PROspective Multicenter Observational Study on Elective Pelvic Nodes (PRO-EPI) Irradiation in Patients With Intermediate/High/Very High Risk Prostate Cancer
Conditions: Intermediate Risk Prostate Cancer, High Risk Prostate Cancer
Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Final Version 1.0 – 18/01/2016 
 
1 
 
PROspective multicenter observational study on Elective Pelvic nodes 
(PRO-EPI) Irradiation in Patients with intermediate/high/very high risk 
prostate cancer submitted to adjuvant or radical Radiotherapy with or 
without concomitant Androgen Deprivation 
“PRO-EPI” 
 
 
COORDINATOR CENTER and Sponsor 
Spedali Civili, Istituto del Radio “O. Alberti” 
Radiation Oncology Department 
Piazzale Spedali Civili, 1 
25123 Brescia - Italy 
Phone +39 030 3995271 
Fax +39 030 3996109 
 
Study Coordinator 
Prof. Stefano Maria Magrini, MD 
University of Brescia – Spedali Civili, Istituto del Radio “O. Alberti” 
Radiation Oncology Department, Professor 
Mail: stefano.magrini@unibs.it 
Principal Investigator 
Michela Buglione di Monale e Bastia, MD 
Senior Researcher, Aggregate Professor 
University of Brescia – Spedali Civili, Istituto del Radio “O. Alberti” 
Radiation Oncology Department 
Mail: michela.buglione@unibs.it 
 
 
SCIENTIFIC COORDINATION: 
AIRO – Associazione Italiana di Radioterapia Oncologica 

Final Version 1.0 – 18/01/2016 
 
2 
 
 
Executive Committee and Trial Management 
 
Filippo Bertoni, MD 
Medical Advisor to Principal Investigator 
Mail: filippo.bertoni@gmail.com 
 
Prof. Roberto D’Amico 
Associate Professor of Biostatistics 
University of Modena and Reggio Emilia 
Director of the Italian Cochrane Centre 
Mail: roberto.damico@unimore.it 
 
Alessio Bruni, MD 
University of Modena – Azienda Ospedaliera Universitaria Policlinico di Modena 
Radiation Oncology Department 
Mail: brunialessio@virgilio.it 
 
Ercole Mazzeo, MD 
University of Modena – Azienda Ospedaliera Universitaria Policlinico di Modena 
Radiation Oncology Department 
Mail: mazzeo.ercole@policlinico.mo.it  
 
Lilia Bardoscia, MD 
University of  Brescia –  Spedali Civili, Istituto del Radio “O. Alberti” 
Radiation Oncology Department, Radiation Oncologist Registrar 
Mail: liliabardoscia@gmail.com 
 
Simona Borghesi, MD 
Radiation Oncology Department 
Arezzo – San Donato Hospital 
Mail: s.borghesi@gmail.com 
 
 
DATA CENTER SITE 
Spedali Civili, Istituto del Radio “O. Alberti” 
Radiation Oncology Department 
Piazzale Spedali Civili, 1 
25123 Brescia - Italy 
Phone +39 030 3995271 
Fax +39 030 3996109 
 
 
 
 
 

Final Version 1.0 – 18/01/2016 
 
3 
 
 
 
 
 
Table of contents 
 
Clinical study protocol synopsis................................................................................................4 
Background…………………………………………………………………………………....9
Aim of the Study……………………………………………………………………………..12 
Study Design…………………………………………………………………………………13 
Study Duration……………………………………………………………………………….13 
Materials and Methods (Population, Procedures)……………………………………………14 
Toxicity and response evaluation…………………………………………………………….17 
Data Collection, Confidentiality……………………………………………………………..18 
Statistical considerations (Sample size, statistical analyses)....………………………………19 
Ethical committee…………………………………………………………………………….20 
Publication Rules……………………………………………………………………………..20 
References……………………………………………………………………………............22
Summary……………………………………………………………………………………...27 
Signature page…………………………………………..........................................................28 
Attachments………………………………………………………………………………….29

Final Version 1.0 – 18/01/2016 
 
4 
 
Clinical study protocol synopsis 
EUDRACT n. 
 
Study 
Multicenter Observational Prospective study 
Title  
PROspective multicenter observational study on Elective Pelvic nodes 
(PRO-EPI) Irradiation in Patients with intermediate/high/very high risk 
prostate cancer submitted to adjuvant or radical Radiotherapy with or without 
concomitant Androgen Deprivation. 
Background 
Prostate cancer (PCa) is the most common male malignancy all over the 
word causing some concerns for public health. In Italy prostate cancer is in 
the third place of the cancer mortality scale (8% of all cancer related deaths) 
even if a constant, though moderate, annual decrease (-1.8%) has been 
observed for over twenty years as well as a consequent increase in overall 
survival. Despite these data, still now, in the post PSA era, current estimates 
indicate that high-risk disease accounts for 15% of all PCa diagnoses in the 
United States and even more in the low-PSA screening regions. 
  
Radiotherapy for prostate cancer: some open questions 
Several modalities, alone and/or in combination, have been advocated to treat 
patients with intermediate/high/very high risk PCa, but universally accepted 
consensus guidelines are still lacking. Mounting evidence supports the use of 
a multimodality approach to treat locally advanced prostate cancer and in 
particular the combination of Radiation Therapy (RT) with Total Androgenic 
Deprivation (ADT); adjuvant post-surgical RT is also needed in many cases 
submitted to radical prostatectomy (RP) because of unexpected extra-
capsular invasion or microscopically involved margins. In both cases, some 
issues are still present regarding RT: volumes of interest, total dose, radiation 
techniques and fractionation.  
 
Elective nodal irradiation and its association with hormonal manipulation in 
the context of radical exclusive radiotherapy. 
Whether or not elective irradiation of pelvic nodes (ENI) provides any 
benefit over exclusive RT to prostate only, has been a longstanding 
therapeutic dilemma being still now increasingly discussed in the modern 
radiotherapy scenario. Data obtained from international literature are still 
controversial and ENI is not clearly linked to relevant advantages in terms of 
overall survival (OS) according to the few randomized clinical trials 
available and to recent reviews particularly if Whole Pelvic Radiation 
Therapy (WPRT) is associated with ADT.  
Neoadjuvant (NHT), concomitant, or adjuvant  (AHT) androgen deprivation 
therapy (ADT) is recommended for selected men with unfavourable 
intermediate-risk or high risk disease. Long-term ADT is indicated in 
patients with a high/very high risk of disease recurrence and typically 
consists of NHT plus RT followed by AHT (for 2-3 years) Conversely, the 
addition of  RT to ADT is related to a significant reduction of cause-specific 
and all-cause mortality (OS) in comparison with exclusive systemic 
treatments. 
 
Elective nodal irradiation (ENI) and evolving treatment techniques 
Modern technologies contributed to a larger diffusion of ENI after a period 
during which this practice was almost abandoned due to its worse toxicity 

Final Version 1.0 – 18/01/2016 
 
5 
 
profile. Intensity Modulated Radiation Therapy (IMRT) may allow to treat 
larger volumes with better sparing of organs at risk (OARs). Other different 
techniques can also been used to obtain these results, however, there is no 
consensus in the literature on the superiority of any of these techniques in 
terms of tumor control and toxicity reduction. Radiation-induced toxicity is 
most often associated with high total and daily dose, short recovery time, and 
a larger amount of normal tissues included in the high dose regions. Data 
suggest that even in prostate-only RT, toxicity to OARs is more prevalent in 
the “high-dose” group. Acute gastrointestinal (GI) and genitourinary (GU) 
complications were however more frequently reported in patients treated 
with WPRT than in those receiving PORT, possibly due to “old” radiation 
techniques and less sophisticated dosimetric elaboration.  
 
Elective nodal irradiation in the context of postoperative treatments 
Adjuvant RT after RP reduces the risk of PSA failure of about 50% (thus 
ameliorating biochemical relapse free survival- bRFS) in pN0 patients with 
pT3-T4 disease, positive surgical margins (R+), also without any association 
with ADT, and seems to increase survival, particularly metastasis free 
survival. Patients with negative lymph nodes, but unfavorable prognostic 
factors such as positive surgical margins, extracapsular involvement (pT3a) 
and/or seminal vesicles infiltration (pT3b) are therefore recommended to 
undergo adjuvant RT. In patients with severe post- surgical side effects 
(urinary incontinence, persistent bleeding) intensive follow up followed by 
salvage RT at the time of biochemical relapse represents an alternative 
choice for patients with severe post-surgical side effects (such as urinary 
incontinence, persistent bleeding).  
  
In the adjuvant setting, sterilizing microscopic disease potentially persistent 
after radical surgery, particularly in high-risk patients, represents the 
rationale of adding WPRT to prostatic bed radiotherapy in pN0 patients. 
Goldner et al. evaluated the clinical impact of prostate only adjuvant RT in 
pN0 patients showing a 5-year biochemical relapse free survival of 100% 
and 58% in patients with a risk of nodal involvement <15% and >15%, 
respectively. These findings may be explained by a microscopic involvement 
of pelvic structures (lymph nodes, bone) other than prostate bed. However, 
the role of adjuvant post-surgical WPRT need to be validated by large 
prospective studies, not actually ongoing to our knowledge. Moreover, no 
clear-cut guidelines are available about the usefulness of adding ADT to 
adjuvant RT in the different subsets of pN0 patients. 
 
On the other hand, nodal involvement (pN1) is a strong negative prognostic 
factor and adjuvant RT in these patients may be useful to optimize loco-
regional control deferring first or second line systemic therapies. The 
standard adjuvant treatment for pN1 PCa patients is represented by long term 
ADT, but the association with WPRT might significantly increase survival 
outcomes. 
Rationale 
Open questions are still needed to be answered:  
- 
In the exclusive radiotherapy scenario, does ENI produce an overall 
or biochemical relapse free survival advantage over prostate only 
radiotherapy for intermediate/high/very high-risk cases? 
- 
If 
ADT 
is 
added 
to 
prostate 
only 
radiotherapy, 
in 
intermediate/high/very high-risk cases, ENI is any longer needed? 

Final Version 1.0 – 18/01/2016 
 
6 
 
- 
Is ENI, associated or not to ADT, linked with an OS or bRFS survival 
advantage in patients submitted to adjuvant postsurgical prostate 
radiotherapy? 
- 
Additional toxicity due to the larger volumes treated might be 
reduced by more sophisticated radiotherapy techniques when ENI is 
added to prostate? 
- 
How many Radiation Oncology centers use ENI to treat patients with 
intermediate/high/very high-risk prostate cancer, with or without 
ADT?  
 
- 
The data obtained from the present observational study will be 
helpful for designing a subsequent randomized controlled trial. 
End-points 
Primary:  
- Overall survival; 
Secondary: 
- Cause-specific (CSS) and Biochemical Relapse Free survival (bRFS);  
- acute and late toxicity evaluation (rectal, bladder, bowel toxicity, according 
to CTCAE v.4 scale): 
-  Quality of Life deterioration (according to the UCLA-PCI scale).  
 
Study design 
 
This is a prospective, multicenter, observational cohort study aimed to 
describe the advantage/disadvantage of different treatments of patients with 
intermediate/high/very high risk prostate cancer, through a web-based 
database. 
 
The study will include all consecutive patients affected by intermediate, 
high or very high-risk prostate cancer that fit to the inclusion criteria 
and who are evaluated at each Centre involved in the study. Patients may 
have already undergone or not to radical prostatectomy and/or pelvic 
lymphadenectomy.   
 
Phase 1: Establishment of the network of Centers involved in the study 
Phase 2: Activation and recruitment of eligible cases 
Phase 3: Follow-up (1,3,6,12/18,24/30/36 months)  
 
Statistical 
considerations 
 
Sample size 
From previous experiences of the AIRO Prostate Cancer Study Group (AIRO 
PCSG), at least 15-20 Radiotherapy Centers from different regions of the 
country will be able to participate to the study. It is conceivable an accrual of 
at least 400-500 patients within 2 years and a further follow up of at least 3 
years for each patient. For intermediate and high risk patients, an overall 
survival at 5 years of 0.8 has been previously reported (RTOG 94-13). 
According to the primary end-pint of the study, a sample size of 400 patients 
will allow to estimate a 5-year survival of 0.8 with 95% confidence interval 
of 0.76-0.84. 
 
