BJU International最新文献

Objectives: To prospectively compare systemic anti-tumour immune responses induced by irreversible electroporation (IRE) and robot-assisted radical prostatectomy (RARP) in patients with localised intermediate-risk prostate cancer (PCa).

Patients and methods: Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2-3, clinical cancer stage ≤T2c, prostate-specific antigen level <20 ng/mL). Patients were treated with IRE (n = 20) or RARP (n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa-specific T-cell responses to prostatic acid phosphatase (PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY-ESO-1]) were determined by interferon-γ enzyme-linked immunospot assay (ELISpot). Repeated-measures analysis of variance and two-sided Student's t-tests were used to compare immune responses over time and between treatment cohorts.

Results: Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory T cells (P = 0.0001) and a simultaneous increase in activated cytotoxic T-lymphocyte antigen 4 (CTLA-4)⁺ cluster of differentiation (CD)4⁺ (P < 0.001) and CD8⁺ (P = 0.032) T cells, consistent with reduction of systemic immune suppression allowing for effector T-cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY-ESO-1 specific T-cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies (P = 0.047) were consistent with transient immunosuppression after RARP.

Conclusions: Irreversible electroporation induces a PCa-specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA-4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high-risk localised or (oligo)metastatic disease.

Objective: To evaluate the safety, efficacy, tolerability, and cost-effectiveness of bedside or office-based ureteric stent insertion.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) and A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 guidelines, we searched PubMed/the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and Dimensions for English-language studies from 1978 to April 2023. Inclusion criteria focused on primary ureteric stent placements outside of the operating theatre (OT).

Results: A total of 15 studies involving 2072 stents were included. Success rates for correctly positioned stents in bedside or office-based insertions ranged from 60% to 95.8%, with most studies reporting ≥80% success rates. Common failure reasons included impacted stones and difficulty identifying the ureteric orifice. Pain and tolerability were assessed using various methods, with validated tools indicating moderate pain levels, but most patients would undergo the procedure again under local anaesthesia. Complication rates were generally low, with minor complications such as haematuria or postoperative fever being the most common. Procedural costs were significantly lower in non-OT settings, with estimates indicating savings of up to four-fold.

Conclusion: Bedside or office-based ureteric stent insertion is a viable alternative to OT procedures, offering high success rates, manageable pain levels, low complication rates, and substantial cost savings. This approach is particularly advantageous in settings with limited OT access, highlighting its potential for broader adoption in urological practice. Future research should focus on standardising pain assessment methods and randomised studies.

Objective: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC).

Patients and methods: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials.

Results: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030).

Conclusion: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

Objective: To compile and evaluate the heritability and inheritance patterns of lower urinary tract symptoms (LUTS) in adult cohorts.

Methods: Searches of five databases (PubMed, Embase, APA PsycInfo, Global Health, and OVID Medline) commenced on 6 July 2024, resulting in 736 articles retrieved after deduplication. Studies evaluating heritability patterns, gene frequencies, and familial aggregation of symptoms were included for review. Screening and predefined eligibility criteria produced 34 studies for final review. A descriptive analysis of synthesised data was performed, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool and the Johanna Briggs Institute checklist were used to evaluate these studies.

Results: Ten of the 34 studies (29%) described general LUTS, 14 (41%) described symptoms due to benign prostatic enlargement (BPE), nine (26%) described urinary incontinence (UI; urge UI [UUI], stress UI [SUI] and mixed UI [MUI]), four (12%) described nocturia alone, two (6%) described overactive bladder (OAB), and four (13%) described other specific symptoms (frequency, postvoid residual urine volume). BPE symptoms, UI (MUI and UUI), nocturia alone, and frequency alone were associated with genetic predisposition, whilst OAB and SUI had more modest inheritance.

Conclusion: The pathogenetic and pharmacological mechanisms fundamental to LUTS manifestation are highly heterogeneous. Further work is required to evaluate the inheritance patterns of LUTS more extensively.

Objective: To analyse the management and outcomes of individuals diagnosed with prostate cancer either before or after organ transplantation, as the impact of organ transplantation and associated immunosuppression on the incidence, progression, and mortality of prostate cancer remains an area of substantial clinical interest and uncertainty.

Patients and methods: We conducted a retrospective analysis of patients from two tertiary care centres who had solid organ transplantation and were diagnosed with prostate cancer before or after organ transplantation. Data collected included demographics and clinical information.

Results: The cohort consisted of 110 patients with a median (interquartile range [IQR]) age at prostate cancer diagnosis of 62 (56.6-67.2) years and a median (IQR) age at transplantation of 58.6 (52.7-65.3) years. Renal transplantation was the most common (54%). The median (IQR) prostate-specific antigen concentration at prostate cancer diagnosis was 6.2 (4.5-10) ng/mL, and the distribution of American Urological Association risk groups was: low risk, 36%; intermediate risk, 50%; and high risk, 14%. In all, 45 (41%) patients were diagnosed with prostate cancer prior to transplantation. Management included radical prostatectomy (RP; 62%), prostate radiotherapy (RT; 13%), and active surveillance (AS; 18%). During a median (IQR) follow-up of 5.8 (2.5-10) years from prostate cancer diagnosis, one (2%) patient developed metastatic disease. In all, 65 (59%) patients were diagnosed with prostate cancer subsequent to organ transplantation. Management included AS (29%), RT (45%), and RP (15%). During a median (IQR) follow-up of 5.3 (1-8.4) years, three patients (5%) developed metastatic disease. There were no deaths from prostate cancer.

Conclusion: A diagnosis of localised prostate cancer should not preclude solid organ transplantation, and the presence of a transplant does not appear to substantially impact risk of prostate cancer progression.