Hypofractionated radiotherapy of intermediate risk localised prostate cancer: a phase III, randomised, open, multicentre trial
To demonstrate a 10% unit increase (70% to 80%) in freedom from failure (prostate specific antigen [PSA] or any clinical test) in the HYPO-RT arm at 5 years after the end of treatment.
Local medical ethics committee (Regionala etikprövningsnämnden i Umeå) gave approval on the 9th December 2003 (ref: 03-513)
Phase III randomised open multicentre trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Can be found at http://www.oc.umu.se/ (Swedish only) under PDF-dokument/Kliniska studier: HYPO-RT-PC
Intermediate risk localised prostate cancer
The radiation treatment shall be given with external photon beam therapy with three-dimensional conformal radiotherapy (3D-CRT) and/or intensity modulated radiation therapy (IMRT) techniques. It is left to each centre to decide upon the optimal technique (number of beams, beam weights, beam angles, beam shaping, etc). The same treatment technique shall be used in both trial arms within the centre. The position of the prostate shall be verified prior to every fraction with electronic kV or MV portal imaging or x-ray volumetric imaging (cone beam CT) using implanted markers. The treatment should start as soon as readily possible after the verification/correction. The monitor units (dose) used for verification of position should be considered and compensated for if MV portal imaging is used. Each centre should have treated at least two patients with their specific marker and image guidance technique before entering the study.
Fractionation schedule and treatment durations:
Conventional arm: radiotherapy is given daily (5 days/week) with 39 fractions of 2.0 Gy, i.e. total 78.0 Gy. The total treatment time is 53 - 55 days. Maximum allowed treatment days are 65.
Hypofractionated arm: radiotherapy is given working-days with 7 fractions of 6.1 Gy, i.e. total 42.7 Gy. The total treatment time is 15 - 19 days. Treatment is given every other weekday, always including two weekends.
Clinical follow up:
Patients should be seen by a doctor (urologist/surgeon or oncologist) for clinical evaluation every 3 months (+ 14 days) preferentially by an oncologist for the first year, and every six months (+ 28 days) thereafter until metastases are verified. Thereafter patients should be followed for verification of death.
Primary outcome measures
Freedom from failure (PSA or any clinical), measured five years after the end of treatment.
Secondary outcome measures
1. PSA response rate
2. Time to symptoms related to local progression
3. Time to symptoms related to distant progression
4. Cancer specific survival
5. Overall survival
6. Quality of Life (QoL) and side effects with special focus on sexual function, urinary and gastrointestinal morbidity
Measured five years after the end of treatment.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Men less than 75 years of age and, as judged by the doctor, a life expectancy of 10 years (except for cancer) at time of randomisation with performance status World Health Organization (WHO) grades 0 - 2
2. Patients with a histologically verified prostatic cancer
3. Patients with intermediate risk prostatic cancer of clinical category T1c - T3a with one or two of the following risk factors:
3.1. T3a or Gleason greater than 7
3.2. PSA greater than 10 according to the TNM classification system UICC 2002
4. PSA less than 20 µg/L
5. The patients should have no evidence of metastases according to the definition above
6. Patients should be lymph node negative according to the definition above, i.e. staging
7. Patients should be suitable for radiotherapy
8. Patients must have signed informed consent
Target number of participants
In total: 592
Participant exclusion criteria
1. Patients who earlier have undergone any other treatment for prostatic cancer
2. Patients unable to co-operate or suffering from any other form of disease that would interfere with the planned treatment (e.g. colitis)
3. Patients with previous diagnosis of other malignant disease. Exceptions could be made for basal cell carcinoma of the skin or progression free survival at least 10 years after any previous tumour.
4. Previous hormone therapy (castration or anti-androgens)
5. Any condition that prevent markers implantation, i.e. anal fissure
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Department of Oncology
Nordic Cancer Union (Nordiska Cancerunionens [NCU]) (Sweden)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting