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PURPOSE: To investigate tolerability, safety and antitumor effects of a novel intra-prostatic depot formulation of antiandrogen 2-hydroxyflutamide (2-HOF in NanoZolid(®)) in men with localized prostate cancer (PCa). MATERIALS AND METHODS: Two clinical trials, LPC-002 and LPC-003, were conducted on a total of 47 men. The formulation was injected transrectally into the prostate with ultrasound guidance. In LPC-002 the effects on prostate specific antigen (PSA) and prostate volume (PV) were measured over 6 months on 24 patients. In LPC-003, antitumor effects were evaluated with histopathology, magnetic resonance imaging (MRI) including spectroscopy (MRS) during 6 or 8 weeks on 23 patients. In both studies, testosterone and 2-HOF in plasma were measured, as well as quality-of-life parameters. RESULTS: In LPC-002 (mean dose 690 mg) a reduction in PSA and PV was observed. The nadir values for PSA and PV were on average 24.9 % and 14.0 % below baseline, respectively. When increasing the dose in LPC-003 (920 mg and 1740 mg), the average PSA dropped 16 % and 23 %, respectively, after 6 and 8 weeks. MRI/MRS showed morphological changes and a global drop in metabolite concentrations following treatment indicating an antitumor response. The injections did not result in hormone related side effects. In total, three serious adverse events were reported, all resolved by oral antibiotic treatment. CONCLUSIONS: The intraprostatic injections of 2-HOF depot formulations indicated anti-tumor effects and proved safe and tolerable. However, for better anti-cancer effects higher doses and better dose distribution are suggested.

OBJECTIVE: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale. MATERIALS AND METHODS: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed. RESULTS: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001). CONCLUSION: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.

PURPOSE: To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Forty-six prostate cancer patients were scanned at 3T. Spectra were acquired with the point-resolved spectroscopy (PRESS) localization technique. Single-voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content. RESULTS: The T1 value, 708 ± 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 ± 1 mM, Spm, 13.0 ± 4.4 mM, Cit, 64.4 ± 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 ± 1 mM, Spm, 13.3 ± 4.5 mM, Cit, 34.3 ± 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265). CONCLUSION: We have shown that it is possible to perform water-referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite-to-citrate ratios.

OBJECTIVES: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine. PATIENTS AND METHODS: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions. RESULTS: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data. CONCLUSION: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread.

AIM: To prospectively validate 3 T magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) for preoperative lymph node (LN) staging in a clinical setting, in intermediate- and high-risk prostate cancer (PCa) patients using laparoscopic extended LN dissection (ePLND) as the reference standard. MATERIALS AND METHODS: Between August 2011 and May 2013, 40 newly diagnosed intermediate and high-risk PCa patients underwent preoperative LN staging with 3 T MRI DWI using histopathology of ePLND as the reference standard. The sensitivity, specificity, and accuracy of MRI DWI were calculated. A subgroup analysis of proven LN-positive patients was made to investigate differences in PSA, Gleason score, number, and size of LN metastases, estimated risk of LN involvement, and if curative treatment was indicated, between the true-positive and the false-negative groups. RESULTS: A total of 728 LN were harvested from six anatomical regions per patient (external, obturator, internal) with a mean number of 18 LNs per patient (range 11-40). Twenty patients had histologically proven LN-positive disease. MRI DWI was true positive in 11 patients, false negative in nine patients, false positive in two patients, and true negative in 18 patients, resulting in 90% specificity, 55% sensitivity, and 72.5% accuracy. The true-positive patients had significantly more involved LNs (mean 6.9 versus 2.7, p = 0.017), with larger diameter (mean 12.3 versus 5.2 mm, p = 0.048) and fewer were treated with curative intent (six versus nine, p = 0.03), compared with the false-negative group. CONCLUSION: MRI DWI LN staging has a low sensitivity but high specificity. The true-positive patients have a considerably higher burden of LN metastases compared to false-negative patients.

The diagnostic accuracy of standard transrectal ultrasound-guided (TRUL) biopsy is limited due to the finite number of cores that can be obtained. It has been shown that the technique is not sufficiently reliable in defining the location and extent of prostatic cancer. The main aim of this study was to investigate the effectiveness of magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) imaging techniques in pinpointing potential tumour lesions prior to prostate biopsy. Material and methods The study cohort consisted of 45 men with a raised prostate specific-antigen (PSA) level and/or suspected prostate cancer (PCa) at digital rectal examinations (DRE). Of the 45 patients, 23 had PCa detected with core needle biopsy (CNB). All had 11C acetate PET/CT imaging. Ten of those 23 patients underwent radical prostatectomy (RP), of those ten patients, eight patients had MR spectroscopic imaging (MRSI) with 3 T and six had diffusion weighted imaging (DWI) with apparent diffusion coefficient calculation (MRI DWI ADC). CNB, PET/CT, 2D MRSI and ADC map results were compared with postoperative specimen histopathology. Results The sensitivity of CNB, PET/CT, MRSI and DWI ADC were 0.53, 0.55, 0.79 and 0.95, whereas the specificity of was 0.88, 0.87, 0.46 and 0.73, respectively. Conclusion MRI improves the PCa detection by defining the areas of interest for targeted CNB of the prostate and can reduce the number of biopsies required