Key articles from international medical journals Prof. Serdar Tekgül Section Editor Ankara (TR)
serdartekgul@ gmail.com
Do modern disposable diapers stimulate better bladder control in children? Over the last decades, the availability of modern disposable diapers (DD) has changed the way we manage our children. They are safe, easy to use, comfortable and easy to dispose, compared to cloth diapers used previously. Meanwhile, this has also changed our attitude to toilet training. Initiation of toilet training usually starts later compared to the past. Diapers play an important role in the management of enuresis-related issues and have significantly increased the quality of life of children as well as their family. Although many people will disagree, there is no evidence that the use of DD postpones the time of bladder control attainment, or that removal of the DD leads to resolution of enuresis. Yet many would recommend against using DD, as a first measure towards night-time dryness training. The NICE guideline on enuresis proposes trying non-diaper periods to assess any effect on enuresis frequency.
challenge. Parents have less time for TT, which makes the DD even more convenient, and necessary to cope with incontinence in small children.
were needed and performed in 11 patients. Eight patients were eventually diagnosed with a bulbar stricture, either isolated (n = 5) or combined with a distal stricture (n = 3), without significant relation The studies presented in this review show conflicting with the initial position of meatus. results. Several studies believe firmly in the association between diapering and prolonged Bulbar strictures represent more than 25% of the enuresis, other studies do not find this link. Whether overall strictures diagnosed in adult patients treated or not DD use has different effects on enuresis for hypospadias during childhood, independent of compared to daytime urinary incontinence is hard to the original site of urethral reconstruction. assess from the included studies, as all daytime cessation of DD is combined with some kind of TT. The study did not discuss length and exact location For the children with enuresis, avoidance of night of bulbar strictures, because of absence of data in diapers may lead to discomfort awakenings of both some patients. It was, however, observed that child and parents, interrupted and poor sleep symptomatic bulbar strictures do exist in adults in quality, further motivating the on-going use of DD the long term after penile hypospadias repair during until spontaneous resolution of symptoms occurs. childhood, independent of the initial site of hypospadias, initial success of primary repair, and It is possible to try to see whether children could the type of surgical reconstructions performed actually gain continence just by stopping the use of during childhood. DD, but there is no good evidence to support this Source: Adults with previous hypospadias practice.
Source: Does the development and use of modern disposable diapers affect bladder control? A systematic review. Breinbjerg A, Rittig S, Kamperis K. J Pediatr Urol 2021
Journal of Pediatric Urology, published online November 11 2021.
Aug;17(4):463-471.
High rate of bulbar strictures in patients treated for hypospadias
Although the subject is still insufficiently studied, increasing data appear in literature addressing the The aim of the review by the authors was to evaluate long-term complications of hypospadias repair. The the scientific knowledge on DD use in children with relationship with the initial procedure is a urinary incontinence, to assess whether DD use is challenging process of exploring the frequency of related to continence attainment. complications and understanding the variations. A systematic literature search looked at 400 studies which were eligible for screening. Finally, 12 abstracts and only eight studies were eligible for review. No prospective intervention studies specifically evaluating the effect of a diaper on enuresis were identified.
surgery during childhood: beware of bulbar strictures. Faraj S, Loubersac T, Bouchot O, et al.
There will always be a selection bias in such data, as it is almost impossible to have a good and strict follow-up of children into adulthood. Often we only see patients with problems, but not all the others who had a satisfactory outcome. Additionally, the information available about past surgical history and technique employed is not good enough to draw any conclusion on causative factors.
Outcomes analysis of the phase III ACIS trial for mCRPC In the present article, the authors reported the outcomes analysis of the phase III ACIS trial, comparing abiraterone acetate with or without apalutamide, in addition to androgen blockage, in metastatic, castration-resistant prostate cancer (PCa) patients. So far, no combination trial has proven any survival advantage at the mCRPC stage. The PLATO study, assessing the maintenance of enzalutamide at progression in addition to abiraterone, failed to demonstrate strong efficacy of the new hormonal agent combination, but this trial was conducted in the second-line setting.