 
Statistical Analyses 
In order to describe the data, mean and standard deviation will be used for 
normally distributed continuous variables, median and ranges for non-
normally distributed continuous variables, proportions and percentages for 

Final Version 1.0 – 18/01/2016 
 
7 
 
categorical variables. Associations between two categorical variables will be 
assessed through the Pearson’s chi-squared test or Fisher test, when 
appropriate. Differences between two-sample central tendencies will be 
assessed with a two independent sample t-test or Mann-Whitney U test or 
Wilcoxon, depending on distribution of the continuous variable.  
Analysis of variance and covariance and regression models will be used for 
evaluating the associations of some variables with survival taking account of 
possible confounders. 
In order to compare groups in terms of survival end-points, Kaplan-Meier 
curves will be estimated and log-rank tests will be performed. 
Periodical analyses are planned in order to check the quality of entered data. 
The analyses will be performed by using STATA 13 (StataCorp. 2013. Stata 
Statistical Software: Release 13. College Station, TX: StataCorp LP) or SPSS 
Statistical Software. 
Inclusion/exclusion 
criteria  
 
Every prostate cancer patient consecutively evaluated at the recruiting 
Centers and planned to receive radical exclusive or post-operative 
radiotherapy will be registered; this registration includes demographic  and 
staging results data. 
Only intermediate, high, very high patients will have, however, treatment and 
follow up CRF compiled, based on the inclusion criteria 
 
Inclusion criteria 
Men older than or aged 18 years; 
Histologically confirmed intermediate, high or very high risk prostate cancer 
patients (NCCN classification: Intermediate Risk T2b and T2c or Gleason 
Score 7 or PSA value between 10 and 20 ng/mL; High risk: T3a or Gleason 
score 8-10 or PSA > 20 ng/ml; Very high risk: T3b-T4 or patients with 
multiple adverse risk factors reported in the high risk category that may be 
shifted in the very high risk group  
Patients eligible for -and actually submitted to radical radiotherapy treatment 
(+/- androgen deprivation) or adjuvant radiotherapy treatment after surgery 
(radical prostatectomy +/- pelvic lymphadenectomy); 
No other synchronous or previous malignant tumor other than skin basal cell 
carcinoma; 
Patients able to understand and sign the appropriate informed consent;  
Patients able to fill the Quality of Life (QoL) questionnaire;  
 
Exclusion criteria 
Patients aged less than 18; 
Patients not eligible for -and actually not submitted to- radical radiotherapy 
treatment (+/- androgen deprivation)  or  adjuvant radiotherapy treatment 
after surgery (radical prostatectomy +/- pelvic lymphadenectomy);  
Low risk prostate cancer (<T2b and T2c or < Gleason Score 7 or PSA value 
< 10 ng/mL);  
Patients with synchronous or previous malignancy other than skin basal cell 
carcinoma; 
Patients able to understand and sign the appropriate informed consent (IC) 
who decide not to subscribe IC;  
Patients not able to understand and sign the appropriate informed consent 
(IC) 
Patients unable to fill the QoL questionnaire. 

Final Version 1.0 – 18/01/2016 
 
8 
 
Study duration  
Estimated total time of recruitment is 2 years.  
It will be followed by a 3 years period of follow up for each patient.  
Visits and exams 
Every prostate cancer patient consecutively evaluated at the recruiting 
Centers and planned to receive radical exclusive or post-operative 
radiotherapy will be registered; this registration includes demographic  and 
staging results data. 
Only intermediate, high, very high patients will have, however, treatment and 
follow up CRF compiled, based on the inclusion criteria 
 
Eligible patients will then receive all the information necessary to formulate 
their adhesion to the study and finally the physician will fill in the 
“Pretreatment” 
CRF 
that 
will 
include: 
Demographic 
Information; 
Anamnestic data; Initial diagnosis (date; PSA at diagnosis); Risk factors; 
Staging; Quality of life and symptoms caused by prostate cancer; General 
quality of life; 
The choice of the treatment will be done based on commonly used 
international guidelines and on the specific internal protocol of each 
participating Center.  
Since this study is observational, involved patients will be treated following 
good clinical practice and institutional policies procedures. 
Clinical outcomes and variables, demographic features, dosimetric analysis 
and acute/late toxicities of both RT (with and without ENI) and ADT will be 
reported. 
 
Follow-up visits on 1,3,6,12/18,24/30 and 36 months  
Every patient will be contacted by the physicians to fill a CRF that will 
include: Vital state (mortality, date and causes of death) or loss to follow up; 
Last PSA value; Other treatments (drugs); type of RT and ADT treatment 
Acute and late toxicities; Biochemical Relapse with PSA value and date of 
last PSA; Quality of life and symptoms due to prostate cancer; General 
quality of life. 
Survival status (mortality, date and cause of death) or exit from the study; If 
macroscopical recurrence or disease progression will occur, the radiological 
exams (if performed) will be reported; Further treatments received/planned 
after radiotherapy; The last available PSA; 
 
Acute/Late toxicity 
Genitourinary and gastrointestinal toxicity due to radiation therapy.  
A CRF will be completed regarding: Technical characteristics of the 
radiation treatment; Quality of life and complications due to prostate cancer; 
General quality of life  
Toxicity  
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 
for adverse event (AE) reporting. The CTCAE version 4 is identified and 
located on the CTEP web site at: 
 http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
Quality of Life 
Quality of life and complications due to prostate cancer (Italian UCLA-PCI) 
General quality of life (SF-12 Standard V1) 
 
 
 

Final Version 1.0 – 18/01/2016 
 
9 
 
Background 
The extent of the problem 
Prostate cancer (PCa) is the most common male malignancy in the United States and the rest of the 
Western world and its incidence is rising also in Asia, causing some concerns for public health [1, 
2]. In Italy prostate cancer is in the third place of the cancer mortality scale (8% of all cancer related 
deaths) even if a constant, though moderate, annual decrease (-1.8%) has been observed for over twenty 
years [3] as well as a consequent increase in overall survival [4]. Despite these data, still now, in the 
post PSA era, current estimates indicate that high-risk disease accounts for 15% of all PCa 
diagnoses in the United States [5] and even more in the low-PSA screening regions.  
Radiotherapy for prostate cancer: some open questions 
Several modalities, alone and/or in combination, have been advocated to treat patients with 
intermediate/high/very high risk PCa [6], but universally accepted consensus guidelines are still 
lacking. Mounting evidence supports the use of a multimodality approach to treat locally advanced 
prostate cancer and in particular the combination of Radiation Therapy (RT) with Total Androgenic 
Deprivation (ADT);  adjuvant post-surgical RT is also needed in many cases submitted to radical 
prostatectomy (RP) because of unexpected extracapsular invasion or microscopically involved 
margins. In both cases, some issues are still present regarding RT: volumes of interest, total dose, 
radiation techniques and fractionation.  
The efficacy of elective nodal irradiation and the issue of its association with hormonal 
manipulation in the context of radical exclusive radiotherapy for prostate cancer 
Whether or not elective irradiation of pelvic nodes (ENI) provides any benefit over exclusive RT to 
prostate only, has been a longstanding therapeutic dilemma [7] being still now increasingly discussed 
in the modern radiotherapy scenario [8, 9]. Data obtained from international literature are still 
controversial and ENI is not clearly linked to relevant advantages in terms of overall survival (OS) 
according to the few randomized clinical trials available [10] and to recent reviews [7, 11, 12, 13, 
14, 15], particularly if Whole Pelvic Radiation Therapy (WPRT) is associated with ADT.  
In fact, in the radical setting, the addition of ADT to RT (but not to RP) is linked to a survival benefit 
in men with intermediate- or high risk disease according to Level I evidence; to date, however, it 
remains unclear whether this benefit is driven by an effect on micro metastatic disease in the pelvic 
lymph nodes and/or bones, by hormonal radio sensitization of the primary tumour, or by some 
combination thereof [16, 17, 18, 19]. Consequently, neoadjuvant (NHT), concomitant, or adjuvant 

Final Version 1.0 – 18/01/2016 
 
10 
 
(AHT) androgen deprivation therapy (ADT) is recommended for selected men with unfavourable 
intermediate-risk or high risk disease. Long-term ADT is indicated in patients with a high/very high 
risk of disease recurrence and typically consists of NHT plus RT followed by AHT (for 2-3 years) 
[20, 21, 22, 23]. Conversely, the addition of RT to ADT is related to a significant reduction of 
cause-specific and all-cause mortality (OS) in comparison with exclusive systemic treatments [24, 
25]. 
 
Elective nodal irradiation and evolving treatment techniques 
Modern technologies contributed to a larger diffusion of ENI after a period during which this 
practice was almost abandoned due to its worse toxicity profile. The larger diffusion of Intensity 
Modulated Radiation Therapy (IMRT) may allow to treat larger volumes with better sparing of 
organs at risk (OARs). Modern techniques can also obtain better conformal dose distributions and 
include static fields (“step-and-shoot”) intensity modulated radiotherapy (IMRT), dynamic fields 
(“sliding-window”) IMRT, and, more recently, volumetric modulated arc therapy (VMAT) and 
helical tomotherapy (Tomotherapy ®). However, there is no consensus in the literature on the 
superiority of any of these techniques in terms of tumor control and toxicity reduction. Radiation-
induced toxicity is most often associated with high total and daily dose, short recovery time, and a 
larger amount of normal tissues included in the high dose regions. Data suggest that even in 
prostate-only RT, toxicity to OARs is more prevalent in the “high-dose” group [26, 27]. Acute 
gastrointestinal (GI) and genitourinary (GU) complications were however more frequently reported 
in patients treated with WPRT than in those receiving PORT, possibly due to “old” radiation 
techniques and less sophisticated dosimetric elaboration [28, 29]. Due to its improved ability in 
bowel sparing, IMRT may be an effective tool to reduce the risk of toxicities during WPRT [30, 31, 
32, 33]. Kaidar-Person and colleagues' review [34], summarizes the main international studies on 
WPRT. 
Elective nodal irradiation in the context of postoperative treatments 
 
Adjuvant RT after RP reduces the risk of PSA failure of about 50% (thus ameliorating biochemical 
relapse free survival- bRFS) in pN0 patients with pT3-T4 disease, positive surgical margins (R+), 
also without any association with ADT, and seems to increase survival, particularly metastasis free 
survival [35]. Patients with negative lymph nodes, but unfavorable prognostic factors such as 
positive surgical margins, extracapsular involvement (pT3a) and/or seminal vesicles infiltration 
(pT3b) are therefore recommended to undergo adjuvant RT. In patients with severe post- surgical 
side effects (urinary incontinence, persistent bleeding) intensive follow up followed by salvage RT 

Final Version 1.0 – 18/01/2016 
 
11 
 
at the time of biochemical relapse represents an alternative choice for patients with severe post-
surgical side effects (such as urinary incontinence, persistent bleeding). [36].  
  
In the adjuvant setting, sterilizing microscopic disease potentially persistent after radical surgery, 
particularly in high-risk patients, represents the rationale of adding WPRT to prostatic bed 
radiotherapy in pN0 patients. Goldner et al. evaluated the clinical impact of prostate only adjuvant 
RT in pN0 patients showing a 5-year biochemical relapse free survival of 100% and 58% in patients 
with a risk of nodal involvement <15% and >15%, respectively. These findings may be explained 
by a microscopic involvement of pelvic structures (lymph nodes, bone) other than prostate bed. 
However, the role of adjuvant post-surgical WPRT need to be validated by large prospective 
studies, not actually ongoing to our knowledge. [37, 38, 39, 40].  Moreover, no clear-cut guidelines 
are available about the usefulness of adding ADT to adjuvant RT in the different subsets of pN0 
patients. 
 
On the other hand, nodal involvement (pN1) is a strong negative prognostic factor and adjuvant RT 
in these patients may be useful to optimize loco-regional control deferring first or second line 
systemic therapies [41]. Actually, the standard adjuvant treatment for pN1 PCa patients is 
represented by long term ADT, but the association with WPRT might significantly increase survival 
outcomes [42]. A recent analysis conducted by SEER on “pN1 M0” PCa patients treated with 
adjuvant WPRT seems to confirm the benefit obtained by the association of WPRT with ADT, 
demonstrating a survival advantage for intermediate risk patients [43].  
 
 
Conclusions, rationale and summary of the study 
 
In conclusion, open questions about ENI for prostate cancer still remain: 
 
1. In the exclusive radiotherapy scenario, does ENI produce an overall or biochemical relapse 
free survival advantage over prostate only radiotherapy for intermediate/high/very high risk 
cases? 
 
2. If ADT is added to prostate only radiotherapy, in intermediate/high/very high risk cases, 
ENI is any longer needed? 
 

Final Version 1.0 – 18/01/2016 
 
12 
 
3. Is ENI, associated or not to ADT, linked with an OS or bRFS survival advantage in patients 
submitted to adjuvant postsurgical prostate radiotherapy? 
 
