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.

MRI texture analysis of T2-weighted images is preferred over magnetization transfer imaging for readily longitudinal quantification of gut fibrosis.

OBJECTIVES: To investigate the value of magnetization transfer (MT) MRI and texture analysis (TA) of T2-weighted MR images (T2WI) in the assessment of intestinal fibrosis in a mouse model. METHODS: Chronic colitis was induced in mice by cyclic administration of dextran sodium sulphate (DSS) resulting in chronic inflammation and progressive bowel fibrosis. Mice underwent 7-T MR imaging at various time points. Bowel wall MT ratio (MTR) and textural features (skewness, kurtosis, entropy), extracted by a filtration histogram technique, were correlated with histopathology. Performance of both techniques were validated using antifibrotic therapy. Finally, a retrospective study was conducted in five patients with Crohn's disease (CD) who underwent bowel surgery. RESULTS: MTR and texture entropy correlated with histopathological fibrosis (r = .85 and .81, respectively). Entropy was superior to MTR for monitoring bowel fibrosis in the presence of coexisting inflammation (linear regression R2 = .93 versus R2 = .01). Furthermore, texture entropy was able to assess antifibrotic therapy response (placebo mice versus treated mice at endpoint scan; Δmean = 0.128, p < .0001). An increase in entropy was indicative of fibrosis accumulation in human CD strictures (inflammation: 1.29; mixed strictures: 1.4 and 1.48; fibrosis: 1.73 and 1.9). CONCLUSION: MT imaging and TA of T2WI can both noninvasively detect established intestinal fibrosis in a mouse model. However, TA is especially useful for the longitudinal quantification of fibrosis in mixed inflammatory-fibrotic tissue, as well as for antifibrotic treatment response evaluation. This accessible post-processing technique merits further validation as the benefits for clinical practice as well as antifibrotic trial design would be numerous. KEY POINTS: • Magnetization transfer MRI and texture analysis of T2-weighted MR images can detect established bowel fibrosis in an animal model of gut fibrosis. • Texture entropy is able to identify and monitor bowel fibrosis progression in an inflammatory context and can assess the response to antifibrotic treatment. • A proof-of-concept study in five patients with Crohn's disease suggests that texture entropy can detect and grade fibrosis in human intestinal strictures.

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.

Joint coordinate system for biomechanical analysis of the sacroiliac joint.

Sacroiliac joint (SIJ) biomechanics have been described in both in vitro and in vivo studies. A standard for joint coordinate systems has been created by the International Society of Biomechanics for most of the joints in the human body. However, a standardized joint coordinate system for sacroiliac joint motion analysis is currently still lacking. This impedes the comparison across studies and hinders communication among scientists and clinicians. As SIJ motion is reported to be quite limited, a proper standardization and reproducibility of this procedure is essential for the interpretation of future biomechanical SIJ studies. This paper proposes a joint coordinate system for the analysis of sacroiliac joint motion, based on the procedure developed by Grood and Suntay, using semi-automated anatomical landmarks on 3D joint surfaces. This coordinate system offers high inter-rater reliability and aspires to a more intuitive representation of biomechanical data, as it is aligned with SIJ articular surfaces. This study aims to encourage further reflection and debate on biomechanical data representation, in order to facilitate interpretation of SIJ biomechanics and improve communication between researchers and clinicians. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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.

Feasibility study using iodine quantification on dual-energy CT enterography to distinguish normal small bowel from active inflammatory Crohn's disease.

