Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer.

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.

Direct co-registration of [18F]FDG uptake and histopathology in surgically excised malignancies of the head and neck: a feasibility study.

PURPOSE: Recent technical advancements in PET imaging have improved sensitivity and spatial resolution. Consequently, clinical nuclear medicine will be confronted with PET images on a previously unfamiliar resolution. To better understand [18F]FDG distribution at submillimetric scale, a direct correlation of radionuclide-imaging and histopathology is required. METHODS: A total of five patients diagnosed with a malignancy of the head and neck were injected with a clinical activity of [18F]FDG before undergoing surgical resection. The resected specimen was imaged using a preclinical high-resolution PET/CT, followed by slicing of the specimen. Multiple slices were rescanned using a micro-PET/CT device, and one of the slices was snap-frozen for frozen sections. Frozen sections were placed on an autoradiographic film, followed by haematoxylin and eosin staining to prepare them for histopathological assessment. The results from both autoradiography and histopathology were co-registered using an iterative co-registration algorithm, and regions of interest were identified to study radiotracer uptake. RESULTS: The co-registration between the autoradiographs and their corresponding histopathology was successful in all specimens. The use of this novel methodology allowed direct comparison of autoradiography and histopathology and enabled the visualisation of uncharted heterogeneity in [18F]FDG uptake in both benign and malignant tissue. CONCLUSION: We here describe a novel methodology enabling the direct co-registration of [18F]FDG autoradiography with the gold standard of histopathology in human malignant tissue. The future use of the current methodology could further increase our understanding of the distribution of radionuclides in surgically excised malignancies and hence, improve the integration of pathology and molecular imaging in a multiscale perspective. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05068687.

The Changing Landscape of Systemic Therapy in the Treatment of Synchronous Metastatic Hormone-sensitive Prostate Cancer.

INTRODUCTION: To describe the changes in systemic treatments (ST) of synchronous metastatic hormone-sensitive prostate cancer (mHSPC) patients in a "real-world" setting and to explore reasons why contemporary standard of care (SOC) was not administrated to the patient. PATIENTS AND METHODS: Since 2014, we prospectively register mHSPCpatients. Patients were grouped in 4 time periods: group 1 (Time period 1, January 2014-July 2015), group 2 after introduction of docetaxel (Time period 2, August 2015-July 2017), group 3 after introduction of abiraterone acetate (Time period 3, August 2017-February 2018) and group 4 after introduction of apalutamide (Time period 4, March 2018-October 2021). For every time period, we evaluated the initiated additional ST. In case patients received treatment that differed from contemporary SOC according to guidelines, reasons for this difference were explored. RESULTS: In total, 243 patients were included. A progressive decline in ADT monotherapy from 85% to 29% over time was observed. The proportion of patients receiving additional STs increased from 34% to 59%. Forty percent of patients were not treated according to contemporary SOC, but this percentage varied strongly per time period (10%, 67%, 53%, and 32% from time period 1 to time period 4 respectively). Reasons for these variations were heterogenous and varied across the 4 time periods. Patients being unfit for treatment and treating physicians failing to consider additional STs were the most prevalent reasons. The proportion of patients unfit for additional ST decreased from 18% to 4% over time. CONCLUSION: Use of ADT monotherapy declined gradually after the introduction of additional systemic treatments. The proportion of patients unfit for additional ST declined as more treatments became available. Although compliance to SOC increased over time, these real-world data show that adherence to clinical practice guidelines remains suboptimal. Efforts should be made by clinicians to increase the adherence to practice guidelines.

Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

18F-PSMA-11 Versus 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Staging and Biochemical Recurrence of Prostate Cancer: A Prospective Double-blind Randomised Cross-over Trial.

