Comparison of the Therapeutic Efficacy and Patient Satisfaction of Three Techniques of Bilateral Orchidectomy in Prostate Cancer Patients of a Nigerian Sub-population (TEPSO)
Phase: NA
Conditions: Prostate Cancer, Quality of Life, Orchiectomy
Sponsor: University College Hospital, Ibadan

 
 
 
Title: 
Comparison of the Therapeutic Efficacy and Patient 
Satisfaction of Three Techniques of Bilateral Orchidectomy in 
Prostate Cancer Patients of a Nigerian Sub-population 
(TEPSO) 
 
NCT No:  Not yet assigned 
 
Date:  
30th of July, 2018 
 
 

Study location and population 
The study was conducted among patients of the Urology Division of the University College 
Hospital, Ibadan with locally advanced and metastatic PCa. 
 
Study design 
It was a randomized experimental study. Ethical approval for the study was obtained from the 
UI/UCH Ethical Committee.  
 
Sample size calculation 
The minimum sample size in each group was calculated using the formula shown below 116, 
117: 
n = 2 [(a + b)2s2] 
 
(μ1 − μ2) 
where, 
n = the sample size in each group 
μ1 = population mean in treatment Group 1 
μ2 = population mean in treatment Group 2 
μ1 − μ2 = the difference the investigator wishes to detect = 10% 
s = standard deviation (SD) = 9.711 
a = conventional multiplier for alpha = 0.05 
   = 1.96  
b = conventional multiplier for power = 0.80 
  = 0.842  
n = 2[(1.96+ 0.842)2 9.72] 
 
102 
n = 14.7 
n is approximately 15 per group 
 

To account for 10% attrition,  
n = 15/ 0.9 
  = 17 per group 
Thus, the total minimum sample size for entire sampled population was 51. 
 
Subject recruitment and sampling  
Proficiency in the prosthetic techniques was gained from March 2015. Recruitment was 
between March 2016 and November 2017. The three-month post-operative assessment ended 
in March, 2018. The study spanned 23 months. Informed consent was obtained from the 
patients by the researcher or another medical doctor. 
Inclusion criteria 
 Consecutive consenting patients with histologically confirmed locally advanced or 
metastatic PCa who have accepted to have an orchidectomy  
 
Exclusion criteria were: 
 Patients who have had bilateral orchidectomy 
 Those who opted for medical castration 
 Non-consent  
 
The patients were randomized into three groups by ballotting: Bilateral simple orchidectomy,  
BSO; Bilateral subcapsular orchidectomy, BSCO; and Bilateral epididymal – sparing 
orchidectomy, BESO. The ballot was done by an observer in the theatre suite. The patient was 
blinded to the surgical procedure undertaken. A research bag with a total of fifty one labelled 
choices, comprising 17 labels each for BSO, BSCO and BESO was prepared. These ballots 
were exhausted and refilled for extension of the sample size. 
 
 

Study protocol 
Preoperative component 
 Informed consent was obtained 
 Socio-demographic data and information on the patient’s symptoms, performance score 
and co-morbidities was obtained using a proforma, Fugl Meyer Questionnaire (FMQ) 
and the Expanded Prostate Cancer Index Composite (EPIC) 2.2002 demographic 
questionnaire 
 The preoperative testicular volume was estimated with a Prader orchidometer  
 Pre- operative blood samples were taken for PSA and testosterone  
 The FMQ and the EPIC-26 were administered  
 
Perioperative component 
 A preoperative antibiotic was administered 112  
 The scrotal skin was prepared and isolated with sterile drapes.  
 0.5% lignocaine with adrenaline was used to infiltrate the median raphe, the 
proposed incision site, and block the spermatic cord. Some patients required 
sedation with a combination of Pentazocine, an opioid, and Diazepam, a 
barbiturate. 
 Samples for serum testosterone and PSA were taken at 0 hour (immediately 
after removing both testes or testicular parenchyma), 1, 2 and 3 hours post-
operatively.  
 
 

The surgical technique  
A median raphe scrotal incision was made and deepened to expose the TV on one side. The 
testis, with the TV covering it, was delivered into the wound. The TV was incised and retracted 
proximally over the testis, epididymis and cord structures via pledget dissection.112,122 
Subsequent steps depended on the castration technique employed.     
 
