Multicentre, prospective study on local treatment of metastatic prostate cancer (LoMP study).

OBJECTIVES: To investigate the role of cytoreductive radical prostatectomy in addition to standard of care for patients with newly diagnosed metastatic prostate cancer. MATERIALS AND METHODS: This multicentre, prospective study included asymptomatic patients from 2014 to 2018 (NCT02138721). Cytoreductive radical prostatectomy was offered to all fit patients with resectable tumours, resulting in 40 patients. Standard of care was administered to 40 patients who were ineligible or unwilling to undergo surgery. The primary endpoint was castration resistant cancer-free survival at the time point of ≥50% events. The secondary endpoint was local event-free survival. Kaplan-Meier and Cox regression analyses with propensity-score analysis were applied. RESULTS: After a median (quartiles) follow-up of 35 (24-47) months, 42 patients became castration-resistant or died. The median castration resistant cancer-free survival was 53 (95% confidence interval [CI] 14-92) vs 21 (95% CI 15-27) months for cytoreductive radical prostatectomy compared to standard of care (P = 0.017). The 3-year estimates for local event-free survival were 83% (95% CI 71-95) vs 59% (95% CI 51-67) for cytoreductive radical prostatectomy compared to standard of care (P = 0.012). However, treatment group showed no significance in the multivariable models for castration resistant cancer-free survival (P = 0.5) or local event-free survival (P = 0.3), adjusted for propensity-score analysis. Complications were similar to the non-metastatic setting. Patients undergoing surgery were younger, with lower baseline prostate-specific antigen levels, alkaline phosphatase levels and metastatic burden. CONCLUSION: The present LoMP study was unable to show a difference between the two inclusion groups regarding castration resistant cancer-free survival for asymptomatic patients with newly diagnosed metastatic prostate cancer. These results validate previous evidence that, in well-selected and informed patients, cytoreductive radical prostatectomy is feasible and safe, with corresponding continence rates compared to the non-metastatic, high-risk setting. Whether cytoreductive radical prostatectomy could be a valuable option to achieve good local palliation needs to be further researched. Overall, the role of cytoreductive radical prostatectomy needs to be further explored in randomized studies to correct for potential bias.

Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time.

PURPOSE: Patients with oligometastatic prostate cancer (PC) may benefit from metastasis-directed therapy (MDT), delaying disease progression and the start of palliative systemic treatment. However, a significant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT. METHODS: Patients with asymptomatic biochemical recurrence following primary PC treatment were classified as oligo- or polymetastatic based on 18F-choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had > 3 metastases at baseline or developed > 3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profiles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confirm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease. RESULTS: Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defined by a significantly longer median CRPC-free survival (not reached versus 38 months; 95% confidence interval 31-45 months with P < 0.001). Despite the good performance of a predictive model trained on the discovery cohort, with an AUC of 0.833 (0.693-0.973; 95% CI) and a sensitivity of 0.894 (0.714-1.000; 95% CI) for oligometastatic disease, none of the miRNA targets were found to be differentially expressed between oligo- and polymetastatic PC patients in the signature validation cohort. The multivariate model had an AUC of 0.393 (0.534 after cross-validation) and therefore, no predictive ability. CONCLUSIONS: Although PC patients with oligometastatic disease had a more favorable prognosis, no serum-derived biomarkers allowing for prospective discrimination of oligo- and polymetastatic prostate cancer patients could be identified.

Whole pelvis radiotherapy for pathological node-positive prostate cancer : Oncological outcome and prognostic factors.

PURPOSE: The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors. PATIENTS AND METHODS: All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at a single tertiary care center were evaluated. A total of 154 patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2-3 years of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors. RESULTS: Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5 years. Median follow-up was 55 months (interquartile range 25-87). Multivariate analysis identified having only 1 positive lymph node, a shorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17-1.54) and OS (HR 1.22, 95% confidence interval 1.10-1.36). Bone metastases were the most frequent location of PCa relapse (n = 32, 64%). CONCLUSIONS: Patients with pN1 PCa treated with wpRT and 2-3 years ADT have an encouraging 5­year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment.

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.

Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer.