BACKGROUND: Fluorine-18 (18F)-labelled prostate-specific membrane antigen (PSMA) offers several advantages over gallium-68 (68Ga) in terms of costs, yield, transport/distribution, and image resolution. OBJECTIVE: This trial investigates the new radiotracer 18F-PSMA-11 via a prospective, intraindividual crossover design. The trial was powered for noninferiority of 18F-PSMA-11 over 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) in terms of the number of positive PET scans. Secondary endpoints were as follows: (1) superiority of 18F-PSMA-11 over 68Ga-PSMA-11 with respect to the number of positive PET scans, the total number of suspicious prostate cancer lesions, and the miPSMA expression score of corresponding lesions; (2) correlation of the PET/CT images with available follow-up data for 18F-PSMA-11 and 68Ga-PSMA-11; and (3) assessment of the interobserver variability. DESIGN, SETTING, AND PARTICIPANTS: Prostate cancer patients (primary or biochemical recurrence) were randomised in a double-blind crossover design whereby each patient received both 18F-PSMA-11 and 68Ga-PSMA-11 PET/CT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All scans were reviewed and scored by three independent experienced nuclear physicians following the proposed guideline for the interpretation of PSMA-ligand PET/CT, as described by Eiber et al. RESULTS AND LIMITATIONS: In total, 82 patients were included for scan analyses. The primary endpoint was met: per patient, the proportions of positive scans rated by the three readers were 67%/67%, 65%/65%, and 73%/70% for 18F-PSMA-11/68Ga-PSMA-11 PET/CT. The miPSMA expression score was higher for 18F-PSMA-11 than for 68Ga-PSMA-11 for the reference reader. Follow-up data showed identical estimated sensitivity for both the 18F-PSMA-11 and the 68Ga-PSMA-11 scan (0.92, 0.83, and 0.92 for the three readers). A fair to good agreement among readers (at patient level) was obtained, which was demonstrated by a Light's kappa value of 0.59 for both tracers. CONCLUSIONS: The tracer 18F-PSMA-11 is noninferior to68Ga-PSMA-11. Superiority of 18F-PSMA-11 was limited to the miPSMA expression score, given by the reference reader. Inter-rater agreement was fair to good, and equal for both radiotracers. PATIENT SUMMARY: In this study, we compared two radiotracers: 18F-PSMA-11 and 68Ga-PSMA-11. We proved that 18F-PSMA-11 is not inferior to 68Ga-PSMA-11 for detecting prostate cancer and thus can be used as an alternative. Possible superiority of this tracer should be further investigated in specific subpopulations.

Impact of 18F-PSMA-11 PET/CT on Management of Biochemical Recurrence and High-Risk Prostate Cancer Staging : 18F-PSMA-11 PET/CT and Impact on Prostate Cancer Management.

PURPOSE: In this study, we evaluated the impact of 18F-PSMA-11 PET/CT on the patient management plan in patients with primary or recurrent disease. Furthermore, a correlation between PET findings and other modalities was performed. PROCEDURES: In this prospective observational study, 60 prostate cancer patients (9 primary staging, 51 biochemical recurrence) were imaged with 18F-PSMA-11 PET/CT. Pre- and post-scan questionnaires were completed by the treating physician to observe changes in therapy intent. Follow-up data (histological confirmation, MRI imaging, and PSA values after radiotherapy without implementation of systemic therapy) was correlated with the 18F-PSMA-11 findings. RESULTS: The patient-based detection rate was 82% and a management change was seen in 52% of the cases. The heterogeneous characteristics of the included patients resulted in a widely varying treatment change, mostly originating from an increase of disease extent on 18F-PSMA-11 PET/CT. CONCLUSION: 18F-PSMA-11 PET/CT showed to be a highly promising method for the detection of prostate cancer lesions.

Evaluating the impact of 18F-FDG-PET-CT on risk stratification and treatment adaptation for patients with muscle-invasive bladder cancer (EFFORT-MIBC): a phase II prospective trial.

