The Impact of Metastatic Directed Radiotherapy (MDRT) on Oligoprogressive Castration Resistant Prostate Cancer (CRPC)

In patients with metastatic prostate cancer (PCa) who receive androgen deprivation therapy (ADT), the sensitivity to castration will eventually disappear due to the selection of castration-refractory clones. This will lead to the stage of metastatic castration-refractory prostate can-cer (mCRPC), which is incurable and results in a median overall survival of 2-3 years. Treatment options for patients with mCRPC include several systemic agents, such as andro-gen receptor-targeted agents (ARTA), chemotherapy (docetaxel, cabazitaxel) and bone-targeting agents (radium- 223). Clinical progression and, to a lesser extent, biochemical pro-gression traditionally imply a switch to the next line systemic treatment (NEST). Within patients with mCRPC, there is a subgroup showing oligo-progression, defined as the progression of up to 3 lesions, including both metastatic and/or local relapse. Oligoprogression reflects a heterogeneous treatment response, which, in turn, reflects the heterogeneity of the clonogenic cells that give rise to mCRPC. Retrospective studies suggest that metastasis-directed radiotherapy (MDRT) to these oligoprogressive lesions delayed the need for NEST. Recently, promising results were published on the use of MDRT in the oligopro-gressive mCRPC (omCRPC) setting, with a NEST-free survival (NEST-FS) of 21 months in well selected patients. Currently, in The Netherlands, patients with omCRPC are frequently referred and treated with MDRT, but a clear treatment protocol and inclusion/selection criteria are missing. Moreover, the exact benefit of MDRT in patients with omCRPC remains unclear, as prospective evi-dence for MDRT in omCRPC is lacking.

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

* Adenocarcinoma of the prostate.
* mCRPC setting, with testosterone level \< 50 ng/dl or 1.7 nmol/l.
* Oligoprogressive disease diagnosed on PSMAscan; defined as the progression of pre-existing metastatic disease, and/or the appearance of new metastases and/or the appearance of a local relapse with a maximum of 3 lesions in total.
* Patients currently treated with ADT, whether combined with another systemic treatment such as ARTA, chemotherapy.
* For patients treated with chemotherapy, the course should be completed or stopped before start MORT - In case of treatment with ARTA, a minimal of 3 months response (PSA or clinical response).
* WHO performance status 0-2.
* Age \> = 18 years old.
* Patiënt should be presented at the multidisciplinary tumor board of the local hospital in which the therapy will be given.
* Before patiënt registration, written informed consent must be given according to ICH/GCO and national/local regulations.

Exclusion Criteria:

* Serum testosterone level \> 50 ng/ml or \> 1.7 nmol/l.
* Presence of more than 3 progressive/new metastatic lesions and/or local recurrence (which counts for 1 lesion).
* Active malignancy other than prostate cancer that can potentially interfere with the interpretation of the trial, except non-melanoma skin cancer or non-invasive urothelial cell carcinoma.
* Local recurrence in the prostate after previous radiotherapy
* Previous treatments (RT, surgery) or comorbidities making new treatment with MDRT impossible.
* Disorder precluding understanding of trial Information or informed consent or signing informed consent.
* Evidence of PSMA-negative disease.