Health Status, Quality of Life and Function in Survivors After Radical Treatment for Prostate Cancer. A Cross-sectional Study Focusing on Older Survivors. Part I and IIA
Conditions: Prostate Cancer
Sponsor: Sykehuset Innlandet HF

 
 
 1 
 
 
Title 
Older prostate cancer survivors: health status, quality of life 
and function after radical treatment.  
 
Protocol ID 150410; NCT04863352 
Protocol ID 150410-IIB; NCT05200039 
Protocol dated: September 22, 2020 
Amendment dated: January 5, 2023 
 
 

 
 
 2 
 
Full title: Older Prostate cancer Survivors (OPS): health status, 
quality of life and function after radical treatment  
Short title: The OPS study 
 
The study emerges from Innlandet Hospital Trust and is conducted in co-operation with the 
Norwegian University of Science and Technology (NTNU).  
The study is cross-sectional and has three parts, part I, part IIA and part IIB. Part I and IIA is 
registered jointly at ClinicalTrials.gov as NCT04863352, whereas part IIB has a separate ID: 
NCT05200039 
This protocol covers the overarching design of all parts. 
 
Funding  
The study is made possible by Innlandet Hospital Trust (grant number 150410).  
 
 
 

 
 
 3 
 
Older prostate cancer survivors: health status, quality of life and function after 
radical treatment.  
Introduction 
In this study, addressing older prostate cancer survivors, i.e. men who received potentially curative 
(radical) treatment two to six years ago at the age of > 70 years, we will investigate if older age at 
time of treatment is a detrimental factor with respect to long-term quality of life (Qol), health, and 
function. We will also compare QoL, health and function between the older survivors and matched 
population based cohorts, and thereby provide realistic information on the long-term impact of 
radical prostate cancer treatment in older age. As cancer specific survival after such treatment is 
good,1 evidence for the outcomes addressed in this study, is of major importance to guide treatment 
decisions for older men with prostate cancer, who reportedly are undertreated.2,3 
Background: Prostate cancer is the most common cancer among Norwegian men with about 5000 
new cases each year. Median age at diagnosis is 70 years, and in 2018, 1330 (27%) new cases were 
diagnosed in men who were 75 years or older.1 This implies that at least half of those diagnosed 
with prostate cancer are “older”. There is no definite age limit to define this term, but aging is 
inevitable followed by a gradual reduction of functional reserves, and comorbidities and geriatric 
syndromes become more prevalent.4 Thus, compared to their younger counterparts, men >70 years 
with prostate cancer are in general more vulnerable, and more susceptible to adverse treatment 
effects including functional decline.5  
By the time of diagnosis, about 65-70% of men with prostate cancer will have local or locally 
advanced disease.1 In this situation, the overall 10-year cancer specific survival is good (>90%), but 
varies with risk group (low, intermediate and high risk) decided according to histological 
aggressiveness, extent of local tumor growth, and prostate specific antigen (PSA) level.1 Curative 
treatment options are radical surgery or radiotherapy (RT) with active surveillance as an alternative. 
The latter aims to avoid unnecessary treatment in men not needing immediate treatment, and to 
achieve correct timing for curative intervention in those who eventually do.6 There is no definitive 
evidence of either radical surgery or RT being superior to the other,7,8 but RT tends to be most 
frequently used in the older population. About 27-53% of men will have a biochemical recurrence 
(increasing PSA only),6,9 but only a minority (10-20%) will develop metastases within 10 years.7,9,10 
Survival benefits are mainly detectable after 10 years and/or in patients with intermediate/high risk 
cancer.9-11 Thus, men with shorter life expectancy and/or low risk disease, may be managed with a 
conservative observational approach.12   
Radical surgery, removing the overall prostatic gland, is performed by open-, laparoscopic- or 
robot-assisted (RARP) surgery. Presently, RARP using the da Vinci Surgical System (2002) is the 
preferred minimal-invasive approach.6 In Norway, radical RT is usually delivered as external 
photon beam RT, aiming at a high dose to the cancer site while sparing normal tissue. To increase 
precision, techniques have evolved from 3-dimensional (3-D) conformal techniques to intensity-
modulated RT (IMRT).6 Conventional dose is 74-80 gray (Gy) in 2 Gy fractions, 5 days/week. 
More recently, schedules of fewer fractions and higher fraction-doses have been introduced for 
selected patients.6  For intermediate and high risk disease, external RT is combined with anti-
androgen therapy for 4-6 months and 2-3 years, respectively.6 External RT to the “prostate bed” is 
used for patients with persistent or increasing PSA after radical surgery (salvage RT)  
Both radical surgery and RT are frequently followed by late adverse effects (occurring or persisting 
≥ 12 months after therapy) that may have a severe and long lasting impact on men’s daily life and 
well-being.13-16 These effects can either be local, i.e. functional disturbances and symptoms from 
organs close to the prostate gland,8,14,15 or general, i.e. affecting physical function and overall 
QoL.17 Local effects tend to differ between treatment modalities. Urinary incontinence and erectile 
dysfunction are more prevalent after surgery, whereas bowel symptoms more often occur after 
RT.8,14,15 For general aspects such as global QoL, physical and mental health, no difference has 

