Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy

Metastatic disease in patients involves treatment including systemic chemotherapy, hormonal therapy and androgen deprivation therapy. "Oligometastases" was termed to describe a state of metastatic transition wherein the cancer cells travel from the original site of tumour to other parts of the body and form fewer number of tumours. Sustained systemic therapies such as chemotherapy have been used as the Standard of care (SOC) in most cases. Novel radiotherapy like Lutetium-177 PSMA radionuclide therapy have been explored in earlier disease settings to further improve outcomes. Based on evidence from few previous trials and emerging safety data from ongoing trials, it is an effective addition to SOC to further improve patient outcomes.

The detection of prostate cancer can be done by a highly sensitive and specific test using the PSMA-PET small molecules. The evidence of high uptake of these PSMA-PET small molecules assists in selection of patients potentially suitable for novel PSMA targeted radionuclide therapy. Previous studies have demonstrated novel molecular imaging techniques, particularly PSMA PET/CT in the biochemical recurrence setting is leading to an increasing number of patients being diagnosed with oligometastatic disease which would not have been detected using conventional imaging techniques.

The Stereotactic ablative body radiotherapy (SABR) is also an emerging localised treatment option for oligometastatic prostate cancer. It delivers a highly focused beam of external radiation concentrated over a tumour and has been used to treat low volume metastatic disease to delay the use of systemic therapies. Results from previous studies show that it a safe, well-tolerated and progressively used in real-world clinical practice to treat patients with low volume of metastatic cancer. Based on the results of a previous trial done by this team, patients with one to three sites of disease treated with a single session of SABR showed promising outcomes.

The aim of this trial is to evaluate the progression free survival of SABR alone and SABR + 177Lu-prostate-specific membrane antigen (PSMA) in patients with oligometastatic prostate cancer undergoing PSMA positron emission tomography (PET) staging.

92 men with oligometastatic prostate cancer will be enrolled in this trial and split into 1:1 ratio to either stereotactic ablative body radiotherapy (SABR) alone or SABR plus 2 cycles of 177Lu-PSMA over a period of 24 months.

• The AEs according to CTCAE v5.0 [Time frame: Through study completion, up until 4 months ± 10 days from the commencement of ADT following progression]
• The PSA-response rate [Time frame: Through study completion, up until time of biochemical progression +/- 10 days]
• The ADT-free survival [Time frame: Through study completion, up until biochemical progression +/- 10 days]
• The pattern of recurrence on PSMA PET [Time frame: Time of biochemical progression +/-10 days]
• The patient reported quality of life [Time frame: From the date of randomisation to the date of progression]
• The MDT PFS [Time frame: Time point after Cycle 2 (28 days follow up post Cycle 2) until biochemical progression]
• The overall survival [Time frame: Time point post randomisation to the date of death from any cause]
• Healthcare costs associated with delivering the intervention and management of AEs [Time frame: Through study completion, an average of 3 years]
• The PET-PFS [Time frame: Through study completion, from the date of randomisation to the date of radiological progression or death from any cause, whichever comes first.]