BACKGROUND: Assessment of Crohn's disease (CD) activity is important to identify patients with active inflammation for therapy management. Quantitative analysis can provide objective measurement of disease presence. PURPOSE: To evaluate the feasibility of quantitative analysis of contrast-enhanced dual-energy computed tomography (DECT) data in detection of small bowel inflammation in patients with CD with an emphasis on iodine quantification. MATERIAL AND METHODS: DECT enterography was prospectively performed in 20 patients with active CD and in 20 healthy individuals, as the control group. Iodine overlay images were created. Wall thickness, attenuation, absolute iodine density, relative iodine density, and fat fraction were measured in the terminal ileum of all patients by two radiologists. Intraclass correlation coefficients were calculated to assess inter-rater agreement. Parameters were compared between patient groups using mixed model analysis. Receiver operating characteristic (ROC) analysis was performed. RESULTS: Both absolute and relative iodine density were significantly higher in active disease than in normal small bowel (all P < 0.001). In contrast, measurement of fat fraction was not significantly different in affected terminal ileal loops compared to normal terminal ileum ( P = 0.075). ROC analysis demonstrated a similar excellent diagnostic accuracy of wall thickness, attenuation, and absolute and relative iodine density with area under the ROC curve (AUC) values in the range of 0.96 for attenuation to 1 for relative iodine density. CONCLUSION: DECT with iodine quantification can be used in distinguishing normal small bowel from active inflammatory CD. Further research should investigate the value of iodine quantification in grading CD activity and in monitoring therapeutic response.

Benefits of Elective Para-Aortic Radiotherapy for pN1 Prostate Cancer Using Arc Therapy (Intensity-Modulated or Volumetric Modulated Arc Therapy): Protocol for a Nonrandomized Phase II Trial.

BACKGROUND: In patients with prostate cancer (PCa) with histopathologically proven pelvic lymph node (LN) metastasis (pN1) after extended pelvic lymph node dissection (ePLND), multimodality treatment consisting of treatment of the primary tumor and whole pelvic radiotherapy (WPRT) combined with androgen deprivation therapy (ADT) offers promising results, leading to better cause-specific survival rates compared with ADT alone. However, in case more than one pelvic LN is invaded by the tumor, approximately 40% of the patients relapse biochemically and clinically. Clinical relapse is present in the para-aortic LNs (M1a disease) in up to 77% of the relapsing cases. OBJECTIVE: We hypothesize that, based on the evidence that positive LNs represent the door to hematogenous dissemination, elective para-aortic irradiation will reduce the development of both retroperitoneal nodal (M1a) and distant metastasis (M1b or M1c disease), postpone the need for palliative ADT, and prolong the time to castration-refractory disease. METHODS: To test this hypothesis, we will conduct a prospective, nonrandomized phase II trial to study the efficacy of additional elective para-aortic radiotherapy (PART) in pN1 patients compared with those who were historically treated with adjuvant WPRT alone. We aim to include 137 patients with PCa and presence of pN1 disease after ePLND. With this number of patients, an improvement of 15% in the 5-year clinical relapse-free survival can be detected with a power of 80%. RESULTS: Recruitment of patients for this trial started in 2017 and will be completed approximately by March 2020. CONCLUSIONS: This is the first phase II trial to investigate the benefits of an elective PART in patients with PCa. The results of this trial will potentially serve as a sound base for a later randomized phase III trial. All participants are given a PART information sheet and required to give written informed consent. Results are expected to be published in a peer-reviewed journal. TRIAL REGISTRATION: ClinicalTrials.gov NCT03079323; https://clinicaltrials.gov/ct2/show/NCT03079323 (Archived by WebCite at http://www.webcitation.org/73ELimv1d). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11256.

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial.

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients.

We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT) and axial skeleton magnetic resonance imaging (MRI) prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3-4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC) defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases.

Prevalence and prognosis of low-volume, oligorecurrent, hormone-sensitive prostate cancer amenable to lesion ablative therapy.

