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e16003 Background: Patients with rising PSA levels after definitive local therapy of prostate carcinoma often present a diagnostic dilemma . A local recurrence or metastatic lymph node lesions would be amenable to additional local therapy. In this prospective study the effectiveness of 11C-acetate PET (AC-PET) matched with corresponding CT scans in patients with PSA relapse were evaluated. Methods: 103 patients (mean age 70.87 years; range 56 – 90 years) with histologically confirmed adenocarcinoma of the prostate were enrolled in this study because of rising PSA values following RP (n = 97) or radiotherapy (n=6). Whole-body PET images were obtained after iv - administration of 1,000 MBq of 11C-acetate. A CT scan from the neck to the pelvic floor was performed additionally. An image overlay of corresponding CT and PET scans was done. By using attenuation corrected PET data, standardized uptake value (SUV) was calculated, cut-off 2. Results: Out of 103 patients n=42 were AC-PET positive. PSA level in 16 of this subset was between 0.5 and 1.45 ng/mL (mean value 1.14 ng/mL), in 16 patients between 2.7 and 9.01 ng/mL, and 7 patients had a PSA distribution between 13.4 and 30.5 ng/mL, respectively. Analysing the AC-PET positive patients, in 16/42 AC-PET demonstrated hypermetabolic lymphnode lesions, in 10/16 metastatic lesions were histopathologically confirmed, in the remaining 6 unspecific inflammatory tissue alterations were identified. In 9 patients with corresponding AC-PET and CT scans radiotherapy of proven lymphnode metastases was performed followed by decreasing PSA level. 23/42 patients were treated with hormone manipulation (21/23) or chemotherapy (2/23). Combining the patients having undergone surgery and radiotherapy (n=25) there were 19/25 true positive in terms of AC-PET, in 13 / 25 PSA level was < 2.0 ng/mL. Conclusions: Although AC-PET seems to be a promising tool in the detection of recurrent prostate cancer even with PSA levels < 2 ng/ml, false positive patients with a different metabolism marked by 11C-acetate decrease the specificity of the approach. Thus there is still a need for a more specific tracer development.

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Accumulating findings suggest that sequential treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), in either order has limited efficacy for metastatic castration-resistant prostate cancer (mCRPC). Furthermore, there has been a strong trend toward the movement of novel ARAT therapies into the front-line for mCRPC treatment prior to the introduction of docetaxel within the last few years, due to the favorable tolerability of ARAT agents compared with taxanes. Considering these findings, it is still important to determine the optimal sequencing order of novel ARAT agents for mCRPC patients. The objective of this study was to compare the efficacies of sequential therapies with novel ARAT agents in patients with docetaxelnaive mCRPC.METHODS: This study included 108 consecutive mCRPC patients who sequentially received AA and Enz, in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively.RESULTS: Of the 108 patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and that with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the two groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (56.5%) was significantly lower than that to the first-line ARAT agent (21.3%). The combined PSA PFS in the AA-to-Enz group (median, 18.4 months) was significantly superior to that in the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (i.e., AA-to-Enz versus Enzto-AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients.CONCLUSIONS: Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naive mCRPC patients, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series. Thus, when ARAT agents are to be introduced sequentially, it may be advisable to provide ARAT therapy according to the AA-to-Enz sequence.