Feasibility and Initial Results: Fluciclovine Positron Emission Tomography/Ultrasound Fusion Targeted Biopsy of Recurrent Prostate Cancer.

PURPOSE: We assessed the feasibility and cancer detection rate of fluciclovine (18F) positron emission tomography-ultrasound fusion targeted biopsy vs standard template biopsy in the same patient with biochemical failure after nonsurgical therapy for prostate cancer. MATERIALS AND METHODS: A total of 21 patients with a mean ± SD prostate specific antigen of 7.4 ± 6.8 ng/ml and biochemical failure after nonoperative prostate cancer treatment underwent fluciclovine (18F) positron emission tomography-computerized tomography (mean 364.1 ± 37.7 MBq) and planning transrectal prostate ultrasound with 3-dimensional image reconstruction. Focal prostatic activity on positron emission tomography was delineated and co-registered with planning ultrasound. During the subsequent biopsy session computer generated 12-core template biopsies were performed and then fluciclovine defined targets were revealed and biopsied. Histological analysis of template and targeted cores were completed. RESULTS: Template biopsy was positive for malignancy in 6 of 21 patients (28.6%), including 10 of 124 regions and 11 of 246 cores, vs targeted biopsy in 10 of 21 (47.6%), including 17 of 50 regions and 40 of 125 cores. Five of 21 patients had positive findings on targeted biopsy only and 1 of 21 had positive findings on template biopsy only. An additional case was upgraded from Grade Group 2 to 3 on targeted biopsy. Extraprostatic disease was detected in 8 of 21 men (38.1%) with histological confirmation in all 3 who underwent lesion biopsy. CONCLUSIONS: Fluciclovine positron emission tomography real-time ultrasound fusion guidance for biopsy is feasible in patients with biochemical failure after nonsurgical therapy for prostate cancer. It identifies more recurrent prostate cancer using fewer cores compared with template biopsy in the same patient. Further study is required to determine in what manner targeted biopsy may augment template biopsy of recurrent prostate cancer.

Multisite Experience of the Safety, Detection Rate and Diagnostic Performance of Fluciclovine (18F) Positron Emission Tomography/Computerized Tomography Imaging in the Staging of Biochemically Recurrent Prostate Cancer.

PURPOSE: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine (18F) after biochemical recurrence. MATERIALS AND METHODS: A total of 596 patients underwent fluciclovine (18F) positron emission tomography/computerized tomography at 4 clinical sites. Detection rate determinations were stratified by the baseline prostate specific antigen value. Diagnostic performance was assessed against a histological reference standard in 143 scans. RESULTS: The subject level fluciclovine (18F) positron emission tomography/computer tomography detection rate was 67.7% (403 of 595 scans). Positive findings were detected in the prostate/bed and pelvic lymph node regions in 38.7% (232 of 599) and 32.6% of scans (194 of 596), respectively. Metastatic involvement outside the pelvis was detected in 26.2% of scans (155 of 591). The subject level detection rate in patients in the lowest quartile for baseline prostate specific antigen (0.79 ng/ml or less) was 41.4% (53 of 128). Of these patients 13 had involvement in the prostate/bed only, 16 had pelvic lymph node involvement without distant disease and 24 had distant metastases. The positive predictive value of fluciclovine (18F) positron emission tomography/computerized tomography scanning for all sampled lesions was 62.2%, and it was 92.3% and 71.8% for extraprostatic and prostate/bed involvement, respectively. Fluciclovine (18F) was well tolerated and the safety profile was not altered following repeat administration. CONCLUSIONS: Fluciclovine (18F) is well tolerated and able to detect local and distant prostate cancer recurrence across a wide range of prostate specific antigen values.

Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT.