OBJECTIVES: To describe the anatomical patterns of prostate cancer (PCa) recurrence after primary therapy and to investigate if patients with low-volume disease have a better prognosis as compared with their counterparts. MATERIALS AND METHODS: Patients eligible for an 18-F choline positron-emission tomography (PET)-computed tomography (CT) were enrolled in a prospective cohort study. Eligible patients had asymptomatic biochemical recurrence after primary PCa treatment and testosterone levels >50 ng/mL. The number of lesions was counted per scan. Patients with isolated local recurrence (LR) or with ≤3 metastases (with or without LR) were considered to have low-volume disease and patients with >3 metastases to have high-volume disease. Descriptive statistics were used to report recurrences. Cox regression analysis was used to investigate the influence of prognostic variables on the time to developing castration-resistant PCa (CRPC). RESULTS: In 208 patients, 625 sites of recurrence were detected in the lymph nodes (N1/M1a: 30%), the bone (18%), the prostate (bed; 11%), viscera (4%), or a combination of any of the previous (37%). In total, 153 patients (74%) had low-volume recurrence and 55 patients (26%) had high-volume recurrence. The 3-year CRPC-free survival rate for the whole cohort was 79% (95% confidence interval 43-55), 88% for low-volume recurrences and 50% for high-volume recurrences (P < 0.001). Longer PSA doubling time at time of recurrence and low-volume disease were associated with a longer time to CRPC. CONCLUSIONS: Three out of four patients with PCa with a 18-F choline PET-CT-detected recurrence have low-volume disease, potentially amenable to local therapy. Patients with low-volume disease have a better prognosis as compared with their counterparts. Lymph node recurrence was the most dominant failure pattern.

Prevalence of CT features of axial spondyloarthritis in patients with Crohn's disease.

Background The sacroiliac joint and spine are seen on abdominal computed tomography (CT) and may show structural lesions as part of spondyloarthritis. Purpose To determine the prevalence of CT features of spondyloarthritis in patients with Crohn's disease (CD). Material and Methods A retrospective study of structural lesions of spondyloarthritis on abdominal CT was performed. The sacroiliac joints and spine of 120 patients were studied: study group I consisted of 40 patients with known CD and inflammatory back pain, group II involved 40 patients with CD without inflammatory back pain, and group III consisted of 40 patients without known joint or inflammatory bowel disease. Recorded CT features included sclerosis, erosions or ankylosis of the sacroiliac joint, enthesopathy, spinal syndesmophytes, and costovertebral joint lesions. Results CT showed structural lesions of the sacroiliac joints in 19/40 (48%) patients with CD and inflammatory back pain (sclerosis [n = 14; 35%], erosions [n = 14; 35%], ankylosis [n = 3; 8%]), in 8/40 (8%) patients with CD without inflammatory back pain (sclerosis [n = 3; 8%], erosions [n = 4; 10%], ankylosis [n = 3; 8%]), and in 3/40 (8%) patients without known joint or bowel disease (sclerosis [n = 2; 5%], ankylosis [n = 1; 3%]). Syndesmophytes were exclusively seen in group I (n = 6; 15%). Conclusion CT of the abdomen in patients with CD and inflammatory back pain shows structural lesions of the sacroiliac joint, entheses, or spine in almost half of the patients. Awareness and knowledge of these findings may guide the referring clinician to further clinical evaluation, imaging, and biomarker evaluation of the disease.

Understanding Thiel embalming in pig kidneys to develop a new circulation model.