 
 
 4 
 
been found.13,14 Androgen therapy, frequently added to RT, may, however, negatively affect overall 
health and contribute to treatment related morbidity.18 
Decisions to offer radical treatment for localized/locally advanced prostate cancer are based on 
tumor- and patient characteristics, and patients’ preferences, and require an evaluation of potential 
adverse effects against benefits in terms of cancer control and survival. With older age, more men 
have high risk cancer and suffer from cancer-related symptoms.3,19  Despite this, increasing age 
seems to be the major determinant for omitting curative treatment.2,19,20 Older men are also 
underrepresented in clinical studies, 9-11  and studies specifically addressing older men are scarce.21 
Consequently, knowledge on the long-term outcomes in older prostate cancer survivors is limited. 
There is some evidence that older men may tolerate and benefit from curative treatment as well as 
their younger counterparts, but other reports indicate that adverse effects are more common.3,21,22 A 
recent review on patient reported symptoms and QoL following radical treatment, concluded that 
the studies were of insufficient quality “to permit precise guidance to men about the risks to these 
aspects of their lives.”23  Furthermore, few studies evaluated general QoL aspects, physical function 
included, and the majority targeted men aged 56-70 years.23  
 
Needs description 
To select the best treatment for individual patients, actively involving them in decision-making, and 
providing health care that sustains their overall health, sound evidence on long-term health, function 
and QoL following cancer treatment is a pre-requisite. This is particularly important for older men 
with localized/locally advanced prostate cancer since ten years cancer specific survival is high, and 
maintenance of QoL, function and independence are highly prioritized outcomes.24 However, for 
this large group of men with prostate cancer, information on these crucial outcomes is largely 
missing. This may substantially hamper treatment decisions and shared decision-making, and lead 
to suboptimal treatment caused by unfounded fear of adverse effects in a vulnerable population. 
The present study will fill the existing knowledge gaps. We will provide evidence whether older age 
at time of treatment has a negative impact on prostate cancer survivors’ health, function, and QoL. 
More importantly, through cooperation with The Trøndelag Health Survey 4 (HUNT4)25 and the 
corresponding sub-survey including adults ≥ 70 years (HUNT4 70+), we have a unique opportunity 
to evaluate how prostate cancer survivors may differ from the general male population of the same 
age. Health conditions may rapidly change after the age of 70, and local late effects of prostate 
cancer treatment, i.e. urinary incontinence, erectile dysfunction and bowel problems, are frequent in 
older men without prostate cancer. Hence, comparison to population-based data is crucial. 
To capture the patients’ voice, we will use well-validated patient reported outcome measures 
(PROMs) to assess the older prostate cancer survivor’s potential problems and needs. Additionally, 
we will assess physical performance, physical- and sedentary activity using established tests and 
electronic devices and compare the results to identical assessments in the general male population 
of the same age. To the best of our knowledge, no such comparison has formerly been performed. 
Our study will provide new evidence of the late effects of modern radical treatment in older prostate 
cancer survivors and may thereby contribute to reduce current risks of unfounded under-treatment. 
The study will increase the knowledge base needed for patients to choose treatment according to 
their preferences, and provide a new, excellent basis for subsequent development of supportive 
rehabilitation measures that may minimize potentially negative impacts of radical treatment.  
Aims and objective 
The overarching aim is to investigate the long-term impact of radical treatment on older (>70 years 
by the time of treatment) prostate cancer survivors’ QoL, health, physical function and activity with 
comparisons to their younger counterparts and a general male population of the same age.  
The objectives for the present PhD project are to investigate: 