Simple orchidectomy 
The spermatic vessels were isolated from the vas deferens, double clamped proximally, 
singularly clamped distally, and divided. A free tie was applied proximal to the 
proximal clamp and suture ligation done distal to that, using 1 vicryl. The vas deferens 
was clamped and ligated separately with 2/0 vicryl. 112,122 Haemostasis was ensured. 
 
 
Subcapsular orchidectomy 
The TA was incised longitudinally and its edges held with haemostats. Haemostasis 
was secured. The testicular parenchyma was scraped off the TA by pledget dissection 
moving towards the hilus, was secured with 3/0 vicryl. Water-tight closure of the TA 
ensued with continuous sutures using 2/0 vicryl.11,112,122 
Epididymal – sparing orchidectomy  
A vasectomy was done and the vas ligated with 2/0 vicryl. The plane between the 
epididymis and the testis was developed 122 The caudal, middle and superior epididymal 
vessels as well as the spermatic artery to the testis were clamped and ligated with 3/0 
vicryl.112 The testis was then excised. The epididymis was folded on itself to create a 
pseudotesticle and a continuous suture with 3/0 vicryl used to complete the 
epididymoplasty.34 
 

The dartos muscle layer was closed with a continuous suture using 3/0 vicryl. The procedure 
was repeated on the contralateral side. Subcuticular skin closure was done with 3/0 vicryl. Firm 
scrotal dressing with scrotal support was applied.112,122 
 
Postoperative component 
 Day 3 
o Wound review 
o Further reviews were dictated by the state of the wound at initial review 
 Day 7  
o Samples for serum testosterone and PSA would be taken  
 Three months post-operatively 
o The QoL would be assessed with the FMQ and EPIC-26  
o Each patient would assess their scrotal appearance with a graduated VAS, on a 
scale from 0 – 100 % satisfaction 118 
o Prader orchidometric pseudotesticular volume estimation was done for all 
patients in the BSCO and BESO groups 
 
 Technique of serum assay  
Enzyme-linked Immunosorbent Assay (ELISA) was used for the quantitative determination of 
serum testosterone levels. Two millilitres of blood was collected, centrifuged and the serum 
(supernatant) decanted off. This was the test sample. It was stored at -80oC. This process was 
carried out by a laboratory scientist and myself. Further processing would be done by another 
more specialized medical laboratory scientist and myself.  
3.5.5.1 Serum testosterone assay 
Enzyme immunoassay Bio-Inteco test kit (Inteco, Beechwood, Egland, QC16-885) was used. 
Ten microliter of controls, standards and samples were places on the wells. 50µl of anti-

testosterone antibodies and 100µl of conjugate reagent were added.  This was incubated at 370C 
for 90 minutes. A wash buffer was diluted at a ratio of 50 to 1, and used to rinse the wells to 
remove any unbound material. A resultant blue colour change was observed, the intensity of 
which was inversely proportional to the testosterone concentration in the antibody-
testosterone-conjugate complex. 100µl of substrate was then added. It was incubated for 
another twenty minutes. A stop solution (Hydrochloric acid) was added to terminate the 
reaction. The colour change was measured in terms of absorbance using a microtitre plate 
reader. Reliability of test results was increased by running controls with each batch of samples, 
use of distilled water to rinse the unbound materials off, avoiding bubbles in the microwells 
and using reagents at room temperature.123 
The optical density of the absorbance was converted to serum testosterone in mg/dl by using 
the using calibration curves. The values obtained were multiplied by 28.85 to convert to nmol/l.  
 
3.5.5.2 Serum PSA assay 
An Enzyme Immunoassay test kit for total PSA (Rapid Labs, Essex, United Kingdom, LOT: 
1701020, B031568-01) was used. Twenty microliters of controls and samples, and 100µl of 
anti-PSA peroxidase conjugate were inserted in the microwells. This was agitated gently. The 
microwell was covered by a plate sealer and incubated for 30 minutes at 300C. A buffer was h 
solution was diluted 1:25, and used to rinse the microwells, which were dried. To each 
microwell was added 50µl of two substrates, with a colour change. It was agitated gently, 
covered, and incubated for 15 minutes longer. Sulphuric acid (50 µl) was added as a stop 
solution. The optical density of the microwells was obtained using a plate reader at 450nm. 
Calibration curves were used to calculate the PSA concentration in ng/ml. 
 
