Performance In Prostate Cancer Research Articles

Follicular thyroid carcinoma detected in ⁶⁸Ga-PSMA PET/CT imaging. Case report.

Introduction: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein located on the cell membrane, initially discovered in prostate cells, and highly expressed in the cells and metastases of prostate carcinoma. 68Ga-PSMA PET/CT is a molecular imaging technique widely used in the algorithm of this pathology. PSMA expression has been observed in several malignancies, usually incidentally. We report a case of follicular thyroid carcinoma detected in ⁶⁸Ga-PSMA PET/CT. To our knowledge, only 3 cases have been reported in the literature to date. Clinical findings: Patient with a history of prostate cancer adenocarcinoma, who after initial treatment, presented biochemical recurrence. A Ga68-PSMA PET/CT was performed, showing uptake of the radiopharmaceutical in the left thyroid lobe. Interventions: The patient was evaluated by the head and neck specialty, taken to total thyroidectomy plus central dissection. The pathology report confirms a follicular thyroid carcinoma. Conclusion: Ga68-PSMA PET/CT is a molecular image with high diagnostic performance in prostate cancer, however, its uptake in other solid tumors is well established, so attention should be paid to these uptakes, since the the vast majority may be related to another type of primary tumor. This is an example of PSMA uptake in follicular carcinoma of the thyroid.

Circulating plasma miR222-3P status and its potential diagnostic performance in prostate cancer.

Although studies suggest that miR222-3p is dysregulated in prostate cancer (PC) cells and tissues, the possible changes in the level of miR222-3p in the plasma samples of PC patients remained unclear. The present study aimed to evaluate the diagnostic value of the plasma miR222-3p expression level as a potential biomarker in PC, benign prostatic hyperplasia (BPH) and healthy people. Blood samples were collected from 100 adult males (54 patients with PC, 27 patients with BPH and 19 healthy individuals) referred to our affiliated hospital. The expression level of miR222-3p was evaluated using a quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic curves were used to evaluate miR222-3p diagnostic accuracy for discriminating between the PC, BPH and healthy individuals. The expression level of miR222-3p was significantly higher in PC patients compared to healthy individuals as a fold change of 5.3 (p = 0.009), but not for BPH individuals. The diagnostic value of the plasma miR222-3p for discrimination of the PC patients from healthy individuals was reasonable [cut-off value (fold change relative to miR16-5p) = 1.69, area under the curve = 0.73, sensitivity = 0.75 and specificity = 0.74]. Circulating plasma miR-222-3p significantly upregulated in PC patients, but not in BPH ones. Besides these preliminary results showed that miR222-3p has the potential to discriminate PC patients from healthy ones. Addittional studies with a larger sample size are required to confirm these data.

Patient-level grading prediction of prostate cancer from mp-MRI via GMINet

Magnetic resonance imaging (MRI) is considered the best imaging modality for non-invasive observation of prostate cancer. However, the existing quantitative analysis methods still have challenges in patient-level prediction, including accuracy, interpretability, context understanding, tumor delineation dependence, and multiple sequence fusion. Therefore, we propose a topological graph-guided multi-instance network (GMINet) to catch global contextual information of multi-parametric MRI for patient-level prediction. We integrate visual information from multi-slice MRI with slice-to-slice correlations for a more complete context. A novel strategy of attention folwing is proposed to fuse different MRI-based network branches for mp-MRI. Our method achieves state-of-the-art performance for Prostate cancer on a multi-center dataset (N = 478) and a public dataset (N = 204). The five-classification accuracy of Grade Group is 81.1 ± 1.8% (multi-center dataset) from the test set of five-fold cross-validation, and the area under curve of detecting clinically significant prostate cancer is 0.801 ± 0.018 (public dataset) from the test set of five-fold cross-validation respectively. The model also achieves tumor detection based on attention analysis, which improves the interpretability of the model. The novel method is hopeful to further improve the accurate prediction ability of MRI in the diagnosis and treatment of prostate cancer.