 
 
 5 
 
1. if older age at the time of radical treatment has a negative impact on self-reported QoL, 
function and local late treatment effects in prostate cancer survivors  
2. if health status, health problems and use of health care services in older prostate cancer 
survivors differ from a general male population of the same age 
3. if objectively assessed physical performance, physical and sedentary activity in older 
prostate cancer survivors differ from a general male population of the same age 
Additional/secondary objectives: focusing on older prostate cancer survivors: a) investigate how 
objectively assessed physical performance is associated with self-reported health, QoL, and 
physical function; b) investigate how local late effects may influence self-reported health, QoL and 
physical function; c) describe the course of local effects of surgery (from pre-surgery and onward) 
by joining data from the present study with data from the existing quality database at the Urological 
Surgery Unit (USU), Hamar Hospital, SI.26  
The pre-defined secondary objectives are subjects for additional research based on the data 
collected through the present project. Thus, these objectives are not further addressed in this 
protocol. 
Project methodology 
The project emerges from Innlandet Hospital Trust (SI) and will be conducted in close co-operation 
with researchers from the HUNT4 study. Two centers will contribute to participant enrolment: the 
Radiotherapy Unit (RTU), Gjøvik Hospital, and the USU, Hamar Hospital. Jointly they serve all 
patients with localized/locally advanced prostate cancer in Innlandet, annually about 280 patients. 
About 40% are ≥70 years, 2/3 undergo radical surgery, and 1/3 receive RT. Our target group are 
patients treated with radical RT or RARP from 2014 to 2018.   
Both the RTU and USU have complete, easily accessible registries of their patients.26  Since 2014, 
the RTU has provided radical RT using modern, high dose RT in accordance with official 
guidelines.6 From 2014 to 2016, RT was given as 3-D conformal external RT, thereafter IMRT 
techniques have been used. RARP using the da Vinci Surgical System® has been the only approach 
for radical surgery at the USU. 
The project is designed as two cross-sectional studies with matched control groups drawn from the 
HUNT4 and HUNT4 70+ surveys. Figure 1 below gives an overview  
Received RARP at SI
2014 – 2018
Living in Innlandet
Received RT at SI 
2014 – 2018
Living in Innlandet
Study I. Cross-sectional survey, all 
survivors
PROMs covering health status, QoL, 
physical activity, late adverse effects
Study II. Expanded cross-sectional
survey of older survivors: 
a) PROMs: detailed health problems 
and needs
HUNT4 data
HUNT4 70+ data
Figure 1: Overview – study design
Older:  >= 70 years by the time of RARP or RT
RARP:   robot assisted radical prostatectomy
RT:        radiotherapy
PROM: patient reported outcome measure
HUNT:  Trøndelag Health Study
Primary objective 1:
The impact of older age at the
time of RARP or RT
Primary objective 2:
Comparison of older survivors vs
older controls
b) performance tests, registrations
of physical and sedentary activity
Primary objective 3:
Comparisons older survivors vs
older controls
Prostate cancer survivors
Matched population
based control groups
 

 
 
 6 
 
Study I: PROMs survey targeting all patients from Innlandet having received radical treatment for 
localized/locally advanced prostate cancer at SI from 2014 to 2018 (Study I)  
Study II: targeting older participants from Study I who were >70 years at time of treatment: 
expanded PROMs survey (Study IIa), performance tests and activity registrations (Study IIb). 
For Study I, we will use validated PROMs to retrieve information on several aspects of prostate 
cancer survivors’ QoL and health, including local late treatment effects, and investigate the 
association between older age and these outcomes, taking relevant confounders into account (e.g. 
treatment modality, cancer status, civil status, education, comorbidity) (Objective 1). Study I will 
also include PROMs used in HUNT4 to allow for comparison to matched population-based controls 
(Objective 2). For a broader evaluation of older prostate cancer survivors, Study II will include an 
additional set of PROMs which was used in HUNT4 70+ (Study IIa), and objective physical 
performance tests and activity registrations performed in a randomly drawn sub-group (Study IIb). 
Data will be compared to matched control groups from the HUNT4 70+ survey, which has 
performed identical assessments (Objective 2 and 3). All PROMs (Study I and II) will be 
administered as questionnaires to be filled in by the patients. 
The data collection is broad and will provide basis for more than one PhD project (see secondary 
objectives). However, being cross-sectional collections of PROMs, neither Study I, nor Study IIa 
are time- or resource consuming. Based on former experience, we expect compliance to be good. 
Study IIb is the main challenge, but we have performed similar tests in other cohorts, and with the 
established co-operation with HUNT4/HUNT4 70+, we expect the tests to be successfully 
performed provided that funding for a project nurse is granted from SI as applied for.  
 
