TPS192 Background: Radiotherapy of the primary tumor in metastatic prostate cancer is life-prolonging in patients with limited disease spread. Several different fractionation schedules have been used, most widely used is a four-week schedule of 2.75-3 Gy in 19-20 fractions. More data is emerging around hypo-fractionated radiotherapy in the curative setting. We hypothesize that a modified version of the Scandinavian Hypo-trial fractionation 6.1Gy per fraction x 6 fractions over a span of 2½ week will be non-inferior in side-effects as a 4-week schedule but more convenient for patients and caregivers. Methods: The Hypo-M1 trial is a randomized, stratified, multi-center, phase 3 clinical trial recruiting 420 patients in 9 Swedish centers. Key eligibility criteria include histological confirmed prostate cancer, indication for radiotherapy of low burden metastatic prostate cancer, defined as a max of 4 skeletal metastases at any site or lymph node metastases outside the pelvis and no other diseases or treatments interfering with radiotherapy or a score > 20 on the International prostate symptom score (IPSS) scale. Patients will be randomized to either 3 Gy x 19 or 6.1Gy x 6. Stratification factors are T1-T3 vs T4 and randomizing centre. Type of staging procedures performed, CT and whole-body bone scan is recommended, PSMA-PET allowed and further treatment beyond ADT is recorded but not stratification variables. Standard treatment may include docetaxel, apalutamide, abiraterone and enzalutamide at the treating physician’s discretion. Toxicity will be measured before, at the end of radiotherapy and at 1, 3, 6, 12 months and at 3 years. Measures used are the CTCAE v 5.0 and RTOG scales and QoL life will be measured at the same time points with the Prostate Cancer Symptom Scale (PCSS), a validated QoL instrument focusing on prostate cancer radiotherapy. The primary endpoint is QoL at 3 months and key secondary is acute toxicity at 3 months, late toxicity and QoL at 12 months, failure free survival and cause specific survival. The sample size is calculated for a continuous outcome non-inferiority trial with a one-sided alpha-value of 2.5 % and a beta-value of 80 %. The non-inferiority limit is set to 7.5 % This will require 175 patients with complete follow up in each treatment arm. Expecting a response rate of 80 % for the PCSS at the main time end point the total number of patients in each arm will be 210. The National Prostate Cancer Registry, covering 98% of all prostate cancer cases in Sweden, will be used as CRF including also a randomization module, making this a truly population based clinical trial. As of October 12, 2021, accrual is set to begin in December. The Hypo-M1 trial is an investigator-led, academic trial sponsored by the Swedish Society of Urological Oncology with study coordination provided by Cancer Center of Umeå University Hospital, Umeå, Sweden. Clinical trial information: NCT04612907.