BACKGROUND: The outcome of patients with muscle-invasive bladder cancer (MIBC) remains poor, despite aggressive treatments. Inadequate primary staging, classically performed by computed tomography (CT)-imaging, could lead to inappropriate treatment and might contribute to these poor results. Although not (yet) adapted by international guidelines, several reports have indicated the superiority of 18F-fluorodeoxyglucose-positron emission tomography-CT (18F-FDG-PET-CT) compared to CT in the detection of lymph node and distant metastases. Thereby the presence of extra-vesical disease on 18F-FDG-PET-CT has been correlated with a worse overall survival. This supports the hypothesis that 18F-FDG-PET-CT is useful in stratifying MIBC patients and that adapting the treatment plan accordingly might result in improved outcome. METHODS: EFFORT-MIBC is a multicentric prospective phase II trial aiming to include 156 patients. Eligible patients are patients with histopathology-proven MIBC or ≥ T3 on conventional imaging treated with MIBC radical treatment, without extra-pelvic metastases on conventional imaging (thoracic CT and abdominopelvic CT/ magnetic resonance imaging (MRI)). All patients will undergo radical local therapy and if eligible neo-adjuvant chemotherapy. An 18F-FDG-PET-CT will be performed in addition to and at the timing of the conventional imaging. In case of presence of extra-pelvic metastasis on 18F-FDG-PET-CT, appropriate intensification of treatment with metastasis-directed therapy (MDT) (in case of ≤3 metastases) or systemic immunotherapy (> 3 metastases) will be provided. The primary outcome is the 2-year overall survival rate. Secondary endpoints are progression-free survival, distant metastasis-free survival, disease-specific survival and quality of life. Furthermore, the added diagnostic value of 18F-FDG-PET-CT compared to conventional imaging will be evaluated and biomarkers in tumor specimen, urine and blood will be correlated with primary and secondary endpoints. DISCUSSION: This is a prospective phase II trial evaluating the impact of 18F-FDG-PET-CT in stratifying patients with primary MIBC and tailoring the treatment accordingly. We hypothesize that the information on the pelvic nodes can be used to guide local treatment and that the presence of extra-pelvic metastases enables MDT or necessitates the early initiation of immunotherapy leading to an improved outcome. TRIAL REGISTRATION: The Ethics Committee of the Ghent University Hospital (BC-07456) approved this study on 11/5/2020. The trial was registered on ClinicalTrials.gov (NCT04724928) on 21/1/2021.

The Role of Cytoreductive Radical Prostatectomy in the Treatment of Newly Diagnosed Low-volume Metastatic Prostate Cancer. Results from the Local Treatment of Metastatic Prostate Cancer (LoMP) Registry.

BACKGROUND: Radiotherapy to the prostate (RTp) prolongs survival for patients with low-volume, newly diagnosed metastatic prostate cancer (ndmPC). OBJECTIVE: to evaluate whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp in low-volume ndmPC. DESIGN SETTING AND PARTICIPANTS: A multicenter prospective registry was established in 2014 to observe patients with ndmPC. Eligible patients were offered cRP or RTp. For this study we selected only patients with low-volume ndmPC (n = 109). Of these, 48, 26, and 35 patients underwent cRP, RTp, and no local therapy (NLT), respectively. Median follow-up was 32 mo (interquartile range 16-49). INTERVENTION: cRP was compared with RTp and NLT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), cancer-specific survival (CSS), and local event-free survival (LEFS) were calculated using the Kaplan-Meier method. Factors prognostic for OS were identified using univariate and multivariate Cox regression analysis. RESULTS AND LIMITATIONS: The 2-yr OS was 93%, 100%, and 69%, and 2-yr CSS was 93%, 100%, and 75% for cRP, RTp, and NLT, respectively. The cRP and RTp groups had better OS compared to NLT and there was no significant difference between cRP and RTp. The 2-yr LEFS was 92%, 77%, and 60% for cRP, RTp, and NLT, respectively. The cRP group had better LEFS compared to RTp and NLT, and there was no significant difference between RTp and NLT. Advanced tumor stage, Eastern Cooperative Oncology Group performance status ≥2, and NLT were negative prognostic factors for OS. The main limitation is selection of fitter patients with less advanced tumors for cRP and the small sample size. CONCLUSIONS: For selected patients with low-volume ndmPC, cRP is able to achieve similar OS and CSS to RTp. cRP is effective in preventing local events due to disease progression. PATIENT SUMMARY: Patients with a low volume of newly diagnosed prostate cancer that has spread beyond the prostate gland might benefit from removal of the prostate, which we found was as effective as radiotherapy to the prostate in prolonging survival. Removal of the prostate is effective in preventing urinary problems caused by cancer progression.

Neuroendocrine tumor with diarrhea: not always the usual suspects - a case report of metastatic calcitoninoma with literature review.