Project arrangements, method selection and analyses 
Subjects  
Main eligibility criteria  
Study I: 
 received radical RT or RARP at SI between 01.01.2014 and 31.12.2018 
 alive and living in Innlandet County 
 fluent in Norwegian (orally and in writing) 
 written informed consent 
Study IIa) the subgroup of participants in Study I who were > 70 years by the time of treatment.  
Study IIb) a random sub-sample from Study IIb, excluding survivors with clinically significant 
relapse (verified metastases/local progression and/or start of lifelong antiandrogen therapy) 
Clinically significant cancer relapse, occurring in approximately 10-20%, may affect all outcomes. 
Reliable information on this aspect cannot be retrieved before consent to participation, and as 
outcomes for the overall cohorts are of interest, all eligible and consenting survivors will be 
enrolled, and recurrence taken into account in the analyses. The exception is the subsample drawn 
for performance tests in Study II b (as explained above). 
Control groups: For comparison with a general population, a control group of males matched on 
age and education will be drawn from the HUNT4/HUNT4 70+ surveys performed in 2017-2019, 
targeting all inhabitants and inhabitants >70 years in Trøndelag County, respectively.25 Jointly these 
surveys include broad health assessments using questionnaires, physical examinations and tests.  
 
Outcomes (overview Table 1, page 7) 
Predefined primary outcomes are: 
 Global QoL as measured by the European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire-C30 (QLQ-C30) (Objective 1: assessing the impact of age).27  

 
 
 7 
 
 Overall health - self-reported, item one from HUNT428(Objective 2: assessing differences 
between older prostate cancer survivors and matched controls). 
 Short Physical Performance Battery (SPPB) score (Objective 3, physical performance in older 
prostate cancer survivors vs controls).29 
The QLQ-C30 is a widely used and validated 30-item questionnaire designed for cancer patients. 
National and international norm data from general populations are available.30 In addition to global 
QoL, the QLQ-C30 comprises physical function (PF), emotional-, role- and cognitive function, and 
nine symptoms that are frequent in patients with cancer.27  
The SPPB tests balance and mobility, and is a validated screening tool for physical performance in 
older people.29  
Table 1: Overview over pre-defined primary and secondary outcome measures: 
  
Predefined secondary outcomes are:  
 Physical function (PF) (measured by the QLQ-C30) (objective 1).  
 Local late effects (measured with the Expanded Prostate Composite Instrument for Clinical 
Practice (EPIC-CP) (objective 1) 
 Activities of daily living (as in HUNT4 70+)31 (objective 2) 
 Objectively measured physical and sedentary activity (accelerometer counts from seven 
consecutive days), handgrip strength, and one-legged balance (objective 3). 
Expanded Prostate Cancer Index Composite for Clinical Practice, EPIC-CP is a 16-item, widely 
used questionnaire designed for prostate cancer patients, comprising items on urinary, bowel and 
sexual disturbances.32 It is currently in routine use in the quality database at USU, Hamar.26  
Objective registrations of physical- and sedentary activity will be performed using the 
accelerometer Axivity AX3, which assesses time spent sitting, lying, standing, walking, running 
etc. Participants will wear two devices on all waking hours for seven days, one attached to their hip 
and one to their back. The registrations will be transferred to a designated software for analysis. 
 
