Toxicity and Efficacy of Local Ablative, Image-guided Radiotherapy in Gallium-68 Prostate-specific Membrane Antigen Targeted Positron Emission Tomography–staged, Castration-sensitive Oligometastatic Prostate Cancer: The OLI-P Phase 2 Clinical Trial

• Published in: European urology oncology Vol. 5; no. 1; pp. 44 - 51
• Main Authors: Hölscher, Tobias, Baumann, Michael, Kotzerke, Jörg, Zöphel, Klaus, Paulsen, Frank, Müller, Arndt-Christian, Zips, Daniel, Koi, Lydia, Thomas, Christian, Löck, Steffen, Krause, Mechthild, Wirth, Manfred, Lohaus, Fabian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2022
• Subjects: Adult; Androgen Antagonists - therapeutic use; Androgens; Castration; Gallium Radioisotopes; Humans; Image guided, Radiosurgery; Male; Neoplasm metastasis; Positron emission tomography; Prospective Studies; Prostate - pathology; Prostate-Specific Antigen; Prostatic neoplasms; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - radiotherapy; Radiotherapy; Radiotherapy, Image-Guided; Prostatic neoplasms; Prostate-specific antigen; Adult; Male; Image guided, Radiosurgery; Prospective studies; Radiotherapy; Neoplasm metastasis; Positron emission tomography
• ISSN: 2588-9311; 2588-9311
• DOI: 10.1016/j.euo.2021.10.002

In selected patients with prostate-specific membrane antigen targeted positron emission tomography (PSMA-PET)-staged oligometastatic prostate cancer, local ablative radiotherapy is well tolerated, may improve midterm outcome, and may delay the onset of systemic therapy. One in five patients has no progression at 3 yr. Local ablative radiotherapy (aRT) of oligometastatic prostate cancer (PCa) is very promising and has become a focus of current clinical research. We hypothesize that aRT is safe and effective in gallium-68 prostate-specific membrane antigen targeted positron emission tomography (PSMA-PET)-staged oligometastatic PCa patients. A nonrandomized, prospective, investigator-initiated phase 2 trial recruited patients with oligometastatic PCa (five or fewer lymph node or osseous metastases) after local curative therapy, without significant comorbidity and androgen deprivation therapy (ADT), at two German centers from 2014 to 2018. All PSMA-PET–positive metastases were treated with aRT. No systemic therapy was initiated. The primary endpoint was treatment-related toxicity (grade ≥2) 24 mo after aRT. A one-sided single-sample test of proportions was planned to test whether the endpoint occurs in <15% of the patients. Key secondary endpoints were time to progression of prostate-specific antigen (PSA) and time to ADT, which were associated with potential prognostic factors by Cox regression. Of 72 patients, 63 received aRT (13% dropout rate). The median follow-up was 37.2 mo. No treatment-related grade ≥2 toxicity was observed 2 yr after treatment. The median time to PSA progression and time to ADT were 13.2 and 20.6 mo, respectively. Of the patients, 21.4% were free of PSA progression after 3 yr. It was observed that aRT is safe, and midterm PSA progression and ADT-free time were achieved in one of five patients. Randomized clinical trials are indicated to further evaluate the option of delaying ADT in selected patients. In this clinical trial, 63 patients with up to five metastases of prostate cancer without androgen deprivation therapy were included. We showed that local ablative radiotherapy is safe and that one in five patients had no recurrent prostate-specific antigen value after 3 yr. Local ablative radiotherapy might be an option to avoid systemic therapy in selected patients.