1782P - Prostate radiotherapy reduces long-term risk of obstructive uropathy in metastatic hormone sensitive prostate cancer (mHSPC): Results from the STAMPEDE M1|RT comparison

Background

Men with advanced prostate cancer are at risk of upper urinary tract obstruction (UUTO) due to local progression leading to increased morbidity. Primary site radiotherapy (RT) improves overall survival in patients with low volume metastatic hormone sensitive prostate cancer (mHSPC), with limited data available to demonstrate its impact on local progression. Accessible, high quality healthcare systems data (HSD) provides accurate event data beyond standard trial follow up, permitting evaluation of the impact of primary RT on need for UUTO interventions.

Methods

Linked HSD from Hospital Episode Statistics (HES) with follow-up to March 2021 were available for patients randomised 1:1 in England between arms A (standard of care [SOC]) and H (SOC+RT). Radiotherapy was delivered either daily: 55 Gy in 20 fractions over 4 weeks or weekly: 36 Gy in six fractions over 6 weeks. Interventions for UUTO (including percutaneous nephrostomy and or ureteric stent insertion) were identified using a comprehensive coding framework using International Classification of Diseases (ICD 10) diagnosis and Classification of Interventions and Procedures (OPCS 4) codes Multivariate flexible parametric survival models adjusted for randomisation stratification factors were used to estimate the treatment effect of primary RT on the cumulative incidence of UUTO and sub distribution hazard ratios (SDHR).

Results

1791/2061 (88%) were followed up by English hospitals; connected HSD were available for 1724/1791 (96%). After excluding 19 patients who had a UUTO intervention in the 90 days leading to randomisation, model-based 5-year incidence of UUTO requiring intervention was 5% [4; 7%] in patients randomised to SOC, and 3% [2; 4%] in patients randomised to SOC + RT (SDHR 0.568, 95% CI 0.353-0.912; p=0.017). Treatment effects were comparable in high- and low-volume metastasis subgroups.

Conclusions

UUTO interventions are performed in a modest proportion of mHSPC patients. Prostate radiotherapy significantly reduced the use of UUTO interventions. These data support the use of prostate radiotherapy in men with mHSPC at risk of UUTO.

Clinical trial identification

NCT00268476.

Editorial acknowledgement

Legal entity responsible for the study

MRC Clinical Trials Unit and UCL.

Funding

Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.

Disclosure

C. Jones: Financial Interests, Personal, Invited Speaker: Janssen. P. Dutey-Magni, M.R. Sydes: Financial Interests, Institutional, Research Funding: Janssen, Astellas, Novartis, Sanofi, and Clovis. L.R. Murphy, M. Murray, L.C. Brown: Non-Financial Interests, Institutional, Research Funding: Janssen, Astellas, Novartis, Sanofi, and Clovis. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis; Financial Interests, Institutional, Advisory Board, Assisted with submissions regarding licensing for abiraterone: Janssen; Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi; Financial Interests, Institutional, Advisory Board, Providing STAMPEDE trial data to facilitate license extensions internationally for docetaxel: Sanofi; Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck; Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer; Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited; Financial Interests, Institutional, Coordinating PI, Funding for STAMPEDE trial: Janssen, Astellas; Financial Interests, Institutional, Coordinating PI, Funding for RADIO trial bladder cancer: AstraZeneca. C. Parker: Other, Personal, Advisory Board: ITM Radiopharma; Financial Interests, Institutional, Advisory Board: AAA. N.W. Clarke: Financial Interests, Personal, Invited Speaker: Janssen, Astellas. All other authors have declared no conflicts of interest.