HER2-dependent signaling may support the development of metastatic castration-resistant prostate cancer (mCRPC) by activating androgen receptor signaling through ligand-independent mechanisms. From ...41 mCRPC patients (including 31 treated with Androgen Receptor Signaling Inhibitors ARSI), Circulating Tumor Cells (CTCs) were prospectively enriched with AdnaTest platform and analyzed with a multiplexed assay for HER2 and AR-V7 mRNA expression. Then, we evaluated the impact of HER2 expression on PSA-response, Progression Free Survival (PFS) and Overall Survival (OS). HER2 expression was detected in CTCs of 26 patients (63%). Although PSA response was similar regardless of HER2 status, patients with HER2 positive CTCs had shorter PSA-PFS (median: 6.2 months versus 13.0 months, p = 0.034) and radiological-PFS (6.8 months versus 25.6 months, p = 0.022) than patients without HER2 expression. HER2 expression was also associated with a shorter OS (22.7 months versus not reached, p = 0.05). In patients treated with ARSI, multivariate analyses revealed that the prognostic impact of HER2 status on PSA-PFS was independent of AR-V7 expression and of the detection of CTCs by an AdnaTest. We showed for the first time the poor prognostic value of HER2 expression in CTCs from patients with mCRPC. The therapeutic interest of targeting this actionable pathway remains to be explored.
Background
The purpose of this study was to compare the postsurgical survival of UUT-UC patients treated with ONU and LNU.
Methods
Using a multi-institutional, national, retrospective database, we ...identified patients with UUT-UC who underwent radical nephroureterectomy by open access (ONU) or by the minimally invasive alternative (LNU). Survival curves were estimated using Kaplan-Meier method. A multivariate Cox model was used to evaluate the association between surgical approach and disease recurrence.
Results
Overall, 609 patients were included (ONU = 459 and LNU = 150). The median age was 69.8 years (range 61.9–76), and the male-to-female ratio was 2:1. Postoperative complications occurred in 80 patients, with no significant difference between ONU and LNU on the whole (
P
= 0.64). The median follow-up was 27 months. There was no difference between the 2 procedures in the 5-year CSS or 5-year RFS. Moreover, the 5-year CSS (
P
= 0.053) and 5-year RFS (
P
= 0.9) for cases with locally advanced disease (pT3/pT4) were similar between ONU and LNU. In the multivariate analysis, the surgical procedure used was not found to be associated with survival. The main limitation of the study is its retrospective design, which is the result of the rarity of the disease.
Conclusions
There is no evidence that oncological outcomes for LNU are inferior to those for open surgery, provided that the appropriate precautionary measures are taken.
What's known on the subject? and What does the study add?
Novel therapeutic methods have emerged in recent years as ‘focal’ treatment alternatives in which cancer foci can be eradicated and greatly ...reducing the associated side‐effects of radical treatment. High‐intensity focused ultrasound (HIFU) seems to result in a well fitted technology, which has proven short‐ to medium‐term cancer control, with a low rate of complications comparable with those of established therapies.
This is an up‐to‐date review of the available literature on HIFU as a definitive treatment of prostate cancer. It describes the technique in a comprehensive approach in terms of technical features, procedure, indications, and gives an overview of its historical background; finally, we present the future applications of HIFU and its development trend.
OBJECTIVES
•
To provide an up‐to‐date review of the available literature on high‐intensity focused ultrasound (HIFU) as a definitive treatment of prostate cancer.
•
To present the technique in a comprehensive approach, comparing the available devices according to the existing evidence in terms of technical features, procedure, indications, and to give an overview of its historical background; and finally, to discuss future applications of HIFU and its development trend.
MATERIALS AND METHODS
•
A systematic literature search was conducted using MEDLINE and EMBASE via Ovid databases (January 2000 to December 2011), to identify studies on HIFU for treatment of prostate cancer.
•
Only English‐language and human‐based full manuscripts that reported on case series studies with >50 participants, patient characteristics, efficacy and safety data were included.
RESULTS
•
No randomised controlled trials were identified by the literature search. We identified 31 uncontrolled studies that examined the efficacy of HIFU as primary treatment and two studies that examined the efficacy of HIFU as salvage treatment.
•
Most treated patients had localised prostate cancer (stage T1–T2); Gleason scores of 2–10 and mean prostate specific antigen (PSA) values of 4.6–12.7 ng/mL. The mean age range of the patients was 64.1–72 years. The mean follow‐up ranged from 6.4 to 76.8 months. Negative biopsy rates ranged from 35 to 95%. PSA nadirs ranged from 0.04 to 1.8 ng/mL. The 5‐year disease‐free survival rates ranged from 61.2 to 95%; 7‐ and 8‐year disease free survival rates ranged from 69 to 84%.