We describe a case of a 59-year-old man without relevant past medical history, presenting with chronic diarrhea and weight loss. Extensive laboratory analysis, stool cultures and gastro- and ileocolonoscopy could not identify a diagnosis. Abdominal imaging revealed a mass in the uncinate process of the pancreas with mesenteric adenopathies and liver metastases. Fine needle aspiration was compatible with a pancreatic neuroendocrine tumor with low proliferative capacity (Ki-67 <1%). Immunohistochemical staining was positive for calcitonin and serum calcitonin levels were clearly elevated. Surprisingly, 18FDG PET-CT scan was positive, but no tracer uptake was seen on 68Gallium-DOTATOC PET-CT scan. Treatment with somatostatin analogues was not successful, but long-term tumor control could be obtained with Everolimus. However, no significant effect was seen on stool frequency despite additional treatment with multiple symptomatic therapies, liver-directed therapy with radio- and chemoembolization and additional external radiotherapy to the primary pancreatic tumor. Ondansetron, eventually, seems to be the only therapy, until now, causing a decrease in stool frequency.Functioning pancreatic calcitoninomas are considered to be a rare disease entity with few literature on optimal (nuclear) imaging and treatment. We discuss molecular insights regarding these aspects that can be of great interest to nuclear medicine physicians, pathologists, endocrinologists and gastroenterologists.

Intrapancreatic accessory spleen mimicking pancreatic NET: can unnecessary surgery be avoided?

Pancreatic nodules are frequently found incidentally and often pose a diagnostic and therapeutic challenge when surgery is considered. We present the case of a 66-year-old cirrhotic patient with a pancreatic nodule with signal intensity and contrast enhancement pattern suggestive for a non-functional neuroendocrine lesion. A 68Gallium-DOTATOC PET-CT scan revealed a correspondent focal tracer uptake in the pancreatic tail. After distal pancreatectomy, the specimen surprisingly revealed intrapancreatic splenic tissue. Nuclear imaging has previously been reported to produce a false-positive result for the presence of a neuroendocrine tumor when an intrapancreatic accessory spleen is present. This case reminds us of the diagnostic pitfalls in pancreatic nodules, to consider a broad differential diagnosis and to remain critical before referring the patient for surgery.

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice.

Recently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq 18F-PSMA-11 and 68Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq 18F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUVmean, SUVmax, TBRmean and TBRmax). Mice underwent ex vivo biodistribution where 18F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (Kd) of 18F-PSMA-11 and 68Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both 18F-PSMA-11 and 68Ga-PSMA-11, while no difference was found for 18F-FDG uptake (except for SUVmax). Tumor uptake of 18F-PSMA-11 showed a similar trend over time as 68Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBRmean and TBRmax were significantly higher at the later timepoint, as well as the SUVmax of 68Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for 18F-PSMA-11 compared to 68Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late 18F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of 18F-PSMA-11 as well as no significant increase in bone uptake.

Splenic 18F-FDG uptake on baseline PET/CT is associated with oncological outcomes and tumor immune state in uterine cervical cancer.

OBJECTIVE: The spleen represents an important contributor to tumor immune escape, but the relevance of increased splenic metabolic activity remains to be fully elucidated. METHODS: We retrospectively measured the spleen-to-liver standard uptake value (SLR) on 18F-FDG PET/CT examinations of 92 consecutive patients with FIGO stage IB1 to IVA cervical cancer and integrated the results with survival, response to treatment, tumor immune infiltrate, and baseline characteristics. RESULTS: SLRmax > 0.92 (p = .026) and SLRmean > 0.94 (p = .005) were significantly associated with decreased DFS in univariable analysis. Multivariable models were built using best subset selection; ΔSLRmax and either SLRmax or SLRmean were consistently selected, strongly reinforcing the association between SLR variables and DFS in relation to potential confounders (all models p ≤ .002). Independent associations were found for SLRmax using multivariable Cox regression models for DFS (all p ≤ .003). Further, uni- and multivariable analyses demonstrated the negative impact of higher SLR values on pathological complete response. A statistically significant higher proportion of patients with high SLRmax had a dense infiltrate of CD20+ (p = .036) and CD68+ (p = .015) immune cells, as well as PD-L1+ tumor cells (p = .019) as compared to those with low SLRmax. Finally, high SLRmax status was neither associated with systemic inflammatory markers (except for an increased white blood cell count; p = .038), nor with clinically overt infection. CONCLUSION: This hypothesis-generating study provides the first evidence that increased splenic metabolic activity is a negative prognostic and predictive biomarker in locally advanced cervical cancer. In addition, it might help to discriminate immunologically 'hot' from 'cold' cervical tumors.