Other assessments  
These data will be used for description, for adjustment in outcome analyses and/or for comparison 
to corresponding data on the matched control groups from HUNT4/HUNT4 70+. 
Study I: Patient reported: major demographics including social status and education, cancer 
status, emotional-, role and cognitive function and common symptoms (QLQ-C30) and daily life, 
comorbidity, medications, use of health care services and physical activity (as in HUNT4). From 
medical records: comorbidity and prostate cancer details (e.g. risk group, RT regimen, treatment 
for relapse if present)  
Study II a): health problems (including problems gastrointestinal/urinary tract, sexuality and 
urinary leakage, fatigue, falls) and use of health care services (patient reported as in HUNT4 70+).  
Study I 
(all participants)
Study II Expanded assessment
(older participants > 70 years by the time of treatment) 
PROMs
PROMs (all older participants)
Global QoL (subscale QLQ-C30)1
Activities of daily living (as in HUNT4 70+)
Local late effects (EPIC-score) 2
Tests (subgroup of older participants) (as in HUNT4 70+)
Overall health status (as in HUNT4)
SPPB3 – physical performance including mobility and balance
Self-report physical function (sub-scale
Hand grip strength using the Jamar digital hand dynamometer
QLQ-C30)
One legged balance test (Flamingo test)
Physical activity and sedentary activity, objectively measure by 
counts/readings from 7 days wearing accelerometer AxivityAX3. 
1 QLQ-C30 – European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30
2 Expanded Prostate Cancer Index Composite Instrument for Clinical Practice (EPIC-CP); 3 Short physical 
performance battery

 
 
 8 
 
Study IIb): test of cognitive function using the Montreal Cognitive Assessment (MoCA).33  
 
Study conduct 
Eligible subjects will be identified through the RT registry at the RTU, Gjøvik, and the quality 
database at the USU, Hamar,26 respectively. Each unit will contact their former patients to ask for 
consent to participation. Study information (Study I and II), consent form (consent to both studies 
for older participant) and questionnaire for Study I will be administered by post. Consenting 
participant will be asked to mail the signed consent form and the completed questionnaire to the 
research center using pre-paid envelops. If no reply is received, one reminder will be mailed. 
Subsequently, consenting older participants will receive the questionnaires for Study II, and a 
random sub-sample of this group will be invited to performance tests and activity registration. 
Testing will take place at present and former SI locations, and will be arranged for groups of about 
12 at the time. Each participant’s tests will take about 30-45 min. The PhD student and a project 
nurse will perform the testing, instruct the participants how to wear the accelerometers, and to 
return the devices in a pre-paid envelope. Consenting participants, unable to meet at the arranged 
occasions, will be tested locally/at home by community cancer nurses/physiotherapists trained 
through other studies by our group.  
 
Strategy for analyses and sample size 
Available and expected number of participants: About 400 men with prostate cancer received 
curative RT at SI from 2014 to 2018, about 250 of these were older (≥70 years) by time of 
treatment. In the same period about 1000 men underwent RARP, about 1/3 (330) being older. Thus, 
our target population includes about 1400 men of all ages, and about 580 older men. Estimating a 
response rate of 60%, our overall sample will include about 840 men of all ages (about 240 and 600 
men having undergone RT and RARP, respectively), and about 350 older men (about 150 and 200 
receiving RT and RARP, respectively). Matched controls will be drawn from the HUNT4 and 
HUNT4 70+ surveys, distribution 1:3 (cancer survivors : controls). 
General statistical approach1: Simple descriptive statistics will be used to describe our cohorts. 
Comparison between groups will be made using parametric and non-parametric statistics as 
appropriate. To assess the impact of age, treatment regimen and relevant confounding factors on 
outcomes, multiple regression models will be estimated.  
Objective 1. Statistical approach: To investigate if global QoL (scores 1-100) (primary outcome) 
is associated to age at the time of treatment, we will estimate a linear regression model, allowing us 
to assess possibly non-linear association between global QoL and age. Since several factors may 
influence QoL, we will adjust the analysis for potential confounders in a multiple linear regression 
model. The confounders to be included are treatment modality (surgery, RT and surgery followed 
by RT), cancer characteristic (low/intermediate/high risk), clinical relapse (yes/no), androgen 
therapy (yes/no), time from treatment, social status (living alone/with partner), education (four 
categories), and comorbidity score. To avoid uncertainties related to any cancer relapse, we will 
estimate a similar regression model for patients with no biochemical and clinical relapse as 
sensitivity analysis. Sample size: For the multiple linear regression analyses, sample size according 
to Green’s rule of thumb should at least be 50+8*m, where m is the number of variables in the 
model. Due to categorical nature of some of the confounders, the number of variables in the model 
will be 13, requiring at least 154 participants. The size of the enrolled cohort of approximately 840 
participants is clearly sufficient to perform the analysis with enough power. 
Objective 2. Statistical approach: We will compare health status (a four-category primary 
outcome) between all older prostate cancer survivors and their matched controls by ordinal 
                                                 