•
The most common complications associated with the HIFU procedure as the primary treatment included: urinary retention (<1–20%); urinary tract infections (1.8–47.9%); stress or urinary incontinence (<1–34.3%); and erectile dysfunction (20–81.6%).
•
Recto‐urethral fistula was reported in <2% of patients.
•
Treatment‐related morbidity appeared to be reduced by the combination of transurethral resection (TURP) of the prostate and HIFU.
CONCLUSIONS
•
Novel therapeutic methods have emerged in recent years as ‘focal’ treatment alternatives, in which cancer foci could be eradicated by greatly reducing the associated side‐effects of radical treatment.
•
HIFU seems to result in short‐ to medium‐term cancer control, with a low rate of complications comparable with those of established therapies.
•
However, longer‐term follow‐up studies are needed to evaluate cancer‐specific and overall survival. If available promising results on HIFU for definitive treatment of prostate cancer are confirmed in future prospective trials, focal therapy could start to challenge the current standard of care.
The brain exhibits organized fluctuations of neural activity, even in the absence of tasks or sensory input. A prominent type of such spontaneous activity is the alpha rhythm, which influences ...perception and interacts with other ongoing neural activity. It is currently hypothesized that states of decreased prestimulus α oscillations indicate enhanced neural excitability, resulting in improved perceptual acuity. Nevertheless, it remains debated how changes in excitability manifest at the behavioral level in perceptual tasks. We addressed this issue by comparing two alternative models describing the effect of spontaneous α power on signal detection. The first model assumes that decreased α power increases baseline excitability, amplifying the response to both signal and noise, predicting a liberal detection criterion with no effect on sensitivity. The second model predicts that decreased α power increases the trial-by-trial precision of the sensory response, resulting in improved sensitivity. We tested these models in two EEG experiments in humans where we analyzed the effects of prestimulus α power on visual detection and discrimination using a signal detection framework. Both experiments provide strong evidence that decreased α power reflects a more liberal detection criterion, rather than improved sensitivity, consistent with the baseline model. In other words, when the task requires detecting stimulus presence versus absence, reduced α oscillations make observers more likely to report the stimulus regardless of actual stimulus presence. Contrary to previous interpretations, these results suggest that states of decreased α oscillations increase the global baseline excitability of sensory systems without affecting perceptual acuity.
Spontaneous fluctuations of brain activity explain why a faint sensory stimulus is sometimes perceived and sometimes not. The prevailing view is that heightened neural excitability, indexed by decreased α oscillations, promotes better perceptual performance. Here, we provide evidence that heightened neural excitability instead reflects a state of biased perception, during which a person is more likely to see a stimulus, whether or not it is actually present. Therefore, we propose that changes in neural excitability leave the precision of sensory processing unaffected. These results establish the link between spontaneous brain activity and the variability in human perception.
Objectives
To evaluate the oncological and functional outcomes of salvage high‐intensity focused ultrasound (S‐HIFU) for locally recurrent prostate cancer after low‐dose‐rate (LDR) brachytherapy.
...Patients and Methods
Clinical phase II studies (2003–2015) included 50 consecutive patients with post‐brachytherapy local recurrence treated by S‐HIFU. S‐HIFU was performed with post‐external beam radiotherapy (EBRT) parameters and, since 2008, with specific post‐brachytherapy parameters. Treatments were whole‐gland ablation and, since 2009, hemi‐ablation in cases of unilateral prostate cancer. The primary objective was to assess oncological outcomes: treatment failure‐free survival, progression‐free survival (PFS), overall survival (OS), cancer‐specific survival (CSS), and metastasis‐free survival (MFS) rates. The secondary objective was to evaluate adverse events, continence, and erectile function. Kaplan–Meier analysis estimated oncological outcomes.
Results
In all, 13 patients were treated with post‐EBRT parameters, 37 with post‐brachytherapy parameters, 35 with whole‐gland treatment, and 15 with hemi‐ablation. The median follow‐up was 4.6 years. After S‐HIFU, the median prostate‐specific antigen level was 0.3 ng/mL. At 6 years, treatment failure‐free survival, PFS, OS, CSS, and MFS rates were 41%, 45%, 93%, 98%, and 80%, respectively. Post‐brachytherapy compared with post‐EBRT parameters reduced Grade 2–3 incontinence (34% vs 62%, P = 0.015). Incontinence, bladder outlet obstruction and Grade ≥III complications were significantly reduced with hemi‐ablation compared with whole‐gland treatment (14% vs 54%, P < 0.001; 13% vs 46%, P = 0.03; 13% vs 63%, P = 0.001; respectively). Before S‐HIFU, 25 patients had a five‐item version of the International Index of Erectile Function score of ≥17, which was maintained in 48% at 12 months.