4. Additional toxicity due to the larger volumes treated might be reduced by more sophisticated 
radiotherapy techniques when ENI is added to prostate? 
 
5. How many Radiation Oncology centers use ENI to treat patients with intermediate/high/very 
high-risk prostate cancer, with or without ADT? 
 
We propose a no-profit, multicenter observational study to collect data of consecutive patients 
treated with ENI both in the exclusive radical radiotherapy scenario and in the adjuvant postsurgical 
setting. Cases treated both with and without associated ADT will be recruited to evaluate Overall 
survival (OS) (that will be the main endpoint),  Cause-specific (CSS) and  Biochemical Relapse 
Free survival (bRFS), toxicity and Quality of Life  (QoL) (the secondary endpoints). 
 
Aims of the study 
Clinical features and outcomes will be assessed as better detailed in the following lines: 
1. To define the diffusion of the practice of treating pelvic lymph-nodes in patients affected by 
intermediate/high/very high risk non-metastatic prostate cancer (PCa) among Italian 
Radiation Oncology Centres, submitted to radical or post-operative radiotherapy; 
2. To define the diffusion of the different radiotherapy techniques used to treat pelvic nodes 
and the other features of the radiation treatment; 
3. To register prospectively biochemical and clinical failure, prostate cancer deaths and deaths 
for any cause in the population studied; 
4. To register prospectively the toxicity due to radiotherapy and androgen deprivation therapy 
in patients treated with pelvic nodes radiotherapy; 
5. To compare clinical outcomes and toxicities observed in the different clinical and therapeutic 
subgroups with the corresponding historical data relative to PCa patients treated with 
radiotherapy with or without elective pelvic nodal irradiation, already available in the 
existing AIRO (Italian Society of Radiation Oncology) databases; 

Final Version 1.0 – 18/01/2016 
 
13 
 
6. To exploit the collected data to define the need and the features of a prospective randomized 
trial evaluating the efficacy of elective pelvic nodal irradiation in patientsts with 
intermediate/high/very high risk non-metastatic prostate cancer. 
7. The data obtained from the present observational study will be helpful for designing a 
subsequent randomized controlled trial. 
In summary, the study aims at the definition of survival, toxicity and QoL data in a representative 
sample of intermediate, high and very high risk prostate cancer patients consecutively recruited in 
Italian Radiation Oncology Centres over two years. Parameters considered will be OS, CSS and 
bRFS, toxicity (rectal, bladder, bowel toxicity, according to CTCAE v.4 scale) and QoL (according 
to the SF-12 scale and UCLA-PCI scale). Primary end point will be OS. Secondary endpoints will 
be CSS, bRFS, gastrointestinal and genitourinary toxicity, QoL deterioration. 
 
Study Design   
This is a prospective, multicenter, observational cohort study aimed to describe the 
advantage/disadvantage of different treatments of patients with intermediate/high/very high risk 
prostate cancer, through a web-based database. 
 
Study Duration  
The recruitment period, taking into account the needed sample size (v.infra) will be of two years, 
followed by three-year follow up period for each patient, with an accrual of at least 400-500 
patients. 
 
 

Final Version 1.0 – 18/01/2016 
 
14 
 
Population, Procedures  
The study will include all consecutive patients affected by intermediate, high or very high-risk 
prostate cancer that fit the inclusion criteria and who are evaluated at each Centre involved in the 
study. Patients may have already undergone or not to radical prostatectomy and/or pelvic 
lymphadenectomy.   
Inclusion criteria 
• Men older than or aged 18 years; 
• Histologically confirmed intermediate, high or very high risk prostate cancer patients 
(NCCN classification: Intermediate Risk T2b and T2c or Gleason Score 7 or PSA value 
between 10 and 20 ng/mL; High risk: T3a or Gleason score 8-10 or PSA > 20 ng/ml; Very 
high risk: T3b-T4 or patients with multiple adverse risk factors reported in the high risk 
category that may be shifted in the very high risk group  
• Patients eligible for -and actually submitted to- radical radiotherapy treatment (+/- androgen 
deprivation) or adjuvant radiotherapy treatment after surgery (radical prostatectomy +/- 
pelvic lymphadenectomy); 
• No other synchronous or previous malignant tumor other than skin basal cell carcinoma; 
• Patients able to understand and sign the appropriate informed consent;  
• Patients able to fill the QoL questionnaire;  
 
Exclusion criteria 
• Patients aged less than 18; 
• Patients not eligible for -and actually not submitted to- radical radiotherapy treatment (+/- 
androgen deprivation)  or  adjuvant radiotherapy treatment after surgery (radical 
prostatectomy +/- pelvic lymphadenectomy);  
• Low risk prostate cancer (<T2b and T2c or < Gleason Score 7 or PSA value < 10 ng/mL);  
• Patients with synchronous or previous malignancy other than skin basal cell carcinoma; 
• Patients able to understand and sign the appropriate informed consent (IC) who decide not to 
subscribe IC;  
• Patients not able to understand and sign the appropriate informed consent (IC) 

Final Version 1.0 – 18/01/2016 
 
15 
 
• Patients unable to fill the QoL questionnaire. 
 
Involved Centers 
The Radiation Oncology Unit of the University and Spedali Civili of Brescia will be the promoter 
and coordinator Center. From previous studies of the AIRO Prostate Study Group it can be inferred 
that at least 15-20 Radiation Oncology Centers from different areas of Italy will be involved; this 
will assure the widest and homogenous participation throughout the country.  
Accrual and timeline 
The study will start when a sufficient number of Centres will have obtained EC approval. 
Estimated total time of recruitment is 2 years. It will be followed by a three years period of follow 
up for each patient.  
Phase 1: Establishment of the network of Centers involved in the study 
During this phase the study protocol has to be shared as much as possible within the Italian 
radiation oncology community in order to identify and involve as many as possible interested 
Centres throughout the country. 
This will be done in official sessions of the Prostate Cancer Study Group (PCSG) of AIRO 
meetings. 
Each center that will become a part of the study will identify a referring physician who must 
accomplish the systematic recruitment of eligible patients and provide the collection of data on the 
appropriate web portal established in Brescia. 
Phase 2: Activation and recruitment of eligible cases 
Centers involved will identify all the eligible cases with biopsy proven prostate adenocarcinoma. 
Patients who are candidate to get involved in the study will be contacted by the physician in charge 
of the study for each Center. Every prostate cancer patient consecutively evaluated at the recruiting 
Centers and planned to receive radical exclusive or post-operative radiotherapy will be registered; 
this registration includes demographic and staging results data; only intermediate, high, very high 
patients will have, however, treatment and follow up CRF compiled (both treated with or without 
ENI; +/- ADT).  

Final Version 1.0 – 18/01/2016 
 
16 
 
Eligible patients will then receive all the information necessary to formulate their adhesion to the 
study and finally the physician will fill in the “Pretreatment” Case Report Form (CRF) that will 
include: 
- 
Demographic Information (date of birth, study title, civil state, working information);  
- 
Another person (relatives, friends,…) as a contact to minimize follow up loss; 
- 
Anamnestic data (height, weight, smoking habit, comorbidities, Cumulative Illness Rating 
Scale [44], Attachment 1); 
- 
Initial diagnosis (date; PSA at diagnosis); 
- 
Risk factors;  
- 
Staging (clinical TNM, date of biopsy, Gleason score, total number of samples, number of 
positive samples); 
- 
Quality of life and symptoms caused by prostate cancer (using Italian UCLA Prostate 
Cancer Index) [45, 46]; 
- 
General quality of life (SF-12 Standard V1) [47]. 
The choice of the treatment will be done based on commonly used international guidelines and on 
the specific internal protocol of each participating Center.  
Since this study is observational, involved patients will be treated following good clinical practice 
and institutional policies procedures. 
Clinical outcomes, (such as overall survival and biochemical relapse free survival) and variables, 
demographic features, dosimetric analysis and acute/late toxicities of both RT and ADT will be 
reported. 
Phase 3: Follow-up (1, 3, 6, 12, 18, 24, 30, 36 months)  
After the end of the radiotherapy treatment patients will be evaluated 1, 3, 6, 12, 18, 24, 30 and 36 
months since the last session. 
Every patient will be contacted by the physicians to fill a CRF that will include: 
- 
Vital state (mortality, date and causes of death) or loss to follow up; 
- 
Last PSA value; 

Final Version 1.0 – 18/01/2016 
 
17 
 
- 
Other treatments (drugs); 
- 
Treatment : type of treatment, start date, PSA value before treatment; if surgery type of 
surgery and pathological TNM, margins, Gleason Score, number of positive lymph nodes; if 
external RT (intent, modality, technique, dose/fraction, volumes, concomitant hormonal 
therapies); if brachytherapy (type, intent, dose); if hormone therapy (type of drugs, start  and 
end date, total duration); 
- 
Acute and late toxicities; 
- 
Biochemical Relapse with PSA value and date of last PSA;  
- 
Quality of life and symptoms due to prostate cancer (Italian UCLA-PCI); 
- 
General quality of life SF-12. 
 
Toxicity and response evaluation 
The enrolled patients will undergo the first follow up visit one month after the end of radiotherapy. 
On that occasion, clinical examination will be performed and previously prescribed blood tests, if 
required, will be evaluated. Genitourinary and gastrointestinal toxicity due to radiation therapy for 
prostate cancer will be reported according to the NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 4 for adverse event (AE) reporting. The CTCAE version 4 is identified 
and located on the CTEP web site at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm [48] 
In addition, a Case Report Form (CRF) will be completed (see Attachment 2), regarding: 
• Technical characteristics of the radiation treatment (dose, volume, technique, association 
or not with hormonal therapy); 
• Quality of life and complications due to prostate cancer (according to Italian UCLA-
PCI) [45, 46]; 
• General quality of life (SF-12 Standard V1) [47]. 
Thereafter patients will be evaluated at 3-months, 6-months and 12-months after the end of 
radiotherapy, and then every 6 months for at least 24 months. During all those scheduled follow up 
visits, PSA level (jointly with testosterone, in case of association with hormonal therapy) and 

Final Version 1.0 – 18/01/2016 
 
18 
 
previously prescribed blood texts if required, will be evaluated. Patients will undergo clinical 
examination, and genitourinary and gastrointestinal toxicity will be assessed according to the 
CTCAE v4.0 classification scale). In addition, a CRF (see Attachment 3) will be completed at each 
visit, regarding: 
• Survival status (mortality, date and cause of death) or exit from the study; 
• If macroscopical recurrence or disease progression  occurred, the radiological exams (if 
performed); 
• Further treatments received/planned after radiotherapy;  
• The last available PSA; 
• Quality of life and complications due to prostate cancer (Italian UCLA-PCI) [45, 46]; 
• General quality of life (SF-12 Standard V1) [47]. 
The Italian UCLA-PCI and SF-12 Standard V1 questionnaires reported in Attachment 2 and 
Attachment 3 [45, 46, 47] will be given by the referring physician and self-compiled by patients in 
physician's absence, eventually with the help of a nurse if necessary; thereafter, the referring 
physician will insert the data to the database. 
 
Data Collection, Confidentiality 
Data will be collected through an ad hoc web based software, built to guarantee: 
1. Respect of the Italian laws and of the international rules about GMP and privacy, according also 
to the general principles fixed by the Helsinki declaration and its subsequent updates; 
2. The anonymization of the patient records; 
3. The possibility for each participating Center to have unrestricted access to its own data; 
4. The restriction of the access to the full dataset composed by the sum of the records provided by 
the single Centers; this will be allowed only after the authorization of the PI and the Study 
Coordinator. Once the study will be completed, access to the whole database will be possible only 
after having obtained the authorization of the AIRO President in charge and of the AIRO Board; 
5.  The safe storage of the data, along with that of the previous AIRO-PCSG studies, along with. 
The use of the software will be elucidated to the single participating  Centers in ad hoc start up 

Final Version 1.0 – 18/01/2016 
 
19 
 
meetings, to guarantee an appropriate and homogeneous data collection; a tool bar will however be 
devised, to automatically verify inconsistencies in the data collected. 
 
Statistical Considerations 
Sample size 
From previous experiences of the AIRO PCSG [49, 50], at least 15-20 Radiotherapy Centers from 
different regions of the country will be able to participate to the study. It is conceivable  an accrual 
of at least 400-500 patients within 2 years and a further follow up of at least 3 years for each 
patient. For intermediate and high risk patients, an overall survival at 5 years of 0.8 has been 
previously reported (RTOG 94-13) [51]. According to the primary end-point of the study, a sample 
size of 400 patients will allow to estimate a 5-year survival of 0.8 with 95% confidence interval of 
0.76-0.84 [52].  
 
