Optimal therapeutic management for cN1 M0 bladder cancer consists of perioperative systemic therapy and radical cystectomy. For patients with cN2-3 M0 disease, evidence supports upfront systemic therapy, preferably with...Optimal therapeutic management for cN1 M0 bladder cancer consists of perioperative systemic therapy and radical cystectomy. For patients with cN2-3 M0 disease, evidence supports upfront systemic therapy, preferably with enfortumab vedotin + pembrolizumab. Consolidative locoregional therapy may be an option in selected responders. Questions remain regarding the optimal duration of systemic therapy and the role of biomarkers. Multidisciplinary expert opinion can be critical for informed shared decision-making.
Radical cystectomy (RC) is the standard care for muscle-invasive or very high-risk non-muscle-invasive bladder cancer (BC), but optimal management for bladder preservation remains uncertain. In this multicentre, open-lab...Radical cystectomy (RC) is the standard care for muscle-invasive or very high-risk non-muscle-invasive bladder cancer (BC), but optimal management for bladder preservation remains uncertain. In this multicentre, open-label, phase 2 trial, patients with cT1-3 N0 M0 muscle-invasive BC received radiation therapy (RT; 41.4 Gy to the small pelvis and 16.2 Gy to the whole bladder) and atezolizumab (1200 mg) every 3 wk. The primary endpoint was progression-free survival (PFS) at 3 yr. Key secondary endpoints included the clinical complete response (cCR) rate at 24 wk, overall survival (OS), and the bladder-intact recurrence-free rate (BIRFR). From 2019 to 2021, 41 of the 45 patients enrolled received treatment. The median age was 71 yr and most patients (73%) had T2 tumours. At 24 wk, 84% achieved cCR. The 3-yr PFS rate was 70% (95% confidence interval [CI] 54-81%), with the lower limit of the 95% CI exceeding the prespecified threshold of 45%. The 3-yr OS rate was 91% and the 3-yr BIRFR was 89%. Grade ≥3 adverse events occurred in 55% of patients, but no treatment-related deaths were observed. Limitations include the single-arm design and cohort size. Bladder preservation therapy with atezolizumab and RT showed favourable treatment effects with manageable toxicity for patients unfit for or refusing RC.
Prostate-specific membrane antigen (PSMA)-targeting strategies in prostate cancer have evolved rapidly from early antibody-based approaches to highly effective diagnostic and therapeutic agents. While PSMA remains a cent...Prostate-specific membrane antigen (PSMA)-targeting strategies in prostate cancer have evolved rapidly from early antibody-based approaches to highly effective diagnostic and therapeutic agents. While PSMA remains a central benchmark in metastatic disease, biological heterogeneity and therapy resistance underscore the need for continued innovation and rational combination strategies.
Early studies highlight the promise of prostate-specific membrane antigen-targeted fluorescence-guided surgery. Realization of the full potential of this strategy will require ongoing technical refinement and the integra...Early studies highlight the promise of prostate-specific membrane antigen-targeted fluorescence-guided surgery. Realization of the full potential of this strategy will require ongoing technical refinement and the integration of hybrid-guided approaches, supported by high-quality clinical evidence, to translate feasibility into meaningful oncological benefits.