 

Data analysis 
Data analysis was with the Statistical Package for Social Sciences Version 20 (SPSS 20) and 
STATA version 12. Measures of central tendency and dispersion were used to analyse the 
quantitative parameters. The qualitative parameters were ranked. Variation in serum 
testosterone and PSA, sociodemographic and technical parameters, pre- and post-operative 
testicular volumes, cosmetic appeal and HRQoL parameters were compared between the three 
groups and analysed using univariate (ANOVA) and multivariate analyses, student t-test for 
the continuous and Wilcoxon rank-sum test for the non-parametric measures. A repeated 
measures ANOVA with Greenhouse-Geisser correction was modeled for the average log 
testosterone and PSA concentration declines. A Post-hoc test, the least significant difference 
(LSD) was applied to the curves. Kaplan-Meier analyses of the PSA and testosterone kinetics 
and patient survival were plotted. The level of statistical significance, p, used was ≤ 0.05. The 
groups were dichotomised into those with and without prostheses, and the associations re-
evaluated.  
 
3.7 Ethical Considerations 
This study was conducted in compliance with the guidelines of the Nigerian Code of Health 
Research Ethics.  
Costs to participants: Participation in the study did not increase the financial cost of care for 
the participants. The serum testosterone and PSA estimations were funded by the lead 
researcher. The patients funded the surgery. There was no increase in the frequency of hospital 
visits because of the study as the routine scheduled visits for all patients who have had 
orchidectomies as per our unit protocol was adhered to.  
Benefits: The participants did not have to pay for the routine pre- and post-operative serum 
testosterone or PSA assessments. Participants may benefit from the aesthetic outcome of the 
technique used, however, this would be determined by the results of the study. Information 

obtained from the study would be beneficial to future patients with prostate cancer. Medical 
personnel would be able to objectively state which type of orchidectomy gives the most patient 
satisfaction and what the levels of efficacy are.  
Confidentiality: All information collected was de-identified with code numbers which cannot 
be linked to the participants in anyway.  
Voluntariness: The patients’ participation in this research was entirely voluntary. The 
participants were informed that they could withdraw from the research at any time. No undue 
coercion or incentives were used. Non-consent did not jeopardise patient care. 
Non-maleficence to participants: There was minimal undue harm to be borne by the patient 
for participating in this study. It was explained that orchidectomy, irrespective of the technique, 
may be complicated by wound infection, haematoma, seroma, wound dehiscence, operative 
site pain, breast pain, breast swelling, hot flashes and loss of sexual drive. The entire blood 
sample required for the study amounted to a volume of 32 ml over a three month period. This 
did not cause undue harm. The participants were informed that some of the questions asked 
required introspection and may broach sensitive topics. 
Compensation: There was no monetary compensation for participating in this research. 
However, the burden of your perioperative serum testosterone investigations which are 
routinely done would be borne by the primary investigator.  
Translation of protocol to the local language: The informed consent and questionnaires were 
translated to Yoruba, the indigenous language of Ibadan. 
 
 

CONSENT FORM 
IRB Research approval number: UI/EC/15/01/2008a  
Title of research: Comparison of the therapeutic efficacy and patient satisfaction of three 
techniques of bilateral orchidectomy in prostate cancer patients of a Nigerian sub - population 
Name and affiliation of researcher: Dr I. N. Chibuzo of the University College Hospital, 
Ibadan is the primary investigator, supervised by Professor Linus I. Okeke and Dr Augustine 
O. Takure. This project would be done in part fulfilment of Part II dissertation for the National 
Postgraduate Medical Council of Nigeria. 
Sponsor of research: The study is self-sponsored.  
Purpose of research: The purpose of this research is to compare the therapeutic efficacy of 
bilateral total orchidectomy with endogenous testicular prosthetic techniques of subcapsular 
and epididymal – sparing orchidectomy and to determine which technique is associated with a 
higher level of patient desirability.  
Procedure of the research: You are being asked to participate in this study because you have 
locally advanced or metastatic prostate cancer and have consented to an orchidectomy under 
local anaesthesia. If you agree to participate in the study, the following will be required of you: 
1. One of our members of staff will ask you about yourself, your work, your lifestyle, your 
health condition, your symptoms, especially those related to urinary, bowel and sexual 
function. We will obtain information of the treatments that you are receiving or have received 
and how these treatments have affected your bodily function and/ or lifestyle. The information 
would be recorded in a form called a questionnaire.   
2. 2 ml blood samples would be taken each for serum testosterone and Prostate specific antigen 
(PSA) before the surgery.  You would be selected to have one of three types of orchidectomy: 
either a bilateral total orchidectomy, in which both testes are removed or a subcapsular 
orchidectomy that removes the tissue within the testes and leaves the covering or an 