Statistical Analyses 
In order to describe the data, mean and standard deviation will be used for normally distributed 
continuous variables, median and ranges for non-normally distributed continuous variables, 
proportions and percentages for categorical variables. Associations between two categorical 
variables will be assessed through the Pearson’s chi-squared test or Fisher test, when appropriate. 
Differences between two-sample central tendencies will be assessed with a two independent sample 
t-test or Mann-Whitney U test or Wilcoxon, depending on distribution of the continuous variable. 
Analysis of variance and covariance and regression models will be used for evaluating the 
associations of some variables with survival taking account of possible confounders. 
In order to compare groups in terms of survival end-points, Kaplan-Meier curves will be estimated 
and log-rank tests will be performed. 
Periodical analyses are planned in order to check the quality of entered data. 
The analyses will be performed by using STATA 13 (StataCorp. 2013. Stata Statistical Software: 
Release 13. College Station, TX: StataCorp LP) or SPSS Statistical Software. 
 

Final Version 1.0 – 18/01/2016 
 
20 
 
Ethical committee 
After the final approval by the AIRO-PCSG, the Protocol will be submitted to the Ethical 
Committee (EC) of the Study Coordinating Centre; when it will be approved, the single 
participating Centres will consequently apply for approval of their EC. According to the judgment 
of the PI and of the Study Coordinator, the first patient will be enrolled when a sufficient number of 
Centres will have obtained EC approval. This will be the starting date for the study. 
The present study will be performed in accordance with the present protocol, with the principles of 
Good Clinical Practice in the respect of the ICH GCP guidelines and the ethical principles contained 
in the Helsinki declaration. 
 
Publication rules 
Interim and final results of the study will be published under the final responsibility of the PI and of 
the Study Coordinator.  
The following publication rules will be enforced: 
1. The participating Centers should approve the paper; 
2. Only Centers contributing to more than 5% of the cases collected will have a person quoted as 
Author of the paper; however, every Center contributing to the common database, as well as the 
people working to realize the Study, will be publicly quoted and their contribution acknowledged in 
the paper; 
3. Authorship is granted in proportion to: 
a. the cases contributed to the database; 
b. the contribution to: 
- study concept ; 
- study organization; 
- study conduction; 
- article conception; 

Final Version 1.0 – 18/01/2016 
 
21 
 
- article drafting and writing; 
- article reviewing; 
- article approval. 

Final Version 1.0 – 18/01/2016 
 
22 
 
References 
 
1. Siegel R et al. Cancer statistics, 2014. CA Cancer J Clin 2014; 64:9–29 
2. Ferlay J et al. GLOBOCAN 2012 v1.0, Cancer Incidence and mortality Worldwide: IARC 
Cancer Base No.11. Lyon: International Agency for Research on Cancer (2013) 
3.  AIOM-AIRTUM. I numeri del cancro in Italia 2014 
4. Coleman MP et al. Cancer survival in Australia, Canada, Norway, Sweden, Denmark, and 
the UK, 1995-2007: an analysis of population-based cancer registry data. Lancet 2011; 
377:127-138 
5. Rosenthal SA, Sandler HM et al. Treatment strategies for high-risk locally advanced prostate 
cancer. Nat Rev Urol 2010; 7:31–8 
6. D’Amico AV, Whittington R, Malkowicz B et al. Biochemical Outcome After Radical 
prostatectomy, External Beam Radiation Therapy for Clinically Localized Prostate Cancer. 
JAMA 1998; 280(11):969-974 
7.  Pommier P, Chabaud S et al. Is there a role for pelvic irradiation in localized prostate 
adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol 2007; 25:5366–73 
8. NCCN Guidelines, 2014 
9. EAU Guidelines 2013  
10. Roach M, De Silvio M et al. Phase III trial comparing whole-pelvic versus prostate-only 
radiotherapy and neo-adjuvant versus adjuvant combined androgen suppression: radiation 
therapy oncology group 9413. J Clin Oncol 2003; 21:1904–11 
11. Dirix P et al. The role of elective pelvic radiotherapy in clinically node-negative prostate 
cancer: A systematic review. Radiotherapy and Oncology 2014; 110: 45–54 
12. Lawton CA, De Silvio M et al. An update of the phase III trial comparing whole pelvic to 
prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated 
analysis of RTOG94-13, with emphasis on unexpected hormone/radiation interactions. Int J 
Radiat Oncol Biol Phys 2007; 69:646–55 
13. Aizer AA, Yu JB et al. Whole pelvic radiotherapy versus prostate only radiotherapy in the 
management of locally advanced or aggressive prostate adenocarcinoma. Int J Radiat Oncol 

Final Version 1.0 – 18/01/2016 
 
23 
 
Biol Phys 2009; 75:1344-9 
14. Braunstein LZ, Ming-Hui C et al.  Whole Pelvis Versus Prostate-Only Radiotherapy With or 
Without Short-Course Androgen Deprivation Therapy and Mortality Risk. Clinical 
Genitourinary Cancer Month 2015 (Epub Ahead of Print)  
15. Mantini G. et al. Effect of whole pelvic radiotherapy for patients with locally advanced 
prostate cancer treated with radiotherapy and long-term androgen deprivation therapy. Int J 
Radiat Oncol Biol Phys 2011; 81(5):e721–e726 
16. Bolla M, Van Tienhoven G et al. External irradiation with or without long-term androgen 
suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC 
randomised study. Lancet Oncol 2010; 11: 1066-73 
17. Horwitz EM, Bae K, Hanks GE, et al. Ten-year follow-up of radiation therapy oncology 
group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in 
locally advanced prostate cancer. J Clin Oncol 2008; 26:2497-504 
18. Bastian PJ, Boorjian SA, Bossi A, et al. High-risk prostate cancer: from definition to 
contemporary management. Eur Urol 2012; 61:1096-1106 
19.  Mohler JL, Armstrong AJ, et al. Prostate cancer, Version 3.2012: featured updates to the 
NCCN guidelines. J Natl Compr Canc Netw 2012; 10:1081-1087 
20.  Pilepich MV, Winter K, Lawton CA, et al. Androgen suppression adjuvant to definitive 
radiotherapy in prostate carcinoma–long-term results of phase III RTOG 85-31. Int J Radiat 
Oncol Biol Phys 2005; 61: 1285-1290 
21.  Bolla M et al. High-risk prostate cancer: combination of high-dose, high-precision 
radiotherapy and androgen deprivation therapy. Curr Opin Urol 2013;23 (4):349-54 
22. Polkinghorn WR, Zelefsky MJ Improving outcomes in high-risk prostate cancer with 
radiotherapy. Rep Pract Oncol Radiother 2013 Nov 11;18 (6):333-7 
23. Roach M. III Current Trends for the Use of Androgen Deprivation Therapy in Conjunction 
With Radiotherapy for Patients With Unfavorable Intermediate-Risk, High-Risk, Localized, 
and Locally Advanced Prostate Cancer. Cancer 2014, Jun 1;120 (11):1620-9 
24. Bekelman JE et al. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for 
Older Men With Locally Advanced Prostate Cancer J Clin Oncol. 2015 Mar 1; 33 (7):716-
22  

Final Version 1.0 – 18/01/2016 
 
24 
 
25. Pearse M, Fraser-Browne C. et al. A Phase III trial to investigate the timing of radiotherapy 
for prostate cancer with high-risk features: background and rationale of the Radiotherapy – 
Adjuvant Versus Early Salvage (RAVES) trial. BJU Int 2014; 113, Supplement 2, 7–12 
26. Dearnaley DP, Sydes MR, Graham JD, et al. Escalated-dose versus standard-dose conformal 
radiotherapy in prostate cancer: First results from the MRC RT01 randomised controlled 
trial. Lancet Oncol 2007;8:475-48 
27.  Zietman AL, De Silvio ML, Slater JD, et al. Comparison of conventional-dose vs high-dose 
conformal radiation therapy in clinically localized adenocarcinoma of the prostate: A 
randomized controlled trial. JAMA 2005;294:1233-1239 
28. Magrini SM, Bertoni F, Vavassori V et al. Practice patterns for prostate cancer in nine 
central and northern Italy radiation oncology centres : a survey including 1759 patients 
treated during two decades (1980-1998) Int J Radiat Oncol Biol Phys 2002; 52(5):1310-
1319  
29. Yu-Wei L, Li-Ching L and Kuei-Li L The early result of whole pelvic radiotherapy and 
stereotactic body radiotherapy boost for high-risk localized prostate cancer. Front Onc 2014, 
Vol.4:279: 1-8 
30. Ashman JB, Zelefsky MJ et al. Whole pelvic radiotherapy for prostate cancer using 3D 
conformal and intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 2005; 
63:765–771 
31.  Sanguineti G, Cavey ML, Endres EJ, et al. Is IMRT needed to spare the rectum when pelvic 
lymph nodes are part of the initial treatment volume for prostate cancer? Int J Radiat Oncol 
Biol Phys 2006; 64:151–160 
32. Arcangeli S, Saracino B, Petrongari MG, et al. Analysis of toxicity in patients with high risk 
prostate cancer treated with intensity modulated pelvic radiation therapy and simultaneous. 
Radiother Oncol 2007; 84:148–155 
33. Fiorino C, Alongi F, et al. Dose–volume relationships for acute bowel toxicity in patients 
treated with pelvic nodal irradiation for prostate cancer. Int J Radiation Oncology Biol Phys. 
2009; 75(1):29–35 
34. Kaidar-Person O, Roach M, III, and Créhange G Whole-Pelvic Nodal Radiation Therapy in 
the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward, 
Int J Radiat Oncol Biol Phys 2013; 86(4):600-605 

Final Version 1.0 – 18/01/2016 
 
25 
 
 
35. Tran PT, Bevilacqua TJ, Dicker AP Adjuvant radiation for node-positive disease after 
prostatectomy: more good news, but who will listen?, J Clin Oncol 2014; 32(35):3917-3919 
36. Jarrard DF, Blute ML Jr, Ritter MA Potential role of androgen-deprivation therapy and 
pelvic radiation therapy in node-positive post prostatectomy prostate cancer, J Clin Oncol 
2014; 32(35):3926-3929 
37. Roach M 3rd, Marquez C, Yuo HS, Narayan P, Coleman L et al. Predicting the risk of lymph 
node involvement using the pre-treatment prostate specific antigen and Gleason score in 
men with clinically localized prostate cancer, Int J Radiat Oncol Biol Phys 1994; 28:33-37 
38. Goldner G, Dimopoulos J, Potter R Is the Roach formula predictive for biochemical 
outcome in prostate cancer patients with minimal residual disease undergoing local 
radiotherapy after radical prostatectomy?, Radiother Oncol 2010; 94:324-327 
39. Briganti A, Joniau S, Gandaglia G, Cozzarini C et al. Patterns and predictors of early 
biochemical recurrence after radical prostatectomy and adjuvant radiation therapy in men 
with pT3N0 prostate cancer: implications for multimodal therapies, Int J Radiat Oncol Biol 
Phys 2013; 87(5):960-7 
40. Song C, Kang HC, Kim JS et al. Elective pelvic versus prostate bed-only salvage 
radiotherapy following radical prostatectomy, Strahlenther Onkol 2015 Jul 10 
41. Abdollah F, Karnes RJ, Suardi N, Cozzarini C et al. Impact of adjuvant radiotherapy on 
survival of patients with node-positive prostate cancer, J Clin Oncol 2014; 32(35):3939-
3947 
42. Créhange G, Chen PC, Hsu CC et al. Management of prostate cancer pazients with lymph 
node involvement: a rapidly evolving paradigm, Cancer Treat Rev 2012; 38(8):956-967 
43. Rusthoven CG, Carlson JA and Kavanagh BD External validation of the benefit of adjuvant 
radiotherapy for pathologic N1M0 prostate cancer, J Clin Oncol 2015; 33(17):1987-1988 
44. Conwell Y, Forbes NT, Cox C, Caine ED. Validation of a measure of physical illness burden 
at autopsy: the Cumulative Illness Rating Scale, J Am Geriatr Soc 1993; 41:38-41. 
45. Gacci M, Livi L, Paiar F et al. Quality of life after radical treatment of prostate cancer: 
validation of the Italian version of the University of California-Los Angeles Prostate Cancer 
Index, Urology 2005; 66(2):338-43 

