The goal of this clinical trial is to combine several optimized treatments of high risk prostate cancer. The main question to answer is: is it safe to combine these optimized treatments.

• patients will be irradiated on the prostate and (elective) lymph nodes more concentrated but with fewer hospital visits (hypofractionation)
• the tumor will get a higher dose
• androgen deprivation therapy will be reduced as much al possible preventing side effects

Researchers will compare oncological outcome and toxicity.

Rationale: Recently several randomized trial have shown benefits of changes made to radiotherapy of (high risk) localized prostate cancer patients: A focal boost was shown to improve outcome in men with intermediate/high risk prostate cancer (FLAME trial). Elective lymph node irradiation was shown to improve outcome in high risk prostate cancer patients (POP-RT). (Extreme) hypo fractionation was shown to be safe for low/intermediate risk prostate cancer patients. In addition: the added benefit of ADT (with substantial toxicity) seems reduced with improvements made to treatment and diagnosis in recent years (DART 01/05); own recent work on this topic; to be published)). None off the above were combined into one ideal treatment for high risk prostate cancer.

Objective: Determine the safety (oncological outcome and toxicity) of an comprehensive treatment combining recent advances in the treatment of high risk prostate cancer.

Study design: prospective cohort study with matched contemporary control group Study population: Men with high risk prostate cancer with an indication for elective lymph node irradiation Intervention: hypo fractionated pelvic radiotherapy with boost to primary tumour in the prostate Main study parameters/endpoints: biochemical recurrence free survival and late toxicity Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The additional burden of the study is considered to be low, as additional tests or site visits in comparison to current clinical follow up are not planned. Regarding safety, different parts of the investigational treatment were already shown to be safe in previous studies. The current study aims to combine these different parts into one treatment. We estimate that the risks associated with combining these treatments are very limited.

Inclusion Criteria:

• Men (aged ≥18 years of age) diagnosed within 6 months before inclusion with high risk prostate cancer:

  • T3 based on digital rectal examination AND/OR
  • Grade >= 4 AND/OR
  • PSA >=20 ug/L

• Indication for elective lymph node irradiation (based on current clinical guidelines) OR N1 on imaging (with a maximum of 4 suspect lymph nodes)

Exclusion Criteria:

• Prior pelvic radiotherapy
• TransUrethral Resection of the Prostate (TURP) < 3 months ago
• Prostatectomy or other primary treatment for prostate cancer (e.g. HIFU, cryotherapy, etc)
• contraindications to MRI
• no visible lesion on MRI in prostate for boost
• no PSMA-PET scan
• inflammatory bowel disease
• metastatic disease (M1)
• PSA >50
• unsuitable for SBRT or WPRT
• medical history of cancer other than basal cell carcinoma of the skin