PURPOSE: To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[(18)F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma. METHODS: This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated. Positivity rates and diagnostic performance were calculated for fluciclovine PET/CT and CT. RESULTS: Of 53 fluciclovine PET/CT and 53 CT examinations, 41 (77.4 %) and 10 (18.9 %), respectively, had positive findings for recurrent disease. Positivity rates were higher with fluciclovine PET/CT than with CT at all prostate-specific antigen (PSA) levels, PSA doubling times and original Gleason scores. In the prostate/bed, fluciclovine PET/CT was true-positive in 31 and CT was true-positive in 4 of 51 patients who met the reference standard. In extraprostatic regions, fluciclovine PET/CT was true-positive in 12 and CT was true-positive in 3 of 41 patients who met the reference standard. Of the 43 index lesions used to prove positivity, 42 (97.7 %) had histological proof. In 51 patients with sufficient follow-up to calculate diagnostic performance in the prostate/bed, fluciclovine PET/CT demonstrated a sensitivity of 88.6 %, a specificity of 56.3 %, an accuracy of 78.4 %, a positive predictive value (PPV) of 81.6 %, and a negative predictive value (NPV) of 69.2 %; the respective values for CT were 11.4 %, 87.5 %, 35.3 %, 66.7 % and 31.1 %. In 41 patients with sufficient follow-up to calculate diagnostic performance in extraprostatic regions, fluciclovine PET/CT demonstrated a sensitivity of 46.2 %, a specificity of 100 %, an accuracy of 65.9 %, a PPV of 100 %, and an NPV of 51.7 %; the respective values for CT were 11.5 %, 100 %, 43.9 %, 100 % and 39.5 %. CONCLUSION: The diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer is superior to that of CT and fluciclovine PET/CT provides better delineation of prostatic from extraprostatic recurrence.

Sarcomatoid urothelial carcinoma of the bladder: a contemporary clinicopathologic analysis of 37 cases.

INTRODUCTION: Sarcomatoid urothelial carcinoma is a dedifferentiated biphasic tumor that exhibits morphological and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. In this series, we analyzed the clinicopathologic features of this rare variant of urothelial carcinoma. MATERIALS AND METHODS: A search was made through our surgical pathology files and consultation files of the senior author for cases of sarcomatoid urothelial carcinoma of the bladder from 2005-2014. All the slides were retrieved and re-reviewed, and clinical data was also obtained including follow up. RESULTS: Thirty-seven cases of sarcomatoid urothelial carcinoma of the bladder were identified. Mean patient age was 71 years (range: 51 to 88 years). Twenty-six of 37 (70%) patients were male and 11/37 (30%) patients were female. Twenty-five cases were from cystectomy/cystoprostatectomy specimens, 8 cases from transurethral resection of bladder tumor specimens and 4 cases were from biopsy specimens. The mean tumor size was 5 cm (range: 1.4 cm to 13.0 cm). Four of 37 (10%) cases had focal heterologous components; 1 case with both chondroid and osteoid, 2 cases with chondroid and 1 case rhabdoid elements. Twenty-one of 37 (56%) patients died within a year of presentation. CONCLUSIONS: Sarcomatoid urothelial carcinoma of the bladder is more prevalent in males, with the mean age of 71 years in our series. Smoking is an important risk factor. Sarcomatoid urothelial carcinoma is an aggressive variant of urothelial carcinoma which commonly presents at an advanced stage, and over 50% of patients in our series died of disease within 1 year of presentation.

Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial.

PURPOSE: We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[(18)F]FACBC compared to ProstaScint® ((111)In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. MATERIALS AND METHODS: A total of 93 patients met study inclusion criteria who underwent anti-3-[(18)F]FACBC positron emission tomography-computerized tomography plus (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. RESULTS: In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[(18)F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to (111)In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[(18)F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to (111)In-capromab pendetide with 10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[(18)F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. CONCLUSIONS: Better diagnostic performance was noted for anti-3-[(18)F]FACBC positron emission tomography-computerized tomography than for (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for prostate carcinoma recurrence. The former method detected significantly more prostatic and extraprostatic disease.

External validation of the modified Glasgow prognostic score for renal cancer.

PURPOSE: The modified Glasgow prognostic Score (mGPS) incorporates C-reactive protein and albumin as a clinically useful marker of tumor behavior. The ability of the mGPS to predict metastasis in localized renal cell carcinoma (RCC) remains unknown in an external validation cohort. PATIENTS AND METHODS: Patients with clinically localized clear cell RCC were followed for 1 year post-operatively. Metastases were identified radiologically. Patients were categorized by mGPS score as low-risk (mGPS = 0 points), intermediate-risk (mGPS = 1 point) and high-risk (mGPS = 2 points). Univariate, Kaplan-Meier and multivariate Cox regression analyses examined Recurrence -free survival (RFS) across patient and disease characteristics. RESULTS: Of the 129 patients in this study, 23.3% developed metastases. Of low, intermediate and high risk patients, 10.1%, 38.9% and 89.9% recurred during the study. After accounting for various patient and tumor characteristics in multivariate analysis including stage and grade, only mGPS was significantly associated with RFS. Compared with low-risk patients, intermediate- and high-risk patients experienced a 4-fold (hazard ratios [HR]: 4.035, 95% confidence interval [CI]: 1.312-12.415, P = 0.015) and 7-fold (HR: 7.012, 95% CI: 2.126-23.123 P < 0.001) risk of metastasis, respectively. CONCLUSIONS: mGPS is a robust predictor of metastasis following potentially curative nephrectomy for localized RCC. Clinicians may consider mGPS as an adjunct to identify high-risk patients for possible enrollment into clinical trials or for patient counseling.