1 Detailed plan for analyses in separate document «statistical analysis plan» 

 
 
 9 
 
regression model (nominal if proportional odds assumption is violated). The results will be adjusted 
for potential pre-defined confounder (social status, comorbidity scores, and relapse), and matching 
variables (age and education) to avoid residual confounding in a multiple regression model. As 
sensitivity analysis, the same analysis will be performed excluding survivors with clinical cancer 
relapse. Sample size: For regression model with categorical outcome to yield stable estimates, it is 
required at least 10 cases in the smallest outcome category per variable in the model.  As the model 
includes 8 variables, at least 80 cases in the smallest category is required, which should be 
unproblematic given the expected number of older survivors (350) and thrice as many controls. 
Objective 3. Statistical approach: We will compare SPPB scores (primary outcome) between the 
older prostate cancer survivors and their matched controls by bivariate linear regression model, and 
adjust the results for potential pre-defined confounders (social status, comorbidity scores and health 
status) and matching variables (age and education) to avoid the residual confounding in a multiple 
linear regression model. Sample size: According to Greens’s rule of thumb, with 10 variables in the 
multiple model we will need at least 130 participants to obtain valid estimates. To cover for 
possible registration failures for some participants, we will include a random sample of 150 from 
the older participant group and thrice as many matched controls for these analyses. 
Secondary outcomes will be assessed in the same way as the primary ones for each objective. The 
same confounders will be included into the multiple models. The type of regression model will be 
considered based on the nature of each outcome analysed 
 
Participants, organization and collaborations 
Participants/scientific project group 
Project leader is Marit Slaaen (professor, MD, oncologist), the Cancer Unit, Hamar and the 
Research Centre for Age-related Functional Decline and Disease (AFS), SI and Institute of Clinical 
Medicine (ICM), University of Oslo (UiO).  
The scientific project group consists of the following members: Reidun Sletten (MD), PhD 
student, resident physician at the RTU, Gjøvik SI. Øyvind Kirkevold, (professor, ass. research 
director), Faculty of Health, Care and Nursing, NTNU Gjøvik and AFS SI; Sverre Bergh (MD, 
PhD, leader of research), AFS, SI; Ola Christiansen (MD, urologist, PhD-student, former Head of 
Dept), Unit of Urologic Surgery, Hamar hospital, and AFS, SI; Bjørn Henning Grønberg 
(professor, MD, oncologist), Department of Cancer Research and Molecular Medicine, NTNU and 
the Cancer Clinic, St Olav Hospital (SOH); Asta Bye (associated professor, PhD, nutritionist), Oslo 
Metropolitan University; Line Merethe Oldervoll (professor, rehabilitation medicine), Department 
of Public Health and Nursing (ISM), NTNU and Norwegian Heart and Lung Patient Organization; 
Siri Rostoft (professor, MD, geriatric oncology), Dept. Geriatric Medicine, OUS and ICM, UiO;  
Håvard Skjellegrind (associated professor, specialist in Family Medicine, project leader HUNT 
70+), ISM, NTNU and Steinkjer Municipality; Jūratė Šaltytė Benth (PhD, statistician), SI and UiO; 
Lennart Åstrøm (MD, PhD, uro-oncology), Dept of Immunology, Genetics and Pathology, Uppsala 
University and Dept of Oncology, Uppsala University Hospital, and Paul Jarle Mork (PhD, 
professor), ISM, NTNU. 
 
Organization and collaboration 
This project emerges from AFS, SI, and will be performed as a joint effort with the Radiotherapy 
unit at Gjøvik Hospital, SI and the Unit of Urologic Surgery at Hamar Hospital, SI, and with an. 
active collaboration with HUNT survey researchers. The study is organized with a project leader 
and a multiprofessional scientific project group as explained above. This scientific group works 
with input from a group of three user representatives.  
 

 
 
 10 
 
 
 
User involvement  
A group of three user representatives from The Norwegian Prostate Cancer Society was established 
in December 2019. Meetings have been arranged to discuss study design and focus to ensure that 
issues of importance to prostate cancer survivors are addressed by the assessments. The user 
representatives will further participate in all parts of the study conduct, including evaluation of 
assessment procedures and the information and consent form, and interpretation and dissemination 
of results to the public, patients and relatives. Furthermore, through their society, the user 
representatives will provide an important contribution by motivating their members to participate. 
 
