IntroductionSurvival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.MethodsA phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and disseminationApproved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03763253; ISCRTN58401737
Context White light (WL) cystoscopy and transurethral resection of bladder tumour (TURBT) comprise the current gold standard technique for detecting and grading bladder cancer. However, with WL cystoscopy, recurrence following initial TURBT is high, and identification of smaller tumours and carcinoma in situ is poor. Photodynamic diagnosis (PDD) has been developed to improve the detection of bladder. Objective To assess the effect of PDD-guided TURBT compared with WL on recurrence rates (RRs) in non–muscle-invasive bladder cancer (NMIBC). Evidence acquisition A systematic review of the literature from inception to April 2020 using Medline, EMBASE, and CENTRAL was undertaken. Randomised control trials comparing TURBT undertaken with PDD to WL that reported RRs of at least 12 mo were included in the analysis. The primary outcomes were RRs at 12 and 24 mo. The secondary outcomes were reported adverse effects. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of the evidence. Evidence synthesis Twelve randomised controlled trials (2288 patients) were included for the meta-analysis. PDD was found to reduce RRs at 12 mo (RR 0.73, confidence interval [CI] 0.60–0.88) and 24 mo (RR 0.75, CI 0.62–0.91). There was an increased risk of recurrence for patients undergoing WL at 12 mo (hazard ratio [HR] 1.14, CI 1.05–1.23) and 24 mo (HR 1.25, CI 1.15–1.35). Two studies reported recurrence data at 60 mo showing statistically significant outcomes in favour of PDD: one showed lower RRs for PDD (49% PDD vs 68% WL), whilst the other showed increased recurrence-free survival (68.2% PDD vs 57.3% WL). Adverse effects appeared to be minimal, though poorly reported. A GRADE analysis showed the evidence to be of moderate certainty overall. Conclusions This systematic review found that PDD reduced RRs and improved recurrence-free survival compared with WL in NMIBC over at least 2-yr follow-up. These effects may persist up to 5 yr. Further research in a pragmatic study looking at longer-term outcomes beyond 24 mo will help guide recommendations on clinical adoption. Patient summary This review suggests that photodynamic diagnosis, compared with white light cystoscopy, improves recurrence-free survival in non–muscle-invasive bladder cancer over at least 2 yr of follow-up. However, confirmatory pragmatic studies with longer-term outcomes are required for its clinical adoption.
Robot-assisted surgical systems (RASS) have revolutionised the management of many urological conditions over the last two decades with robot-assisted radical prostatectomy (RARP) now being considered by many to be the preferred surgical approach. Intuitive Surgical has dominated the market during this time period with successive iterations of the da Vinci model. The expiration of patents has opened the RASS market and several new contenders have become available or are currently in development. This comprehensive narrative review aims to explore the merits of each robotic system as well as the evidence and barriers to their use. The newly developed RASS have increased the versality of robotic surgical systems to a wider range of settings through advancement in technology. The increased competition may result in an overall reduction in cost, broadening the accessibility of RASS. Learning curves and training remain a barrier to their use, but the situation appears to be improving through dedicated training programmes. Outcomes for RARP have been well investigated and tend to support improved early functional outcomes. Overall, the rapid developments in the field of robot-assisted surgery indicate the beginning of a promising new era to further enhance urological surgery.
Purpose of Review Upper tract urothelial carcinoma (UTUC) is uncommon accounting for less than 10% of all urothelial tumours. Ureteroscopic management (URS) is the first line treatment for low-risk disease and has been increasingly utilised due to technological advances and increasing surgical experience. This review looks at patient outcomes relating to URS, emerging technologies and the role of adjuvant intracavitary therapy in the management of UTUC. Recent Findings URS has firmly established itself in the management algorithm for UTUC, and a good body of evidence supports its use for low-risk disease, wherein oncological outcomes are comparable to traditional nephroureterectomy (RNU). Larger tumours can now be managed using URS with a lower morbidity than radical surgery, though with higher associated local recurrence rate and risk of progression to RNU, and as a result, patient selection and close surveillance remains key. There is limited evidence for adjuvant intracavitary therapy (Mitomycin C or BCG) in UTUC although the development of novel polymers and biodegradable stents may improve drug delivery to the upper urinary tract. Summary URS has a clearly defined role in low-risk UTUC, and its use in larger tumours appears to be appropriate in a selected cohort of patients. The efficacy of adjuvant intracavitary therapy is as of yet undetermined, though developments in delivery techniques are promising. Likewise further developments of laser technology are anticipated to further expand the role of URS.
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