Preliminary Evaluation of 68Ga-P16-093, a PET Radiotracer Targeting Prostate-Specific Membrane Antigen in Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a promising molecular target for imaging of prostate adenocarcinoma. 68Ga-P16-093, a small molecule PSMA ligand, previously showed equivalent diagnostic performance compared to 68Ga-PSMA-11 PET/CT in a pilot study of prostate cancer patients with biochemical recurrence (BCR). We performed a pilot study for further characterization of 68Ga-P16-093 including comparison to conventional imaging. Patients were enrolled into two cohorts. The biodistribution cohort included 8 treated prostate cancer patients without recurrence, who underwent 6 whole body PET/CT scans with urine sampling for dosimetry using OLINDA/EXM. The dynamic cohort included 15 patients with BCR and 2 patients with primary prostate cancer. Two patients with renal cell carcinoma were also enrolled for exploratory use. A dynamic PET/CT was followed by 2 whole body scans for imaging protocol optimization based on bootstrapped replicates. 68Ga-P16-093 PET/CT was compared for diagnostic performance against available 18F-fluciclovine PET/CT, 99mTc-MDP scintigraphy, diagnostic CT, and MRI. 68Ga-P16-093 deposited similar effective dose (0.024mSv/MBq) and lower urinary bladder dose (0.064mSv/MBq) compared to 68Ga-PSMA-11. The kidneys were the critical organ (0.290mSv/MBq). While higher injected activities were preferable, lower injected activities at 74-111MBq (2-3mCi) yielded 80% retention in signal-to-noise ratio. The optimal injection-to-scan interval was 60min, with acceptable delay up to 90min. 68Ga-P16-093 PET/CT showed superior diagnostic performance over conventional imaging with overall patient-level lesion detection rate of 71%, leading to a change in management in 42% of the patients. Based on its favorable imaging characteristics and diagnostic performance in prostate cancer, 68Ga-P16-093 PET/CT merits further investigation in larger clinical studies.

Can serum endoglin be used to improve the diagnostic performance in prostate cancer?

New biomarkers may contribute to avoid unnecessary biopsies resulting from the suboptimal performance of prostate-specific antigen (PSA) testing. This study aimed to assess serum endoglin as a prostate cancer (PCa) diagnostic tool among biopsy candidates. A total of 262 consecutive patients referred for prostate biopsy based on abnormal digital rectal examination and/or elevated total PSA (tPSA) who had serum endoglin assessed by solid-phase enzyme-linked immunosorbent assay were selected. Receiver operating characteristic curves were used to compare the predictive accuracy of different combinations of biomarkers to distinguish between PCa and benign prostatic conditions, and to identify cut-offs that maximize the ability of endoglin to rule out patients for biopsy (highest sensitivities). Serum endoglin levels were higher in patients with PCa (median: 7.86 vs. 5.88 pg/mL, P < 0.001). Among patients with baseline tPSA ≤ 10 ng/mL the area under the curve was 0.69 for endoglin. Approximately one-quarter of the patients had serum endoglin < 4.92 ng/mL (sensitivity: 90.3%; specificity: 32.8%), and the probability of PCa varied from 37.7% before testing to 15.2% among those with low endoglin levels [negative predictive value (NPV) = 84.8%]. When restricting the analyses to patients with free/total PSA ratio > 0.25, the probability of cancer was less than 5% among those with serum endoglin < 6.04 ng/mL (sensitivity: 93.8%; specificity: 56.1%), corresponding to a NPV of 95.8%; this could allow sparing approximately 40% of patients from biopsy. Serum endoglin may be useful in clinical practice to distinguish between PCa and non-cancer patients among prostatic biopsy candidates.

A randomized trial comparing fluorocholine-PET/CT with conventional imaging in prostate cancer.

2 Background: We conducted a randomised trial comparing 18Flourocholine-PET/CT (FCH) to Computed Tomography (abdomen and pelvis) plus 99mTc-Whole Body Bone Scan (Conventional Imaging [CIm]) to determine imaging performance in prostate cancer (PC). Methods: This prospective two-arm 1:1 randomised trial enrolled men with newly diagnosed or biochemically recurrent PC to first-line imaging (FLI) with either CIm or FCH. Participants without evidence of metastases proceeded to second-line imaging (SLI) using the alternative imaging strategy. The primary aim was to determine whether FCH was more effective as a FLI approach in changing management. Secondary endpoints included incremental utility of SLI and negative predictive value (NPV) based on progression-free survival (PFS). Australian New Zealand Clinical Trials Registry ACTRN12608000641392. Results: 108 men were enrolled; 44% were for staging of newly-diagnosed PC and median follow-up 43 months. Imaging impacted clinical management in 32.4% of men (95% CI=23.7-42.1%), mostly with FLI (n=30). High-impact management changes occurred in 27.8% (95% CI=16.5-41.6%) of FCH cases compared with 11.1% (95% CI=4.2-22.6%) in the CIm arm (p=0.032). The final management plan was derived using FCH in 98.1% (95% CI = 90.1-100%) of cases and 92.6% (95%CI = 82.1-97.9%) of CIm cases (p=0.242). FLI with FCH showed unequivocally N1 or M1 disease in 22.2% (95% CI = 12-35.6%), and 16.7% (95% CI = 7.9-29.3%; p= 0.531) of CIm cases. The overall NPV for stage TxN0M0 (from all imaging) was 26.3% (95% CI: 13.9 - 41.2%), with no significant difference between arms (p=0.9). For N1M0 cases, the NPV was 14.3% (95% CI: 7.1 - 35.7%). The identification of N1M0 by FCH resulted in a longer time to identification of progressive disease, with a median PFS of 32 months (95% CI=2-68months) compared with 3 months (95% CI=1-16 months) in the CIm N1M0 cohort (p=0.05). Conclusions: FCH-PET/CT identifies more high-clinical-impact lesions than CIm as first-line imaging. All imaging modalities were poor at predicting subsequent progressive disease. Isolated node-positive disease seen with FCH is associated with a longer time to - but similarly high rates of - recurrence, suggesting a lead-time bias. Clinical trial information: ACTRN12608000641392.

