Urologyhttp://hdl.handle.net/20.500.12904/1682024-03-29T06:39:42Z2024-03-29T06:39:42ZPatient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancerKynaston, Hhttp://hdl.handle.net/20.500.12904/182432024-02-16T14:19:56Z2016-10-13T00:00:00ZPatient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer
Kynaston, H
Background: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. Conclusions: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).
2016-10-13T00:00:00ZAnticancer actions of carnosine in cellular models of prostate cancerKhan, M Ahttp://hdl.handle.net/20.500.12904/180572024-01-10T12:09:24Z2023-11-29T00:00:00ZAnticancer actions of carnosine in cellular models of prostate cancer
Khan, M A
Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (β-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments.
2023-11-29T00:00:00ZA repurposing programme evaluating repurposing transdermal oestradiol patches for the treatment of prostate cancer within the PATCH and STAMPEDE Trials: current results and adapting trial designKockelbergh, Rogerhttp://hdl.handle.net/20.500.12904/179202023-11-29T09:03:12Z2023-11-08T00:00:00ZA repurposing programme evaluating repurposing transdermal oestradiol patches for the treatment of prostate cancer within the PATCH and STAMPEDE Trials: current results and adapting trial design
Kockelbergh, Roger
Aims: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. Materials and methods: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. Results: to date: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. Future: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.
2023-11-08T00:00:00ZBladder pain syndrome and pregnancyIvare, AmyOblozo, Anetahttp://hdl.handle.net/20.500.12904/177702023-11-03T11:40:36Z2023-06-22T00:00:00ZBladder pain syndrome and pregnancy
Ivare, Amy; Oblozo, Aneta
Bladder pain syndrome (BPS) is a poorly understood condition. In pregnancy, lower urinary tract symptoms and pain are common, but the possibility of BPS is rarely considered and almost never explored. The consequences of BPS on pregnancy and vice versa are poorly understood, and management options appear to be limited. This article reviews the current evidence to allow us to better counsel, investigate, diagnose and manage patients with suspected or known BPS who fall pregnant or who are considering pregnancy. MEDLINE, EMBASE and PubMed were searched for a combination of mesh terms of keywords: 'cystitis', 'interstitial', 'bladder', 'pain' and 'pregnancy'. Relevant articles were identified, reviewed and further relevant articles identified from the references. CONCLUSION: BPS symptoms are very common in pregnancy, with limited data suggesting significant negative effects on the woman and pregnancy. There are safe options for investigation, diagnosis and management in pregnancy. There is a need to raise awareness of the impact of BPS symptoms in pregnancy and the available options for diagnoses and management, improving patient experience and outcomes. PATIENT SUMMARY: Patients with BPS or symptoms akin to BPS need not be abandoned in pregnancy. There is data to support them in making decisions around investigation and management in pregnancy.
2023-06-22T00:00:00Z