A randomised feasibility trial of stereotactic prostate radiotherapy with or without elective nodal irradiation in high-risk localised prostate cancer (SPORT Trial)

PURPOSE: 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.

MATERIALS & METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.