Prebiopsy mp-MRI Can Help to Improve the Predictive Performance in Prostate Cancer: A Prospective Study in 1,478 Consecutive Patients

Purpose: To investigate whether prebiopsy multi-parametric (mp) MRI can help to improve predictive performance in prostate cancer.Experimental Design: Based on a support vector machine (SVM) analysis, we prospectively modeled clinical data (age, PSA, digital rectal examination, transrectal ultrasound, PSA density, and prostate volume) and mp-MRI findings [Prostate Imaging and Reporting and Data System (PI-RADS) score and tumor-node-metastasis stage] in 985 men to predict the risk of prostate cancer. The new nomogram was validated in 493 patients treated at the same institution. Multivariable Cox regression analyses assessed the association between input variables and risk of prostate cancer, and area under the receiver operating characteristic curve (Az) analyzed the predictive ability.Results: At 5-year follow-up period, 34.3% of patients had systemic progression of prostate cancer. Nomogram (SVM-MRI) predicting 5-year prostate cancer rate trained with clinical and mp-MRI data was accurate and discriminating with an externally validated Az of 0.938, positive predictive value (PPV) of 77.4%, and negative predictive value of 91.5%. The improvement was significant (P < 0.001) compared with the nomogram trained with clinical data. When stratified by PSA, SVM-MRI nomogram had high PPV (93.6%) in patients with PSA > 20 ng/mL, with intermediate to low PPV in PSA 10 to 20 ng/mL (64%), PSA 4 to 10 ng/mL (55.8%), and PSA 0 to 4 ng/mL (29%). PI-RADS score (Cox HR, 2.112; P < 0.001), PSA level (HR, 1.435; P < 0.001), and age (HR, 1.012; P = 0.043) were independent predictors of prostate cancer.Conclusions: Featured with low false positive rate, mp-MRI could be the first investigation of a man with a raised PSA before prostate biopsy. Clin Cancer Res; 23(14); 3692-9. ©2017 AACR.

Treatment planning comparison of IMPT, VMAT and 4\u03c0 radiotherapy for prostate cases

BackgroundIntensity-modulated proton therapy (IMPT), non-coplanar 4π intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) represent the most advanced treatment methods based on heavy ion and X-rays, respectively. Here we compare their performance for prostate cancer treatment.MethodsTen prostate patients were planned using IMPT with robustness optimization, VMAT, and 4π to an initial dose of 54 Gy to a clinical target volume (CTV) that encompassed the prostate and seminal vesicles, then a boost prescription dose of 25.2 Gy to the prostate for a total dose of 79.2 Gy. The IMPT plans utilized two coplanar, oblique scanning beams 10° posterior of the lateral beam positions. Range uncertainties were taken into consideration in the IMPT plans. VMAT plans used two full, coplanar arcs to ensure sufficient PTV coverage. 4π plans were created by inversely selecting and optimizing 30 beams from 1162 candidate non-coplanar beams using a greedy column generation algorithm. CTV doses, bladder and rectum dose volumes (V40, V45, V60, V65, V70, V75, and V80), R100, R50, R10, and CTV homogeneity index (D95/D5) were evaluated.ResultsCompared to IMPT, 4π resulted in lower anterior rectal wall mean dose as well as lower rectum V40, V45, V60, V65, V70, and V75. Due to the opposing beam arrangement, IMPT resulted in significantly (p < 0.05) greater femoral head doses. However, IMPT plans had significantly lower bladder, rectum, and anterior rectal wall max dose. IMPT doses were also significantly more homogeneous than 4π and VMAT doses.ConclusionCompared to the VMAT and 4π plans, IMPT treatment plans are superior in CTV homogeneity and maximum point organ-at-risk (OAR) doses with the exception of femur heads. IMPT is inferior in rectum and bladder volumes receiving intermediate to high doses, particularly to the 4π plans, but significantly reduced low dose spillage and integral dose, which are correlated to secondary cancer for patients with expected long survival. The dosimetric benefits of 4π plans over VMAT are consistent with the previous publication.