OBJECTIVES: To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors. MATERIALS AND METHODS: Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients. RESULTS: In ADT treatment-naïve PCa patients, the AR expression was higher in tumor epithelial cells versus surrounding stromal cells (p < 0.001) and versus normal epithelium in the same patient (p = 0.043). The difference between tumoral AR expression and expression in normal epithelium was higher in patients with ≥15% of tumor cells with increased AR copy number (p = 0.019). Peritumoral stroma had lower AR expression in patients with lymph-node or distant metastases compared to those without metastases (p = 0.038). CONCLUSIONS: This research evaluates the link between AR gene status, expression profile, and possible prognostic factors. Furthermore, it highlights the importance of the peritumoral environment in PCa. Additional research is needed to further clarify the role of stromal AR in PCa dissemination and identify possible therapeutic strategies to target this mechanism.

Robot-assisted pyeloplasty: How to deal with anatomic variants? A step-by-step video presentation.

INTRODUCTION: Pyeloplasty (open or Robot-assisted) is the gold standard of a symptomatic UPJ stenosis. Sometimes anatomic variants make the procedure challenging. This video describes a step-by-step approach in three settings: a crossing blood vessel and two different presentations of incomplete duplicated system. MATERIALS AND METHODS: Under general anesthesia, patient positioned in lateral decubitus, three trocars are placed. After mobilization of the colon, the Gerota's fascia is opened, and the renal pelvis is dissected off the surrounding structures. Ureter and obstructed pyelum were subsequently identified, mobilized, and hinged on a traction stitch. The pyelum and ureter are divided and spatulated according to the Anderson-Hynes technique; anastomosis is achieved. In variants, the drainage is one of the challenging steps, needing custom-made drainage of both moieties. Correct positioning of the drainage is confirmed with reflux of methylene blue from the bladder. RESULTS: JJ stent was removed 6 weeks postoperatively in surgical day-clinic, additional drainage was removed 1 week after surgery in the outpatient clinic. All three children remain asymptomatic with over a year of follow-up. CONCLUSION: A step-by-step plan for pyeloplasty in case of anatomic variants is presented with a video demonstrating a robot-assisted approach in duplicated systems. Moiety drainage can be challenging.

Pediatric Challenges in Robot-Assisted Kidney Transplantation.

Kidney transplantation is universally recognized as the gold standard treatment in patients with End-stage Kidney Disease (ESKD, or according to the latest nomenclature, CKD stage 5). Robot-assisted kidney transplantation (RAKT) is gradually becoming preferred technique in adults, even if applied in very few centra, with potentially improved clinical outcomes compared with open kidney transplantation. To date, only very few RAKT procedures in children have been described. Kidney transplant recipient patients, being immunocompromised, might be at increased risk for perioperative surgical complications, which creates additional challenges in management. Applying techniques of minimally invasive surgery may contribute to the improvement of clinical outcomes for the pediatric transplant patients population and help mitigate the morbidity of KT. However, many challenges remain ahead. Minimally invasive surgery has been consistently shown to produce improved clinical outcomes as compared to open surgery equivalents. Robot-assisted laparoscopic surgery (RALS) has been able to overcome many restrictions of classical laparoscopy, particularly in complex and demanding surgical procedures. Despite the presence of these improvements, many challenges lie ahead in the surgical and technical-material realms, in addition to anesthetic and economic considerations. RALS in children poses additional challenges to both the surgical and anesthesiology team, due to specific characteristics such as a small abdominal cavity and a reduced circulating blood volume. Cost-effectiveness, esthetic and functional wound outcomes, minimal age and weight to undergo RALS and effect of RAKT on graft function are discussed. Although data on RAKT in children is scarce, it is a safe and feasible procedure and results in excellent graft function. It should only be performed by a RAKT team experienced in both RALS and transplantation surgery, fully supported by a pediatric nephrology and anesthesiology team. Further research is necessary to better determine the value of the robotic approach as compared to the laparoscopic and open approach. Cost-effectiveness will remain an important subject of debate and is in need of further evaluation as well.

Genitoplasty in newborn females with adrenogenital syndrome: Focus on the reconstruction technique and its outcomes.

The adrenogenital syndrome is an autosomal recessive disorder in which an enzyme defect in the steroid pathway leads to excessive prenatal exposure of androgens. In the female fetus, masculinization of the external genitalia is observed. Surgery aims for functional and aesthetical reconstruction. Many techniques have been described. A video of our modified pull-through reconstruction technique is hereby presented. A retrospective descriptive database was created with patients who underwent genitoplasty for a CAH-associated genital condition. A video demonstrating the reconstructive technique was recorded while operating on a 9-month-old girl. Prior to surgery a cystoscopy is performed to evaluate the length of the urogenital sinus. Surgery starts with creating a reversed U-flap, after which the urogenital sinus is mobilized. The corpora cavernosa are released and the neurovascular bundle is isolated. To create vaginal space the urogenital sinus is subsequently separated. The vaginal introitus is anchored to the perineal skin flap. Labia minora are created by splitting the preputial skin. Finally excessive skin tissue is resected. Twenty-two female patients underwent reconstructive surgery for the adrenogenital syndrome in a tertiary referral centre over 16 years. Median age at surgery was 3 months (0-190). Median follow-up was 36 months (0-108) after surgery. A good functional and aesthetical outcome was observed. The modified pull-through technique, illustrated by this video, provided satisfactory results with a low complication rate. Follow-up until adulthood is needed to evaluate long-term outcomes.