The quality of tissue preservation in Thiel embalmed bodies varies. Research on the administered embalming volume and its vascular distribution may elucidate one of the mechanisms of tissue preservation and allow for new applications of Thiel embalming. Vascular embalming with (group 1, n = 15) or without (group 2, n = 20) contrast agent was initiated in pig kidneys. The distribution of Thiel embalming solution in group 1 was visualized using computed tomography. The kidneys in both groups were then immersed in concentrated salt solutions to reduce their weight and volume. Afterwards, to mimic a lifelike circulation in the vessels, group 2 underwent pump-driven reperfusion for 120 minutes with either paraffinum perliquidum or diluted polyethylene glycol. The circulation was imaged with computed tomography. All of the kidneys were adequately preserved. The embalming solution spread diffusely in the kidney, but fluid accumulation was present. Subsequent immersion in concentrated salt solutions reduced weight (P < 0.01) and volume (P < 0.01). Reperfusion for 120 minutes was established in group 2. Paraffinum perliquidum filled both major vessels and renal tissue, whereas diluted polyethylene glycol spread widely in the kidney. There were no increases in weight (P = 0.26) and volume (P = 0.79); and pressure further decreased (P = 0.032) after more than 60 minutes of reperfusion with paraffinum perliquidum, whereas there were increases in weight (P = 0.005), volume (P = 0.032) and pressure (P < 0.0001) after reperfusion with diluted polyethylene glycol. Arterial embalming of kidneys results in successful preservation due to complete parenchymatous spreading. More research is needed to determine whether other factors affect embalming quality. Dehydration is an effective method to regain the organs' initial status. Prolonged vascular reperfusion with paraffinum perliquidum can be established in this model without increases in weight, volume and pressure.

Salvage pelvic lymph node dissection in recurrent prostate cancer: surgical and early oncological outcome.

METHODOLOGY: Seventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (<4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases >0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if >3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied. RESULTS: Clavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%. CONCLUSION: SLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT.

Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence (STOMP): study protocol for a randomized phase II trial.

BACKGROUND: Metastases-directed therapy (MDT) with surgery or stereotactic body radiotherapy (SBRT) is emerging as a new treatment option for prostate cancer (PCa) patients with a limited number of metastases (≤3) at recurrence - so called "oligometastases". One of the goals of this approach is to delay the start of palliative androgen deprivation therapy (ADT), with its negative impact on quality of life. However, the lack of a control group, selection bias and the use of adjuvant androgen deprivation therapy prevent strong conclusions from published studies.The aim of this multicenter randomized phase II trial is to assess the impact of MTD on the start of palliative ADT compared to patients undergoing active surveillance. METHODS/DESIGN: Patients with an oligometastatic recurrence, diagnosed on choline PET/CT after local treatment with curative intent, will be randomised in a 1:1 ratio between arm A: active surveillance only and arm B: MTD followed by active surveillance. Patients will be stratified according to the location of metastasis (node vs. bone metastases) and PSA doubling time (≤3 vs. > 3 months). Both surgery and SBRT are allowed as MDT. Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression. The primary endpoint is ADT-free survival. ADT will be started in both arms at time of polymetastatic disease (>3 metastatic lesions), local progression or symptoms. The secondary endpoints include progression-free survival, quality of life, toxicity and prostate-cancer specific survival. DISCUSSION: This is the first randomized phase 2 trial assessing the possibility of deferring palliative ADT with MDT in oligometastatic PCa recurrence. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01558427.

Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence.

PURPOSE: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT). METHODS: Non-castrate patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography - computed tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions or 30 Gy in 3 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary endpoint. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic. Secondary endpoints were local control, progression free survival (PFS) and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. RESULTS: With a median follow-up from time of SBRT of 2 years, we treated 50 patients with 70 metastatic lesions with a local control rate of 100%. The primary involved metastatic sites were lymph nodes (54%), bone (44%), and viscera (2%). The median PFS was 19 mo (95% CI: 13-25 mo) with 75% of recurring patients having ≤3 metastases. A 2nd and 3rd course of SBRT was delivered in 19 and 6 patients respectively. This results in a median ADT-FS of 25 months (20-30 mo). On univariate analysis, only a short PSA doubling time was a significant predictor for both PFS (HR: 0.90, 95% CI: 0.82 - 0.99) and ADT-FS (HR: 0.83; 95% CI: 0.71 - 0.97). Ten patients (20%) developed toxicity following treatment, which was classified as grade I in 7 and grade II in 3 patients. CONCLUSION: Repeated SBRT for oligometastatic prostate cancer postpones palliative androgen deprivation therapy with 2 years without grade III toxicity.