Optimization of PET protocol and interrater reliability of 18F-PSMA-11 imaging of prostate cancer.

BACKGROUND: Several scan parameters for PET imaging with 18F-PSMA-11 such as dosage, acquisition time and scan duration were evaluated to determine the most appropriate scan protocol, as well as the effect of furosemide administration on lesion visualization. Forty-four patients were randomly assigned to a dosage group (2.0 ± 0.2 or 4.0 ± 0.4 MBq/kg 18F-PSMA-11). All patients received a full-body PET/CT 1 h and 3 h after radiotracer injection with a scan duration of 3 min/bed position. For comparison of the scan duration, images were reconstructed for 1.5 and 3 min/bed position. Patients were intravenously administered 0.5 mg/kg furosemide with a maximum dose of 40 mg. To evaluate the furosemide effect, 22 additional patients were recruited and received one full-body PET/CT 1 h after administration of 2.0 ± 0.2 MBq/kg 18F-PSMA-11 with a scan duration of 3 min/bed position. To this group, no furosemide was administered. Images were scored on image quality using a 7-point scale and each suspicious lesion was described. To assess interrater reliability, two nuclear physicians scored all scans independently and described all observed suspicious lesions. RESULTS: The 4 MBq/kg group received for all reconstructed images (60 min p.i., 1.5 and 3 min/bed position and 180 min p.i., 1.5 and 3 min/bed position) the highest median image quality score compared to the 2 MBq/kg group (p values < 0.01). When comparing all reconstructed images, the highest image quality score was given to images at 60 min p.i., 3 min/bed position for both dosage groups (score 5 and 6 for 2 and 4 MBq/kg, respectively). The addition of furosemide administration decreased the interference score with one point (p = 0.01106) and facilitated the evaluation of lesions in proximity to the ureters. The interrater reliability for the comparison of each lesion separately after more than 40 18F-PSMA-11 scan readings showed an increasing κ value from 0.78 (95% CI, 0.65-0.92) to 0.94 (95% CI, 0.87-1). CONCLUSION: Although the results indicate an administered activity of 4.0 ± 0.4 MBq/kg, preference will be given to 2.0 ± 0.2 MBq/kg due to the small difference in absolute score (max 1 point) and the ALARA principle. For evaluation of lesions in proximity to the ureters, the co-administration of a diuretic can be useful. The increase of the κ value from 0.78 to 0.94 suggests a learning curve in the interpretation of 18F-PSMA-11 images. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03573011. Retrospectively registered 28 June 2018.

Radiation Dosimetry and Biodistribution of 18F-PSMA-11 for PET Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is highly overexpressed in prostate cancer. Many PSMA analog radiotracers for PET/CT prostate cancer staging have been developed, such as 68Ga-PSMA-11. This radiotracer has achieved good results in multiple clinical trials, but because of the superior imaging characteristics of 18F-fluoride, 18F-PSMA-11 was developed. The aim of this study was to evaluate the administration safety and radiation dosimetry of 18F-PSMA-11. Methods: Six patients (aged 62-68 y; mean, 66 ± 2 y) with suspected prostate cancer recurrence after previous treatment were administered 2 MBq of 18F-PSMA-11 per kilogram of body weight and then underwent low-dose PET/CT imaging at 0, 20, 50, 90, and 300 min after injection. To evaluate the safety of administration, vital parameters were monitored. To assess toxicity, full blood count and biochemical parameters were determined. According to the latest International Commission on Radiological Protection recommendations, radiation dosimetry analysis was performed using IDAC-Dose 2.1. For blood activity measurement, small samples of venous blood were collected at various time points after injection. The unbound 18F-fluoride fraction was determined in plasma at 20, 50, and 90 min after administration to evaluate the defluorination rate of 18F-PSMA-11. Results: After injection, 18F-PSMA-11 cleared rapidly from the blood. At 5 h after injection, 29.0% ± 5.9% of the activity was excreted in urine. The free 18F fraction in plasma increased from 9.7% ± 1.0% 20 min after injection to 22.2% ± 1.5% 90 min after injection. The highest tracer uptake was observed in kidneys, bladder, spleen, and liver. No study drug-related adverse events were observed. The calculated mean effective dose was 12.8 ± 0.6 µSv/MBq. Conclusion:18F-PSMA-11 can be safely administered and results in a mean effective dose of 12.8 ± 0.6 µSv/MBq. Therefore, the total radiation dose is lower than for other PSMA PET agents and in the same range as 18F-DCFPyL.

