Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

PurposeTo assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT).MethodsNon-castrate patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography - computed tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions or 30 Gy in 3 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary endpoint. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic. Secondary endpoints were local control, progression free survival (PFS) and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events.ResultsWith a median follow-up from time of SBRT of 2 years, we treated 50 patients with 70 metastatic lesions with a local control rate of 100%. The primary involved metastatic sites were lymph nodes (54%), bone (44%), and viscera (2%). The median PFS was 19 mo (95% CI: 13–25 mo) with 75% of recurring patients having ≤3 metastases. A 2nd and 3rd course of SBRT was delivered in 19 and 6 patients respectively. This results in a median ADT-FS of 25 months (20–30 mo). On univariate analysis, only a short PSA doubling time was a significant predictor for both PFS (HR: 0.90, 95% CI: 0.82 – 0.99) and ADT-FS (HR: 0.83; 95% CI: 0.71 – 0.97). Ten patients (20%) developed toxicity following treatment, which was classified as grade I in 7 and grade II in 3 patients.ConclusionRepeated SBRT for oligometastatic prostate cancer postpones palliative androgen deprivation therapy with 2 years without grade III toxicity.

[FU] protracted intravenous infusion 300 mg/m(2) days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m(2) days 1 through 14 then 300 mg/m(2) days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A. RESULTS: Forty-six patients were randomly assigned and 44 were eligible for analy... Document type : Article de périodique (Journal article)Référence bibliographique A B S T R A C T PurposeLiver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the ␤-emitting isotope yttrium-90 ( 90 Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues. Patients and MethodsWe conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m 2 days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m 2 days 1 through 14 then 300 mg/m 2 days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A. ResultsForty-six patients were randomly assigned and 44 were eligible for analysis (arm A, n ϭ 23; arm B, n ϭ 21). Median follow-up was 24.8 months. Median TTLP was 2.1 and 5.5 months in arms A and B, respectively (hazard ratio [HR] ϭ 0.38; 95% CI, 0.20 to 0.72; P ϭ .003). Median time to tumor progression (TTP) was 2.1 and 4.5 months, respectively (HR ϭ 0.51; 95% CI, 0.28 to 0.94; P ϭ .03). Grade 3 or 4 toxicities were recorded in six patients after FU monotherapy and in one patient after radioembolization plus FU treatment (P ϭ .10). Twenty-five of 44 patients received further treatment after progression, including 10 patients in arm A who received radioembolization. Median overall survival was 7.3 and 10.0 months in arms A and B, respectively (HR ϭ 0.92; 95% CI, 0.47 to 1.78; P ϭ .80). Conclusion Radioembolization with90 Y-resin microspheres plus FU is well tolerated and significantly improves TTLP and TTP compared with FU alone. This procedure is a valid therapeutic option for chemotherapy-refractory liver-limited mCRC.