Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific ...membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of 68Ga-PSMA PET in this setting.
To perform a systematic review and meta-analysis to update reported predictors of positive 68Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles.
We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.
A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive 68Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0–0.19, 0.2–0.49, 0.5–0.99, 1–1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed.
Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2–0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings.
Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard-of-care imaging modalities to improve the detection of metastatic disease in prostate cancer. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Background
The diagnosis of prostate cancer has long been plagued by the absence of an imaging tool that reliably detects and localises significant tumours. Recent evidence suggests that ...multi‐parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. This review serves as a background to a recent USANZ position statement. It aims to provide an overview of MRI techniques and to critically review the published literature on the clinical application of MRI in prostate cancer.
Technical Aspects
The combination of anatomical (T2‐weighted) MRI with at least two of the three functional MRI parameters – which include diffusion‐weighted imaging, dynamic contrast‐enhanced imaging and spectroscopy – will detect greater than 90% of significant (moderate to high risk) tumours; however MRI is less reliable at detecting tumours that are small (<0.5 cc), low grade (Gleason score 6) or in the transitional zone. The higher anatomical resolution provided by 3‐Tesla magnets and endorectal coils may improve the accuracy, particularly in primary tumour staging.
Screening
The use of mpMRI to determine which men with an elevated PSA should undergo biopsy is currently the subject of two large clinical trials in Australia. MRI should be used with caution in this setting and then only in centres with established uro‐radiological expertise and quality control mechanisms in place. There is sufficient evidence to justify using MRI to determine the need for repeat biopsy and to guide areas in which to focus repeat biopsy.
Image‐Directed Biopsy
MRI‐directed biopsy is an exciting concept supported by promising early results, but none of the three proposed techniques have so far been proven superior to standard biopsy protocols. Further evidence of superior accuracy and core‐efficiency over standard biopsy is required, before their costs and complexities in use can be justified.
Treatment Selection and Planning
When used for primary‐tumour staging (T‐staging), MRI has limited sensitivity for T3 disease, but its specificity of greater than 95% may be useful in men with intermediate‐high risk disease to identify those with advanced T3 disease not suitable for nerve sparing or for surgery at all. MRI appears to be of value in planning dosimetry in men undergoing radiotherapy, and in guiding selection for and monitoring on active surveillance.
Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available.
To determine the safety and ...feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response.
In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo.
A single fraction of 20-Gy SABR to each lesion.
Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval CI: 91–100) and 93% (95% CI: 84–100), and DPFS was 58% (95% CI: 43–77) and 39% (95% CI: 25–60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm.
A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy.
This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.
For patients with one to three oligometastases from prostate cancer, single fraction 20-Gy stereotactic ablative body radiotherapy was both safe and feasible. Local and distant progression-free survival at 2 yr were 93% and 39%, respectively. Quality of life was maintained at baseline levels using this treatment strategy.
We performed an updated systematic review and meta-analysis of outcomes important to patients in those undergoing robot-assisted and open radical cystectomy.
Multiple scientific databases were ...searched up to July 2018 for randomized, controlled trials comparing robot-assisted and open radical cystectomy. The primary outcomes of interest were disease progression, major (Clavien III-V) complications and 90-day quality of life. The quality of evidence was evaluated according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions.
Five studies with a total of 540 participants were included in this review. There was no difference between robot-assisted and open radical cystectomy in disease progression (RR 0.94, 95% CI 0.69-1.29), major complications (RR 1.06, 95% CI 0.75-1.49) or quality of life (standardized mean difference -0.03, 95% CI -0.27-0.21). However, robot-assisted radical cystectomy demonstrated a reduced risk of perioperative blood transfusion (RR 0.58, 95% CI 0.43-0.80) and a marginally shorter hospital stay (RR -0.63 days, 95% CI -1.21-0.05). Operative time was longer in the robot-assisted group (mean difference 68.51 minutes, 95% CI 30.55-105.48). There was no statistically significant difference in local recurrence rates between the procedures (RR 2.08, 95% CI 0.96-4.50) but this difference may be clinically significant and it favored open radical cystectomy. The overall quality of evidence was judged to be moderate.
Surgical approach does not have a considerable impact on oncologic, safety and quality of life outcomes in patients who undergo radical cystectomy. The benefits conferred by robot-assisted radical cystectomy are a decreased need for blood transfusion and earlier hospital discharge.