Final Version 1.0 – 18/01/2016 
 
26 
 
46. Gacci M, Simonato A, Masieri L et al. Urinary and sexual outcomes in long-term (5+ years) 
prostate cancer disease free survivors after radical prostatectomy, Health and Quality of Life 
Outcomes 2009; 7:94 
47. Apolone G, Mosconi P, Quattrociocchi L, Gianicolo EAL, Growth N and Ware JJE 
Questionario sullo stato di salute SF-12. Versione Italiana, Guerini e Associati Editore. 
Milano, 2001. 
48. U.S Department of Health and Human Services – National Institutes of Health, National 
Cancer Institute, “Common Terminology Criteria for Adverse Events (CT CAE) Version 
4.0”, 
Published: 
May 
28, 
2009 
(v4.02: 
Sept. 
15, 
2009) 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
49. Pegurri L et al. Changes in patterns of practice for prostate cancer radiotherapy in Italy 
1995-2003. A survey of the Prostate Cancer Study Group of the Italian Radiation Oncology 
Society, Tumori 2014; 100:31-7 
50.  Malinverni G, Greco C, Bianchi P et al. Italian survey in postoperative radiation therapy for 
prostate carcinoma by the AIRO National Working Group on Prostate Radiotherapy: 
definitive results. Tumori 2005; 91(2) 156-162 
51. Lawton CA, De Silvio M, Roach M, et al. An Update of the Phase III Trial Comparing 
Whole-Pelvic (WP) to Prostate Only (PO) Radiotherapy and Neoadjuvant to Adjuvant Total 
Androgen Suppression (TAS): Updated Analysis of RTOG 94-13, with Emphasis on 
Unexpected Hormone/Radiation Interactions. Int J Radiat Oncol Biol Phys 2007; 69(3): 
646-655  
52. Lemeshow S, Hosmer DW, Klar J and Lwanga SK Adequacy of Sample Size in Health 
Studies, W.H.O./Wiley 1990 
 
 

Final Version 1.0 – 18/01/2016 
 
27 
 
Summary of the study 
 
 
 

Final Version 1.0 – 18/01/2016 
 
28 
 
Signature page 
 
Coordinating Investigator: Prof. Stefano Maria Magrini 
Place and date, ___Brescia li 18/01/2016_____ 
 
Signature, _______________________ 
 
 
Principal Investigator: Michela Buglione di Monale e Bastia, MD 
Place and date, ___Brescia li 18/01/2016_____ 
 
Signature, _______________________ 
 
 

Final Version 1.0 – 18/01/2016 
 
29 
 
ATTACHMENT 1 –  CRF PRE TREATMENT 
                                                       GENERAL HISTORY 
 
Date of Birth 
|__|__| / |__|__| / |__|__|__|__| 
  day             month               year 
Educational qualification 
  1 . 
Academic degree or Bachelor's degree 
 
  2.. 
High school diploma or high school degree (4-5 years) 
 
  3.. 
High school diploma or high school degree  (2-3 years) 
 
  4.. 
Secondary school diploma/Professional training  diploma 
 
  5.. 
Elementary school diploma (3-5 years) 
 
  6 . 
No degree 
Marital status 
  1 . 
Married/Cohabitant 
 
  2 . 
Widower 
 
  3 . 
Separated/divorced 
 
  4 . 
Unmarried 
Job status 
  1 . 
Employed
  2 . 
Unemployed or job quest 
 
  3 . 
Retiree 
 
  4 . 
Never worked 
Contact people 
  1 . 
 Wife, cohabitant 
Phone number 
 
  2.. 
Daughter/son 
Phone number 
 
  3.. 
Daughter-in-law /son-in-law 
Phone number 
 
  4.. 
Other, 
specify_______________________ Phone number 
 
 
Weight 
|__|__|__|.|__| kg  
Smoke 
  1 .No 
 
  2..Yes, in the past, no more now 
 
  3..Yes 
Hemoglobin (from bood tests reported in 
the last 6 months) 
|__|__|__|.|__| g/dl 
Blood tests date 
|__|__| / |__|__| / |__|__|__|__|  
  day             month               year 

Final Version 1.0 – 18/01/2016 
 
30 
 
CUMULATIVE ILLNESS RATING SCALE (CIRS) 
(Conwell Y et al, 1993) 
Indicate for each apparatus the score that best expresses the degree of injury. For diseases that produce lesions in more than one apparatus all present 
lesions must be reported. For example, an acute cerebrovascular accident (stroke) can damage neurological, vascular, musculoskeletal apparatus and skin at 
the same time. A metastasized tumor has to be reported either at the apparatus site of the primary tumor or at the vascular system, indicating the extent of 
the lymph node involvement. If an apparatus is affected by more diseases, the total damage resulted from various diseases must be reported. 
For each apparatus  the score is so allocated: 
1 = ABSENT: "no injuries of an organ / apparatus". 
2 = MILD: "the damage does not interfere with the normal activities; therapy is not necessarily required; the prognosis is favorable (eg. hernias, 
hemorrhoids). " 
3 = MODERATE: "the lesion interferes with normal life activities; therapy is required; the prognosis is good (eg. stones, diabetes, fractures). " 
4 = SERIOUS: "The injury is debilitating; urgent treatment is required; the prognosis is doubtful (eg. inoperable cancer, emphysema, heart failure).” 
5 = VERY SERIOUS: "the injury can be fatal; emergency treatment is required or it is no longer indicated any treatment; the prognosis is severe (eg. 
myocardial infarction, stroke, intestinal bleeding, embolism). " 
 
 
None 
Mild 
Moderate 
Serious 
Very serious
1. 
Cardiac 
1.. 
2.. 
3.. 
4.. 
5.. 
2. 
Hypertension (rating is based on 
severity) 
1.. 
2.. 
3.. 
4.. 
5.. 
3. 
Vascular, lymphatics, haematopoietic 
1.. 
2.. 
3.. 
4.. 
5.. 
4. 
Respiratory (under the larynx) 
1.. 
2.. 
3.. 
4.. 
5.. 
5. 
Eye, ear, nose, throat, larynx 
1.. 
2.. 
3.. 
4.. 
5.. 
6. 
Upper gastro-intestinal 
1.. 
2.. 
3.. 
4.. 
5.. 
7. 
Lower GI (intestines, hernias) 
1.. 
2.. 
3.. 
4.. 
5.. 
8. 
Hepatic (liver only) 
1.. 
2.. 
3.. 
4.. 
5.. 
9. 
Renal (kidneys only) 
1.. 
2.. 
3.. 
4.. 
5.. 
10. Genito-urinary (ureter,-genitals) 
1.. 
2.. 
3.. 
4.. 
5.. 
11. Musculoskeletal and - integumentary 
1.. 
2.. 
3.. 
4.. 
5.. 
12. Neurological (except  dementia) 
1.. 
2.. 
3.. 
4.. 
5.. 
13.
Endocrine- metabolic, infections, 
toxicity 
1.. 
2.. 
3.. 
4.. 
5.. 
14. Cognitive-psychiatric behaviour 
1.. 
2.. 
3.. 
4.. 
5.. 

Final Version 1.0 – 18/01/2016 
 
31 
 
 
DIAGNOSIS AT PRESENTATION 
First diagnosis date 
 |__|__| / |__|__| / |__|__|__|__| 
  day             month               year 
 
 
PSA at diagnosis 
 |__|__|__|__|.|__|__|__| ng/mL  
 
Risk factors 
 
Yes 
No 
 
Family history for prostate cancer 
0 
1 
 
If  yes, specify the degree of kinship 
  1.. first degree (father, son) 
  2.. second degree (brother , grandfather , nephew, 
paternal or maternal uncle) 
 
 
 
Diabetes 
Yes 
No 
 
 
0 
1 
Clinical TNM Staging 
T |__|__| 
N |__|__| 
M |__|__| 
 
Biopsy date 
|__|__| / |__|__| / |__|__|__|__| 
    day            month              year 
 
 
Gleason Score 
|__| + |__| = |__|__| 
 ISUP1:   1.. before 2005 
        2.. after 2005 
 
 
Number of blood tests 
 |__|__| 
 
 
Number of positive blood tests 
 |__|__| 
 
 
 
 
 
1. Epstein JI, Allsbrook WC Jr., Amin MB, et al. The 2005 International Society of Urological 
Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J 
Surg Pathol 2005;29:1228–1242 

Final Version 1.0 – 18/01/2016 
 
32 
 
DRUG THERAPY 
Does the patient take any sexual rehabilitation drugs? 
  0  
No 
  1   
Yes 
      If yes, specify: 
Commercial name 
Formulation
Dosage 
Unit 
of 
measure
ment 
Frequence 
Continuity 
of therapy 
Since  
number 
period 
_____________________________ 
 
|__|__|__| 
 
|__|__|/qd 
|__|__|/weekly 
|__|__|/monthly 
other 
|__|__|/_____ 
 
  . continuous 
  . discontinuous 
  . when required 
 
|__|__| 
  . days 
  . weeks 
  . months 
  . years 
 
_____________________________ 
 
|__|__|__| 
 
|__|__|/qd 
|__|__|/weekly 
|__|__|/monthly 
other|__|__|/____ 
 
  . continuous 
  . discontinuous 
  . when required 
 
|__|__| 
  . days 
  . weeks 
  . months 
  . years 
 
 
_____________________________ 
 
|__|__|__| 
 
|__|__|/qd 
|__|__|/weekly 
|__|__|/monthly 
other|__|__|/____ 
 
  . continuous 
  . discontinuous 
  . when required 
 
|__|__| 
  . days 
  . weeks 
  . months 
  . years 
 
_____________________________ 
 
|__|__|__| 
 
|__|__|/qd 
|__|__|/weekly 
|__|__|/monthly 
other|__|__|/____ 
 
  . continuous 
  . discontinuous 
  . when required 
 
|__|__| 
  . days 
  . weeks 
  . months 
  . years 
 
 
Does the patient take any other medications? 
  0 .  
No 
  1   
Yes 
   If yes, specify: 
      Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________ 
        Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________ 
      Commercial name
____________________________________________________________________
 

Final Version 1.0 – 18/01/2016 
 
33 
 
TREATMENT CHARACTERISTICS 
Aim of Radiation Therapy                          1        Definitive 
                                                                       2        Adjuvant 
 
If adjuvant RT, specify: 
Surgery 
Surgical approach 
  1 .Open 
 
  2 .Laparoscopy 
 
  3 .Robot assisted 
 
  4 .Conversion to open 
 
  5 .TURP 
 
  6 .Other, specify_______________________ 
Lymphadenectomy 
  1 .No 
 
  2 . Yes 
 
 
If  yes, number of removed nodes |__|__| 
Number  of positive nodes |__|__| 
Nerve Sparing 
  1 .No 
 
  2 . Yes, monolateral 
 
  3 .Yes, bilateral 
Pathological TNM after 
surgery 
T |__|__|          N |__|__|          M |__|__| 
Margins 
  1R0 
 
2
3
R1 
R2 
Gleason Score after surgery
 
    |__| + |__| = |__|__| 
 
Pre-treatment PSA  |__|__|__|__|.|__|__|__| ng/mL 
PSA date 
    |__|__| / |__|__| / |__|__|__|__| 
                                                             day          month               year

Final Version 1.0 – 18/01/2016 
 
34 
 
SF-12 STANDARD ITALIAN VERSION 
(Apolone G et al. 2001) 
 
Eccellent 
Very good 
Good 
Fair 
Poor 
1 
In general, you would say that your health 
condition is: 
1 
2 
3 
4 
5 
The following questions regard some activities you might do during a typical day. Does your health condition actually limit you in 
doing these activities? 
 
Yes, it limits a lot 
Yes, it limits a little 
No, it does not limit at 
all 
2 
Activities of moderate physical effort , such 
as moving a table , using the vacuum cleaner , 
playing bowls or a riding a bicycle 
1 
2 
3 
3 
Climbing several flights of stairs 
1 
2 
3 
During the last 4 weeks have you had the following problems at work or during other daily activities, because of your physical health 
condition? 
 
Yes 
No 
4 
Accomplished less than you would like 
1 
2 
5 
You had to limit certain kinds of occupation 
or other activities 
1 
2 
During the last 4 weeks have you had the following problems at work or during other daily activities, because of your emotional state 
(such as feeling depressed or anxious)? 
 
Yes 
No 
6 
Accomplished less than you would like 
1 
2 
7 
You did not do work or other activities as carefully 
as usual 
1 
2 
 
Not at all 
A little bit 
Moderat
ely 
Quite a bit 
Not at all 
8 
During the last 4 weeks, How much has pain 
hindered your usual work (at home and 
outside)? 
1 
2 
3 
4 
5 
How long during the last 4 weeks have you felt 
 
All of 
the time 
Most of 
the time 
A good bit 
of time 
Some of the 
time 
A little of 
the time 
All of 
the time 
9 
calm and serene? 
1 
2 
3 
4 
5 
6 
10 
full of energy? 
1 
2 
3 
4 
5 
6 
11 
discouraged and sad 
1 
2 
3 
4 
5 
6 
 
All of the 
time 
Most of the 
time 
A good bit 
of time 
Some of the 
time 
A little of the 
time 
12 
During the last 4 weeks, how long have your 
physical health condition or your emotional state 
interfered with your social activities, with family, 
with friends? 
1 
2 
3 
4 
5 
 
 
 

Final Version 1.0 – 18/01/2016 
 
35 
 
COMPLICATIONS DUE TO PROSTATE CANCER 
ITALIAN UCLA PROSTATE CANCER INDEX 
(Gacci M et al, 2005) 
URINARY FUNCTION 
This session regards the urinary routine. Please consider only the last 4 weeks. 
  
