculate and relative mean testicular dose was assessed using longitudinal regression analysis (GEE).p-value: 0.00895% CI: [-6.9, -1]Regression, Linear
Primary
Sexual Function
Time frame: 2 years