Progression-Directed Therapy in Oligoprogressive Castration-Refractory Prostate Cancer: Results of the Prospective Single-Arm Phase II MEDCARE Trial

Abstract

Next-line systemic treatment (NEST) for progressive metastatic castration-refractory prostate cancer (mCRPC) is associated with significant costs and non-negligible toxicity. For oligoprogressive (OP) disease, defined as the appearance of up to 3 progressive and/or new lesions and/or local recurrence on conventional imaging, progression-directed therapy (PDT) may prolong the efficacy of ongoing systemic therapy and delay initiation of NEST. To investigate whether PDT could postpone NEST in patients with OP mCRPC in the prospective, single-arm, monocentric MEDCARE trial. We enrolled patients with OP mCRPC while on ongoing treatment with androgen deprivation therapy (ADT), with or without an androgen receptor-targeted agent (ARTA). Progression was detected with conventional imaging (bone scan and CT of MRI). A history of docetaxel treatment was allowed. All progressive lesions had to be treatable with PDT, either (stereotactic body) radiation therapy ((SB)RT) or metastasectomy. Repeated PDT was allowed at the time of further oligoprogression. The primary endpoint was NEST-free survival. Secondary outcomes of the trial included clinical progression-free survival (cPFS), prostate cancer specific survival (PCSS), overall survival (OS) as well as acute and late toxicity. Between January 2020 and January 2021, 20 patients were included. Median age was 74 years. Median PSA level and PSA doubling at the time of inclusion were 4 ng/ml (IQR 2-11) and 4 months (IQR 3-5), respectively. Median follow-up was 28 months (IQR 5-33). A total of 31 lesions were treated with SBRT to 22.5-30 Gy in 3-5 fractions of 7.5-10 Gy. 11, 7 and 2 patients had one, two and three concurrent lesions respectively. At the time of inclusion, sixteen patients had bone metastases, two patients had only lymph node metastases, one patient a liver metastasis and one patient had local recurrence. If the primary tumor had not yet been treated, local radiotherapy to the prostate was given (n = 5). Five patients received repeated PDT for oligoprogression. Ongoing therapy at time of inclusion was ADT (n = 8) alone or ADT + ARTA (n = 12). The number of different systemic treatment lines received before inclusion was one, two and three for 5, 13 and 2 patients respectively. The median NEST-free survival was 17 months (95% CI: 9-25). The median cPFS was 6 months (95% CI: 5-7). The median PCSS was not reached while the median OS was 29 months (95% CI, 28-30). At last follow-up, 9 patients had died, of whom 6 due to progressive prostate cancer and 3 due to rapid progression of a second primary tumor (small cell lung cancer, leiomyosarcoma and acute myeloid leukemia). PDT was well tolerated with no acute nor late grade ≥3 toxicity. In OP mCRPC patients, PDT postpones the need for NEST for almost 1.5 years without inducing severe toxicity.