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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.

TPS397 Background: Castrate-resistant prostate cancer (CRPC) affects around 3,000 men in Sweden every year. New drugs are available but they have moderate effect, low response rates, are expensive, and lack predictive treatment markers. This will lead to an unsustainable situation for prostate cancer care. Our hypothesis is that treatment decisions based on molecular profiling will significantly increase the response rate at 3 months compared to current clinical care, translating into improved progression free and overall survival. The vast majority of CRPC metastasize to the bone, with low success rate in obtaining sufficient material. Therefore, we will sequence circulating tumor DNA (ctDNA) being present at high levels in plasma. Methods: ProBio-II is an adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven phase 2 trial in men with CRPC . Men (n=750) will be randomized to receive either standard of care (following Swedish national guidelines) or treatment with Enzalutamide, Abiraterone, PARP inhibitors, RA-223, Cabazitaxel, or immune modulators based on molecular subtypes. The molecular subtypes are defined as tumor properties or mutations in certain genes/pathways including: Microsatellite instability; Androgen receptor alterations; DNA-repair deficiency; TP53 inactivation; PTEN inactivation etc. The molecular subtypes will be identified by ctDNA profiling. A specially designed ctDNA profile for CRPC has been developed by our group to detect: mutations, amplifications and genomic rearrangements in the androgen receptor (AR); mutations, genomic rearrangements and amplifications/deletions in 300 key genes involved in prostate cancer; and microsatellite instable and hypermutated cancers. ProBio-II’s design is novel and inspired by successful studies as I-SPY (breast cancer) and the NCI-MATCH trial (metastatic cancer). Novel aspects of the study design includes using prior probability of treatment response; re-randomization of non-responders; and adaptive design. The ProBio II study will start recruiting patients in Sweden in Q1 2018 and recruit patients during a 18 month period. All major oncology departments in Sweden will participate.

217 Background: Bone Scan Index (BSI) is a quantitative measurement that reflects the tumor burden in bone calculated from bone scintigraphy. It also represents a prognostic marker in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). Abiraterone acetate (AA) has showed to prolong survival before and after chemotherapy in this group of pts. In this study we evaluated the predictive value of BSI change as a biomarker of response in mCRPC patients on treatment with AA. Methods: We retrospectively studied 62 mCRPC pats who received AA following disease progression after chemotherapy at 3 different academic hospitals. Automated baseline and follow-up BSI data was obtained from images of whole-body bone scintigraphies performed before and during AA treatment. Data on clinical overall survival (OS), blood levels of prostate-specific antigen (PSA), alkaline phosphatase (ALP) and haemoglobin (Hb) at the time of baseline and upon follow-up was collected from medical records. The association between changes in these parameters at follow-up and survival was evaluated using Cox proportional-hazards regression models and Kaplan-Meier estimates of the survival function. Discrimination between prognostic variables was assessed using the concordance index (C-index). Results: Pts with an increase in BSI of > 0.3 (n=31) had 13% one year-survival rate compared to 42% for pts with improvement or stable disease according to BSI change at follow-up (BSI change < 0.3; n=31) (p< 0.001). Among all parameters evaluated (BSI, PSA, ALP, Hb) in a univariate Cox analysis, BSI change from baseline to follow-up presented the highest and strongest association with OS (C-index=0.7, Hazard ratio= 1.3 and p=0.0001). Conclusions: Increase in BSI of ≥ 0.3 is significantly associated with reduced survival in mCRPC pts under AA treatment following disease progression in a post-chemotherapy setting. BSI is a candidate biomarker to evaluate response and survival in this group, and change in BSI could be a valuable tool in monitoring pts with mCRPC on second-line therapies. BSI could then serve as a decision making tool supporting physicians to continue current treatment or to consider alternative therapies.

49 Background: Men who are curatively treated with radiotherapy (RT) or radical prostatectomy (RP) for localized prostate cancer have long life expectancy but data on long term complications to treatment are scarce. Methods: In the nationwide, population-based Prostate Cancer data Base Sweden (PCBaSe), we identified men who underwent RT or RP between 1997 and 2012. Date of radiotherapy and dose of radiation were reassessed in an audit. For each case five controls from the background population, matched for age and county of residence, had been identified. The National Patient Register was used to identify diagnoses and surgical procedures indicating a complication to treatment, such as urinary incontinence, lower urinary tract symptoms and gastrointestinal symptoms, up to twelve years after treatment. The incidence rate ratio of complications for men who received RT and RP relative to their matched controls was calculated and relative risks (RR) were calculated for RT vs RP adjusted for treatment year, age, Charlson comorbidity index, educational level, PSA-level, clinical T stage and biopsy Gleason score. Results: In total, 37,420 men met the study criteria, of whom 12,534 had undergone RT and 24,886 had undergone RP. There were 186,624 matched controls. The risk of receiving any of the analyzed diagnoses or surgeries at 12 years after treatment was higher after RT; RT vs RP RR 1.20 (95%CI 1.08-1.34) and RT vs RP RR 1.49, (95% CI 1.36-1.64) for the diagnoses and surgical procedures respectively. At 3 years the risk of receiving any of the analyzed diagnoses was comparable between the treatments; RT vs RP RR 1.02 (95% CI 0.91-1.16) but the risk of undergoing any of the analyzed surgical procedures remained higher after RT during the entire study period. Men who underwent RP had a higher risk of being diagnosed or treated for urinary incontinence; RT vs RP RR 0.09 (95% CI 0.04-0.19) and RR 0.04 (95% CI 0.01-0.11) for the selected diagnoses and surgical procedures respectively. Conclusions: Complications after RP mostly occurred within the first 3 years after surgery whereas complications after RT were more frequent at a later date after treatment.