A rare case of solitary metastatic non-seminomatous malignant germ cell tumor to the prostate.

Testicular cancer is the most common solid malignancy of men aged 15-40 years and metastasizes in a predictable manner via lymphatic spread. Involvement of metastatic testicular cancer to the prostate is an exceedingly rare event which has only been previously described in patients with seminomatous germ cell tumors. In this report, we present a case of a 42-year-old man who presented with metastatic testicular cancer to the prostate 8 years after his original diagnosis of a mixed germ cell left testicular tumor.

Detection of recurrent prostate carcinoma with anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT and 111In-capromab pendetide SPECT/CT.

PURPOSE: To compare the diagnostic performance of the synthetic amino acid analog radiotracer anti-1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid (anti-3-(18)F-FACBC) with that of indium 111 ((111)In)-capromab pendetide in the detection of recurrent prostate carcinoma. MATERIALS AND METHODS: This prospective study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained. Fifty patients (mean age, 68.3 years ± 8.1 [standard deviation]; age range, 50-90 years) were included in the study on the basis of the following criteria: (a) Recurrence of prostate carcinoma was suspected after definitive therapy for localized disease, (b) bone scans were negative, and (c) anti-3-(18)F-FACBC positron emission tomography (PET)/computed tomography (CT) and (111)In-capromab pendetide single photon emission computed tomography (SPECT)/CT were performed within 6 weeks of each other. Studies were evaluated by two experienced interpreters for abnormal uptake suspicious for recurrent disease in the prostate bed and extraprostatic locations. The reference standard was a combination of tissue correlation, imaging, laboratory, and clinical data. Diagnostic performance measures were calculated and tests of the statistical significance of differences determined by using the McNemar χ(2) test as well as approximate tests based on the difference between two proportions. RESULTS: For disease detection in the prostate bed, anti-3-(18)F-FACBC had a sensitivity of 89% (32 of 36 patients; 95% confidence interval [CI]: 74%, 97%), specificity of 67% (eight of 12 patients; 95% CI: 35%, 90%), and accuracy of 83% (40 of 48 patients; 95% CI: 70%, 93%). (111)In-capromab pendetide had a sensitivity of 69% (25 of 36 patients; 95% CI: 52%, 84%), specificity of 58% (seven of 12 patients; 95% CI: 28%, 85%), and accuracy of 67% (32 of 48 patients; 95% CI: 52%, 80%). In the detection of extraprostatic recurrence, anti-3-(18)F-FACBC had a sensitivity of 100% (10 of 10 patients; 95% CI: 69%, 100%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 100% (17 of 17 patients; 95% CI: 80%, 100%). (111)In-capromab pendetide had a sensitivity of 10% (one of 10 patients; 95% CI: 0%, 45%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 47% (eight of 17 patients; 95% CI: 23%, 72%). CONCLUSION: anti-3-(18)F-FACBC PET/CT was more sensitive than (111)In-capromab pendetide SPECT/CT in the detection of recurrent prostate carcinoma and is highly accurate in the differentiation of prostatic from extraprostatic disease. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11102023/-/DC1.

Percutaneous endoscopic holmium laser lithotripsy for management of complicated biliary calculi.

BACKGROUND AND OBJECTIVES: Advances in endoscopic techniques have transformed the management of urolithiasis. We sought to evaluate the role of such urological interventions for the treatment of complex biliary calculi. METHODS: We conducted a retrospective review of all patients (n=9) undergoing percutaneous holmium laser lithotripsy for complicated biliary calculi over a 4-year period (12/2003 to 12/2007). All previously failed standard techniques include ERCP with sphincterotomy (n=6), PTHC (n=7), or both of these. Access to the biliary system was obtained via an existing percutaneous transhepatic catheter or T-tube tracts. Endoscopic holmium laser lithotripsy was performed via a flexible cystoscope or ureteroscope. Stone clearance was confirmed intra- and post-operatively. A percutaneous transhepatic drain was left indwelling for follow-up imaging. RESULTS: Mean patient age was 65.6 years (range, 38 to 92). Total stone burden ranged from 1.7 cm to 5 cm. All 9 patients had stones located in the CBD, with 2 patients also having additional stones within the hepatic ducts. All 9 patients (100%) were visually stone-free after one endoscopic procedure. No major perioperative complications occurred. Mean length of stay was 2.4 days. At a mean radiological follow-up of 5.4 months (range, 0.5 to 21), no stone recurrence was noted. CONCLUSIONS: Percutaneous endoscopic holmium laser lithotripsy is a minimally invasive alternative to open salvage surgery for complex biliary calculi refractory to standard approaches. This treatment is both safe and efficacious. Success depends on a multidisciplinary approach.