Ghadjar P, Hayoz S, Zwahlen DR
… +20 more, Hölscher T, Arnold W, Polat B, Hildebrandt G, Hoffmann E, Plasswilm L, Papachristofilou A, Schär C, Sumila M, Zaugg K, Guckenberger M, Ost P, Reuter C, Bosetti DG, Khanfir K, Riesterer O, Beck M, Thalmann GN, Aebersold DM, Swiss Group for Clinical Cancer Research (SAKK)
We report long-term outcomes from the phase 3 SAKK 09/10 trial that randomly assigned men with biochemical progression after radical prostatectomy to conventional-dose (64 Gy) or dose-intensified (70 Gy) salvage radiothe...We report long-term outcomes from the phase 3 SAKK 09/10 trial that randomly assigned men with biochemical progression after radical prostatectomy to conventional-dose (64 Gy) or dose-intensified (70 Gy) salvage radiotherapy (SRT) to the prostate bed without hormonal therapy. The primary endpoint was freedom from biochemical progression (FFBP). Secondary endpoints included clinical progression-free survival (PFS), time to hormonal treatment, overall survival (OS), and late toxicity. Between February 2011 and April 2014, 350 patients were randomly assigned (175 per arm). Median prostate-specific antigen (PSA) at randomization was 0.3 ng/ml. After median follow-up of 8.6 yr, median FFBP was 8.7 yr (95% confidence interval [CI] 7.1-not reached [NR]) after 64 Gy and 8.7 yr (95% CI 6.7-NR) after 70 Gy (log-rank p = 0.87), with a hazard ratio of 1.03 (95% CI 0.75-1.41). There was no significant difference in clinical PFS, time to hormonal treatment, or OS. While late genitourinary toxicity did not significantly differ between the arms, late grade 2 and 3 gastrointestinal toxicity was more frequent with 70 Gy (p = 0.015). After long-term follow-up dose-intensified SRT was not superior to conventional-dose SRT, but was associated with a higher rate of late grade ≥2 gastrointestinal toxicity. PATIENT SUMMARY: The optimal radiotherapy dose for patients who have higher levels of tumor markers after surgery for prostate cancer is unclear. Our long-term follow-up confirms that a higher dose only increases the chances of gastrointestinal side effects without providing any benefits to the patient. This trial is registered on ClinicalTrials.gov as NCT01272050.
Intravesical bacillus Calmette-Guérin (BCG) therapy remains the cornerstone for high-risk non-muscle-invasive bladder cancer (NMIBC), but up to 40% of patients experience disease recurrence or progression within 2 yr. We...Intravesical bacillus Calmette-Guérin (BCG) therapy remains the cornerstone for high-risk non-muscle-invasive bladder cancer (NMIBC), but up to 40% of patients experience disease recurrence or progression within 2 yr. We conducted a systematic review and meta-analysis of three phase 3 randomized trials POTOMAC, CREST, and ALBAN; n = 2590) in BCG-naïve high-risk NMIBC disease treated with a combination of BCG and an immune checkpoint inhibitor (ICI). Overall risk of bias was low for all studies. Combination therapy with BCG maintenance was associated with better event-free survival (EFS) in comparison to BCG alone (pooled hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.60-0.99; Q = 3.29, p = 0.2). Using the HR for high-grade recurrence from ALBAN, the pooled estimate was directionally consistent, but not statistically significant (HR 0.78, 95% CI 0.58-1.04; Q = 3.94, p = 0.1). Overall survival was comparable between groups (HR 0.92, 95% CI 0.67-1.26). Grade ≥3 treatment-related adverse events were more frequent with combination therapy (risk ratio [RR] 3.66, 95% CI 2.56-5.24 for BCG induction only; RR 3.97, 95% CI 2.54-6.21 for BCG induction + maintenance). There was a moderate decline in patient-reported quality of life in the ICI + BCG maintenance arms. These findings are supported by moderate-certainty evidence for EFS. BCG monotherapy remains the benchmark for BCG-naïve high-risk NMIBC. ICI addition improves EFS but increases high-grade toxicity, which should prompt cautious and individualized adoption pending mature survival data.
