Metastasis-Directed Therapy for Oligoprogressive Castration-Resistant Prostate Cancer - Preliminary Results of the Prospective, Single-Arm MEDCARE Trial

PURPOSE/OBJECTIVE(S): In metastatic castration-refractory prostate cancer (mCRPC), clinical progression usually implies the start of a new systemic treatment-line. When clinical progression is limited to a few new and/or progressive lesions, while all other lesions are still responsive to ongoing treatment, the term 'oligoprogression' is used. Retrospective data demonstrated that metastasis-directed therapy (MDT) to the oligoprogressive lesions substantially postponed the start of next-line systemic treatment (NEST). Based on these results, the prospective, single-arm MEDCARE trial was initiated. MATERIALS/METHODS: MEDCARE is a prospective, single-arm, monocentric pilot-study, investigating the use of MDT in oligoprogressive mCRPC. Oligoprogression was defined as ≤3 new and/or progressive metastatic lesions or local progression (counting as 1 new lesion) diagnosed on CT or bone scan. Additional MRI was allowed for confirmation. All patients also underwent an 18F PSMA PET-CT as investigational imaging, to assess its predictive value and impact on treatment policy. Ongoing systemic treatment at the time of oligoprogression was continued. MDT consisted of stereotactic body radiation therapy (SBRT) or metastasectomy. The primary endpoint of the trial was NEST-free survival, calculated from the last day of MDT until the start of NEST. Clinical progression-free survival (cPFS) and toxicity scoring with CTCAE v4 scoring were secondary endpoints. RESULTS: Between January 2020 and January 2021, 20 patients were included in the trial. Median age at time of inclusion was 74 years (IQR 67-78). Median PSA and PSA doubling time were 4 ng/ml (IQR 2-11) and 4 months (IQR 3-5), respectively. Eleven patients had 1 progressive lesion on conventional imaging, 7 patients had 2 progressive lesions and 2 patients had 3 progressive lesions. The most frequent location of progressive lesions was the bone (16/20). One patient was treated for a progressive liver metastasis, and one patient presented with progression in the prostatic fossa. Two more patients had a combination of progression in pelvic and retroperitoneal lymph nodes (N1/M1a disease). All patients with progressive metastatic lesions were treated with SBRT (30 Gy in 3 fractions (BED 130 Gy for a/b = 3). The patient with local progression was treated with conventional radiotherapy (77 Gy in 35 fractions (BED 133 Gy for a/b = 3)). At a median follow-up of 6 months (IQR 2-9), 8 patients experienced clinical progression, and five patients were started on NEST. Median NEST-FS was 12 months. Three patients died, 2 deaths were prostate cancer related and 1 patient died of small cell lung cancer. MDT was well tolerated, with 3 patients experiencing grade 1 toxicity, and two patients grade 2 toxicity (acute GU toxicity). There were no patients with grade 3 or higher toxicity. CONCLUSION: The first results of the MEDCARE trial (NCT04222634) investigating MDT in oligoprogressive CRPC are promising, with negligible toxicity.

Publication year:2021