Comparison of Outcomes in Patients With Muscle-invasive Bladder Cancer Treated With Radical Cystectomy Versus Bladder Preservation.

PURPOSE: Radical cystectomy currently remains the standard of care for muscle-invasive bladder cancer. However, surgery can be associated with considerable morbidity and mortality, including the removal of the bladder. An alternative strategy is to preserve the bladder through concurrent chemoradiation following a maximal transurethral resection of the tumor. National protocols using a bladder-preservation approach have demonstrated disease-specific outcomes comparable to radical cystectomy in selected patients, but these results have not been replicated in previously reported population-based series. Here, we describe an outcomes analysis of patients with muscle-invasive bladder cancer treated with either radical surgery or bladder-preserving chemoradiation (BPCRT) for those patients meeting BPCRT criterion using the National Cancer Database (NCDB). MATERIALS AND METHODS: Using the NCDB, patients with American Joint Commission on Cancer clinical T2-3, N0, M0 urothelial carcinoma diagnosed between 2004 and 2013 were included for analysis. Only patients treated with definitive intent with either radical cystectomy or concurrent chemotherapy and radiation after a maximal transurethral tumor resection were included. Propensity-score matching was used. RESULTS: Among 8454 eligible patients, 7276 (86%) underwent radical cystectomy, and 1178 (14%) underwent BPCRT. Patients undergoing BPCRT were significantly older (median age, 77 vs. 68 y; P<0.001) and had higher Charlson-Deyo comorbidity scores (P=0.002). Using propensity-matched analysis, 1002 patients remained in each cohort, and there was no significant difference in survival found between the 2 cohorts (median overall survival, 2.7 vs. 3.0 y [P=0.20]; 4-year overall survival, 39.1% and 42.6% [P=0.15], for BPCRT and surgery, respectively). In addition, the hazard ratio (HR) of surgery versus BPCRT decreased over time, with an initial HR of 1.27 favoring BPCRT which decreased by a factor of 0.85 per year. CONCLUSIONS: From 2004 to 2013, ∼14% of patients from the NCDB who potentially met bladder-preservation criteria underwent the procedure. Our propensity-matched analysis is the only report of its kind to demonstrate similar survival outcomes with bladder preservation when patients are properly selected. This study is also the first to demonstrate a dynamic HR between radical surgery and BPCRT over time.

18F-Fluciclovine Parameters on Targeted Prostate Biopsy Associated with True Positivity in Recurrent Prostate Cancer.

We evaluated 18F-fluciclovine uptake parameters that correlate with true positivity for local recurrence in non-prostatectomy-treated patients. Methods: Twenty-one patients (prostate-specific antigen level, 7.4 ± 6.8 ng/mL) with biochemical recurrence after nonprostatectomy local therapy (radiotherapy and cryotherapy) underwent dual-time-point 18F-fluciclovine (364.1 ± 37.7 MBq) PET/CT from pelvis to diaphragm. Prostatic uptake over background was delineated and coregistered to a prostate-biopsy-planning ultrasound. Transrectal biopsies of 18F-fluciclovine-defined targets were completed using a 3-dimensional visualization and navigation platform. Histologic analyses of lesions were completed. Lesion characteristics including SUVmax, target-to-background ratio (TBR), uptake pattern, and subjective reader's suspicion level were compared between true-positive (malignant) and false-positive (benign) lesions. Univariate analysis was used to determine the association between PET and histologic findings. Receiver-operating-characteristic curves were plotted to determine discriminatory cutoffs for TBR. Statistical significance was set at a P value of less than 0.05. Results: Fifty lesions were identified in 21 patients on PET. Seventeen of 50 (34.0%) targeted lesions in 10 of 21 patients were positive for malignancy. True-positive lesions had a significantly higher SUVmax (6.62 ± 1.70 vs. 4.92 ± 1.27), marrow TBR (2.57 ± 0.81 vs. 1.69 ± 0.51), and blood-pool TBR (4.10 ± 1.17 vs. 2.99 ± 1.01) than false-positive lesions at the early time point (P < 0.01) and remained significant at the delayed time point, except for blood-pool TBR. Focal uptake (odds ratio, 12.07; 95% confidence interval, 2.98-48.80; P < 0.01) and subjective highest suspicion level (odds ratio, 10.91; 95% confidence interval, 1.19-99.69; P = 0.03) correlated with true positivity. Using the receiver-operating-characteristic curve, optimal cutoffs for marrow TBR were 1.9 (area under the curve, 0.82) and 1.8 (area under the curve, 0.85) at early and delayed imaging, respectively. With these cutoffs, 15 of 17 malignant lesions were identified at both time points; however, fewer false-positive lesions were detected at the delayed time point (5/33) than at the early time point (11/33). Conclusion: True positivity of 18F-fluciclovine-targeted prostate biopsy in non-prostatectomy-treated patients correlates with focal uptake, TBR (blood pool and marrow), and subjective highest suspicion level. A marrow TBR of 1.9 at the early time point and 1.8 at the delayed time point had optimal discriminating capabilities. Despite the relatively low intraprostate positive predictive value (34.0%) with 18F-fluciclovine, application of these parameters to interpretative criteria may improve true positivity in the treated prostate.