Effect of caffeine on exercise capacity and function in prostate cancer survivors.

This study aimed to examine the acute effect of caffeine on exercise capacity, exercise-related fatigue, and functional performance in prostate cancer survivors. In this randomized, placebo-controlled, double-blind crossover study, 30 prostate cancer survivors (age, 70.3 ± 7.7 yr; body mass, 80.5 ± 13.0 kg; mean ± SD) consumed 6.04 ± 0.16 mg·kg(-1) of anhydrous caffeine or a placebo 1 h before completing a battery of exercise capacity and functional performance tests. Testing sessions were separated by 3-4 wk. Immediate fatigue and perceived exertion were measured directly pre- and postexercise at both testing sessions. Caffeine increased exercise capacity by 7.93 s (+3.0%; P = 0.010); however, postexercise fatigue and perception of exertion were comparable with the placebo session (P = 0.632 and P = 0.902, respectively). Increases in isometric grip strength trended toward significance in both dominant (+2.9%; P = 0.053) and nondominant (+2.1%; P = 0.061) hands in the caffeine trial compared with placebo. Caffeine ingestion did not result in improvements in performance for any of the remaining functional measures, including the timed up-and-go test, repeated chair stands, 6-m fast walk, and 6-m backward tandem walk. Systolic blood pressure and HR were significantly increased (P = 0.006 and P = 0.040, respectively) upon completion of the testing battery when compared with placebo. Consumption of caffeine 1 h before exercise induced improvements in exercise capacity and muscular strength in prostate cancer survivors. However, there was no change in exercise-related fatigue when compared with placebo despite reduction in timed performance of the 400-m walk. Caffeine seems to enhance exercise tolerance through improved performance with no subsequent increase in fatigue or perception of exertion and may be an appropriate strategy to promote exercise participation in prostate cancer survivors.

Staging Prostate Cancer with Dynamic Contrast-enhanced Endorectal MR Imaging prior to Radical Prostatectomy: Experienced versus Less Experienced Readers

To prospectively determine the accuracy of experienced and less experienced readers in the interpretation of combined T2-weighted fast spin-echo (SE) magnetic resonance (MR) images and dynamic contrast material-enhanced MR images compared with T2-weighted fast SE alone, with respect to differentiation of stage T2 versus stage T3 prostate carcinoma, with histologic analysis serving as the reference standard. Institutional review board approval and informed consent were obtained, and 124 consecutive men (age range, 42-74 years; median age, 63 years) with biopsy-proved prostate cancer underwent MR imaging and were candidates for radical prostatectomy. T2-weighted fast SE MR images and multisection dynamic contrast-enhanced MR images with a 2-second time resolution for the whole prostate were obtained. The T2-weighted and fused color-coded parametric dynamic contrast-enhanced MR images with T2-weighted images were evaluated prospectively and scored with regard to local extent by one experienced reader and evaluated retrospectively by two less experienced readers working in consensus by using a five-point scale; images with a score greater than or equal to four were considered indicative of T3 disease. Results were correlated with whole-mount section histopathologic findings, and receiver operating characteristics analysis was performed. Twenty-five patients were excluded because of positive findings in the lymph nodes (n = 16), preoperative biopsy-proved seminal vesicle invasion (n = 5), and an absent dynamic dataset (n = 4). Ninety-nine patients were included in this study. The overall sensitivity, specificity, and accuracy of MR staging performance in prostate cancer with dynamic contrast-enhanced MR imaging was 69% (24 of 35 patients), 97% (62 of 64 patients), and 87% (86 of 99 patients), respectively, for the experienced reader. This difference was not significant (P = .48) when results were compared with results from the T2-weighted images. Staging performance for the less experienced readers with parametric dynamic contrast-enhanced MR imaging, however, resulted in significant improvement of the area under the receiver operating characteristics curve (A(z)) compared with T2-weighted MR imaging alone (A(z) = .66 and .82, respectively; P = .01). The use of multisection dynamic contrast-enhanced MR imaging in staging prostate cancer showed significant improvement in staging performance for the less experienced readers but had no benefit for the experienced reader.