Ethical considerations  
Approval for all parts of the project has been granted from the Regional Committee for Medical 
Research Ethics, Health Region South-East (REK HSØ) (ID 183868 and 266644) and the Data 
Protection Official for Research, SI. The study is performed according to the rules of the Helsinki-
declaration and registered at ClinTrials.gov. Participation does not inflict upon the participants´ 
medical treatment and does not imply any health risks or deviation from good clinical practice. All 
participants provide written informed consent. 
 
References 
1. 
Kreftregisteret: Årsrapport 2018 med resultater og forbedringstiltak fra Nasjonalt kvalitetsregister for prostatakref, 2019 
2. 
Bratt O, Folkvaljon Y, Hjalm Eriksson M, et al: Undertreatment of Men in Their Seventies with High-risk Nonmetastatic 
Prostate Cancer. Eur Urol 68:53-8, 2015 
3. 
Jha GG, Anand V, Soubra A, et al: Challenges of managing elderly men with prostate cancer. Nat Rev Clin Oncol 11:354-
64, 2014 
4. 
Liang Y, Rausch C, Laflamme L, et al: Prevalence, trend and contributing factors of geriatric syndromes among older 
Swedes: results from the Stockholm County Council Public Health Surveys. BMC Geriatr 18:322, 2018 
5. 
Wildiers H, Heeren P, Puts M, et al: International Society of Geriatric Oncology consensus on geriatric assessment in older 
patients with cancer. J Clin Oncol 32:2595-603, 2014 
6. 
Mottet N CP, van den Bergh RCN, et al: European Association of Urology: Guidelines. Prostate cancer. 
https://uroweb.org/guideline/prostate-cancer/#6, European Association of Urology 
7. 
Neal DE, Metcalfe C, Donovan JL, et al: Ten-year Mortality, Disease Progression, and Treatment-related Side Effects in 
Men with Localised Prostate Cancer from the ProtecT Randomised Controlled Trial According to Treatment Received. Eur 
Urol 77:320-330, 2020 
8. 
Wallis CJD, Glaser A, Hu JC, et al: Survival and Complications Following Surgery and Radiation for Localized Prostate 
Cancer: An International Collaborative Review. Eur Urol 73:11-20, 2018 
9. 
Wilt TJ, Jones KM, Barry MJ, et al: Follow-up of Prostatectomy versus Observation for Early Prostate Cancer. N Engl J 
Med 377:132-142, 2017 
10. Bill-Axelson A, Holmberg L, Garmo H, et al: Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J 
Med 370:932-42, 2014 
11. Hamdy FC, Donovan JL, Lane JA, et al: 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized 
Prostate Cancer. N Engl J Med 375:1415-1424, 2016 
12. Solberg A, Angelsen A, Berge V, et. al: Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og 
oppfølging av prostatakreft,  (ed 7). http://www.helsedirektoratet.no/publikasjoner/, Helsedirektoratet, 2015 
13. Wallis CJD, Saskin R, Choo R, et al: Surgery Versus Radiotherapy for Clinically-localized Prostate Cancer: A Systematic 
Review and Meta-analysis. Eur Urol 70:21-30, 2016 
14. Donovan JL, Hamdy FC, Lane JA, et al: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for 
Prostate Cancer. N Engl J Med 375:1425-1437, 2016 
15. Lardas M, Liew M, van den Bergh RC, et al: Quality of Life Outcomes after Primary Treatment for Clinically Localised 
Prostate Cancer: A Systematic Review. Eur Urol 72:869-885, 2017 
16. Johansson E, Steineck G, Holmberg L, et al: Quality of Life after Radical Prostatectomy or Watchful Waiting With or 
Without Androgen Deprivation Therapy: The SPCG-4 Randomized Trial. Eur Urol Oncol 1:134-142, 2018 
17. Fossa SD, Bengtsson T, Borre M, et al: Reduction of quality of life in prostate cancer patients: experience among 6200 
men in the Nordic countries. Scand J Urol 50:330-7, 2016 
18. Rhee H, Gunter JH, Heathcote P, et al: Adverse effects of androgen-deprivation therapy in prostate cancer and their 
management. BJU Int 115 Suppl 5:3-13, 2015 
19. Loffeler S, Halland A, Fawad H, et al: Non-metastatic prostate cancer: rationale for conservative treatment and impact on 
disease-related morbidity and mortality in the elderly. Scand J Urol 54:105-109, 2020 

