Study protocol of a randomised controlled trial of prostate radiotherapy in high-risk and node-positive disease comparing moderate and extreme hypofractionation (PRIME TRIAL).

There has been an interest in studying the efficacy of extreme hypofractionation in low and intermediate risk prostate cancer utilising the low alpha/beta ratio of prostate. Its role in high-risk and node-positive prostate cancer, however, is unknown. We hypothesise that a five-fraction schedule of extreme hypofractionation will be non-inferior to a moderately hypofractionated regimen over 5 weeks in efficacy and will have acceptable toxicity and quality of life while reducing the cost implications during treatment.

This is an ongoing, non-inferiority, multicentre, randomised trial (NCT03561961) of two schedules for National Cancer Control Network high-risk and/or node-positive non-metastatic carcinoma of the prostate. The standard arm will be a schedule of 68 Gy/25# over 5 weeks while the test arm will be extremely hypofractionated radiotherapy with stereotactic body radiation therapy to 36.25 Gy/5# (7 to 10 days). The block randomisation will be stratified by nodal status (N0/N+), hormonal therapy (luteinizing hormone-releasing hormone therapy/orchiectomy) and centre. All patients will receive daily image-guided radiotherapy.The primary end point is 4-year biochemical failure free survival (BFFS). The power calculations assume 4-year BFFS of 80% in the moderate hypofractionation arm. With a 5% one-sided significance and 80% power, a total of 434 patients will be randomised to both arms equally (217 in each arm). The secondary end points include overall survival, prostate cancer specific survival, acute and late toxicities, quality of life and out-of-pocket expenditure.

The trial aims to establish a therapeutically efficacious and cost-efficient modality for high-risk and node-positive prostate cancer with an acceptable toxicity profile. Presently, this is the only trial evaluating and answering such a question in this cohort.

The trial has been approved by IEC-III of Tata Memorial Centre, Mumbai.

Registered with CTRI/2018/05/014054 (http://ctri.nic.in) on 24 May 2018.

BMJ open. 2020 Feb 28*** epublish ***

Vedang Murthy, Indranil Mallick, Abhilash Gavarraju, Shwetabh Sinha, Rahul Krishnatry, Tejshri Telkhade, Arunsingh Moses, Sadhna Kannan, Gagan Prakash, Mahendra Pal, Santosh Menon, Palak Popat, Venkatesh Rangarajan, Archi Agarwal, Sheetal Kulkarni, Ganesh Bakshi

Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India ., Department of Radiation Oncology, Tata Medical Centre, Kolkata, India., Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India., Clinical Research Secretariat, Tata Memorial Centre, Mumbai, India., Division of Uro-Oncology, Tata Memorial Centre, Mumbai, India., Department of Pathology, Tata Memorial Centre, Mumbai, India., Department of Radiology, Tata Memorial Centre, Mumbai, India., Department of Nuclear Imaging and Bio imaging, Tata Memorial Centre, Mumbai, India.