1. 
Over the LAST 4 WEEKS, how often have you leaked urine? 
1  Every day. 
  
2  About once a week 
  
3  Less than once a week 
  
4  Not at all. 
 
2. 
Which of the following best describes your urinary control during the LAST 4 WEEKS? 
1  No control whatsoever 
  
2  Frequent dribbling 
  
3  Occasional dribbling 
  
4  Total control 
 
3. 
How many pads or adult diapers per day have you usually used to control leakage during the LAST 4 
WEEKS? 
 1  3 or more pads per day 
 2  1-2 pads per day 
 3  No pads 
 
4. 
How big a problem, if any,  has each of the following been for you? 
 
Dripping urine or wetting your pants? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
3  Moderate problem 
  
4  Big problem 
 
Urine leakage interfering with your sexual activity? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
  
3  Moderate problem 
  
4  Big problem 
 
5. 
Overall, how big a problem has your urinary function been for you during the LAST 4 WEEKS? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
  
3  Moderate problem 
  
4  Big problem 
 
 
BOWEL FUNCTION 
The following section talks about all the bowel function and abdominal pain. Please consider only the last 4 weeks. 
 
6. 
How often have you had  rectal urgency (felt like you had to pass stool, but did not) during the LAST 4 WEEKS? 
 1  More than once a day 
 2 About once a day 
 3 More than once a week 
 4 About once a week 
 5 Rarely or never 
 
7. 
How much distress have your bowel movements caused you during the LAST 4 WEEKS? 
 1  Severe distress 

Final Version 1.0 – 18/01/2016 
 
36 
 
 2  Moderate distress 
 3  A little distress 
 4  No distress 
 
8. 
How often have you had crampy pain in your abdomen or pelvis during the LAST 4 WEEKS? 
 
 1 Several times a day 
 
 2 About once a day 
 
 3 Several times a week 
 
 4 About once this month 
 5 Rarely or never 
 
9. 
In particular, how big was the problem of bowel habits during the LAST 4 WEEKS? 
 
 1 Big problem 
 
 2 Moderate problem 
 
 3 Little problem 
 
 4 Very small problem 
 
 
 5 No problem 
 
SEXUAL FUNCTION 
THE NEXT SECTION IS ABOUT YOUR SEXUAL FUNCTION AND SEXUAL SATISFACTION. MANY OF THE 
QUESTIONS ARE VERY PERSONAL, BUT THEY WILL HELP US UNDERSTAND THE IMPORTANT ISSUES 
THAT YOU FACE EVERY DAY. REMEMBER THAT YOUR ANSWERS TO THIS QUESTIONNAIRE WILL BE 
KEPT CONFIDENTIAL AND WILL BE USED ONLY FOR RESEARCH PURPOSES. PLEASE ANSWER HONESTLY 
ABOUT THE LAST 4 WEEKS ONLY. 
 
10. 
HOW WOULD YOU RATE EACH OF THE FOLLOWING DURING THE LAST 4 WEEKS? 
 
Very poor 
Poor 
Fair 
Good 
Very good 
A. Your ability to have an erection?. 
1 
2 
3 
4 
5 
B. Your ability to reach orgasm (clima
1 
2 
3 
4 
5 
 
11. 
How would you describe the usual QUALITY of your erections? 
 1 None at all 
 2 Not firm enough for any sexual activity 
 3 Firm enough for masturbation and foreplay only 
 4 Firm enough for intercourse 
 
12. 
How would you describe the FREQUENCY of your erections? 
 1 I NEVER had an erection when I wanted one 
 2 I had an erection LESS THAN HALF the time I wanted one 
 3 I had an erection ABOUT HALF the time I wanted one 
 4 I had an erection MORE THAN HALF the time I wanted one 
 5 I had an erection WHENEVER I wanted one 
 
13. 
Overall, how would you rate your sexual function during the LAST 4 WEEKS? 
 1 Very poor 
 2 Poor 
 3 Fair 
 4 Good 
 5 Very good 
 
14. 
Overall, how big a problem has your sexual function been for you during the LAST 4 WEEKS? 
 1  No problem 
 2  Very small problem 
 3  Small problem 
 4  Moderate problem 
 5  Big problem 
 
 

Final Version 1.0 – 18/01/2016 
 
37 
 
ATTACHMENT 2 – 1 MONTH FOLLOW UP 
Date of starting treatment
 
  |__|__| / |__|__| / |__|__|__|__| 
      day           month               year
Date of ending treatment
 
  |__|__| / |__|__| / |__|__|__|__| 
      day           month               year
 
Pre-treatment PSA 
 
  |__|__|__|__|.|__|__|__| ng/mL 
 
 
External Beam Radiation Therapy 
Aim of  Radiation Therapy 
 
 
1 
.
   
     Radical exclusive 
 
  
2 
. 
Adjuvant 
 
  
3 
. 
Salvage post-operative 
 
  
4 
. 
Other, specify_________________________ 
Modality 
  
1 
. 
IGRT 
 
  
2 
. 
Non IGRT 
Technique 
 
 1 
   
2 
 
3D-CRT 
 
IMRT (step and shoot) 
 
 
 
3.
 
IMRT (volumetric) 
 
 
Technique-2 
  
4 
 
 
 
SBRT (stereotactic body radiotherapy) 
 
 

Final Version 1.0 – 18/01/2016 
 
38 
 
1 
2 
Sequential RT 
SIB IMRT 
Dose/fraction V1
|__|__|,|__|__| Gy 
Total dose V1
|__|__|,|__|__| Gy 
Dose/fraction V2
|__|__|,|__|__| Gy 
Total dose V2
|__|__|,|__|__| Gy 
Dose/fraction V3
|__|__|,|__|__| Gy 
Total dose V3 
 
 
Rectum V25 
Rectum V50 
Rectum V60 
Rectum D50 
Rectum Dmax 
Bladder Dmax 
Bladder D50 
Bladder V50 
Bladder V70 
Penile Bulb Dmax 
Penile Bulb D90 
Small bowel V15 (contouring individual bowel loops)* 
Small bowel V45 (contour peritoneal space)* 
 
       *contouring of the peritoneal space is required for all       
patients, optional contouring individual bowel loops 
|__|__|,|__|__| Gy  
 
 
Value 
Value 
Value 
Value 
Value 
Value 
Value 
Value 
Value 
Value 
Value 
Value 
Value 
 
Target volume V1 
  
1 
. 
Prostate only 
 
  
2 
. 
Prostate and basis of seminal vescicles 
 
3
Prostate and seminal vescicles
 
  
4 
. 
Prostate plus pelvis (nodal volume) 
 
  
5 
. 
Prostate and seminal vescicles and pelvis (nodal 
volume) 
 
 
 

Final Version 1.0 – 18/01/2016 
 
39 
 
Target volume V2 
1 
Prostate plus pelvis 
 
2 
Nodal volume only 
 
3 
Prostate and seminal vescicles 
 
4 
Prostate and basis of seminal vescicles 
 
5 
Prostate only 
 
Target volume V3 
 
1 
 
Nodal volume only 
 
2 
Prostate and seminal vescicles 
 
3 
Prostate and basis of seminal vescicles 
 
4 
Prostate only 
Association with hormonal therapy 
  
1 
. 
Radiotherapy alone 
 
  
2 
. 
Radiotherapy and neoadjuvant hormonal therapy 
(before radiation therapy) 
 
  
3 
. 
Radiotherapy and adjuvant hormonal therapy (after 
radiation therapy) 
 
4 
Radiotherapy and neoadjuvant + adjuvant hormonal 
therapy 
 
 
 
Hormonal therapy 
Type of hormonal therapy
  1 .
ADT
 
  2 .
Periferic Antiandrogen 
 
 
If antiandrogen, specify the type:
 
 
  1 . 
Acetate ciproterone 
 
 
  2 .
Bicalutamide
 
 
  3 . 
Flutamide 
 
 
  4 .
Other, specify__________________
 
 
If antiandrogen, specify the dose: 
 
 
_____________________________________________
 
  3 .
LHRH Agonist (or GnRH) 
 
  4 .
LHRH Antagonist (or GnRH)
 
  5 .
Other, specify _________________________
 
Date of starting hormonal therapy 
 
 
 
|__|__| / |__|__| / |__|__|__|__| 
    day          month               year 
 

Final Version 1.0 – 18/01/2016 
 
40 
 
 
 
Acute  Toxicities 
 
Rectal Acute Toxicity (Grade) 
Date Tox.  
Urinary Acute Toxicity (Grade) 
Date Tox.  
Small Intestine Acute Toxicity 
(Grade) 
 
 
Date Tox. 
 
 
 
 
 
 
GI Acute Toxicity (small bowel) 
(see Table 1)  
 
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=Unknown) 
Date yyyy-mm-dd 
 
Rectal Acute Toxicity  
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=Unknown) 
Date yyyy-mm-dd 
 
Urinary Acute Toxicity  
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=Unknown) 
     
Date 
 
Late Toxicity bladder/ rectum  
select (1=Yes, 2=No, 3=Unknown) 
Date yyyy-mm-dd 
 
Proctitis  
 
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=I Unknown) 
Data yyyy-mm-dd 
 
Cystitis  
 
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6= Unknown) 
Date yyyy-mm-dd 
 
Impotence  
 
 
 
select (1=No, 2=Yes pre RT, 3=Yes post RT, 4= Unknown) 
Date yyyy-mm-dd 
 
Incontinence   
 
 
select (1=No, 2=Yes pre RT, 3=Yes post RT, 4=Unknown) 
 

Final Version 1.0 – 18/01/2016 
 
41 
 
TABLE 1 – Toxicity 
 
RECTAL/SMALL BOWEL Acute TOX 
G0: No Toxicity 
G1: Increased alvus frequency not requiring any treatment. Rectal pain or abdominal pain not 
requiring any painkillers 
G2: Diarrhoea, mucositis, rectal pain or abdominal pain requiring painkillers 
G3: Diarrhoea requiring parenteral supportive care, severe mucositis or haematological alterations 
requiring treatment. Abdominal distension 
G4: Acute or subacute obstruction, fistula or perforation, haemorrhage requiring blood transfusion. 
Abdominal pain or tenesmus requiring ileostomy 
 
BLADDER Acute TOX 
G0: No Toxicity 
G1: Low urinary tract symptoms (LUTS) and dysuria not requiring any treatment 
G2: LUTS, dysuria and urgency requiring treatment or anaesthetics 
G3: Severe LUTS, urgency, dysuria, pelvic pain or bladder spasms and haematuria 
G4: Haematuria requiring blood transfusion, urinary obstruction, ulceration and necrosis 
 
Late TOX PROCTITIS 
G0: No Toxicity 
G1: Mild rectal pain, Slight diarrhoea (less than 5 discharges). Small bleeding 
G2: Diarrhoea (more than 5 discharges). Significant mucosal secretions and intermittent rectal 
bleeding 
G3: Obstruction or haemorrhage requiring surgery 
G4: Necrosis, perforation or fistula 
 
Late TOX CYSTITIS 
G0: No Toxicity 
G1: Slight epithelial atrophy, small telangiectasia, microscopic haematuria 
G2: Moderate LUTS, Intermittent macroscopic haematuria 
G3: Severe LUTS and dysuria spread of telangiectasia. Frequent haematuria. Reduction in bladder 
capacity (less than 150 cc) 
G4: Necrosis, bladder capacity reduced (less than 100 cc). Severe haemorrhagic cystitis 
 
 

Final Version 1.0 – 18/01/2016 
 
42 
 
SF-12 STANDARD ITALIAN VERSION 
(Apolone G et al. 2001) 
 
Excellent 
Very good 
Good 
Fair 
Poor 
1 
In general, you would say that your health 
condition is: 
1 
2 
3 
4 
5 
The following questions regard some activities you might do during a typical day. Does your health condition actually limit you in 
doing these activities? 
 