BACKGROUND AND OBJECTIVE: Testosterone deficiency (TD) is a common condition affecting patients' health and quality of life. Clinical management has changed over the past decades, particularly regarding the indications a...BACKGROUND AND OBJECTIVE: Testosterone deficiency (TD) is a common condition affecting patients' health and quality of life. Clinical management has changed over the past decades, particularly regarding the indications and outcomes of testosterone therapy (TTh). Our aim was to provide an overview of the available evidence supporting the use of TTh in adult men with TD. METHODS: A nonsystematic literature review was conducted to identify relevant studies on the diagnosis and treatment of TD. The review encompassed lifestyle and pharmacological approaches, summarizing recent advances and highlighting persisting gaps in clinical practice. KEY FINDINGS AND LIMITATIONS: Testosterone deficiency in adult men typically presents with mild, nonspecific symptoms often related to aging, including sexual dysfunction, fatigue, mood changes, and reduced muscle and bone mass. Diagnosis requires a thorough clinical assessment and confirmation of low serum total testosterone. TTh is the standard treatment for symptomatic men with TD and low testosterone levels. Evidence indicates that TTh improves sexual function, body composition, metabolic profile, and bone mineral density without increasing the risk of major cardiovascular events or prostate cancer. Current guidelines recommend maintaining testosterone within the midnormal range (450-600 ng/dl) and monitoring hematocrit, prostate-specific antigen, and metabolic parameters. Follow-up should occur at 3 mo and every 6-12 mo thereafter, with individualized adjustments based on clinical response and safety. CONCLUSIONS AND CLINICAL IMPLICATIONS: TTh is a safe and effective treatment for TD. The selection of the most suitable product should consider patient needs and preferences, as well as the physician's perspective.
Gallagher K, MacLennan S, Bhatt N
… +43 more, Clement K, Zimmermann E, Khadhouri S, Kulkarni M, Gaba F, Anbarasan T, Asif A, Light A, Ng A, Chan VW, Nathan A, Cooper D, Aucott L, Sakthivel D, Akand M, Piazza P, Marcq G, O'Brien T, Nielsen M, Giudice FD, Simpson K, Orecchia L, Teixeira B, Dawam D, Geisenhoff A, Hill G, Fukuokaya W, Hidalgo BG, El-Hajj A, Elgamal M, Fanshawe J, Wang B, Lee T, Manecksha R, McCann C, Rivas JG, Arda E, Elhadi M, Rossi S, Teoh JY, Mariappan P, Kasivisvanathan V, RESECT Global Study Group
BACKGROUND AND OBJECTIVE: We aimed to determine whether audit, feedback, and education improves surgical performance after transurethral resection of bladder tumour surgery for non-muscle-invasive bladder cancer and as a...BACKGROUND AND OBJECTIVE: We aimed to determine whether audit, feedback, and education improves surgical performance after transurethral resection of bladder tumour surgery for non-muscle-invasive bladder cancer and as a secondary aim if it reduced recurrence rates. METHODS: This cluster randomised controlled trial compared audit and feedback plus peer comparison and education, with audit alone for four coprimary outcomes: (1) Single-instillation chemotherapy, (2) detrusor muscle sampling, (3) documentation of tumour features, and (4) resection completeness. Early recurrence was a secondary outcome. KEY FINDINGS AND LIMITATIONS: A total of 100 sites were randomised to intervention and 101 to control. In total, 14 915 patients were included. Intervention sites significantly improved documentation of tumour features (adjusted mean difference [95% confidence interval {CI}]: 6.0 [1.8, 10], p = 0.005) and of resection completeness (adjusted mean difference [95% CI]: 5.5 [1.5, 9.5], p = 0.007). There was no statistically significant difference in chemotherapy use (adjusted mean difference [95% CI]: 0.3 [-4.7, 5.3], p = 0.9) or detrusor muscle sampling (adjusted mean difference [95% CI]: 2.6 [-1.3, 6.4], p = 0.2). There was no statistically significant difference in early recurrence rate between arms (adjusted odds ratio [95% CI]: 1.02 [0.8, 1.4], p = 0.9); however, in the control arm, the early recurrence rate reduced compared with baseline (adjusted odds ratio [95% CI]: 0.7 [0.6, 0.9]). CONCLUSIONS AND CLINICAL IMPLICATIONS: Audit and feedback with education improved the documentation of important surgical findings that influence clinical management, but not the performance of detrusor muscle sampling, adjuvant chemotherapy use, or early recurrence rates. Improvements observed in the control arm may explain a lack of effect of the intervention in some outcomes.