Prognostic and Therapeutic Implications of Circulating Androgen Receptor Gene Copy Number in Prostate Cancer Patients Using Droplet Digital Polymerase Chain Reaction.

BACKGROUND: Resistance mechanisms in the androgen receptor (AR) signaling pathway remain key drivers in the progression to castration-resistant prostate cancer (CRPC) and relapse under antihormonal therapy. MATERIALS AND METHODS: We evaluated the circulating AR gene copy number (CN) gain using droplet digital polymerase chain reaction in 21 control and 91 prostate cancer serum samples and its prognostic and therapeutic implications in prostate cancer. RESULTS: In CRPC, AR CN gain was associated with faster progression to CRPC (P = .026), a greater number of previous treatments (P = .045), and previous chemotherapy (P = .016). Comparing patients with and without CN gain, the median progression-free survival (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004), and the median overall survival (OS) was 7 months versus 20.9 months (P = .020). In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus 6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The presence of more AR copies correlated with shorter androgen deprivation (P = .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039) therapy. CONCLUSION: Circulating AR CN gain predicts for a poor prognosis in CRPC. It is a promising biomarker predetermining rapid CRPC progression and predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is associated with multiple previous treatments and previous chemotherapy.

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.

The independent oncological role for cytoreductive nephrectomy in metastatic renal cell carcinoma: Prognostic features in the era of targeted therapies.

OBJECTIVES: To describe the effects of cytoreductive nephrectomy (CN) on the natural course of metastatic renal cell carcinoma (mRCC). CN appears to stabilize metastatic lesions in mRCC in a subgroup of patients and we hypothesize that systemic treatment might be deferred in these patients with stable disease after CN. SUBJECTS AND METHODS: Overall, 45 patients with mRCC who underwent CN and subsequent oncologic follow-up were included in this retrospective, single-center analysis. After CN, patients were followed at least every 3 months with clinical evaluation, contrast-enhanced computerized tomography scan of chest and abdomen, with additional imaging if needed. At 3 months, patients were radiographically evaluated and categorized into nonresponders (death or progression) or responders (stable disease or remission). Kaplan-Meier and Cox proportional hazards regression statistics were used to describe prognostic factors for overall survival (OS) and systemic therapy-free survival (STFS). RESULTS: Median OS was 31(3-121) months. Further, 24 (53.3%) and 21 (46.7%) patients were classified as responders and nonresponders at 3 months, respectively. Responders had a significant better 2-year OS compared with nonresponders (81.7% vs. 26.5%, P = 0.005). Responders also had a better 2-year STFS (40.3% vs. 6.3%, P = 0.005). On Cox regression analysis, worse OS was found to be associated with low preoperative hemoglobin levels, the absence of postoperative radiographical response, and the presence of non-clear cell pathology. The presence of postoperative radiographical response, normal preoperative lactate dehydrogenase levels, the presence of a single metastasis, and performing metastasis-directed therapy was found to be associated with a longer systemic therapy-free period. CONCLUSION: A beneficial oncologic response is observed in approximately half of the patients undergoing CN. Absence of radiographic progression at 3 months is an important marker for OS and STFS. Therefore, systemic treatment might be postponed in selected patients.

Comparison of the Prostate Imaging Reporting and Data System (PI-RADS) Version 1 and 2 in a Cohort of 245 Patients with Histopathological Reference and Long-Term Follow-Up.