Yes, it limits a lot 
Yes, it limits a little 
No, it does not limit at 
all 
2 
Activities of moderate physical effort , such 
as moving a table , using the vacuum cleaner , 
playing bowls or a riding a bicycle 
1 
2 
3 
3 
Climbing several flights of stairs 
1 
2 
3 
During the last 4 weeks have you had the following problems at work or during other daily activities, because of your physical health 
condition? 
 
Yes 
No 
4 
Accomplished less than you would like 
1 
2 
5 
You had to limit certain kinds of occupation 
or other activities 
1 
2 
During the last 4 weeks have you had the following problems at work or during other daily activities, because of your emotional state 
(such as feeling depressed or anxious)? 
 
Yes 
No 
6 
Accomplished less than you would like 
1 
2 
7 
You did not do work or other activities as carefully 
as usual 
1 
2 
 
Not at all 
A little bit 
Moderat
ely 
Quite a bit 
Not at all 
8 
During the last 4 weeks, How much has pain 
hindered your usual work (at home and 
outside)? 
1 
2 
3 
4 
5 
How long during the last 4 weeks have you felt 
 
All of 
the time 
Most of 
the time 
A good bit 
of time 
Some of the 
time 
A little of 
the time 
All of 
the time 
9 
calm and serene? 
1 
2 
3 
4 
5 
6 
10 
full of energy? 
1 
2 
3 
4 
5 
6 
11 
discouraged and sad 
1 
2 
3 
4 
5 
6 
 
All of the 
time 
Most of the 
time 
A good bit 
of time 
Some of the 
time 
A little of the 
time 
12 
During the last 4 weeks, how long have your 
physical health condition or your emotional state 
interfered with your social activities, with family, 
with friends? 
1 
2 
3 
4 
5 
 
 
 

Final Version 1.0 – 18/01/2016 
 
43 
 
COMPLICATIONS DUE TO PROSTATE CANCER 
ITALIAN UCLA PROSTATE CANCER INDEX 
(Gacci M et al, 2005) 
URINARY FUNCTION 
This session regards the urinary routine. Please consider only the last 4 weeks. 
  
1. 
Over the LAST 4 WEEKS, how often have you leaked urine? 
1  Every day. 
  
2  About once a week 
  
3  Less than once a week 
  
4  Not at all. 
 
2. 
Which of the following best describes your urinary control during the LAST 4 WEEKS? 
1  No control whatsoever 
  
2  Frequent dribbling 
  
3  Occasional dribbling 
  
4  Total control 
 
3. 
How many pads or adult diapers per day have you usually used to control leakage during the LAST 4 
WEEKS? 
 1  3 or more pads per day 
 2  1-2 pads per day 
 3  No pads 
 
4. 
How big a problem, if any,  has each of the following been for you? 
 
Dripping urine or wetting your pants? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
3  Moderate problem 
  
4  Big problem 
 
Urine leakage interfering with your sexual activity? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
  
3  Moderate problem 
  
4  Big problem 
 
5. 
Overall, how big a problem has your urinary function been for you during the LAST 4 WEEKS? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
  
3  Moderate problem 
  
4  Big problem 
 
 
BOWEL FUNCTION 
The following section talks about all the bowel function and abdominal pain. Please consider only the last 4 weeks. 
 
6. 
How often have you had rectal urgency (felt like you had to pass stool, but did not) during the LAST 4 WEEKS? 
 1  More than once a day 
 2 About once a day 
 3 More than once a week 
 4 About once a week 
 5 Rarely or never 
 
7. 
How much distress have your bowel movements caused you during the LAST 4 WEEKS? 
 1  Severe distress 

Final Version 1.0 – 18/01/2016 
 
44 
 
 2  Moderate distress 
 3  A little distress 
 4  No distress 
 
8. 
How often have you had crampy pain in your abdomen or pelvis during the LAST 4 WEEKS? 
 
 1 Several times a day 
 
 2 About once a day 
 
 3 Several times a week 
 
 4 About once this month 
 5 Rarely or never 
 
9. 
In particular, how big was the problem of bowel habits during the LAST 4 WEEKS? 
 
 1 Big problem 
 
 2 Moderate problem 
 
 3 Little problem 
 
 4 Very small problem 
 
 
 5 No problem 
 
SEXUAL FUNCTION 
THE NEXT SECTION IS ABOUT YOUR SEXUAL FUNCTION AND SEXUAL SATISFACTION. MANY OF THE 
QUESTIONS ARE VERY PERSONAL, BUT THEY WILL HELP US UNDERSTAND THE IMPORTANT ISSUES 
THAT YOU FACE EVERY DAY. REMEMBER THAT YOUR ANSWERS TO THIS QUESTIONNAIRE WILL BE 
KEPT CONFIDENTIAL AND WILL BE USED ONLY FOR RESEARCH PURPOSES. PLEASE ANSWER HONESTLY 
ABOUT THE LAST 4 WEEKS ONLY. 
 
10. 
HOW WOULD YOU RATE EACH OF THE FOLLOWING DURING THE LAST 4 WEEKS? 
 
Very poor 
Poor 
Fair 
Good 
Very good 
A. Your ability to have an erection?. 
1 
2 
3 
4 
5 
B. Your ability to reach orgasm (clima
1 
2 
3 
4 
5 
 
11. 
How would you describe the usual QUALITY of your erections? 
 1 None at all 
 2 Not firm enough for any sexual activity 
 3 Firm enough for masturbation and foreplay only 
 4 Firm enough for intercourse 
 
12. 
How would you describe the FREQUENCY of your erections? 
 1 I NEVER had an erection when I wanted one 
 2 I had an erection LESS THAN HALF the time I wanted one 
 3 I had an erection ABOUT HALF the time I wanted one 
 4 I had an erection MORE THAN HALF the time I wanted one 
 5 I had an erection WHENEVER I wanted one 
 
13. 
Overall, how would you rate your sexual function during the LAST 4 WEEKS? 
 1 Very poor 
 2 Poor 
 3 Fair 
 4 Good 
 5 Very good 
 
14. 
Overall, how big a problem has your sexual function been for you during the LAST 4 WEEKS? 
 1  No problem 
 2  Very small problem 
 3  Small problem 
 4  Moderate problem 
 5  Big problem 
 
 
 

Final Version 1.0 – 18/01/2016 
 
45 
 
ATTACHMENT 3 – 3, 6, 9, 12, 18, 24, 36 MONTHS FOLLOW UP 

Final Version 1.0 – 18/01/2016 
 
46 
 
At ….. months from Radiation 
Therapy, the patient is: 
  1 . 
Alive
 
  1    NED – no evidence of disease
 
  2 With biochemical recurrence  (only defined by PSA level according to 
Phoenix Criteria1) 
 
Date of defining biochemical recurrence 
 |__|__| / |__|__| / |__|__|__|__| 
      day          month               year 
 
  3 With biochemical and clinical recurrence (also defined through methods 
other than PSA level): 
o 
Clinical examination 
o 
ultrasonography 
o 
MRI 
o 
CT scan 
o 
Bone scintigraphy 
o 
PET-choline 
 
Date of defining clinical recurrence
 |__|__| / |__|__| / |__|__|__|__|
     day          month               year 
 
 4 [metastatic]Castration Resistant 
Prostate Cancer ([m]CRPC according to 
EAU guidelines2-3): 
 
o 
Oligometastases (max 3 lesions 
in max 2 non-visceral districts) 
 
o 
Extended disease 
Type of [m]CRPC: 
o 
Local and/or nodal 
(pelvic and lumbar-
aortic)  
o 
Only bone metastases 
o 
local bone and nodal 
o visceral 
 
 
Date of defining
  [m]CRPC
|__|__| / |__|__| / |__|__|__|__| 
     day          month               year 
 
 
 
Plasmatic Testosterone at [m]CRPC |__|__|__|__|.|__|__|__|ng/mL 
  2.. 
Died 
 
Date of the death 
|__|__| / |__|__| / |__|__|__|__| 
    day          month               year 
 
 
 
Cause of the death  
________________________________________________________________ 
 
  3.. 
Lost at follow-up, explain the reason: 

Final Version 1.0 – 18/01/2016 
 
47 
 
 
 
  1 He does not adhere anymore for health reasons, 
specify_________________________ 
 
 
  2 He is not interested anymore to take part in the study 
 
 
  3 He is not traceable 
Does the patient still undergo 
Hormonal Therapy? 
  1. 
Yes 
 
 
 
If yes:  
 
(FILL IN POINT   4   BELOW) 
 
 
  0 
No 
 
 
 
If no: 
Date of ending hormonal therapy  |__|__| / |__|__| / |__|__|__|__| 
                                                                              day          month              year 
Has he developed new 
comorbidities? 
(It is possible to fill in more than 
one option) 
 
  0 . No 
 
 
  1 . Yes 
 
 
 
If yes:  
 
 
1 
Cardiac (specify _______________)
 
 
2 
Vascular (including hypertension) 
 
 
3 
Pulmonary (specify _______________) 
 
 
4 
Eye, ear, nose, throat, larynx 
 
 
5 
Gastro-intestinal (specify _______________) 
 
 
6 
Hepatic (liver only) 
 
 
7 
Renal (kidneys only) 
 
 
8 
Musculo-skeletal (specify _______________) 
 
 
9 
Intertegumentary (skin) 
 
 
10 
Neurological (specify _______________) 
 
 
11 
Endocrine-metabolic (specify _______________) 
 
 
12 
Cognitive-psychiatric, behaviour 
 
 
13 
Genito-urinary (ureter-genitals) (specify _______________) 
 
 
14 
Other malignancies (including Haematopoietic malignancies) 

Final Version 1.0 – 18/01/2016 
 
48 
 
 
 
15 
Other, specify ________________________________________ 
Has he undergone further 
treatments for prostate cancer, 
subsequent to those reported in 
Attachment 1 (1-month follow 
up)? 
  0 . 
No 
  1 . 
Yes 
 
If  yes: 
 
  1 . 
Surgery 
 
 
  2 . 
External Beam Radiation Therapy 
 
 
  3 . 
Brachytherapy 
 
 
  4 . Radiometabolic Therapy 
 
 
  5 . 
Hormonal Therapy  
 
 
  6 . Focal Therapy 
 
 
  7 . 
Chemotherapy 
 
 
8 
Others, specify _________________________________________ 
 
  If he has undergone further treatments, specify: 
  Date of starting the new treatment  |__|__| / |__|__| / |__|__|__|__| 
                                                                  day         month               year 
  PSA before starting the new treatment |__|__|__|__|.|__|__|__| ng/mL  
  1 . External Beam Radiotherapy 
 Aim of Radiotherapy 
  1 . Palliative 
 
  2 . Other, 
specify_________________________ 
Modality  
  1 . IGRT  
 
  2 . Non IGRT 
Technique 
  1 . 3D-CRT 
 
  2 . IMRT  
 
  3 . SBRT (stereotactic body radiotherapy) 
If palliative Radiotherapy, site  
  1 . Bone lesions 

Final Version 1.0 – 18/01/2016 
 
49 
 
 
  2 . Nodal lesions 
 
  3 . Visceral metastases 
 
  4 . Pelvic lesions  
 
  5 . Others 
  
Dose/fraction 
|__|__|,|__|__| Gy 
Total dose 
 
|__|__|,|__|__| Gy 
 
Association with Hormonal Therapy
  1 . Radiotherapy alone 
 
  2 . Radiotherapy and neoadjuvant Hormonal 
Therapy (before RT) 
 
  3 . Radiotherapy and adjuvant Hormonal 
Therapy (after RT) 
 
4 
Radiotherapy and neoadjuvant + adjuvant 
Hormonal Therapy 
  2Brachytherapy 
Type of  brachytherapy 
  1 . LDR (internal radiation therapy) 
 
  2 . HDR 
Aim of  brachytherapy 
  1 . Exclusive 
 
  2 . Other, 
specify_________________________ 
  3.Radiometabolic Therapy 
If yes 
  1 . With alfa-emittent particles 
 
  2 . Other, specify ______________________ 
 
  4 . Hormonal Therapy 
Type of Hormonal Therapy 
  1 . ADT 
 
  2 . Antiandrogen 

Final Version 1.0 – 18/01/2016 
 
50 
 
 
 
If  antiandrogen, specify the type: 
 
 
  1 . 
Ciproterone acetate 
 
 
  2 . 
Bicalutamide 
 
 
  3 . 
Flutamide 
 
 
  4 . 
Other, specify________________    
 
 
If  antiandrogen, specify the dose: 
 
 
__________________________________ 
 
  3 . LHRH-Agonist (or GnRH) 
 
  4 . LHRH-Antagonist (or GnRH) 
 
  5 . Other, specify 
_________________________ 
              The used drugs 
_______________________________________ 
  5 . Focal Therapy 
Type of Focal Therapy 
  1 . High Intensity Focused Ultrasound  
 
  2 . Criotherapy 
 
  3 . Other, specify 
_________________________ 
Aim of Focal Therapy 
  1 . Curative 
 
  2 . Palliative 
 
  3 . Other, specify______________________ 
  6 . Chemotherapy 
Type of drug 
________________________________ 
Treatment scheme 
 
  7 . Second line Hormonal Therapy 
Type of drug 
 
Treatment scheme 
 

Final Version 1.0 – 18/01/2016 
 
51 
 
Has he planned further 
treatments related to prostate 
cancer, subsequent to those 
reported in Attachment 1 (1-
month follow up)? 
  