Conclusion
S‐HIFU for locally recurrent prostate cancer after LDR brachytherapy is associated with favourable survival rates at a price of significant morbidity. Dedicated post‐brachytherapy parameters and hemi‐ablation improve the safety of the treatment.
Abstract Natural orifice translumenal endoscopic surgery (NOTES) within urology has largely been limited to experimental animal studies and diagnostic procedures in humans. Attempts to complete a ...pure NOTES transvaginal nephrectomy have thus far been unsuccessful. We report the first clinical experience with pure NOTES transvaginal nephrectomy. A 58-year-old woman presented with recurrent urinary tract infections and an atrophic right kidney. Transvaginal access was obtained through a 3-cm posterior colpotomy. The right kidney was mobilized, the renal hilum was divided, and the specimen was removed through the vaginal incision. Operative time was 420 min. Estimated blood loss was 50 ml. There were no perioperative complications.
Objective
To assess PI-RADSv2.1 and PI-RADSv2 descriptors across readers with varying experience.
Methods
Twenty-one radiologists (7 experienced (≥ 5 years) seniors, 7 less experienced seniors and 7 ...juniors) assessed 240 ‘predefined’ lesions from 159 pre-biopsy multiparametric prostate MRIs. They specified their location (peripheral, transition or central zone) and size, and scored them using PI-RADSv2.1 and PI-RADSv2 descriptors. They also described and scored ‘additional’ lesions if needed. Per-lesion analysis assessed the ‘predefined’ lesions, using targeted biopsy as reference; per-lobe analysis included ‘predefined’ and ‘additional’ lesions, using combined systematic and targeted biopsy as reference. Areas under the curve (AUCs) quantified the performance in diagnosing clinically significant cancer (csPCa; ISUP ≥ 2 cancer). Kappa coefficients (
κ
) or concordance correlation coefficients (CCC) assessed inter-reader agreement.
Results
At per-lesion analysis, inter-reader agreement on location and size was moderate-to-good (
κ
= 0.60–0.73) and excellent (CCC ≥ 0.80), respectively. Agreement on PI-RADSv2.1 scoring was moderate (
κ
= 0.43–0.47) for seniors and fair (
κ
= 0.39) for juniors. Using PI-RADSv2.1, juniors obtained a significantly lower AUC (0.74; 95% confidence interval 95%CI: 0.70–0.79) than experienced seniors (0.80; 95%CI 0.76–0.84;
p
= 0.008) but not than less experienced seniors (0.74; 95%CI 0.70–0.78;
p
= 0.75). As compared to PI-RADSv2, PI-RADSv2.1 downgraded 17 lesions/reader (interquartile range IQR: 6–29), of which 2 (IQR: 1–3) were csPCa; it upgraded 4 lesions/reader (IQR: 2–7), of which 1 (IQR: 0–2) was csPCa. Per-lobe analysis, which included 60 (IQR: 25–73) ‘additional’ lesions/reader, yielded similar results.
Conclusions
Experience significantly impacted lesion characterization using PI-RADSv2.1 descriptors. As compared to PI-RADSv2, PI-RADSv2.1 tended to downgrade non-csPCa lesions, but this effect was small and variable across readers.
Key points
Juniors characterized aggressive cancers less well than experienced seniors on prostate MRI.
Agreement between readers remained moderate even for experienced readers.
As compared to version 2, PI-RADSv2.1 descriptors tended to show improved specificity.
Purpose
Living donor nephrectomy is a high-stake procedure involving healthy individuals, therefore every effort should be made to define each patient’s individualized risk and improve potential ...donors’ information. The aim of this study was to evaluate the interest of the Mayo adhesive probability (MAP) score, an imaging-based score initially designed to estimate the risk of adherent perinephric fat in partial nephrectomy, to predict intra- and postoperative complications of living donor nephrectomy.
Materials and methods
We retrospectively reviewed the imaging, clinical, and follow-up data of 452 kidney donors who underwent laparoscopic donor nephrectomy in two academic centers.
Results
Imaging and follow-up data were available for 307 kidney donors, among which 44 (14%) had a high MAP score (≥ 3). Intraoperative difficulties were encountered in 50 patients (16%), including difficult dissection (
n =
35) and bleeding (
n =
17). Conversion to open surgery was required for 13 patients (4.2%). On multivariate analysis, a MAP score ≥ 3 was significantly associated with the risk of intraoperative difficulty OR 14.12 (5.58–35.7),
p
< 0.001 or conversion to open surgery OR 18.96 (3.42–105.14),
p
= 0.0042. Postoperative complications were noted in 99 patients (32%), including 12 patients (3.9%) with Clavien–Dindo grade III–IV complications. On multivariate analysis, a high MAP score was also associated with the risk of postoperative complications OR 2.55 (1.20–5.40),
p
= 0.01.
