Abstract
PurposeMultiparametric 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 Methods10 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.ResultsMedian 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.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.
Highlights
Radiotherapy (RT) of primary Prostate cancer (PCa) is currently experiencing an individualization, utilizing modern imaging techniques for staging and definition of intraprostatic gross tumor volume (GTV)
This planning study aims to investigate whether urethral sparing in moderately hypofractionated RT (MHRT) with focal dose escalation delivered to multiparametric magnetic resonance tomography (mpMRI) and PSMA-PET/CT defined GTVs, influences tumor control probability (TCP) and normal tissue complication probability (NTCP)
NTCP was calculated based on the Lyman-Kutcher-Burman (LKB) model with parameters defined by Panettiere et al [21], tissue control probabilities (TCP) was calculated based on 3D dose distribution in co-registered histopathology as standard of reference
Summary
Radiotherapy (RT) of primary Prostate cancer (PCa) is currently experiencing an individualization, utilizing modern imaging techniques for staging and definition of intraprostatic gross tumor volume (GTV). The long-term result of the phase III FLAME trial demonstrated that mpMRI-defined focal dose escalation significantly improves biochemical disease free survival [4]. Earlier publications from this trial demonstrated the feasibility and reported no significant increase in acute and late toxicities [5]. The impact of accountable structures such as bladder, bladder trigone and urethra stay vague, the urethra as a serial organ may be of particular importance in this setting This planning study aims to investigate whether urethral sparing in MHRT with focal dose escalation delivered to mpMRI and PSMA-PET/CT defined GTVs, influences tumor control probability (TCP) and normal tissue complication probability (NTCP). The influence of intrafractional movement was assessed [22]
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