First-line management of metastatic urothelial cancer: Current and future perspectives after the EV-302 and CcheckMate-901 studies

The standard of care for the first-line management of metastatic urothelial carcinoma has been recently challenged, with the combination of pembrolizumab and enfortumab vedotin (P-EV) strongly arising as a practice-changing option from classical platinum-based chemotherapies. With this paradigm shift on the horizon new questions, including the most suitable second line of treatment for these patients, and the role that the molecular characterization of these tumours will have when selecting these therapies will inevitably arise. Furthermore, after the negative results of the Keynote 361 and IMvigor 130 trials, the combination of nivolumab with platinum-based chemotherapy followed by nivolumab maintenance (Nivo GC-Nivo) has also shown positive results when compared with chemotherapy alone. Translational studies at a molecular, cellular, and functional level will be key to better explain these discordant results. In this Current Perspective, we discuss the potential impact of these results in clinical practice and propose specific guidance for prospective translational research

Focal therapy of prostate cancer index lesion with irreversible electroporation. A prospective study with a median follow-up of 3 years

Purpose: Our aim was to assess oncologic, safety, and quality of lifeerelated outcomes of focal therapy with irreversible electroporation in men with localized prostate cancer. Materials and Methods: This was a single-center, phase II study. Inclusion criteria: prostate cancer International Society of Urological Pathology grade 1-2, prostate specific antigen 15 ng/ml, cT2b. Patients were selected based on multiparametric magnetic resonance imaging and transperineal systematic and targeted magnetic resonance imagingeultrasound fusioneguided biopsy. Ablation of index lesions with safety margin was performed. Primary end point was cancer control, defined as the absence of any biopsy-proven tumor. A control transperineal biopsy was planned at 12 months and when suspected based on prostate specific antigen and/or multiparametric magnetic resonance imaging information. Quality of life was assessed using Expanded Prostate Cancer Index Composite Urinary Continence domain, International Index of Erectile Function, and International Prostate Symptom Score. Results: From November 2014 to July 2021, 41 consecutive patients were included with a median follow-up of 36 months. Thirty patients (73%) had International Society of Urological Pathology grade 1 tumors, 10 (24%) grade 2, and 1 (2.4%) grade 3. Recurrence was observed in 16 of 41 (39%) of the whole cohort, and 16 of 33 (48.4%) who underwent biopsy. In-field recurrence was detected in 5 (15%) and out-of-field in 11 (33.3%). Ten of 41 (24.6%) including 3 of 5 (60%) with in-field recurrences had significant tumors (Gleason pattern 4-5; more than 1 core or any >5 mm involved). Median recurrence-free survival was 32 months (95% CI 6.7-57.2). Twentysix patients (63.4%) were free from salvage treatment. All patients preserved urinary continence. Potency was maintained in 91.8%. Conclusions: Irreversible electroporation can achieve satisfactory 3-year in-field tumor control with excellent quality of life results in selected patients

What is the impact of post‐radical prostatectomy urinary incontinence on everyday quality of life? Linking Pad usage and International Consultation on Incontinence Questionnaire Short‐Form (ICIQ‐SF) for a COMBined definition (PICOMB definition)

Aims: To identify the definition for urinary continence (UC) after radical prostatectomy (RP) which reflects best patients' perception of quality of life (QoL). Methods: Continence was prospectively assessed in 634 patients, 12 months after RP using the International Consultation on Incontinence Questionnaire Short‐Form (ICIQ‐SF) and the number of pads employed in a 24‐hour period (pad usage). We used the one‐way ANOVA technique with posthoc pairwise comparisons according to Scheffé's method (homogeneous subsets) for assessing the degree of QoL deficit related to urinary incontinence (UI). Results: The continence prevalence is 64.4%, 74.1%, 88.3%, and 35.8% using “0 pads,” “1 safety pad,” “1 pad,” and “ICIQ score 0” definitions, respectively. Pad usage is moderately strongly associated with ICIQ 1, 2, and 3 (ρ = 0.744, 0.677, and 0.711, respectively; p < 0.001). Concordance between classical UC definitions is acceptable between “0 pads—ICIQ score 0” (K = 0.466), but poor for “1 safety pad” and “1 pad” (K = 0.326 and 0.137, respectively). Patients with “0 pad usage” have better QoL related to urine leakage than patients with “1 safety pad” or “1 pad” (1.41 vs. 2.44 and 3.11, respectively; p < 0.05). There were no significant differences found regarding QoL between patients with ICIQ score 0 and ICIQ score 2 (1.01 vs. 1.63; p = 0.63).Conclusions: Pad usage and the ICIQ‐SF's answers provide useful information. We propose a combined definition (0 pads and ICIQ score ≤2) as it is the definition with the least impact on daily QoL