OBJECTIVE: To compare the performance of PI-RADSv2 with PI-RADSv1 in patients with elevated PSA before biopsy. METHODS: 245 patients with elevated PSA underwent mpMRI before biopsy between May 2011 and December 2014 at 3.0 Tesla without endorectal coil. Patients underwent transrectal ultrasound-guided systematic 12-core biopsy followed by radical prostatectomy (N = 68), radiation therapy (N = 91) or clinical follow-up for at least two years (N = 86). All exams were scored on a per-patient basis according to PI-RADSv1 and PI-RADSv2. ClinsigPC was defined as Gleason score ≥7 (including 3+4 with prominent but not predominant Gleason 4 component), and/or tumour volume of ≥0.5cc, and/or tumour stage ≥T3a. RESULTS: In 144 patients (58.8%) a ClinsigPC was found within two years after mpMRI. The PI-RADSv1 and PI-RADSv2 overall assessment scores were significantly higher (P < 0.001) in patients with ClinsigPC as compared to patients without ClinsigPC. ROC analysis showed an area under the curve of 0.82 (CI 0.76-0.87) for PI-RADSv1 and 0.79 (CI 0.73-0.85) for PI-RADSv2 (P: NS). A threshold score of 3 exhibited sensitivities of 88.2% and 79.2% (P = 0.001) and specificities of 64.4% and 67.3% (P: NS) with PI-RADSv1 and PI-RADSv2, respectively. CONCLUSIONS: The mpMRI scoring systems PI-RADSv1 and PI-RADSv2 yield similar accuracy to detect ClinsigPC in patients with elevated PSA, although clinicians should be aware that when an overall assessment score of 3 is used as a threshold for a positive mpMRI, PI-RADSv2 has lower sensitivity than PI-RADSv1. Nevertheless, PI-RADSv2 is preferable over PI-RADSv1 because it has the advantage of providing well-defined instructions on how to determine the overall assessment category.

Isolated Male Epispadias: Anatomic Functional Restoration Is the Primary Goal.

Background. Isolated male epispadias (IME) is a rare congenital penile malformation, as often part of bladder-exstrophy-epispadias complex (BEEC). In its isolated presentation, it consists in a defect of the dorsal aspect of the penis, leaving the urethral plate open. Occurrence of urinary incontinence is related to the degree of dorsal displacement of the meatus and the underlying underdevelopment of the urethral sphincter. The technique for primary IME reconstruction, based on anatomic restoration of the urethra and bladder neck, is here illustrated. Patients and Methods. A retrospective database was created with patients who underwent primary IME repair between June 1998 and February 2014. Intraoperative variables, postoperative complications, and outcomes were assessed. A descriptive statistical analysis was performed. Results and Limitations. Eight patients underwent primary repair, with penopubic epispadias (PPE) in 3, penile epispadias (PE) in 2, and glandular epispadias (GE) in 3. Median age at surgery was 13.0 months [7-47]; median follow-up was 52 months [9-120]. Complications requiring further surgery were reported in two patients, while further esthetic surgeries were required in 4 patients. Conclusion. Anatomical restoration in primary IME is safe and effective, with acceptable results given the initial pathology.

Urodynamic studies in children: Standardized transurethral video-urodynamic evaluation.

OBJECTIVE: The aim was too demonstrate standardized video-urodynamic study (VUDS) in children using a transurethral catheter and pressure transducers. METHODS: Data necessary to obtain urodynamic evaluation of bladder sphincter function were gathered by concomitant measurement of bladder, urethral, and abdominal pressure. A 7F transurethral triple-lumen water-filled catheter was used for measuring the bladder and sphincter pressures and a water-filled 8F catheter connected to a pressure transducer was inserted into the rectum for pressure measurement. Cystometry was combined with fluoroscopy, providing simultaneous voiding cystourethrography information. Detrusor activity, bladder sensation, capacity, and compliance were measured during filling cystometry. Voiding cystometry consisted of recording pressures in the bladder sphincter and abdomen with simultaneous urinary flow measurement. RESULTS: Transurethral VUDS was safely and easily performed in a clinical setting adapted to children. CONCLUSIONS: A good and reproducible UDS is mandatory for correct therapeutic decisions. A standardized study associated with fluoroscopic assessment is presented in this video.

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.

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.

Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: a 1H-MRS study.

OBJECTIVE: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). MATERIALS AND METHODS: Proton magnetic resonance spectroscopy (1H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18-76 years, mean±SD, 48.4±16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. RESULTS: Metabolite ratios Ins/tCr and Ins/H2O were found significantly increased with age in the PCC (P<0.05 and P≤0.001, respectively), and in the HC (P<0.01 for both). An increased tCr/H2O was only observed in the PCC (P<0.01). Following absolute quantification based on the internal water signal, significantly increased concentrations of Ins and tCr in the PCC confirmed the relative findings (P<0.01 for both). CONCLUSION: Age-related increases of tCr and Ins are found in the PCC, whereas this holds only true for Ins in the HC, indicating possible gliosis in the ageing brain. No age-dependent NAA decreases were observed in the PCC nor the HC. The 1H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.