Weekly Online CT or MR Adaptive Definitive SBRT for Regionally Metastatic Prostate Cancer

Weekly Online CT or MR Adaptive Definitive SBRT for Regionally Metastatic Prostate Cancer (WARP)

This interventional prospective multicenter international study will include 54 patients with regionally metastatic (i.e. cN1 cM0) prostate cancer according to the NCCN criteria.

Patients will be treated with weekly CT or MR-informed online adaptive SBRT of the prostate and elective pelvic lymph nodes with 5 x 5 Gy. A simultaneous integrated boost (SIB) of involved lymph nodes will be performed. In the case of up to 2 dominant intraprostatic lesion (DIL) a SIB of the DIL can be performed (optional). Importantly, coverage of these DIL volumes must be compromised as needed to respect OAR constraints.

This study is classified as risk category A according to ClinO, Art. 61, as stereotactic radiotherapy (SBRT) for regionally metastatic prostate cancer has been extensively evaluated in prospective interventional trials and is considered an established therapeutic modality.

Weekly CT- or MR-guided online adaptive SBRT to the prostate and elective pelvic lymph nodes with 5 × 5 Gy is, however, not yet routinely implemented for this specific patient population.

A diagnostic high field MRI during radiotherapy, e.g. week 3 is optional.

Follow-up is also according to standard of care (except for patient reported outcome measure using QLQ-C30 and QLQ-PR25 and a diagnostic MRI at 9 months after SBRT (optional), and 12 months in the case of an image non-complete response at 9 months (optional).

Inclusion criteria include:

• Regionally metastatic prostate cancer (cN1, any T, Gleason 6-10, any PSA) according to NCCN guidelines consisting of ≤ 5 regional lymph node metastases
• Good to moderate performance status (WHO 0-2)
• Written informed consent.
• A PSMA PET and multiparametric MRI is mandatory according to staging guidelines.
• Age ≥ 18 years

Exclusion criteria include:

• >5 regional lymph nodes

• Patients with cT4 disease (tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall)

• Previous radiotherapy to the pelvis or prostate

• Previous radical prostatectomy

• Large body size that would not fit into the MRI-simulator bore

• Presence of distant metastases (i.e. cM1)

  • Non-regional lymph nodes (M1a):
  • Bone metastases (M1b)
  • Other sites (M1c)

• Contraindications to CT or MR-adaptive SBRT (e.g., pacemakers, severe claustrophobia).

• Severe comorbidities that may interfere with treatment or follow-up (e.g. inflammatory bowel disease).

• Significant concomitant diseases (e.g. hepatic dysfunction, cardiovascular disease, etc.).

• Inability to follow procedures or insufficient knowledge of project language, inability to give consent.

• Participation in a clinical trial which might influence the results of this project.

• Enrolment of the investigator, his/her family members, employees and other dependent persons.

• Severe genitourinary or gastrointestinal symptoms (e.g. recent urinary retention or diarrhea ≥ grade 3 or obstipation to CTCAE v.6.0).

• Severe urinary symptoms (e.g. IPSS >12 and/or prostate volume > 80 mL)