0 
. 
No 
  
1 
. 
Yes, specify:  
 
If yes: 
 
  1 . 
Surgery 
 
  2 . 
Esternal Beam Radiation Therapy 
 
 
  3 . 
Brachytherapy 
 
 
  4 . 
Radiometabolic Therapy 
 
 
  5 . 
Hormonal Therapy  
 
 
  6 . 
Focal Therapy 
 
 
  7 . 
Chemotherapy 
 
 
  8 . 
 
Others, specify 
____________________________________________________ 
If he does not have undergone 
further treatments, is he able 
to remember the last PSA 
value? 
  
1. 
Yes 
 
If yes: 
 
PSA  
|__|__|__|__|.|__|__|__|ng/mL 
 
Date of the PSA value 
test 
|__|__| / |__|__| / |__|__|__|__| 
   day         month              year 
  
0. 
No 
 
If no: 
 
Does he agree to ask it to his family 
doctor? 
  0. 
No 
  1. 
Yes 
 
What is his family doctor’s name? 
____________________________________________ 
 
 
PSA referred by the family doctor 
|__|__|__|__|.|__|__|__|ng/mL 
 
 
Date of the PSA value test referred by 
the family doctor 
|__|__| / |__|__| / |__|__|__|__| 
      day         month               year 
 
 

Final Version 1.0 – 18/01/2016 
 
52 
 
References 
1. Buyyounouski MK, Hanlon AL, Eisenberg DF, Horwitz EM, Feigenberg SJ, Uzzo RG, 
Pollack A. “Defining biochemical failure after radiotherapy with and without androgen 
deprivation for prostate cancer”, Int J Radiat Oncol Biol Phys. 2005; 63(5):1455-62. 
2. Heidenreich A, Bastian PJ, Bellmunt J “EAU Guidelines on Prostate Cancer. Part II: 
Treatment of Advanced, Relapsing, and Castration-Resistant Prostate Cancer”, Eur Urol 
2014; 65: 467-479. 
3. Kirby M, Hirst C, Crawford ED “Characterising the castration-resistant prostate cancer 
population: a systematic review”, Int J Clin Pract 2011; 65(11):1180–1192. 
 
 
 
Acute  Toxicities 
 
Rectal Acute Toxicity (Grade) 
Date Tox.  
Urinary Acute Toxicity (Grade) 
Date Tox.  
Small Intestine Acute Toxicity 
(Grade) 
 
 
Date Tox. 
 
 
 
 
 
GI Acute Toxicity (small bowel) 
(see Table 1)  
 
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=Unknown) 
Date yyyy-mm-dd 
 
Rectal Acute Toxicity  
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=Unknown) 
Date yyyy-mm-dd 
 
Urinary Acute Toxicity  
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=Unknown) 
     
Date 
 
Late Toxicity bladder/ rectum  
select (1=Yes, 2=No, 3=Unknown) 
Date yyyy-mm-dd 
 
Proctitis  
 
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6=I Unknown) 
Data yyyy-mm-dd 
 
Cystitis  
 
 
 
select (1=G0, 2=G1, 3=G2, 4=G3, 5=G4, 6= Unknown) 
Date yyyy-mm-dd 
 
Impotence  
 
 
 
select (1=No, 2=Yes pre RT, 3=Yes post RT, 4= Unknown) 
Date yyyy-mm-dd 
 
Incontinence   
 
 
select (1=No, 2=Yes pre RT, 3=Yes post RT, 4=Unknown) 

Final Version 1.0 – 18/01/2016 
 
53 
 
 
TABLE 1 – Toxicity 
 
RECTAL/SMALL BOWEL Acute TOX 
G0: No Toxicity 
G1: Increased alvus frequency not requiring any treatment. Rectal pain or abdominal pain not 
requiring any painkillers 
G2: Diarrhoea, mucositis, rectal pain or abdominal pain requiring painkillers 
G3: Diarrhoea requiring parenteral supportive care, severe mucositis or haematological alterations 
requiring treatment. Abdominal distension 
G4: Acute or subacute obstruction, fistula or perforation, haemorrhage requiring blood transfusion. 
Abdominal pain or tenesmus requiring ileostomy 
 
BLADDER Acute TOX 
G0: No Toxicity 
G1: Low urinary tract symptoms (LUTS) and dysuria not requiring any treatment 
G2: LUTS, dysuria and urgency requiring treatment or anaesthetics 
G3: Severe LUTS, urgency, dysuria, pelvic pain or bladder spasms and haematuria 
G4: Haematuria requiring blood transfusion, urinary obstruction, ulceration and necrosis 
 
Late TOX PROCTITIS 
G0: No Toxicity 
G1: Mild rectal pain, Slight diarrhoea (less than 5 discharges). Small bleeding 
G2: Diarrhoea (more than 5 discharges). Significant mucosal secretions and intermittent rectal 
bleeding 
G3: Obstruction or haemorrhage requiring surgery 
G4: Necrosis, perforation or fistula 
 
Late TOX CYSTITIS 
G0: No Toxicity 
G1: Slight epithelial atrophy, small telangiectasia, microscopic haematuria 
G2: Moderate LUTS, Intermittent macroscopic haematuria 
G3: Severe LUTS and dysuria spread of telangiectasia. Frequent haematuria. Reduction in bladder 
capacity (less than 150 cc) 
G4: Necrosis, bladder capacity reduced (less than 100 cc). Severe haemorrhagic cystitis 
 
 

Final Version 1.0 – 18/01/2016 
 
54 
 
SF-12 STANDARD ITALIAN VERSION 
(Apolone G et al. 2001) 
 
Excellent 
Very good 
Good 
Fair 
Poor 
1 
In general, you would say that your health 
condition is: 
1 
2 
3 
4 
5 
The following questions regard some activities you might do during a typical day. Does your health condition actually limit you in 
doing these activities? 
 
Yes, it limits a lot 
Yes, it limits a little 
No, it does not limit at 
all 
2 
Activities of moderate physical effort , such 
as moving a table , using the vacuum cleaner , 
playing bowls or a riding a bicycle 
1 
2 
3 
3 
Climbing several flights of stairs 
1 
2 
3 
During the last 4 weeks have you had the following problems at work or during other daily activities, because of your physical health 
condition? 
 
Yes 
No 
4 
Accomplished less than you would like 
1 
2 
5 
You had to limit certain kinds of occupation 
or other activities 
1 
2 
During the last 4 weeks have you had the following problems at work or during other daily activities, because of your emotional state 
(such as feeling depressed or anxious)? 
 
Yes 
No 
6 
Accomplished less than you would like 
1 
2 
7 
You did not do work or other activities as carefully 
as usual 
1 
2 
 
Not at all 
A little bit 
Moderat
ely 
Quite a bit 
Not at all 
8 
During the last 4 weeks, How much has pain 
hindered your usual work (at home and 
outside)? 
1 
2 
3 
4 
5 
How long during the last 4 weeks have you felt 
 
All of 
the time 
Most of 
the time 
A good bit 
of time 
Some of the 
time 
A little of 
the time 
All of 
the time 
9 
calm and serene? 
1 
2 
3 
4 
5 
6 
10 
full of energy? 
1 
2 
3 
4 
5 
6 
11 
discouraged and sad 
1 
2 
3 
4 
5 
6 
 
All of the 
time 
Most of the 
time 
A good bit 
of time 
Some of the 
time 
A little of the 
time 
12 
During the last 4 weeks, how long have your 
physical health condition or your emotional state 
interfered with your social activities, with family, 
with friends? 
1 
2 
3 
4 
5 
 
 
 

Final Version 1.0 – 18/01/2016 
 
55 
 
COMPLICATIONS DUE TO PROSTATE CANCER 
ITALIAN UCLA PROSTATE CANCER INDEX 
(Gacci M et al, 2005) 
URINARY FUNCTION 
This session regards the urinary routine. Please consider only the last 4 weeks. 
  
1. 
Over the LAST 4 WEEKS, how often have you leaked urine? 
1  Every day. 
  
2  About once a week 
  
3  Less than once a week 
  
4  Not at all. 
 
2. 
Which of the following best describes your urinary control during the LAST 4 WEEKS? 
1  No control whatsoever 
  
2  Frequent dribbling 
  
3  Occasional dribbling 
  
4  Total control 
 
3. 
How many pads or adult diapers per day have you usually used to control leakage during the LAST 4 
WEEKS? 
 1  3 or more pads per day 
 2  1-2 pads per day 
 3  No pads 
 
4. 
How big a problem, if any,  has each of the following been for you? 
 
Dripping urine or wetting your pants? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
3  Moderate problem 
  
4  Big problem 
 
Urine leakage interfering with your sexual activity? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
  
3  Moderate problem 
  
4  Big problem 
 
5. 
Overall, how big a problem has your urinary function been for you during the LAST 4 WEEKS? 
  
0  No problem 
  
1  Very small problem 
  
2  Small problem 
  
3  Moderate problem 
  
4  Big problem 
 
 
BOWEL FUNCTION 
The following section talks about all the bowel function and abdominal pain. Please consider only the last 4 weeks. 
 
6. 
How often have you had  rectal urgency (felt like you had to pass stool, but did not) during the LAST 4 WEEKS? 
 1  More than once a day 
 2 About once a day 
 3 More than once a week 
 4 About once a week 
 5 Rarely or never 
 
7. 
How much distress have your bowel movements caused you during the LAST 4 WEEKS? 
 1  Severe distress 

Final Version 1.0 – 18/01/2016 
 
56 
 
 2  Moderate distress 
 3  A little distress 
 4  No distress 
 
8. 
How often have you had crampy pain in your abdomen or pelvis during the LAST 4 WEEKS? 
 
 1 Several times a day 
 
 2 About once a day 
 
 3 Several times a week 
 
 4 About once this month 
 5 Rarely or never 
 
9. 
In particular, how big was the problem of bowel habits during the LAST 4 WEEKS? 
 
 1 Big problem 
 
 2 Moderate problem 
 
 3 Little problem 
 
 4 Very small problem 
 
 
 5 No problem 
 
SEXUAL FUNCTION 
THE NEXT SECTION IS ABOUT YOUR SEXUAL FUNCTION AND SEXUAL SATISFACTION. MANY OF THE 
QUESTIONS ARE VERY PERSONAL, BUT THEY WILL HELP US UNDERSTAND THE IMPORTANT ISSUES 
THAT YOU FACE EVERY DAY. REMEMBER THAT YOUR ANSWERS TO THIS QUESTIONNAIRE WILL BE 
KEPT CONFIDENTIAL AND WILL BE USED ONLY FOR RESEARCH PURPOSES. PLEASE ANSWER HONESTLY 
ABOUT THE LAST 4 WEEKS ONLY. 
 
10. 
HOW WOULD YOU RATE EACH OF THE FOLLOWING DURING THE LAST 4 WEEKS? 
 
Very poor 
Poor 
Fair 
Good 
Very good 
A. Your ability to have an erection?. 
1 
2 
3 
4 
5 
B. Your ability to reach orgasm (clima
1 
2 
3 
4 
5 
 
11. 
How would you describe the usual QUALITY of your erections? 
 1 None at all 
 2 Not firm enough for any sexual activity 
 3 Firm enough for masturbation and foreplay only 
 4 Firm enough for intercourse 
 
12. 
How would you describe the FREQUENCY of your erections? 
 1 I NEVER had an erection when I wanted one 
 2 I had an erection LESS THAN HALF the time I wanted one 
 3 I had an erection ABOUT HALF the time I wanted one 
 4 I had an erection MORE THAN HALF the time I wanted one 
 5 I had an erection WHENEVER I wanted one 
 
13. 
Overall, how would you rate your sexual function during the LAST 4 WEEKS? 
 1 Very poor 
 2 Poor 
 3 Fair 
 4 Good 
 5 Very good 
 
14. 
Overall, how big a problem has your sexual function been for you during the LAST 4 WEEKS? 
 1  No problem 
 2  Very small problem 
 3  Small problem 
 4  Moderate problem 
 5  Big problem