European Urology Today: June/July 2023

Bladder-sparing trimodality therapy for muscle-invasive bladder cancer Radical cystectomy is the most common treatment for muscle-invasive bladder cancer (MIBC). However, the surgery is associated with a substantial risk of complications and potential negative impact on quality of life. Not all patients are candidates for cystectomy due to frailty or comorbidities, and for others the surgery is not an acceptable treatment option. Proposed alternative treatment options in this situation are trimodality therapy (TMT), with maximal transurethral resection of the bladder tumour, radio sensitising chemotherapy and radiotherapy. Randomised clinical trials (RCT) comparing cystectomy with TMT have been tried but stopped early due to accrual problems. Despite the lack of results from RCTs, TMT is mentioned in several guidelines including the EAU Guidelines as an option in select well-informed patients. “This study brings further evidence in support of bladder- sparing TMT as a valid treatment option for the carefully selected and well- informed patient.” Zlotta and colleagues aimed to compare TMT with cystectomy in patients with cT2-4N0M0MIBC, where tumours were solitary and less than 7cm and with no extensive or multifocal carcinoma in situ, and no or only unilateral hydronephrosis. This was done using retrospective data from three large university hospitals in the USA and Canada and by performing a propensity score matched (PSM) and weighted analysis.

Postexposure doxycycline to prevent bacterial sexually transmitted infections In this randomised controlled trial, the authors have evaluated the impact of postexposure doxycycline in order to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM). This was an open-label, randomised study involving MSM and transgender women. All included participants were taking preexposure prophylaxis against human immunodeficiency virus (HIV) infection, were living with HIV infection or had had Neisseria gonorrhoeae (gonorrhoea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. The experimental arm included participants taking 200 mg of doxycycline within 72 hours after condomless sex. The control arm participants received standard care without doxycycline. STI testing was performed quarterly. “Relative risks of recurrent STIs were 0.45 for gonorrhoea, 0.12 for chlamydia, and 0.13 for

PSM was done by age, sex, presence of carcinoma in situ, clinical T-stage, Eastern Cooperative Oncology Group (ECOG) performance status, BMI, hydronephrosis, treatment with neoadjuvant or adjuvant chemotherapy, and smoking history. All patients included would have been candidates for both radical cystectomy and TMT. The decision to opt for TMT was based on patient choice. The authors included data from 722 patients, of which 440 underwent radical cystectomy and 282 TMT. The PSM cohort comprised of 1119 patients after 3:1 matching. The median follow-up time was between four and five years in both groups. In the PSM analysis, the 5-year metastasis-free survival was 74% (68–79) for TMT and 74% (95% CI 70–77) for radical cystectomy. There was no significant difference in 5-year cancer-specific survival, whereas overall survival favoured TMT; 72% (69–75) versus 77% (72–81) (HR 0·75 [0·58–0·97]; p=0.0078). Salvage cystectomy was performed in 38 of the TMT cases (13%) almost exclusively due to invasive recurrence. The authors make a strong conclusion based on their findings and argue that bladder-sparing TMT should be an option for all suitable candidates and part of the shared decision making and not only offered to those not suited for cystectomy. This study brings further evidence in support of bladder-sparing TMT as a valid treatment option for the carefully selected and well-informed patient. However, the nature of the study is still retrospective and despite vigorous efforts to control for confounders there is an unavoidable risk of selection bias, which should be remembered when counselling our patients. Hopefully, these data can inspire new collaborations to do the much-needed larger randomised clinical trial comparing TMT against cystectomy. Source: Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis. Zlotta AR, Ballas LK, Niemierko A, et al. Exp Clin Transplant 2023, 21(5):428-433. doi: 10.6002/ect.2023.0022.

Dr. Guillaume Ploussard Section editor Toulouse (FR)

g.ploussard @

Dr. Peter Østergren Section editor Copenhagen (DK)

peter.busch. oestergren@

main concern could be the number of tetracycline-resistant gonorrhoea in participants with STI (38.5% versus 12.5% in the doxycycline group). This interventional trial in a population at risk demonstrates that postexposure prophylaxis reduced by two thirds the rate of STI, and supports the use of doxycycline as postexposure prophylaxis in case of recent bacterial STIs. Source: Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. Luetkemeyer AF, Donnell D, Dombrowski JC, Cohen S, Grabow C, Brown CE, Malinski C, Perkins R, Nasser M, Lopez C, Vittinghoff E, Buchbinder SP, Scott H, Charlebois ED, Havlir DV, Soge OO, Celum C; DoxyPEP Study Team. N Engl J Med. 2023 Apr 6;388(14):1296-1306. doi: 10.1056/NEJMoa2211934

syphilis in the cohort of participants taking HIV prophylaxis.“

Overall, 501 participants were included, mostly those who were taking pre-exposure prophylaxis against HIV. An STI in quarterly visits was diagnosed in 10.7% of participants in the doxycycline group versus 31.9% in the standard-care group (OR 0.34 ; P<0.001). The same differences were seen whatever the inclusion criteria used. The relative risks of recurrent STIs were 0.45 (95% CI, 0.32 to 0.65) for gonorrhoea, 0.12 (95% CI, 0.05 to 0.25) for chlamydia, and 0.13 (95% CI, 0.03 to 0.59) for syphilis in the cohort of participants taking HIV prophylaxis. Only 5 grade 3 adverse events occurred without link with doxycycline. The

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European Urology Today June/July 2023


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