A Randomised Feasibility Trial of Stereotactic Prostate Radiotherapy with or without Elective Nodal Irradiation in High-Risk Localised Prostate Cancer (SPORT Trial).

To establish the feasibility of a randomised clinical trial comparing stereotactic ablative radiotherapy (SABR) to the prostate-only (P-SABR) or to prostate plus pelvic lymph nodes (PPN-SABR) in patients with unfavourable intermediate- or high-risk localised prostate cancer and explore potential toxicity biomarkers.

Thirty adult men with at least one of the following features; clinical MRI stage T3a N0 M0, Gleason score ≥ 7 (4+3), PSA > 20 ng/mL were randomised 1:1 to P-SABR or PPN-SABR. P-SABR patients received 36.25Gy/5 fractions/29 days, PPN-SABR patients also received 25Gy/5 fractions to pelvic nodes with the final cohort receiving a boost to the dominant intraprostatic lesion of 45-50 Gy. γH2AX foci numbers, citrulline levels and circulating lymphocyte counts were quantified. Acute toxicity information (CTCAE v4.03) was collected weekly at each treatment and at six weeks and three months. Physician-reported late RTOG toxicity was recorded from 90 days to 36 months post-completion of SABR. Patient-reported quality of life (EPIC and IPSS) scores were recorded with each toxicity timepoint.

The target recruitment was achieved and treatment successfully delivered in all patients.0% and 6.7% (P-SABR) and 6.7% and 20.0% (PPN-SABR) experienced acute grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) toxicity respectively. At 3 years, 6.7% and 6.7% (P-SABR) and 13.3% and 33.3% (PPN-SABR) had experienced late grade ≥ 2 GI and GU toxicity respectively. One patient (PPN-SABR) had late grade 3 GU toxicity (cystitis and haematuria), no other grade ≥ 3 toxicity was observed. 33.3% and 60% (P-SABR) and 64.3% and 92.9% (PPN-SABR) experienced a minimally clinically important change (MCIC) in late EPIC bowel and urinary summary scores respectively. γH2AX foci numbers at 1 hour post-first fraction were significantly higher in PPN-SABR arm compared to P-SABR arm (p=0.04). Patients with late grade ≥ 1 GI toxicity had significantly larger falls in circulating lymphocytes (12 weeks post-radiotherapy, p=0.01), and a trend towards higher γH2AX foci numbers (p=0.09), than patients with no late toxicity. Patients with late grade ≥ 1 bowel toxicity and late diarrhoea experienced greater falls in citrulline levels (p=0.05).

A randomised trial comparing P-SABR to PPN-SABR is feasible with acceptable toxicity. Correlations of γH2AX foci, lymphocyte counts and citrulline levels with irradiated volume and toxicity suggest potential as predictive biomarkers. This study has informed a multicentre UK randomised phase III clinical trial.

International journal of radiation oncology, biology, physics. 2023 Mar 07 [Epub ahead of print]

Orla A Houlihan, Kelly Redmond, Ciaran Fairmichael, Ciara A Lyons, Conor K McGarry, Darren Mitchell, Aidan Cole, John O'Connor, Stephen McMahon, Denise Irvine, Wendy Hyland, Michael Hanna, Kevin M Prise, Alan R Hounsell, Joe M O'Sullivan, Suneil Jain

Department of Clinical Oncology, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, Northern Ireland; Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland. Electronic address: ., Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland., Department of Clinical Oncology, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, Northern Ireland; Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland., Department of Radiotherapy Medical Physics, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, Northern Ireland., Department of Clinical Oncology, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, Northern Ireland., Northern Ireland Cancer Trials Network, Belfast City Hospital, Belfast, Northern Ireland.