In the ACIS trial, the primary endpoint was radiographic progression-free survival. Overall, 982 mCRPC, first-line, chemo-naive patients were included in this combination trial between 2014 and 2016. Secondary endpoints were overall survival, The general idea is that disposable diapers have time to initiation of cytotoxic chemotherapy, time to made a significant impact on toilet training in chronic opioid use, and time to pain progression. children, however, based on the available literature Treatment with apalutamide plus abiraterone led to Bulbar strictures are unexpectedly no secure conclusions can be drawn. There does a significant improvement in radiographic common among patients treated for progression-free survival compared with abiraterone seem to be some proof that diaper use is related to a delay in obtaining continence in children. (plus placebo) at the primary analysis (HR 0.69, 95% hypospadias and later presenting CI 0.58–0.83; p < 0.0001). At the final analysis (4.5 with urethral strictures …. years of follow-up), the significant radiographic … a robust correlation between progression-free survival benefit persisted (HR 0.70; Long-term hypospadias complications leading to p < 0.0001). Thus, despite the use of an active and diaper use and continence adult urologist consultation typically include established therapy as the comparator, apalutamide attainment cannot be found. stricture, cosmesis dissatisfaction, abnormal position plus abiraterone– prednisone improved radiographic of the meatus, urethrocutaneous fistula, and progression-free survival. The concordance between The use of DD is increasing as they become more persistent penile curvature. Urethral strictures stand central and investigator review of radiographic safe, reliable and accessible. DD have several as the most frequent long-term complication after progressive disease was 75%, with a high positive advantages in terms of comfort; newer materials hypospadias surgery during childhood. Urethral correlation coefficient for both treatments. decrease the risk of diaper dermatitis, and many strictures are more common at the site of the initial argue that they increase sleep quality in children surgery or along the neo-urethra. No overall survival benefit was achieved by the with enuresis. Along with the development of better combination. The median overall survival surpassed DD, there is a concern about an increase in age of The management in adult men remains challenging, 3 years with apalutamide plus abiraterone (36.2 initiating TT as well as an increase in the prevalence with several surgical strategies available and versus 33.7 months). At progression, about twoof LUTS in children, including enuresis. Although it is inconsistent results. This is especially true in men thirds of the patients who discontinued treatment tempting, a robust correlation between diaper use with a personal history of multiple stages of urethral received subsequent life-prolonging therapy. and continence attainment cannot be found, as no reconstruction during childhood. large randomised prospective studies have been Positive signal for combined performed evaluating only diapering as intervention. Bulbar strictures are unexpectedly common among hormone therapy in mCRPC The evidence on the effect of DD on enuresis and TT patients treated for hypospadias and later is not clear. It is not possible to draw any presenting with urethral strictures in adulthood. conclusions, although it seems that DD use might Moreover, none of the other secondary endpoints of have a negative influence on continence attainment. In this study, the authors look into a cohort of time to initiation of cytotoxic chemotherapy, time to One study reports a better chance of success when a patients who had hypospadias surgery in childhood chronic opioid use, and time to pain progression child wears diapers, but these findings were in and presented with urethral strictures. Hence there reached significance. Analyses of prespecified children > 11 years of age, and therefore not is a potential bias in the recruitment pattern and the biomarker subgroups based on molecular signatures comparable to the other cohorts described. lack of knowledge of the denominator (namely the (PAM50-luminal and androgen receptor signalling Therefore, impact of DD on TT is debatable. A number of hypospadias patients treated during activity) did not find any significant correlation with common assumption would be that the more childhood) and unavailability of medical detail in radiographic progression-free survival. Overall comfortable and convenient a diaper gets, the more ancient operative records. incidence of adverse events was similar between it takes to motivate the child and the parents to stop groups. Serious adverse events occurred in 40% using them. Of the 42 consecutive adults eligible, a total of 28 versus 37% of patients receiving apalutamide plus patients had a persistent urethral stricture. During abiraterone versus placebo plus abiraterone. Grade Because of the lack of comfortable and convenient adulthood, initial urethral assessment revealed 29 3-4 adverse events were reported in 60% versus diapers or better alternatives, TT was initiated at an urethral strictures in 28 patients (penile urethra 51% of patients receiving apalutamide plus earlier age in the past. The fact that more parents 23/29, bulbar urethra 8/29). The early initial success abiraterone versus placebo plus abiraterone. The both have full-time jobs and children spend the rate of stricture treatment was 50% (median most common adverse event was hypertension largest part of the day in day-care is an extra follow-up: 4 years). Additional surgical procedures (10%-17%). Cardiac disorders occurred with similar Key articles
8
Dr. Guillaume Ploussard Section editor Toulouse (FR)
g.ploussard@ gmail.com
frequency in both groups (19%) leading to 1% of deaths in both groups. Globally, safety was consistent with the previously reported tolerability profiles. Quality-of-line maintenance was equivalent in both arms. This trial is the first combo phase 3 study in castration-resistant prostate cancer that has met its primary endpoint. Nevertheless, no benefit was observed in terms of overall survival. Such a combination probably does not lead to changes in current guideline treatment recommendations. However, subgroup analyses may help to identify patients that would be more likely to benefit. A positive signal was seen in patients aged 75 years and older. For this specific population who may be unfit to receive subsequent therapy sequences, the initial combination of two active drugs could be interesting to consider. Future trials are awaited to better define combinations and sequencing at the mCRPC stage, in the era of the use of new hormonal agents in the metastatic castration-sensitive prostate cancer stage.
Source: Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castrationresistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Saad F, Efstathiou E, Attard G, et al; ACIS Investigators. Lancet Oncol. 2021 Sep 30:S1470-2045(21)00402-2
STAMPEDE trial: Comparison of quality-of-life outcomes Intensified systemic treatment is currently the standard treatment in metastatic prostate cancer. The choice is mainly based on new generation hormone therapy or docetaxel in addition to androgen therapy (ADT). Recently, after the presentation of the preliminary results of the PEACE1 trial during ESMO, the combination of abiraterone and docetaxel therapy has also been found to have an additional favourable impact. However, these different treatments may induce clinically meaningful side effects which may impact on the patient’s quality of life. In the present study, Rush et al report quality of life outcomes of men included in the same period in the Stampede trial, who were assigned to hormonal therapy plus docetaxel versus hormonal therapy plus abiraterone. Quality of life (QoL) was measured using the QLQ-C30 and PR25 questionnaires during a 2-year period.
This data, derived from a randomised controlled trial, provides important insight in a field where not much level 1 evidence is available. Interestingly, patients who received ADT plus abiraterone were found to have a more favourable global quality of life score than men who received upfront docetaxel, mainly during the first year after treatment initiation. Thereafter, the differences in QoL between the arms decreased with little differences in the second year. The toxicity of docetaxel mainly explained the QoL scores differences. Short-term differences in fatigue, pain, physical functioning, social functioning, and role functioning were also observed, favouring abiraterone treatment over docetaxel. This data, derived from a randomised controlled trial, provide important insight in a field where not much level 1 evidence is available. Patient-reported
EAU EU-ACME Office
European Urology Today
October/January 2022