 
 
 11 
 
20. de Camargo Cancela M, Comber H, Sharp L: Age remains the major predictor of curative treatment non-receipt for 
localised prostate cancer: a population-based study. Br J Cancer 109:272-9, 2013 
21. Mandel P, Chandrasekar T, Chun FK, et al: Radical prostatectomy in patients aged 75 years or older: review of the 
literature. Asian J Androl, 2017 
22. Traboulsi SL, Nguyen DD, Zakaria AS, et al: Functional and perioperative outcomes in elderly men after robotic-assisted 
radical prostatectomy for prostate cancer. World J Urol, 2020 
23. Whiting PF, Moore TH, Jameson CM, et al: Symptomatic and quality-of-life outcomes after treatment for clinically 
localised prostate cancer: a systematic review. BJU Int 118:193-204, 2016 
24. Celis EDPs LD, Sun C-L,: Patient-defined goals and preferences among older adults with cancer starting chemotherapy 
(CT). Journal of Clinical Oncology 36:1, 2018 
25. HUNT4 2017-2019, in NTNU (ed). https://www.ntnu.no/hunt/hunt4, NTNU 
26. Christiansen O, Bratt O, Haug ES, et al: TECLA-an innovative technical approach for prostate cancer registries. Scand J 
Urol 53:229-234, 2019 
27. Aaronson NK, Ahmedzai S, Bergman B, et al: The European Organization for Research and Treatment of Cancer QLQ-
C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365-76, 1993 
28. Questionnaire HUNT4. https://www.ntnu.no/documents/10304/901151116/HUNT4_Q1.pdf/edaa10d7-faa7-4899-8b28-
f714adf13d30, NTNU 
29. Guralnik JM, Ferrucci L, Simonsick EM, et al: Lower-extremity function in persons over the age of 70 years as a predictor 
of subsequent disability. N Engl J Med 332:556-61, 1995 
30. Nolte S, Liegl G, Petersen MA, et al: General population normative data for the EORTC QLQ-C30 health-related quality 
of life questionnaire based on 15,386 persons across 13 European countries, Canada and the Unites States. Eur J Cancer 
107:153-163, 2019 
31. Questionnaire HUNT4 70+. https://www.ntnu.no/documents/10304/901151116/HUNT4_Q2_M70%2B.pdf/e1ec2df5-6fee-
478a-9cd1-96e85250412a, NTNU 
32. Chang P, Szymanski KM, Dunn RL, et al: Expanded prostate cancer index composite for clinical practice: development 
and validation of a practical health related quality of life instrument for use in the routine clinical care of patients with 
prostate cancer. J Urol 186:865-72, 2011 
33. Nasreddine ZS, Phillips NA, Bedirian V, et al: The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild 
cognitive impairment. J Am Geriatr Soc 53:695-9, 2005 
 
 
 
 

 
 
 12 
 
Amendment 
Changes to the original protocol 
All changes affecting participants in any way (measurements, choice of instruments etc.) were 
approved by Regional Ethics Committee prior to enrolment of subjects in the research project. 
 Predefined secondary outcome, page 7 [Local late effects (measured with the Expanded 
Prostate Composite Instrument for Clinical Practice (EPIC-CP) (objective 1)]. Instrument 
was changed from EPIC-CP to EPIC-26 (1). Approved by the Regional Ethics Committee 
(REC) March 10, 2021. 
 Study IIB: Objective registrations of physical- and sedentary activity performed using the 
accelerometer Axivity AX3, page 7. The location of the accelerator was changed to 
subjects’ back and right thigh, not hip and back as originally stated. Moreover, the 
participants would wear the accelerators continuously for seven days, not restricted to 
waking hours. Approved by the REC, January 19, 2022. 
 Study IIB, page 8: test of cognitive function using the Montreal Cognitive Assessment 
(MoCA) was omitted from the project. Approved by the REC, November 30, 2021. 
 Study IIB: the following registrations were added to those described in the protocol: Height, 
weight, waist circumference and resting heart rate. Approved by the REC, November 30, 
2021. 
 
 
 
(1) Szymanski KM, Wei JT, Dunn RL, Sanda MG. Development and validation of an abbreviated 
version of the expanded prostate cancer index composite instrument for measuring health-
related quality of life among prostate cancer survivors. Urology. 2010;76(5):1245-50