Nodal Oligorecurrent Prostate Cancer: Anatomic Pattern of Possible Treatment Failure in Relation to Elective Surgical and Radiotherapy Treatment Templates.

BACKGROUND: Patients with biochemical recurrence following primary prostate cancer (PCa) treatment often experience relapse in the lymph nodes (LNs). Both salvage LN dissection (sLND) and elective nodal radiotherapy (ENRT) are potential treatment options. OBJECTIVE: To describe anatomic patterns of nodal oligorecurrent PCa in relation to different surgical and radiotherapy templates. DESIGN, SETTING, AND PARTICIPANTS: Patients with biochemical recurrence following primary PCa treatment were eligible for 18F-choline positron emission tomography/computed tomography (CT). Patients with five or fewer LN recurrences (N1/M1a) were eligible for the current retrospective analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All LN recurrences were mapped on a reference patient CT, as well as different surgical templates (limited to superextended) and an adapted version of the PIVOTAL ENRT template, blinded for the recurrences. Descriptive statistics were used to report recurrences in relation to the different templates and to compare LN coverage between templates. RESULTS AND LIMITATIONS: In total, 158 LN recurrences (N1: 88; M1a: 70) in 82 patients (median age: 67yr; prostate-specific antigen [PSA]: 3.1ng/ml; PSA doubling time of 7.8mo at the time of clinical recurrence) were mapped. In 49% of patients, recurrences were exclusively located in the true pelvis, followed by the common iliac LN (10%), retroperitoneal/inguinal LN (10%), or a combination (31%). There was up to 40% volume overlap between ENRT and the surgical templates. Theoretically, with ENRT more patients are fully covered (p<0.02) and the total number of covered lesions is higher (p<0.001) when compared to all types of sLND, except for superextended sLND, which is comparable to ENRT (patient-level: p=0.6; lesion-level: p=0.09). With 22% of all 158 lesions located outside all templates (N1: 7%; M1a: 15%), at least 31% of all 82 patients would not be salvaged using any of the templates. CONCLUSIONS: More than half of nodal recurrences are located outside the true pelvis. Limited or standard extended sLND is considered insufficient as a salvage treatment approach and is thus not recommended for use. To maximize treatment outcomes for nodal recurrences, ENRT or superextended sLND should be preferred. PATIENT SUMMARY: We compared two possible treatment options, elective nodal radiotherapy and salvage lymph node dissection, for patients with prostate cancer recurrence limited to five or fewer lymph nodes and reported the nodal distrubution. Radiotherapy and surgery cover different areas with possible different outcomes.

Importance of metastatic volume in prognostic models to predict survival in newly diagnosed metastatic prostate cancer.

PURPOSE: To explore the prognostic importance of metastatic volume in a contemporary daily practice cohort of patients with newly diagnosed metastatic hormone-naive prostate cancer (mHNPC) and to develop a pragmatic prognostic model to predict survival for these patients. METHODS: Since 2014, 113 patients with newly diagnosed mHNPC were prospectively registered. Statistical analysis was performed using SPSS 25.0™ with two-sided p value < 0.05 indicating statistical significance. Univariate and multivariate cox regression analyses were performed to identify prognostic risk factors. Kaplan-Meier method with log-rank statistics was constructed to analyze difference in survival in the prognostic groups. Model performance was assessed using the Concordance-index (C-index) and cross-validated in R v3.4.1. High-volume mHNPC (HVD) was defined as the presence of visceral metastasis or ≥ 4 bone metastases with ≥ 1 appendicular lesion. RESULTS: Multivariate analysis identified HVD (p = 0.047) and elevated alkaline phosphatase (ALP) (p = 0.018) as independent prognostic risk factors for overall survival (OS). Consequently, three prognostic groups were created: a good (no risk factors), intermediate (1 risk factor) and poor prognosis group (2 risk factors). Median OS for the good, intermediate and poor prognosis group was not reached, 73 and 20 months (95% CI 9-31 months with p < 0.001 and Correspondence-index of 0.78), respectively. CONCLUSIONS: We developed a pragmatic and qualitative prognostic model consisting of three prognostic risk groups for OS in a daily practice cohort of patients with newly diagnosed mHNPC. Independent prognostic risk factors included in the model were HVD and abnormal ALP.

