A First Step Towards Ultra-hypofractionation for Unfavourable Intermediate and High-risk Prostate Cancer: a Prospective Safety and Feasibility Study in Patients With Metastatic Prostate Cancer

Rationale:

One of the key treatment modalities for prostate cancer is external beam radiation therapy. Considering the relatively low alpha/beta ratio of prostate cancer, increasing the dose per fraction could yield higher tumour control rates with acceptable toxicity in a reduced number of treatment fractions (hypofractionation). Ultrahypofractionation (fraction dose > 5 Gy) has shown promising results for low- and intermediate risk prostate cancer.

Ultrahypofractionation for high-risk prostate cancer however is challenging as the seminal vesicles (SV) are included in the target volume, which is not the case for intermediate and low-risk prostate cancer patient. These SV belong to the male reproduction system and their exact shape and size can differ substantially. The SV are attached bilaterally to the prostate and, similarly to the prostate, their motion is caused by changes in bladder and rectal filling status. However, although the cause of motion is similar for both the prostate and the SV, multiple studies report that the inter- and intra-fraction motion of the SV remain significant and largely uncorrelated to the prostate motion.

Considering the SV must be included in the target volume, the significant SV motion has to be accounted for during treatment. A solution is to use safety margins to extend the clinical target volume (CTV) to the planning target volume (PTV). Due to their substantial inter- and intra-fraction motion, the SV require a relatively large PTV-margin of 8 mm, which causes the bladder and rectum to receive more dose per fraction, which in combination with a higher fraction dose could result in unacceptable genitourinary and gastrointestinal toxicity rates.

This means that to safely introduce ultra-hypofractionation for high-risk prostate cancer patients, strategies to minimize PTV-margins around the SV are required. To account for the inter-fraction motion of the SV, adaptive radiotherapy (ART) in the form of online re-planning could be the solution. Online re-planning is a workflow in which a new treatment plan is generated for each fraction, optimized on the anatomy of the day. ART accounting for the intra-fraction motion of the prostate has been studied well, for example by tracking the intra-prostatic markers with the CyberKnife system. Using the in-room Computed Tomography (CT) scan of our institution's CyberKnife, it is feasible to combine online re-planning with intra-fraction fiducial tracking.