Objective
To assess and measure the capability of a single‐use disposable digital flexible ureteroscope, the LithoVue™ (Boston Scientific, Marlborough, MA, USA), and to assess if there is a benefit ...to switching to single‐use scopes.
Patients and Methods
The LithoVue was compared to two commonly used reusable flexible ureteroscopes (Olympus URF‐V Olympus, Tokyo, Japan and Karl Storz Flex‐Xc Karl Storz & Co. KG, Tuttlingen, Germany) ex vivo. An analysis of reusable ureteroscope usage was performed to evaluate damage, durability, and maintenance costs. This was then compared to the projected costs of using single‐use disposable scopes.
Results
Flexion, deflection and irrigation flow of the LithoVue was equivalent, if not better than the reusable flexible ureteroscopes. An analysis of 234 procedures with seven new Olympus URF‐V scopes, revealed 15 scope damages. Staghorn stones and lower pole/mid‐zone stones were significant risk factors for damage (P = 0.014). Once damage occurred it was likely to occur again. Total repair costs were $162 628 (Australian dollars) (£92 411 in Great British pounds), the mean cost per case was $695 (£395). Factoring in the purchase cost, cleaning and repair costs, the cumulative cost of 28 reusable flexible ureteroscopy procedures was ~$50 000 (£28 412). If the LithoVue was priced at $1 200 (£682), switching to a single‐use scope would cost ~$35 000 (£19 888).
Conclusion
The LithoVue is analogous to reusable flexible ureteroscopes in regard to standard technical metrics. Depending on its purchase cost it may also represent a cost saving for hospitals when compared to the cumulative costs of maintaining reusable scopes. Additionally, urologist may consider using the scope in cases in which reusable scope damage is anticipated.
There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing ...androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy.
To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC.
We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease.
We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37–0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons.
Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients.
Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.
Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant overall survival (OS) benefit when compared with androgen-deprivation therapy alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options allow clinicians considerable flexibility when selecting options for individual patients.
Non-muscle-invasive bladder cancer (NMIBC) represents a significant global therapeutic challenge, particularly in the era of Bacillus Calmette–Guérin (BCG) shortage. High-risk NMIBC can progress to ...muscle invasive or metastatic disease in 25% of patients. Optimal treatment selection, according to risk stratification, is imperative. International guidelines slightly differ in their categorisation of low, intermediate and high-risk NMIBC. Nonetheless, a single post-operative instillation of chemotherapy with Mitomycin C (MMC) or Gemcitabine improves relapse-free survival (RFS) in low-risk NMIBC. Induction and maintenance intravesical BCG remains the historical gold standard for patients with intermediate or high-risk NMIBC. However, clinicians may be forced to consider alternatives given the current BCG shortage. Both intravesical MMC and Gemcitabine have been associated with similar efficacy to BCG, albeit in smaller studies. MMC may also be manipulated using a variety of methods to potentiate its effects. BCG treatment delivery may also be modified without affecting efficacy through dose reduction and abbreviation or omission of maintenance therapy. Preliminary data also highlight that directly proceeding to radical cystectomy may not adversely affect long-term quality of life measures. Access to new systemic and intravesical therapies must be prioritised for patients with BCG recurrent or unresponsive disease. When used in conjunction with molecularly defined biomarkers, these agents herald the potential for improved survival outcomes and alleviation of the current BCG shortage.
Background
Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision‐making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, ...represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate‐specific membrane antigen (PSMA) positron‐emission tomography (PET)/computed tomography (CT) is a new whole‐body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA‐PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA‐PET/CT should be used as a first‐line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA‐PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA‐PET/CT is incorporated into the management algorithm.
Objectives and Methods
The proPSMA trial is a prospective, multicentre study in which patients with untreated high‐risk PCa will be randomized to gallium‐68‐PSMA‐11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single‐photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high‐risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate‐specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line‐imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA‐PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow‐up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second‐line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter‐observer agreement and safety of PSMA‐PET/CT. Longer‐term follow‐up will also assess the prognostic value of a negative PSMA‐PET/CT.
Outcome and Significance
This trial will provide data to establish whether PSMA‐PET/CT should replace conventional imaging in the primary staging of select high‐risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.
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