Endourological management of urolithiasis in hepatically compromised patients.

PURPOSE: Hepatic insufficiency is a medically debilitating disease state, resulting in coagulopathy, malnutrition and immunological suppression. Before and after liver transplantation patients are at increased risk for urolithiasis due to nutritional factors, acidosis and hyperoxaluria. MATERIALS AND METHODS: We retrospectively reviewed our experience with endourological procedures for nephrolithiasis in hepatic compromised patients awaiting transplants and recipients. A total of 16 patients, including 13 males and 3 females, with a mean age of 52.8 years (range 46 to 59) underwent a total of 24 endoscopic stone procedures at 23 anesthesia sessions. Procedures included 18 ureteroscopies (extraction with or without lithotripsy), 5 percutaneous nephrolithotomies and 1 cystoscopic stone manipulation. Of the patients 12 patients had significant hepatic insufficiency and were evaluated for transplantation. Four patients had a prior orthotopic liver transplant at surgery. The most common causes of cirrhosis were hepatitis C and ethanol abuse. Of 22 sessions 12 were preceded by the use of fresh frozen plasma, platelets, vitamin K, desmopressin or recombinant factor VIIa for reversing severe coagulopathy. In 4 patients procedures were preceded by transfusion for anemia. RESULTS: All 24 procedures were successfully accomplished. Average hospital stay was 2.8 days (range 0 to 8) with 5 patients treated on an outpatient basis. A total of 52 calculi with a mean size of 10.7 mm (range 2 to 40) were treated. Of the 17 evaluated stone analyses 15 revealed pure or mixed calcium oxalate calculi, while the remaining 2 were struvite. Morbidity included 2 postoperative transfusions and 1 rehospitalization for urinary tract infection. One death was due to multisystem organ failure in a pretransplant patient who underwent bilateral ureteroscopy. CONCLUSIONS: Endourological procedures may be accomplished in this morbid group of patients. Mandatory preoperative medical evaluation, selective prehospitalization with supportive services and pre-stenting patients for passive ureteral dilation have led to successful endourological outcomes. Our experience has led us to adopt protocols and apply a team approach for the successful endoscopic management of urolithiasis in this complicated group of patients.

A semiautomatic algorithm for three-dimensional segmentation of the prostate on CT images using shape and local texture characteristics.

Prostate segmentation in computed tomography (CT) images is useful for planning and guidance of the diagnostic and therapeutic procedures. However, the low soft-tissue contrast of CT images makes the manual prostate segmentation a time-consuming task with high inter-observer variation. We developed a semi-automatic, three-dimensional (3D) prostate segmentation algorithm using shape and texture analysis and have evaluated the method against manual reference segmentations. In a training data set we defined an inter-subject correspondence between surface points in the spherical coordinate system. We applied this correspondence to model the globular and smoothly curved shape of the prostate with 86, well-distributed surface points using a point distribution model that captures prostate shape variation. We also studied the local texture difference between prostate and non-prostate tissues close to the prostate surface. For segmentation, we used the learned shape and texture characteristics of the prostate in CT images and we used a set of user inputs for prostate localization. We trained our algorithm using 23 CT images and tested it on 10 images. We evaluated the results compared with those of two experts' manual reference segmentations using different error metrics. The average measured Dice similarity coefficient (DSC) and mean absolute distance (MAD) were 88 ± 2% and 1.9 ± 0.5 mm, respectively. The averaged inter-expert difference measured on the same dataset was 91 ± 4% (DSC) and 1.3 ± 0.6 mm (MAD). With no prior intra-patient information, the proposed algorithm showed a fast, robust and accurate performance for 3D CT segmentation.

Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data.

OBJECTIVE: To provide an update on SpaceOAR System, a Food and Drug Administration-approved hydrogel indicated to create distance between the prostate and the rectum which has been studied in phase 2 and 3 clinical trials. Here, we review and summarize these clinical results including the safety of prostate-rectum spacer application technique, the implant quality and resulting rectal dose reduction, acute and long-term rectal, urinary, and sexual toxicity, as well as patient-reported outcomes. MATERIALS AND METHODS: A prospective, randomized patient-blinded clinical study was performed comparing image-guided intensity modulated prostate radiotherapy (79.2 Gy in 44 fractions) in men with or without prostate-rectum hydrogel spacer. Patients were followed up for 3 years, allowing assessment of long-term safety and efficacy. RESULTS: Spacer application was well tolerated with a 99% technical success rate. The mean additional space created between the prostate and the rectum was just over 1 cm, which allowed significant rectum and penile bulb radiation dose reduction, resulting in less acute pain, lower rates of late rectal toxicity, and improved bowel and urinary quality of life (QOL) scores from 6 months onward. Improvements in sexual QOL were also observed at 37 months in baseline-potent men, with 37.5% of control and 66.7% of spacer men capable of "erections sufficient for intercourse." CONCLUSION: Prostate-rectum hydrogel spacer application is a relatively safe technical procedure that is well tolerated and has a high technical success rate. Spacer application significantly reduces rectal radiation dose and results in long-term reductions in rectal toxicity, as well as improvements in bowel, urinary, and sexual QOL.

Prospective evaluation of fluciclovine (18F) PET-CT and MRI in detection of recurrent prostate cancer in non-prostatectomy patients.

PURPOSE: To investigate the disease detection rate, diagnostic performance and interobserver agreement of fluciclovine (18F) PET-CT and multiparametric magnetic resonance imaging (mpMR) in recurrent prostate cancer. METHODS: Twenty-four patients with biochemical failure after non-prostatectomy definitive therapy, 16/24 of whom had undergone brachytherapy, underwent fluciclovine PET-CT and mpMR with interpretation by expert readers blinded to patient history, PSA and other imaging results. Reference standard was established via a multidisciplinary truth panel utilizing histology and clinical follow-up (22.9 ±â€¯10.5 months) and emphasizing biochemical control. The truth panel was blinded to investigative imaging results. Diagnostic performance and interobserver agreement (kappa) for the prostate and extraprostatic regions were calculated for each of 2 readers for PET-CT (P1 and P2) and 2 different readers for mpMR (M1 and M2). RESULTS: On a whole body basis, the detection rate for fluciclovine PET-CT was 94.7% (both readers), while it ranged from 31.6-36.8% for mpMR. Kappa for fluciclovine PET-CT was 0.90 in the prostate and 1.0 in the extraprostatic regions. For mpMR, kappa was 0.25 and 0.74, respectively. In the prostate, 22/24 patients met the reference standard with 13 malignant and 9 benign results. Sensitivity, specificity and positive predictive value (PPV) were 100.0%, 11.1% and 61.9%, respectively for both PET readers. For mpMR readers, values ranged from 15.4-38.5% for sensitivity, 55.6-77.8% for specificity and 50.0-55.6% for PPV. For extraprostatic disease determination, 18/24 patients met the reference standard. Sensitivity, specificity and PPV were 87.5%, 90.0% and 87.5%, respectively, for fluciclovine PET-CT, while for mpMR, sensitivity ranged from 50 to 75%, specificity 70-80% and PPV 57-75%. CONCLUSION: The disease detection rate for fluciclovine PET-CT in non-prostatectomy patients with biochemical failure was 94.7% versus 31.6-36.8% for mpMR. For extraprostatic disease detection, fluciclovine PET-CT had overall better diagnostic performance than mpMR. For the treated prostate, fluciclovine PET-CT had high sensitivity though low specificity for disease detection, while mpMR had higher specificity, though low sensitivity. Interobserver agreement was also higher with fluciclovine PET-CT compared with mpMR.

Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma.

UNLABELLED: Conventional imaging techniques have serious limitations in the detection, staging, and restaging of prostate carcinoma. Anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid (anti-(18)F-FACBC)is a synthetic l-leucine analog that has excellent in vitro uptake within the DU-145 prostate carcinoma cell line and orthotopically implanted prostate tumor in nude rats. There is little renal excretion compared with (18)F-FDG. The present study examines anti-(18)F-FACBC uptake in patients with newly diagnosed and recurrent prostate carcinoma. METHODS: Fifteen patients with a recent diagnosis of prostate carcinoma (n = 9) or suspected recurrence (n = 6) underwent 65-min dynamic PET/CT of the pelvis after intravenous injection of 300-410 MBq anti-(18)F-FACBC followed by static body images. Each study was evaluated qualitatively and quantitatively. Maximum standardized uptake values were recorded in the prostate or prostate bed, and within lymph nodes at 4.5 min (early) and 20 min (delayed), and correlated with clinical, imaging and pathologic follow-up. Time-activity curves were also generated for benign and malignant tissue. RESULTS: In the 8 patients with newly diagnosed prostate carcinoma who underwent dynamic scanning, visual analysis correctly identified the presence or absence of focal neoplastic involvement in 40 of 48 prostate sextants. Pelvic nodal status correlated with anti-(18)F-FACBC findings in 7 of 9 patients and was indeterminate in 2 of 9. In all 4 patients in whom there was proven recurrence, visual analysis was successful in identifying disease (1 prostate bed, 3 extraprostatic). In 3 of these patients, (111)In-capromab-pendetide had no significant uptake at nodal and skeletal foci. Malignant lymph node uptake in both the staging and restaging patients was significantly higher than benign nodal uptake. Though uptake faded with time, in all 6 patients with either lymph node metastases or recurrent prostate bed carcinoma, there was intense persistent uptake at 65 min. CONCLUSION: Anti-(18)F-FACBC is a promising radiotracer for imaging prostate carcinoma. Radiotracer uptake was demonstrated in primary and metastatic disease. Future research should investigate the mechanism of radiotracer uptake in normal and pathologic tissue and develop a clinical imaging strategy for initial staging and restaging.

Molecular imaging and fusion targeted biopsy of the prostate.

PURPOSE: This paper provides a review on molecular imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI) for prostate cancer detection and its applications in fusion targeted biopsy of the prostate. METHODS: Literature search was performed through the PubMed database using the keywords "prostate cancer", "MRI/ultrasound fusion", "molecular imaging", and "targeted biopsy". Estimates in autopsy studies indicate that 50% of men older than 50 years of age have prostate cancer. Systematic transrectal ultrasound (TRUS) guided prostate biopsy is considered the standard method for prostate cancer detection and has a significant sampling error and a low sensitivity. Molecular imaging technology and new biopsy approaches are emerging to improve the detection of prostate cancer. RESULTS: Molecular imaging with PET and MRI shows promising results in the early detection of prostate cancer. MRI/TRUS fusion targeted biopsy has become a new clinical standard for the diagnosis of prostate cancer. PET molecular image-directed, three-dimensional ultrasound-guided biopsy is a new technology that has great potential for improving prostate cancer detection rate and for distinguishing aggressive prostate cancer from indolent disease. CONCLUSION: Molecular imaging and fusion targeted biopsy are active research areas in prostate cancer research.

Automatic segmentation of the prostate on CT images using deep learning and multi-atlas fusion.

Automatic segmentation of the prostate on CT images has many applications in prostate cancer diagnosis and therapy. However, prostate CT image segmentation is challenging because of the low contrast of soft tissue on CT images. In this paper, we propose an automatic segmentation method by combining a deep learning method and multi-atlas refinement. First, instead of segmenting the whole image, we extract the region of interesting (ROI) to delete irrelevant regions. Then, we use the convolutional neural networks (CNN) to learn the deep features for distinguishing the prostate pixels from the non-prostate pixels in order to obtain the preliminary segmentation results. CNN can automatically learn the deep features adapting to the data, which are different from some handcrafted features. Finally, we select some similar atlases to refine the initial segmentation results. The proposed method has been evaluated on a dataset of 92 prostate CT images. Experimental results show that our method achieved a Dice similarity coefficient of 86.80% as compared to the manual segmentation. The deep learning based method can provide a useful tool for automatic segmentation of the prostate on CT images and thus can have a variety of clinical applications.

