Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference

PURPOSE: Multiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP). PATIENTS AND METHODS: 10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered. RESULTS: Median overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 – 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 – 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1. CONCLUSION: Urethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.