Abstract 1782P
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.
Resources from the same session
1807P - Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Subgroup analyses of the all-comers cohort from TALAPRO-2 by homologous recombination repair (HRR) status
Presenter: Nobuaki Matsubara
Session: Poster session 14
1808P - Pain response and health-related quality of life (HRQL) analysis in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel every 2 weeks (16 mg/m<sup>2</sup>) versus every 3 weeks (25 mg/m<sup>2</sup>) in the CABASTY phase III trial
Presenter: Stephane Oudard
Session: Poster session 14
1809P - Dynamics of plasma tumour DNA and copy number alterations in advanced metastatic castration-resistant prostate cancer (mCRPC) patients treated with cabazitaxel: A prospective biomarker trial
Presenter: Nicole Brighi
Session: Poster session 14
1810P - Association of health-related quality of life with efficacy outcomes in the VISION study of patients with metastatic castration-resistant prostate cancer
Presenter: Michael Morris
Session: Poster session 14
1811P - Patient-reported outcomes (PROs) in men with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA: Results from a phase III (TALAPRO-2) study
Presenter: Andre Fay
Session: Poster session 14
1813P - Phase I/II trial of oral EPI-7386 in combination with enzalutamide (enz) compared to enz alone in metastatic castration-resistant prostate cancer (mCRPC) subjects: Current phase I (PI) results
Presenter: Andrew Laccetti
Session: Poster session 14
1814P - First real-life data on [177Lu]Lu-PSMA-617: Descriptive analysis on the largest metastatic castration-resistant prostate cancer (mCRPC) cohort treated in early access in France
Presenter: Anne-Laure Giraudet
Session: Poster session 14
1815P - Emergent circulating tumor DNA (ctDNA) variants and ctDNA burden dynamics with potential associations with talazoparib antitumor activity in TALAPRO-1
Presenter: Elena Castro
Session: Poster session 14