Robot-assisted Kidney Autotransplantation: A Minimally Invasive Way to Salvage Kidneys.

BACKGROUND: Kidney autotransplantation (KAT) is the ultimate way to salvage kidneys with complex renovascular, ureteral, or malignant pathologies that are not amenable to in situ reconstruction. A minimally invasive approach could broaden its adoption. OBJECTIVE: To describe operative technique, perioperative complications, and early functional outcomes of robot-assisted kidney autotransplantation (RAKAT). DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of prospectively collected data regarding consecutive patients undergoing RAKAT between March 2017 and February 2018 at two university hospitals. INTERVENTION: RAKAT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Technical feasibility, perioperative complications, and early functional results. RESULTS AND LIMITATIONS: Seven patients underwent RAKAT (three male and four female; five left and two right; one totally intracorporeal) for complex ureteral strictures (n=5), severe left renal vein nutcracker (n=1), and loin pain hematuria syndrome (n=1). Two patients underwent bench vascular reconstruction and one patient underwent ex vivo flexible ureterorenoscopy. No patient needed open conversion. Median operative and console time was 370 and 255min, respectively, with median vascular and ureteral anastomosis time of 28 and 23min, respectively. Median warm, cold, and rewarming ischemia time was 2, 178, and 44min, respectively. One major postoperative complication occurred-wound dehiscence needing wound revision (grade 3b). Median hospital stay was 5 d. At 3 mo, all patients were free of indwelling stents, pain, or hematuria. Median serum creatinine at 3 mo was 0.80mg/dl and median calculated autotransplant glomerular filtration rate did not drop significantly. CONCLUSIONS: RAKAT is feasible, safe, and results in good functioning of the autotransplant in selected patients with complex ureteral strictures, loin pain hematuria, or severe nutcracker syndrome. Larger studies with longer follow-up are needed to confirm these findings and to test whether RAKAT is feasible for other KAT indications. PATIENT SUMMARY: We describe the first series worldwide of a minimally invasive technique for kidney autotransplantation. Robot-assisted kidney autotransplantation is a safe and feasible approach to prevent nephrectomy for intractable symptoms in selected patients with complex ureteral or renal pathology.

Metastatic burden in newly diagnosed hormone-naive metastatic prostate cancer: Comparing definitions of CHAARTED and LATITUDE trial.

OBJECTIVES: No uniformity exists in the definition of metastatic burden in metastatic hormone-naive prostate cancer (mHNPC) across clinical trials making their comparison challenging. We explored definition agreement and prognostic significance of bulky mHNPC according to the CHAARTED and LATITUDE trial. MATERIALS AND METHODS: Since 2014, 95 patients with newly diagnosed mHNPC were prospectively registered. For this study, they were categorized as having high-volume (HVD) vs. low-volume (LVD) and high-risk (HRD) vs. low-risk disease (LRD) according to the definition of CHAARTED and LATITUDE, respectively. Agreement was tested using Cohen's κ coefficient. The Kaplan-Meier method was used to compare castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). Prognostic significance was analyzed using Cox regression models. RESULTS: In total, 44 (46%) and 46 (48%) patients showed HVD and HRD, respectively. Cohen's κ coefficient was 0.83 indicating "almost perfect" agreement (P<0.001). Median CRPC-FS was 40 (95% CI: 25-55) vs. 11 months (95% CI: 8-14) for LVD and HVD (P = 0.001); 40 (95% CI: 27-53) vs. 11 months (95% CI: 8-14) for LRD and HRD (P<0.001), respectively. Median OS was not reached vs. 51 months (95% CI: 0-102) for LVD and HVD (P = 0.001); not reached vs. 51 months (95% CI: 2-100) for LRD and HRD (P = 0.003), respectively. The prognostic significance of both definitions remained significant in the multivariate model for CRPC-FS (P = 0.012 and P = 0.003). CONCLUSIONS: There is an excellent agreement between the definitions of bulky mHNPC in the CHAARTED and LATITUDE trial. Both definitions have significant prognostic value for predicting worse CRPC-FS and OS.