epididymal – sparing orchidectomy that removes the testis but leaves the epididymis behind. 
The volume of your testis would be measured before surgery using a meter designed for this 
purpose. At surgery, four 2 – ml samples would be required: at orchidectomy (0 hour), then at 
1, 2 and 3 hours after the surgery for serum testosterone estimation. Another would be required 
seven days after the surgery for serum testosterone estimation. Three months following the 
surgery, serum PSA would be assessed again via a 2 – ml sample of blood.  
3. At this visit, you will be asked to tell us how satisfied you are with the surgery and the 
appearance of your scrotum. Measurements of the post – operative prosthetic volume for those 
concerned would be taken. Another doctor would also assess the appearance of the scrotum at 
this visit. 
4. A questionnaire on your symptoms as well as urinary, bowel and sexual function would be 
administered at this visit. 
This marks the end of your participation in the study. 
Expected duration of study and participants’ involvement in the research:  The duration 
of this study will be 12 months during which we expect to enroll at least 24 patients. However, 
your active participation in this study will be over a three month period. We may call to remind 
you of your appointments. 
Risks: There is minimal undue harm to be borne by you for participating in this study. 
Orchidectomy, irrespective of the technique, may be complicated by wound infection, 
haematoma, seroma, wound dehiscence, operative site pain, breast pain, breast swelling, hot 
flashes and loss of sexual drive. The entire blood sample required for the study amounts to a 
volume of 16 ml over a three month period. This would not cause undue harm. 
Costs to participants: Your participation in this research will not cost you anything other than 
your time as mentioned above. There would be no increase in the frequency of hospital visits 

because of the study. We shall adhere to the routine scheduled visits for all patients who have 
had orchidectomies as per our unit protocol. 
Benefits: Your participation in this study may not be of direct benefit to you, however, 
information obtained would be beneficial to other patients with prostate cancer in future. 
Medical personnel would be able to objectively state which type of orchidectomy had the most 
patient satisfaction and what the levels of efficacy are. 
Confidentiality: The data collected in this study will be used for the purpose stated above. All 
information collected will be de - identified with code numbers which cannot be linked to you 
in anyway. Reports or publications from this study would not bear your name or any form of 
identification traceable to you. Information may be obtained from your medical records only 
for the purpose of the study. To ensure this study is conducted properly, representatives of the 
UI/UCH HREC and National Postgraduate Medical Council of Nigeria may have access to 
these records.  
Voluntariness: Your participation in this research is entirely voluntary. If you choose not to 
participate, this will not affect your treatment in this hospital in any way. You can also choose 
to withdraw from the research at any time.  
Compensation: You will not be paid any fees for participating in this research. However, the 
burden of your peri – operative serum PSA and testosterone investigations which are routinely 
done would be borne by the primary investigator.  
Statement of person obtaining informed consent: 
I have fully explained this research to ____________________________________ and have 
given sufficient information, including about risks and benefits, to make an informed decision. 
DATE: _____________________ SIGNATURE: _______________________________ 
NAME: ______________________________________________ 

Statement of person giving consent: 
I have read the description of the research or have had it translated into language I understand. 
I have also talked it over with the doctor to my satisfaction. I understand that my participation 
is voluntary. I know enough about the purpose, methods, risks and benefits of the research 
study to judge that I want to take part in it. I understand that I may freely stop being part of this 
study at any time. I have received a copy of this consent form and additional information sheet 
to keep for myself. 
DATE: ___________________ SIGNATURE: _________________________________ 
NAME: _____________________________________________ 
WITNESS’ SIGNATURE (if applicable): ___________________________ 
WITNESS’ NAME (if applicable): ______________________________________ 
 
Detailed contact information including contact address, telephone, e-mail and any other 
contact information of researcher(s) and the institutional HREC:  
This research has been approved by the Health Research Ethics Committee of the University of Ibadan 
and the Chairman of this Committee can be contacted at Biode Building, Room T10, 2nd Floor, 
Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, 
Telephone: 08032397993,  E-mail: uiuchirc@yahoo.com. In addition, if you have any question about 
your participation in this research, you can contact the principal investigator, Dr Chibuzo at the 
Department of Surgery, University College Hospital, Ibadan. The contact phone number is 
08065819167.  
 
PLEASE KEEP A COPY OF THE SIGNED INFORMED CONSENT