Online Adaptive Stereotactic Body Radiotherapy for Localized Prostate Cancer (X-SMILE)

The aim of this phase II international multicenter study is to evaluate the safety, feasibility, and efficacy of CT or MRI-adaptive SBRT, delivered in five weekly fractions, in patients with newly diagnosed localized prostate cancer who have lower urinary tract symptoms and/or prostatic hyperplasia.

Background: Stereotactic body radiotherapy (SBRT) for localized prostate cancer has demonstrated non-inferior oncological outcomes and toxicity profiles to conventionally or moderately hypofractioned radiotherapy regimens, while offering the advantage of shorter treatment durations. However, SBRT may not be suitable for all patients, particularly those with lower urogenital tract symptoms and/or prostatic hyperplasia.

Methods: This study aims to evaluate the safety and efficacy of weekly computed tomography (CT) or magnetic resonance image-guided (MRI) online adaptive SBRT in patients with intermediate to (very) high-risk localized prostate cancer who present with lower urinary tract symptoms (International Prostate Symptom Score \[IPSS\] \> 12) and/or have prostate hyperplasia (prostate volume \>60 mL). The primary outcome measure is urogenital toxicity grade ≥3 within 3 months after completion of SBRT (according to CTCAE V5.0 and RTOG) or discontinuation of therapy. Our aim is to show that the event rate is at 3% below a clinically acceptable threshold, which is set at 20%. Under the null hypothesis, this design with an alpha of 0.05 and power of 80% results in an expected number of cases of 30.

Eligibility Criteria:
Inclusion Criteria:

* histologically confirmed localized prostate cancer
* planned treatment is SBRT according to standard of care and consists of definitive CT or MRI online adaptive SBRT of the prostate according to the PACE trial which includes a total dose to clinical target volume 1 (CTV1, i.e. prostate and proximal 1 cm of the seminal vesicle) of 40.0 Gy in 5 weekly fractions (single dose of 8.0 Gy) and total dose to planning target volume 1 (PTV1) of 37.5 Gy in 5 weekly fractions (single dose of 7.5 Gy) with a compromise for bowel sparing allowed. For patients with unfavorable intermediate to very high-risk disease (according to NCCN guidelines) a total dose to the planning target volume 2 (PTV2, i.e. proximal 1-2 cm of the seminal vesicle) of 32.5 Gy in 5 weekly fractions (single dose of 6.5 Gy) will be delivered.
* intermediate to (very) high risk localized prostate cancer (≤ cT3a and Gleason score ≤ 9 and/or PSA ≤ 20 ng/ml)
* prostate volume \> 60 cc and/or IPSS \> 12;

Exclusion Criteria:

* Very high risk localized prostate cancer with indication for ADT and ARPI (i.e. Gleason ≥ 8 and cT3a)
* Involvement of seminal vesicles (cT3b)
* Contraindications against definitive CT or MRI-adaptive radiotherapy of the prostate, e.g. inflammatory bowel disease (IBD); previous radiotherapy in the pelvis, previous local radiotherapy of the prostate, contraindication for MRI or CT;
* Patients with severe genitourinary symptoms (e.g. recent urinary retention ≥ grade 3 according CTCAE v.5.0);
* Lymph node metastases or distant metastases (i.e. no localised prostate cancer);
* Participation in a clinical trial which might influence the results of this project.