Impact of 18F-Fluciclovine PET on Target Volume Definition for Postprostatectomy Salvage Radiotherapy: Initial Findings from a Randomized Trial.

The purpose of this study was to evaluate the role of the synthetic amino acid PET radiotracer 18F-fluciclovine in modifying the defined clinical and treatment-planning target volumes in postprostatectomy patients undergoing salvage radiotherapy and to evaluate the resulting dosimetric consequences to surrounding organs at risk. Methods: Ninety-six patients were enrolled in a randomized, prospective intention-to-treat clinical trial for potential salvage radiotherapy for recurrent prostate cancer after prostatectomy. The initial treatment plan was based on the results from conventional abdominopelvic CT and MRI. The 45 patients in the experimental arm also underwent abdominopelvic 18F-fluciclovine PET/CT, and the images were registered with the conventional images to determine whether the results would modify the initial treatment plan. The 51 patients in the control arm did not undergo 18F-fluciclovine PET/CT. For each patient, the clinical and treatment-planning target volumes that would have been treated before 18F-fluciclovine registration were compared with those after registration. For organs at risk (rectum, bladder, and penile bulb), the volumes receiving 40 Gy and 65 Gy before registration were compared with those after registration. Statistical comparisons were made using the paired t test. Acute genitourinary and gastrointestinal toxicity as defined by the Radiation Therapy Oncology Group was compared between the control and experimental arms using the χ2 test. Results: In 24 cases, radiotherapy was planned to a clinical target volume consisting of the prostate bed alone (CTV) (64.8-66.6 Gy). In 21 cases, radiotherapy was planned to a clinical target volume consisting of the pelvis (CTV1) (45.0 Gy) followed by a boost to the prostate bed (CTV2) (19.8-25.2 Gy). In each case, the respective treatment-planning target volume expansion (PTV, PTV1, or PTV2) was 0.8 cm (0.6 cm posterior). With the exception of PTV2, all postregistration volumes were significantly larger than the corresponding preregistration volumes. Analysis of the rectum, bladder, and penile bulb volumes receiving 40 Gy and 60 Gy demonstrated that only the penile bulb volumes were significantly higher after registration. No significant differences in acute genitourinary or gastrointestinal toxicity were observed. Conclusion: Including information from 18F-fluciclovine PET in the treatment-planning process led to significant differences in the defined target volume, with higher doses to the penile bulb but no significant differences in rectal or bladder dose or in acute genitourinary or gastrointestinal toxicity. Longer follow-up is needed to determine the impact of 18F-fluciclovine PET on cancer control and late toxicity endpoints.

Change in Salvage Radiotherapy Management Based on Guidance With FACBC (Fluciclovine) PET/CT in Postprostatectomy Recurrent Prostate Cancer.

PURPOSE: We explored the influence of FACBC (fluciclovine) PET/CT on the decision to offer radiotherapy and radiotherapy treatment field recommendations in postprostatectomy patients with recurrent prostate cancer. PATIENTS AND METHODS: After obtaining institutional review board approval and informed consent, 87 patients with detectable prostate-specific antigen (PSA) levels were recruited into a prospective clinical trial. After an initial provider-determined radiotherapy plan based on conventional imaging, 44 of 87 patients were randomized to additionally undergo fluciclovine PET/CT. Pre- and post-fluciclovine radiotherapy decisions were compared and changes were noted. Statistical significance of these decision changes was determined. RESULTS: Two of 44 patients in the experimental arm dropped out before fluciclovine scanning. Thirty-four (81.0%) of 42 had positive results on fluciclovine. Overall radiotherapy decision was changed in 17 (40.5%) of 42. Mean PSA, original Gleason score, and prostatectomy-PET interval did not differ significantly between patients with and without radiotherapy decision changes. Two (4.8%) of 42 had the decision for radiotherapy withdrawn due to positive extrapelvic findings. Radiotherapy field decision was changed in 15 (35.7%) of 42. Eleven (73.3%) of 15 had fields changed from prostate bed only to both prostate bed and pelvis, while 4 (26.7%) of 15 had fields changed from both prostate bed and pelvis to prostate bed only. Changes in overall radiotherapy decision and field were statistically significant (P < 0.0001). However, the change in the decision to offer radiotherapy or not was not statistically significant (P = 0.15). CONCLUSIONS: Fluciclovine PET/CT significantly changed radiotherapy management decisions in postprostatectomy patients with recurrent prostate cancer. Further work in determining differences in PSA-free survival is ongoing.