Conclusions
In this retrospective bicentric study, a high MAP score was associated with the risk of intra- and postoperative complications of laparoscopic donor nephrectomy. The MAP score appears of interest in the living donor evaluation process to help improve donors’ information and outcomes.
Objective
To report the oncological and functional outcomes of hemi salvage high‐intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent prostate cancer.
Patients and Methods
...Between 2009 and 2012, 48 patients were prospectively enrolled in two European centres. Inclusion criteria were biochemical recurrence (BCR) after primary radiotherapy (RT), positive magnetic resonance imaging and ≥1 positive biopsy in only one lobe.
BCR was defined using Phoenix criteria (a rise by ≥2 ng/mL above the nadir prostate specific antigen PSA level).
The following schemes and criteria for functional outcomes were used: Ingelman‐Sundberg score using International Continence Society (ICS) questionnaire (A and B), International prostate symptom score (IPSS), International Index of Erectile Function‐5 (IIEF‐5) points, the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ C‐30).
HSH was performed under spinal or general anaesthesia using the Ablatherm® Integrated Imaging device. Patients with obstructive voiding symptoms at the time of treatment underwent an endoscopic bladder neck resection or incision during the same anaesthesia to prevent the risk of postoperative obstruction.
Results
After HSH the mean (sd) PSA nadir was 0.69 (0.83) ng/mL at a median (interquartile range) follow‐up of 16.3 (10.5–24.5) months. Disease progression occurred in 16/48 (33%). Of these, four had local recurrence in the untreated lobe and four bilaterally, six developed metastases, and two had rising PSA levels without local recurrence or radiological confirmed metastasis. Progression‐free survival rates at 12, 18, and 24 months were 83%, 64%, and 52%.
Severe incontinence occurred in four of the 48 patients (8%), eight (17%) required one pad a day, and 36/48 (75%) were pad‐free. The ICS questionnaire showed a mean (sd) deterioration from 0.7 (2.0) to 2.3 (4.5) for scores A and 0.6 (1.4) to 1.6 (3.0) for B.
The mean (sd) IPSS and erectile function (IIEF‐5) scores decreased from a mean (sd) of 7.01 (5.6) to 8.6 (5.1) and from 11.2 (8.6) to 7.0 (5.8), respectively.
The mean (sd) EORTC QLC‐30 scores before and after HSH were 35.7 (8.6) vs 36.8 (8.6).
Conclusion
HSH is a feasible therapeutic option in patients with unilateral radiorecurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves health‐related quality of life.
Abstract Purpose To evaluate pre-operative prognostic risk factors to predict oncologic outcome of Salvage High-Intensity Focused Ultrasound (S-HIFU) for radiorecurrent prostate cancer (PCa). Methods ...and materials A total of 290 men with biopsy-confirmed locally radiorecurrent PCa, underwent S-HIFU. D’Amico risk group before external beam radiotherapy (EBRT), Prostate Specific Antigen (PSA), estimated Gleason score prior HIFU and post HIFU biopsies were analyzed for predictive utility of local cancer control, cancer-specific, metastasis free, and progression free survival rates (PFSR). Results Local cancer control with negative biopsy results was obtained in 81% of the 208 patients who underwent post-S-HIFU biopsies. Median PSA nadir was 0.14 ng/ml and 127 patients did not require androgen deprivation therapy (ADT). The mean follow up was 48 months for cancer-specific survival rates. The cancer-specific and metastasis-free survival rates at 7 years were 80% and 79.6% respectively. The PFSR was significantly influenced by: the pre-HIFU PSA level (hazard ratio (HR): 1.09, 95% CI 1.04–1.13), a Gleason score ⩾8 versus ⩽6 (HR: 1.17, 95% CI 1.03–1.3), and a previous ADT (HR: 1.28, 95% CI 1.09–1.46). The rates of recto-urethral fistula (0.4%) and grade II/III incontinence (19.5%) indicate significant reduction in serious side effects with use of dedicated post-radiation acoustic parameters compared with standard parameters. Conclusion S-HIFU is an effective curative option for radiorecurrent PCa with acceptable morbidity for localized radiorecurrent PCa, but should be initiated early following EBRT failure. Use of prognostic risk factors can optimize patient selection.
PDF
